Portal vein thrombosis(PVT) is encountered in livercirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical out...Portal vein thrombosis(PVT) is encountered in livercirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication.We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation,and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%.PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions.展开更多
AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).
AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastat...AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.展开更多
Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explor...Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer. Methods The expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetraz.olium （MTT） was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin β1 and vascular endothelial growth factor-C （VEGF-C） mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12. Results Under serum-free suboptimal culture conditions, CXCL12 （100 ng/ml） significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups （0.428 ± 0.051 vs. 0.325 ±0.045 and 0.328±0.039, P〈0.05）. This enhancing effect of CXCL12 was significantly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml CXCR4 antagonist AMD3100. However, 10 μg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control （migration： 523.3± 25.2 vs 108.0 ± 7.2; invasion： 39.3 ± 4.0 vs. 4.0 ± 1.0）. The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 （100 ng/ml vs 10 ng/ml： migration, 523.3 ± 25.2 vs 211.7 ± 24.7; invasion, 39.3 ± 4.0 vs 15.7 ± 3.1, P〈0.05）, and was strongly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly展开更多
BACKGROUND Red blood cell distribution width(RDW)is elevated in patients with cardiovascular disease(CVD).AIM To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized...BACKGROUND Red blood cell distribution width(RDW)is elevated in patients with cardiovascular disease(CVD).AIM To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD.METHODS This prospective study included 204 consecutive elderly patients(age 77.5[7.41]years,female 94[46%],left ventricular ejection fraction 53.00%[37.50,55.00])hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital(Larissa,Greece)from January 2019 to April 2019.Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population.Hospitalized patients with acute CVD(acute coronary syndromes,new-onset heart failure[HF],and acute pericarditis/myocarditis),primary isolated valvular heart disease,sepsis,and those with a history of blood transfusions or cancer were excluded.The evaluation of the patients within 24 h from admission included clinical examination,laboratory blood tests,and echocardiography.RESULTS The most common cardiac morbidities were hypertension and coronary artery disease,with acutely decompensated chronic heart failure(ADCHF)and atrial fibrillation(AF)also frequently being present.The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus,chronic obstructive pulmonary disease,and sleep apnea.RDW was significantly elevated 15.48(2.15);121(59.3%)of patients had RDW>14.5%which represents the upper limit of normal in our institution.Factors associated with RDW in stepwise regression analysis were ADCHF(coefficient:1.406;95%confidence interval[CI]:0.830-1.981;P<0.001),AF(1.192;0.673 to 1.711;P<0.001),and anemia(0.806;0.256 to 1.355;P=0.004).ADCHF was the most significant factor associated with RDW.RDW was on average 1.41 higher for patients with than without ADCHF,1.19 higher for patients with than without AF,and 0.81 higher for patients with than without anemia.When patients were grouped based on the presence or absence of anemia,ADCHF 展开更多
Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease asso...Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.展开更多
Background von Willebrand factor （vWF） mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arterial stenosis. On release...Background von Willebrand factor （vWF） mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arterial stenosis. On release from endothelial cells, vWF is rapidly cleaved by ADAMTS13/vWF-cleaving protease （vWF-CP）. We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay （ELISA） and residual collagen binding assay respectively in patients with lupus nephritis （n=31）, primary nephritic syndrome （n=25）, diabetic nephropathy （n=45）, chronic glomerulonephritis （n=38） and 40 normal controls. The relation of their levels with pathological and renal status was analyzed.Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls （both P〈0.01）. vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity, vWF-CP activity was not changed two weeks after renal transplantation. Renal biopsy demonstrated that the vWF level in stage IV was higher than in stages II and III while vWF-CP activity was lower in patients with lupus nephritis. After eight-week treatment, the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema, disease activity index 〈9, but not with index 〉9. Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease, mesangial proliferative glomerulonephritis or IgA glomerulonephritis, the vWF level was not significantly different. Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies. Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF level and lower vWF-CP activity in chronic renal disease and thus展开更多
Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging sys...Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients. Methods Between February 1990 to August 2004, 206 patients （138 men and 68 women, mean aged （59±11） years） who were initially diagnosed as multiple myeloma in Changzheng Hospital （Shanghai, China） and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients. Results The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum β2 microglobulin and high C-reactive protein. Among these, only C-reactive protein, β2 microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System. Conclusions High β2 microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.展开更多
Smart nanoparticles,which can respond to biological cues or be guided by them,are emerging as a promising drug delivery platform for precise cancer treatment.The field of oncology,nanotechnology,and biomedicine has wi...Smart nanoparticles,which can respond to biological cues or be guided by them,are emerging as a promising drug delivery platform for precise cancer treatment.The field of oncology,nanotechnology,and biomedicine has witnessed rapid progress,leading to innovative developments in smart nanoparticles for safer and more effective cancer therapy.In this review,we will highlight recent advancements in smart nanoparticles,including polymeric nanoparticles,dendrimers,micelles,liposomes,protein nanoparticles,cell membrane nanoparticles,mesoporous silica nanoparticles,gold nanoparticles,iron oxide nanoparticles,quantum dots,carbon nanotubes,black phosphorus,MOF nanoparticles,and others.We will focus on their classification,structures,synthesis,and intelligent features.These smart nanoparticles possess the ability to respond to various external and internal stimuli,such as enzymes,pH,temperature,optics,and magnetism,making them intelligent systems.Additionally,this review will explore the latest studies on tumor targeting by functionalizing the surfaces of smart nanoparticles with tumor-specific ligands like antibodies,peptides,transferrin,and folic acid.We will also summarize different types of drug delivery options,including small molecules,peptides,proteins,nucleic acids,and even living cells,for their potential use in cancer therapy.While the potential of smart nanoparticles is promising,we will also acknowledge the challenges and clinical prospects associated with their use.Finally,we will propose a blueprint that involves the use of artificial intelligence-powered nanoparticles in cancer treatment applications.By harnessing the potential of smart nanoparticles,this review aims to usher in a new era of precise and personalized cancer therapy,providing patients with individualized treatment options.展开更多
Objective： To investigate the effect of Yisui Shengxue Granule （益髓生血颗粒, YSSXG）, a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H （HbH） disease. Methods： T...Objective： To investigate the effect of Yisui Shengxue Granule （益髓生血颗粒, YSSXG）, a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H （HbH） disease. Methods： Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin （Hb）, red blood cells （RBCs）, and reticulocyte percent （Ret）] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy （TEM）; activities of antioxidant defense enzymes [superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, and catalase （Cat）] and erythrocyte membrane malondialdehyde （MDA） concentrations were determined. Results： In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment （P〈0.01）. Measured values of Ret from the second to the third months aftertreatment were significantly lower than before treatment （P〈0.05 and P〈0.01, respectively）. Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity （P〈0.01）, a decrease in Cat activity （P〈0.01）, and no significant differences in GSH-Px activity （P〉0.05） or MDA concentration （P〉0.05）. However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels （P〈0.01） both before and after treatment. Conclusions： YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation o展开更多
Objective To screen the key Chinese Herbal Medicines(KCHMs)against breast cancer by data mining,and analyze the potential mechanism of KCHMs using network pharmacology method.Methods Clinical prescriptions consisted o...Objective To screen the key Chinese Herbal Medicines(KCHMs)against breast cancer by data mining,and analyze the potential mechanism of KCHMs using network pharmacology method.Methods Clinical prescriptions consisted of CHMs for treating breast cancer were screened,and then Traditional Chinese Medicine Inheritance Support System(TCMISS)was applied to obtain the KCHMs.Subsequently,active ingredients and corresponding target genes of KCHMs were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,and target genes of breast cancer were collected using OMIM and MalaCards.After that,the overlapping target genes of KCHMs and breast cancer were screened,and the protein-protein interaction(PPI)network was built.In addition,a network of“KCHMs-active ingredients-breast cancer-targets”was constructed by Cytoscape 3.7.1.Finally,Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)analysis were performed with Database for Annotation,Visualization and Integrated Discovery(DAVID)database to reveal the action mechanism of KCHMs.Results A total of 7 KCHMs were identified,whose active ingredients include quercetin,luteolin,nobiletin,kaempferol,isorhamnetin,naringenin,and be-ta-sitosterol,etc.Based on protein-protein interaction analysis,core targets were ESR1,MYC,CCND1,EGFR,CASP3,ERBB2,etc.Several KEGG pathways(e.g,PI3K-Akt,p53,ErbB,and HIF-1 signaling pathways)were found.Conclusion Based on the combination of the data mining method and network pharmacology approach,the therapeutic effect of KCHMs on breast cancer may be realized by acting on target genes and signaling pathways related to the formation and progression of breast cancer.展开更多
The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with signif...The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage IV disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies, improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition. This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.展开更多
Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subseque...Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall s展开更多
Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explo...Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made. Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis （GconC） and their related clinical issues. Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa （12 of 32） and deep ulcers （2 of 7） were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively. Conclusions Following allo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.展开更多
Background In multiple myeloma （MM）, bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and ...Background In multiple myeloma （MM）, bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells. Methods RPMI 8226 cells were cocultured with human umbilical vein endothelial cells （HUVECs） to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol （6.25-50.00 pmol/L） for different times （12-72 hours）. Reverse transcriptase polymerase chain reaction （RT-PCR） was used to assay vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF）, metalloproteinases （MMP）-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay （ELISA）. Results Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPM18226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression. Conclusions Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.展开更多
Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with ...Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.展开更多
Background Multiple sclerosis （MS） is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantati...Background Multiple sclerosis （MS） is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation （ASCT） has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS. Methods Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide, melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months （range, 6 to 59 months）. Results No death occurred following the treatment. The overall confirmed progression free survival rate was 77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation （P=0.000）. Thirteen patients （59%） had remarkable improvement in neurological manifestations, four （18%） stabilized their disability status and five （23%） showed clinical recurrence of active symptoms. Conclusions ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.展开更多
The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal ca...The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage 11 disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.展开更多
The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnos...The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilat展开更多
BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve comp...BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.展开更多
文摘Portal vein thrombosis(PVT) is encountered in livercirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication.We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation,and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%.PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions.
文摘AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).
文摘AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.
文摘Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer. Methods The expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetraz.olium （MTT） was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin β1 and vascular endothelial growth factor-C （VEGF-C） mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12. Results Under serum-free suboptimal culture conditions, CXCL12 （100 ng/ml） significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups （0.428 ± 0.051 vs. 0.325 ±0.045 and 0.328±0.039, P〈0.05）. This enhancing effect of CXCL12 was significantly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml CXCR4 antagonist AMD3100. However, 10 μg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control （migration： 523.3± 25.2 vs 108.0 ± 7.2; invasion： 39.3 ± 4.0 vs. 4.0 ± 1.0）. The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 （100 ng/ml vs 10 ng/ml： migration, 523.3 ± 25.2 vs 211.7 ± 24.7; invasion, 39.3 ± 4.0 vs 15.7 ± 3.1, P〈0.05）, and was strongly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly
文摘BACKGROUND Red blood cell distribution width(RDW)is elevated in patients with cardiovascular disease(CVD).AIM To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD.METHODS This prospective study included 204 consecutive elderly patients(age 77.5[7.41]years,female 94[46%],left ventricular ejection fraction 53.00%[37.50,55.00])hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital(Larissa,Greece)from January 2019 to April 2019.Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population.Hospitalized patients with acute CVD(acute coronary syndromes,new-onset heart failure[HF],and acute pericarditis/myocarditis),primary isolated valvular heart disease,sepsis,and those with a history of blood transfusions or cancer were excluded.The evaluation of the patients within 24 h from admission included clinical examination,laboratory blood tests,and echocardiography.RESULTS The most common cardiac morbidities were hypertension and coronary artery disease,with acutely decompensated chronic heart failure(ADCHF)and atrial fibrillation(AF)also frequently being present.The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus,chronic obstructive pulmonary disease,and sleep apnea.RDW was significantly elevated 15.48(2.15);121(59.3%)of patients had RDW>14.5%which represents the upper limit of normal in our institution.Factors associated with RDW in stepwise regression analysis were ADCHF(coefficient:1.406;95%confidence interval[CI]:0.830-1.981;P<0.001),AF(1.192;0.673 to 1.711;P<0.001),and anemia(0.806;0.256 to 1.355;P=0.004).ADCHF was the most significant factor associated with RDW.RDW was on average 1.41 higher for patients with than without ADCHF,1.19 higher for patients with than without AF,and 0.81 higher for patients with than without anemia.When patients were grouped based on the presence or absence of anemia,ADCHF
基金Supported by Research grant,No.103544/2016-PLaqueIMAGE,contract No.26/01.09.2016financed by the Romanian Ministry of European Funds,the Romanian Government and the European Union
文摘Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 30470732）, the ＂211＂ Engineering Project of Soochow University （No. R2317175）, and the Soochow Science ＆ Technology for Medicine （No. SWQ14）.
文摘Background von Willebrand factor （vWF） mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arterial stenosis. On release from endothelial cells, vWF is rapidly cleaved by ADAMTS13/vWF-cleaving protease （vWF-CP）. We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay （ELISA） and residual collagen binding assay respectively in patients with lupus nephritis （n=31）, primary nephritic syndrome （n=25）, diabetic nephropathy （n=45）, chronic glomerulonephritis （n=38） and 40 normal controls. The relation of their levels with pathological and renal status was analyzed.Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls （both P〈0.01）. vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity, vWF-CP activity was not changed two weeks after renal transplantation. Renal biopsy demonstrated that the vWF level in stage IV was higher than in stages II and III while vWF-CP activity was lower in patients with lupus nephritis. After eight-week treatment, the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema, disease activity index 〈9, but not with index 〉9. Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease, mesangial proliferative glomerulonephritis or IgA glomerulonephritis, the vWF level was not significantly different. Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies. Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF level and lower vWF-CP activity in chronic renal disease and thus
文摘Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients. Methods Between February 1990 to August 2004, 206 patients （138 men and 68 women, mean aged （59±11） years） who were initially diagnosed as multiple myeloma in Changzheng Hospital （Shanghai, China） and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients. Results The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum β2 microglobulin and high C-reactive protein. Among these, only C-reactive protein, β2 microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System. Conclusions High β2 microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.
基金supported by the National Natural Science Foundation of China(U2230123,31900984,81972901,82304969,82304789)the National Key Research and Development Program of China(2020YFC2005500)+2 种基金the Central Guide Local Science and Technology Development Fund(2022ZYD0080)the Key Research and Development Program of Science and Technology Department of Sichuan Province(2023YFS0110,2023YFS0125,2023YFS0131,2023NSFSC0033,2022YFS0159,2022YFS0606,2019YFS0514)China Postdoctoral Science Foundation(2022M710623,2022M720670).
文摘Smart nanoparticles,which can respond to biological cues or be guided by them,are emerging as a promising drug delivery platform for precise cancer treatment.The field of oncology,nanotechnology,and biomedicine has witnessed rapid progress,leading to innovative developments in smart nanoparticles for safer and more effective cancer therapy.In this review,we will highlight recent advancements in smart nanoparticles,including polymeric nanoparticles,dendrimers,micelles,liposomes,protein nanoparticles,cell membrane nanoparticles,mesoporous silica nanoparticles,gold nanoparticles,iron oxide nanoparticles,quantum dots,carbon nanotubes,black phosphorus,MOF nanoparticles,and others.We will focus on their classification,structures,synthesis,and intelligent features.These smart nanoparticles possess the ability to respond to various external and internal stimuli,such as enzymes,pH,temperature,optics,and magnetism,making them intelligent systems.Additionally,this review will explore the latest studies on tumor targeting by functionalizing the surfaces of smart nanoparticles with tumor-specific ligands like antibodies,peptides,transferrin,and folic acid.We will also summarize different types of drug delivery options,including small molecules,peptides,proteins,nucleic acids,and even living cells,for their potential use in cancer therapy.While the potential of smart nanoparticles is promising,we will also acknowledge the challenges and clinical prospects associated with their use.Finally,we will propose a blueprint that involves the use of artificial intelligence-powered nanoparticles in cancer treatment applications.By harnessing the potential of smart nanoparticles,this review aims to usher in a new era of precise and personalized cancer therapy,providing patients with individualized treatment options.
基金Supported by the National Natural Science Foundation of China (No.90409003)the National Basic Research Program(973 Program.No.2010CB530406)
文摘Objective： To investigate the effect of Yisui Shengxue Granule （益髓生血颗粒, YSSXG）, a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H （HbH） disease. Methods： Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin （Hb）, red blood cells （RBCs）, and reticulocyte percent （Ret）] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy （TEM）; activities of antioxidant defense enzymes [superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, and catalase （Cat）] and erythrocyte membrane malondialdehyde （MDA） concentrations were determined. Results： In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment （P〈0.01）. Measured values of Ret from the second to the third months aftertreatment were significantly lower than before treatment （P〈0.05 and P〈0.01, respectively）. Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity （P〈0.01）, a decrease in Cat activity （P〈0.01）, and no significant differences in GSH-Px activity （P〉0.05） or MDA concentration （P〉0.05）. However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels （P〈0.01） both before and after treatment. Conclusions： YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation o
基金the Science and Technology Planning Project of Guangdong Province of China(No.2017A020213017)。
文摘Objective To screen the key Chinese Herbal Medicines(KCHMs)against breast cancer by data mining,and analyze the potential mechanism of KCHMs using network pharmacology method.Methods Clinical prescriptions consisted of CHMs for treating breast cancer were screened,and then Traditional Chinese Medicine Inheritance Support System(TCMISS)was applied to obtain the KCHMs.Subsequently,active ingredients and corresponding target genes of KCHMs were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,and target genes of breast cancer were collected using OMIM and MalaCards.After that,the overlapping target genes of KCHMs and breast cancer were screened,and the protein-protein interaction(PPI)network was built.In addition,a network of“KCHMs-active ingredients-breast cancer-targets”was constructed by Cytoscape 3.7.1.Finally,Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)analysis were performed with Database for Annotation,Visualization and Integrated Discovery(DAVID)database to reveal the action mechanism of KCHMs.Results A total of 7 KCHMs were identified,whose active ingredients include quercetin,luteolin,nobiletin,kaempferol,isorhamnetin,naringenin,and be-ta-sitosterol,etc.Based on protein-protein interaction analysis,core targets were ESR1,MYC,CCND1,EGFR,CASP3,ERBB2,etc.Several KEGG pathways(e.g,PI3K-Akt,p53,ErbB,and HIF-1 signaling pathways)were found.Conclusion Based on the combination of the data mining method and network pharmacology approach,the therapeutic effect of KCHMs on breast cancer may be realized by acting on target genes and signaling pathways related to the formation and progression of breast cancer.
文摘The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage IV disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies, improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition. This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.
基金supported by Grants from the Key Program of the National Natural Science Foundation of China(81230013)the Major State Basic Research Development Program of China(973 Program,2013CB733701)+2 种基金the Nature Science Foundation of China(81170483,81570130 and 81370639)the Beijing Municipal Science and Technology Commission(Z141100000214011)support from the NIHR Biomedical Research Centre funding scheme
文摘Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall s
文摘Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made. Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis （GconC） and their related clinical issues. Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa （12 of 32） and deep ulcers （2 of 7） were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively. Conclusions Following allo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.
文摘Background In multiple myeloma （MM）, bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells. Methods RPMI 8226 cells were cocultured with human umbilical vein endothelial cells （HUVECs） to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol （6.25-50.00 pmol/L） for different times （12-72 hours）. Reverse transcriptase polymerase chain reaction （RT-PCR） was used to assay vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF）, metalloproteinases （MMP）-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay （ELISA）. Results Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPM18226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression. Conclusions Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.
文摘Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.
基金This study was supported by the Education Grant for Talented Person in Beijing (No. 2004ID0501823).
文摘Background Multiple sclerosis （MS） is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation （ASCT） has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS. Methods Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide, melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months （range, 6 to 59 months）. Results No death occurred following the treatment. The overall confirmed progression free survival rate was 77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation （P=0.000）. Thirteen patients （59%） had remarkable improvement in neurological manifestations, four （18%） stabilized their disability status and five （23%） showed clinical recurrence of active symptoms. Conclusions ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.
文摘The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage 11 disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.
基金supported(in part)by the National Key Research and Development Program of China(2020YFC0845500)the Special Project for Emergency of Hubei Province(2020FCA008)the First Level Funding of the Second Medical Leading Talent Project in Hubei Province。
文摘The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilat
基金Supported by the Jinan Clinical Medical Science and Technology Innovation Plan,No.202019141Norman Bethune Foundation-Feifan Iron Supplement Project,No.ffbt-C-2022-010.
文摘BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.
