Background:The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma(HCC)patients with solitary tumor and microvascular invasion(MVI)is controversial.This trial evaluated the effi...Background:The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma(HCC)patients with solitary tumor and microvascular invasion(MVI)is controversial.This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization(TACE)after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor≥5 cm and MVI.Methods:In this randomized,open-labeled,phase III trial,HCC patients with a solitary tumor≥5 cm and MVI were randomly assigned(1:1)to receive either 1-2 cycles of adjuvant TACE after hepatectomy(Hepatectomy-TACE)or hepatectomy alone(Hepatectomy Alone).The primary endpoint was disease-free survival(DFS);the secondary end-points included overall survival(OS)and adverse events.Results:Between June 1,2009,and December 31,2012,250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group(n=125)or the Hepatectomy Alone group(n=125).Clinicopathological characteristics were balanced between the two groups.The median follow-up time from randomization was 37.5 months[interquartile range 18.3-48.2 months].The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[17.45 months(95%confidence interval[CI]11.99-29.14)vs.9.27 months(95%CI 6.05-13.70),hazard ratio[HR]=0.70(95%CI 0.52-0.95),P=0.020],respectively.The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[44.29 months(95%CI 25.99-62.58)vs.22.37 months(95%CI 10.84-33.91),HR=0.68(95%CI 0.48-0.97),P=0.029].Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group,although these were generally mild and manageable.The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.Conclusion:Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor≥5 cm and MVI,with acceptable toxicity.展开更多
The phosphatidylinositol 3-kinase(PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers,contributing to the occurrenee and progression of tumors.Examining the upst...The phosphatidylinositol 3-kinase(PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers,contributing to the occurrenee and progression of tumors.Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function.Based on accumulating evidenee,strategies targeting major components of the pathway might provide new in sights for can cer drug discovery.Researchers have explored the use of some in hibitors targeti ng this pathway to block survival pathways.However,because oncogenic PI3K pathway activation occurs through various mechanisms,the clinical efficacies of these inhibitors are limited.Moreover,pathway activation is accompanied by the development of therapeutic resista nee.Therefore,strategies involvi ng pathway in hibitors and other can cer treatments in combinati on might solve the therapeutic dilemma.In this review,we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes,review the current statuses of different PI3K/Akt in hibitors,and in troduce combi nation therapies con sisti ng of signaling in hibitors and conven tional cancer therapies.The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway,either alone or in combi nation with other therapies,are the most effective treatment strategy for can cer.展开更多
Aims In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention（PCI） compared with heparin and routine glycoprotein Ⅱb / Ⅲa inhibitor...Aims In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention（PCI） compared with heparin and routine glycoprotein Ⅱb / Ⅲa inhibitors（GPI）. It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout. Methods and results In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction（STEMI） were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or nonCABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin（n = 1089） with those receiving heparins with routine upstream GPI（n = 649） and those receiving heparins only with GPI use restricted to bailout（n = 460）. The primary outcome death and major bleeding occurred in5.1% with bivalirudin, 7.6% with heparin plus routine GPI（HR 0.67 and 95% CI 0.46-0.97, P = 0.034）,and 9.8% with heparins plus bailout GPI（HR 0.52 and 95% CI 0.35-0.75, P = 0.006）. Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome（odds ratio 0.53, 95% CI 0.33-0.87） and major bleeding（odds ratio 0.44, 95% CI 0.24 – 0.82） compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin（1.6 vs. 0.6 vs.0.4%, P = 0.09 and 0.09）. Conclusion Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.展开更多
Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting a...Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and bloodbrain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points（20 μL, twice a day, for 2 days） and mild induced hypothermia（6 hours） are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.展开更多
Background Stroke is a major cause of death or long-term disability worldwide.Many patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chin...Background Stroke is a major cause of death or long-term disability worldwide.Many patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chinese medicine(CM),such as acupuncture and Chinese herbal medicine.However,there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation.Aims The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only.Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed.MEDLINE,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI)were searched.The included outcomes were dependency,motor function,depression and swallowing function.Subgroup analysis was performed,and publication bias was assessed using funnel plots.Summary of review 58 studies and 6339 patients were included in the meta-analysis.Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone.Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found.Conclusions Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone.However,most studies were short in duration(2 to 4 weeks)and prone to different types of biases,which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias.So,more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined.展开更多
Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a ...Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.展开更多
Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occul...Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this"occult"HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.展开更多
In this retrospective study, we evaluated and compared the efficacy and toxicities of maximal androgen blockade （MAB） versus castration alone in Chinese patients with advanced prostate cancer. From 1996 to 2004, 608...In this retrospective study, we evaluated and compared the efficacy and toxicities of maximal androgen blockade （MAB） versus castration alone in Chinese patients with advanced prostate cancer. From 1996 to 2004, 608 patients with advanced prostate cancer were included in the study. Patients were retrospectively divided into two groups according to different therapeutic regimens. Of the 608 patients, 300 patients were treated with MAB （castration plus nonsteroidal antiandrogens） and the remaining 308 were treated with castration alone. The 2- and 5-year overall survival rates of these patients were 73.7% and 56%, respectively. Multivariate analysis showed that, in patients with metastatic prostate cancer, MAB was associated with not only the improvement of progression-free survival （PFS） （increased by 10 months） but also a 20.6% reduction in mortality risk compared with castration alone. In contrast, the efficacy of MAB was not superior to castration alone for patients with nonmetastatic prostate cancer. Interestingly, among patients with MAB, those using bicalutamide had a longer PFS than those using flutamide; this was especially so in patients with metastatic prostate cancer. Almost all of the toxicities due to the hormone therapy were mild to moderate and manageable. To conclude, in China, hormone therapies, including MAB and castration alone, have been standard treatments for advanced prostate cancer. For patients with nonmetastatic prostate cancer, castration alone might be adequately practical and efficient. In patients with metastatic prostate cancer, however, MAB has superior efficacy over castration alone. It is clear that MAB should be considered the first-line standard treatment for patients with metastatic prostate cancer.展开更多
Stimulation at specific acupoints can activate cortical regions in human subjects.Previous studies have mainly focused on a single brain region.However,the brain is a network and many brain regions participate in the ...Stimulation at specific acupoints can activate cortical regions in human subjects.Previous studies have mainly focused on a single brain region.However,the brain is a network and many brain regions participate in the same task.The study of a single brain region alone cannot clearly explain any brain-related issues.Therefore,for the present study,magnetic stimulation was used to stimulate the Neiguan（PC6） acupoint,and 32-channel electroencephalography data were recorded before and after stimulation.Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitability.Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions.展开更多
Background:The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer,but the effects on safety and survival are still controversial.The objective of this meta-analysis was to compare the overall sur...Background:The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer,but the effects on safety and survival are still controversial.The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery(NACS)and surgery alone(SA)for locally advanced gastric cancer.Methods:Databases(PubMed,Embase,Web of Science,Cochrane Library,and Google Scholar)were explored for relative studies from January 2000 to January 2021.The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale,respectively.The Review Manager software(version 5.3)was used to perform this meta-analysis.The overall survival was evaluated as the primary outcome,while perioperative indicators and post-operative complications were evaluated as the secondary outcomes.Results:Twenty studies,including 1420 NACS cases and 1942 SA cases,were enrolled.The results showed that there were no significant differences in overall survival(P=0.240),harvested lymph nodes(P=0.200),total complications(P=0.080),and 30-day post-operative mortality(P=0.490)between the NACS and SA groups.However,the NACS group was associated with a longer operation time(P<0.0001),a higher R0 resection rate(P=0.003),less reoperation(P=0.030),and less anastomotic leakage(P=0.007)compared with SA group.Conclusions:Compared with SA,NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage.While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.展开更多
The purpose of the study was to observe changes in endolymphatic hydrops by using intratympanic injection of gadolinium and magnetic resonance imaging（MRI） before and after endolymphatic sac surgery in patients with...The purpose of the study was to observe changes in endolymphatic hydrops by using intratympanic injection of gadolinium and magnetic resonance imaging（MRI） before and after endolymphatic sac surgery in patients with unilateral Meniere＇s disease. Thirteen patients with unilateral Meniere＇s disease undergoing endolymphatic sac surgery were retrospectively and prospectively analyzed. Three-dimensional fluid-attenuated inversion recovery or three-dimensional real inversion recovery MRI was performed 24 h after an intratympanic injection of gadolinium to grade the presence of endolymphatic hydrops. Among the 13 patients with hydrops confirmed by preoperative MRI, vestibular hydrops had no significant change in all patients; cochlear hydrops became negative in 2 patients, and remained unchanged in the other 11 patients after surgery. Definite vertigo attacks were substantially controlled in one patient and completely controlled in 12 patients during a follow-up period of 8-34 months after surgery. The hearing levels were improved in 3 patients, remained unchanged in 7 patients, and decreased in 3 patients. In conclusion, endolymphatic sac surgery does not always alleviate endolymphatic hydrops in patients with Meniere＇s disease. Relief from vertigo cannot always be attributed to the remission of hydrops. A change in hearing levels cannot be explained by hydrops status alone.展开更多
A high-quality genome is the basis for studies on functional,evolutionary,and comparative genomics.The majority of attention has been paid to the solution of complex chromosome structures and highly repetitive sequenc...A high-quality genome is the basis for studies on functional,evolutionary,and comparative genomics.The majority of attention has been paid to the solution of complex chromosome structures and highly repetitive sequences,along with the emergence of a new‘telomere-to-telomere(T2T)assembly’era.However,the bioinformatic tools for the automatic construction and/or characterization of T2T genome are limited.Here,we developed a user-friendly web toolkit,quarTeT,which currently includes four modules:AssemblyMapper,GapFiller,TeloExplorer,and CentroMiner.First,AssemblyMapper is designed to assemble phased contigs into the chromosome-level genome by referring to a closely related genome.Then,GapFiller would endeavor to fill all unclosed gaps in a given genome with the aid of additional ultra-long sequences.Finally,TeloExplorer and CentroMiner are applied to identify candidate telomere and centromere as well as their localizations on each chromosome.These four modules can be used alone or in combination with each other for T2T genome assembly and characterization.As a case study,by adopting the entire modular functions of quarTeT,we have achieved the Actinidia chinensis genome assembly that is of a quality comparable to the reported genome Hongyang v4.0,which was assembled with the addition of manual handling.Further evaluation of CentroMiner by searching centromeres in Arabidopsis thaliana and Oryza sativa genomes showed that quarTeT is capable of identifying all the centromeric regions that have been previously detected by experimental methods.Collectively,quarTeT is an efficient toolkit for studies of large-scale T2T genomes and can be accessed at http://www.atcgn.com:8080/quarTeT/home.html without registration.展开更多
Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. A...Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels：（1） polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury.（2） Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers.（3） Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.展开更多
Objective:We aimed to investigate the value of threedimensional(3D)T1 volumetric isotropic turbo spin echo acquisition(VISTA)in the diagnosis of cervical artery dissection(CAD).Methods:We prospectively included patie...Objective:We aimed to investigate the value of threedimensional(3D)T1 volumetric isotropic turbo spin echo acquisition(VISTA)in the diagnosis of cervical artery dissection(CAD).Methods:We prospectively included patients who were suspected as having a CAD within 1 month of onset.For T1 VISTA,the diagnosis of the dissection was based on the presence of intramural high-signal,intimal flap,double lumen and aneurysmal dilation.The final diagnosis of dissection was based on the clinical history,physical examination,and all of the imaging tests.Results:A total of 46 patients were included in this study.The final diagnosis of CAD was made for 21 patients.Diagnosis of dissection was made for 20 of the 21 patients after assessing T1 VISTA.A definitive diagnosis of dissection was not made for 5 patients(including 3 patients with digital subtraction angiography)before the T1 VISTA examination.The sensitivity and specificity for T1 VISTA were 95.2%(95%CI,76.2%to 99.9%)and 100%(95%CI,86.3%to 100%),respectively.The agreement between the two researchers for T1 VISTA for diagnosis of CAD was very good(k=0.91).For patients without acute artery occlusion,all of them had a definite conclusion with or without dissection by T1 VISTA(n=29).However,for 17 patients with acute artery occlusion,the possibility of dissection could not be excluded for 6 of them by T1 VISTA(p=0.001).Conclusions:3D T1 VISTA at 3.0 Tesla was useful in the diagnosis of acute CAD.However,for some patients with total occlusion of the artery without typical imaging features of dissection,the unequivocal distinction between intramural haematoma and intraluminal thrombus may be not adequate by T1 VISTA alone.Future studies should investigate whether a follow-up scan,a contrast-enhanced imaging or an optimal VISTA technique could be useful.展开更多
Proanthocyanidins(PAs),also known as“condensed tannins”,are colorless metabolites produced through the flavonoid pathway that are involved in stress resistance in plants.Because PAs are involved in the anthocyanin b...Proanthocyanidins(PAs),also known as“condensed tannins”,are colorless metabolites produced through the flavonoid pathway that are involved in stress resistance in plants.Because PAs are involved in the anthocyanin biosynthetic pathway,they play a role in the modification of pigmentation conferred by anthocyanins in ornamental organs.In this study,we isolated the gene and functionally characterized an R2R3-MYB transcription factor(TF),AaMYB3,and a basic helix-loop-helix TF,AabHLH1,from Anthurium andraeanum(Hort.),a typical tropical flower.AaMYB3 is primarily expressed in the spathe and negatively correlates with anthocyanin accumulation.A complementation test in an Arabidopsis tt8 mutant showed that AabHLH1 successfully restores the PA-deficient seed coat phenotype.The ectopic overexpression of AaMYB3 alone or its coexpression with AabHLH1 in transgenic tobacco resulted in light pink or even pale-pink corolla limbs by reducing their anthocyanin levels and greatly enhancing their accumulation of PAs.This overexpression of the anthurium TF genes upregulated the late anthocyanin enzymeencoding genes(NtDFR and NtANS)and the key PA genes(NtLAR and NtANR)in transgenic tobacco.The interaction between AaMYB3 and the AabHLH1 protein was confirmed using yeast two-hybrid(Y2H)and bimolecular fluorescence complementation(BiFC)assays.In the developing red spathes of the cultivars“Vitara”and“Tropical”,the expression of AaMYB3 was closely linked to PA accumulation,and AaMYB3 was coexpressed with AaCHS,AaF3H,AaDFR,AaANS,AaLAR,and AaANR.The expression pattern of AabHLH1 was similar to that of AaF3′H.Our results suggest that AaMYB3 and AabHLH1 are involved in the regulation of PA biosynthesis in anthurium and could potentially be used to metabolically engineer PA biosynthesis in plants.展开更多
基金supported by the National Natural Science Foundation of China(No.81172037)Science and Technology Program of Guangdong Province,China(No.2013B021800159)Clinical Trials Project(308 Project)of Sun Yat-sen University Cancer Center(No.308-2015-014).
文摘Background:The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma(HCC)patients with solitary tumor and microvascular invasion(MVI)is controversial.This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization(TACE)after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor≥5 cm and MVI.Methods:In this randomized,open-labeled,phase III trial,HCC patients with a solitary tumor≥5 cm and MVI were randomly assigned(1:1)to receive either 1-2 cycles of adjuvant TACE after hepatectomy(Hepatectomy-TACE)or hepatectomy alone(Hepatectomy Alone).The primary endpoint was disease-free survival(DFS);the secondary end-points included overall survival(OS)and adverse events.Results:Between June 1,2009,and December 31,2012,250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group(n=125)or the Hepatectomy Alone group(n=125).Clinicopathological characteristics were balanced between the two groups.The median follow-up time from randomization was 37.5 months[interquartile range 18.3-48.2 months].The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[17.45 months(95%confidence interval[CI]11.99-29.14)vs.9.27 months(95%CI 6.05-13.70),hazard ratio[HR]=0.70(95%CI 0.52-0.95),P=0.020],respectively.The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[44.29 months(95%CI 25.99-62.58)vs.22.37 months(95%CI 10.84-33.91),HR=0.68(95%CI 0.48-0.97),P=0.029].Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group,although these were generally mild and manageable.The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.Conclusion:Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor≥5 cm and MVI,with acceptable toxicity.
基金The current work was supported by the National Natural Science Foundation of China(Project nos.31961160727,81773085,82073196,81973339,81873455 and 81803551)the Guangdong Natural Science Research Grant(No.2021A1515011158)the Fundamental Research Funds for the Central Universities(No.21620429).
文摘The phosphatidylinositol 3-kinase(PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers,contributing to the occurrenee and progression of tumors.Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function.Based on accumulating evidenee,strategies targeting major components of the pathway might provide new in sights for can cer drug discovery.Researchers have explored the use of some in hibitors targeti ng this pathway to block survival pathways.However,because oncogenic PI3K pathway activation occurs through various mechanisms,the clinical efficacies of these inhibitors are limited.Moreover,pathway activation is accompanied by the development of therapeutic resista nee.Therefore,strategies involvi ng pathway in hibitors and other can cer treatments in combinati on might solve the therapeutic dilemma.In this review,we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes,review the current statuses of different PI3K/Akt in hibitors,and in troduce combi nation therapies con sisti ng of signaling in hibitors and conven tional cancer therapies.The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway,either alone or in combi nation with other therapies,are the most effective treatment strategy for can cer.
文摘Aims In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention（PCI） compared with heparin and routine glycoprotein Ⅱb / Ⅲa inhibitors（GPI）. It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout. Methods and results In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction（STEMI） were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or nonCABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin（n = 1089） with those receiving heparins with routine upstream GPI（n = 649） and those receiving heparins only with GPI use restricted to bailout（n = 460）. The primary outcome death and major bleeding occurred in5.1% with bivalirudin, 7.6% with heparin plus routine GPI（HR 0.67 and 95% CI 0.46-0.97, P = 0.034）,and 9.8% with heparins plus bailout GPI（HR 0.52 and 95% CI 0.35-0.75, P = 0.006）. Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome（odds ratio 0.53, 95% CI 0.33-0.87） and major bleeding（odds ratio 0.44, 95% CI 0.24 – 0.82） compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin（1.6 vs. 0.6 vs.0.4%, P = 0.09 and 0.09）. Conclusion Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.
基金supported by the National Natural Science Foundation of China,No.31200809
文摘Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and bloodbrain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points（20 μL, twice a day, for 2 days） and mild induced hypothermia（6 hours） are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.
基金funded by Innovative Technology Commission of the government of Hong Kong SAR(GSP/008/18).
文摘Background Stroke is a major cause of death or long-term disability worldwide.Many patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chinese medicine(CM),such as acupuncture and Chinese herbal medicine.However,there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation.Aims The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only.Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed.MEDLINE,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI)were searched.The included outcomes were dependency,motor function,depression and swallowing function.Subgroup analysis was performed,and publication bias was assessed using funnel plots.Summary of review 58 studies and 6339 patients were included in the meta-analysis.Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone.Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found.Conclusions Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone.However,most studies were short in duration(2 to 4 weeks)and prone to different types of biases,which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias.So,more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined.
基金This study was supported by grants from the National Natural Science Foundation of China,NSFC 31671438 and NSFC 31471295the Graduate Innovation Fund of Jilin University,Hyundai Hope On Wheels,the Ring Screw Textron Endowed Chair for Pediatric Cancer Research,Children’s Hospital of Michigan Foundation,Kids Without Cancer,Lafontaine Family/U Can-Cer Vive Foundation,the Decerchio/Guisewite Family,Justin’s Gift,Elana Fund,and the Ginopolis/Karmanos Endowment and supported by Jilin University,Changchun,China,Wayne State University School of Medicine,the China Scholarship Council,and the Barbara Ann Karmanos Cancer Institute.
文摘Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.
文摘Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this"occult"HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.
基金Acknowledgment We thank Professor Qiao Zhou from the Department of Pathology, West China Hospital, Dr Jing Gong from the Laboratory of Pathology, the State Key Laboratory of Biotherapy, and many other clinicians from the Department of Urology, West China hospital for their kind assistance. This work was supported by the National Natural Science Foundation of China （No. NSFC30700977, No. NSFC30800637 and No. NSFC30871383）.
文摘In this retrospective study, we evaluated and compared the efficacy and toxicities of maximal androgen blockade （MAB） versus castration alone in Chinese patients with advanced prostate cancer. From 1996 to 2004, 608 patients with advanced prostate cancer were included in the study. Patients were retrospectively divided into two groups according to different therapeutic regimens. Of the 608 patients, 300 patients were treated with MAB （castration plus nonsteroidal antiandrogens） and the remaining 308 were treated with castration alone. The 2- and 5-year overall survival rates of these patients were 73.7% and 56%, respectively. Multivariate analysis showed that, in patients with metastatic prostate cancer, MAB was associated with not only the improvement of progression-free survival （PFS） （increased by 10 months） but also a 20.6% reduction in mortality risk compared with castration alone. In contrast, the efficacy of MAB was not superior to castration alone for patients with nonmetastatic prostate cancer. Interestingly, among patients with MAB, those using bicalutamide had a longer PFS than those using flutamide; this was especially so in patients with metastatic prostate cancer. Almost all of the toxicities due to the hormone therapy were mild to moderate and manageable. To conclude, in China, hormone therapies, including MAB and castration alone, have been standard treatments for advanced prostate cancer. For patients with nonmetastatic prostate cancer, castration alone might be adequately practical and efficient. In patients with metastatic prostate cancer, however, MAB has superior efficacy over castration alone. It is clear that MAB should be considered the first-line standard treatment for patients with metastatic prostate cancer.
基金supported by the Outstanding Youth Science and Technology Innovation Fund of Hebei University of Technology,No.2013007the Specialized Research Fund for the Doctoral Program of Higher Education of China,No.20131317120007+1 种基金the Natural Science Foundation of Hebei Province in China,No.H2013202176the Natural Science Foundation of China,No.31400844,51377045,61571180 and 31300818
文摘Stimulation at specific acupoints can activate cortical regions in human subjects.Previous studies have mainly focused on a single brain region.However,the brain is a network and many brain regions participate in the same task.The study of a single brain region alone cannot clearly explain any brain-related issues.Therefore,for the present study,magnetic stimulation was used to stimulate the Neiguan（PC6） acupoint,and 32-channel electroencephalography data were recorded before and after stimulation.Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitability.Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions.
基金the Capital Medical Development and Research Foundation(No.2018-2-2153)the National Natural Science Foundation of China(Nos.82073357,81672439,81272766,and 81450028)the Beijing Natural Science Foundation(No.7162039).
文摘Background:The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer,but the effects on safety and survival are still controversial.The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery(NACS)and surgery alone(SA)for locally advanced gastric cancer.Methods:Databases(PubMed,Embase,Web of Science,Cochrane Library,and Google Scholar)were explored for relative studies from January 2000 to January 2021.The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale,respectively.The Review Manager software(version 5.3)was used to perform this meta-analysis.The overall survival was evaluated as the primary outcome,while perioperative indicators and post-operative complications were evaluated as the secondary outcomes.Results:Twenty studies,including 1420 NACS cases and 1942 SA cases,were enrolled.The results showed that there were no significant differences in overall survival(P=0.240),harvested lymph nodes(P=0.200),total complications(P=0.080),and 30-day post-operative mortality(P=0.490)between the NACS and SA groups.However,the NACS group was associated with a longer operation time(P<0.0001),a higher R0 resection rate(P=0.003),less reoperation(P=0.030),and less anastomotic leakage(P=0.007)compared with SA group.Conclusions:Compared with SA,NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage.While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.
文摘The purpose of the study was to observe changes in endolymphatic hydrops by using intratympanic injection of gadolinium and magnetic resonance imaging（MRI） before and after endolymphatic sac surgery in patients with unilateral Meniere＇s disease. Thirteen patients with unilateral Meniere＇s disease undergoing endolymphatic sac surgery were retrospectively and prospectively analyzed. Three-dimensional fluid-attenuated inversion recovery or three-dimensional real inversion recovery MRI was performed 24 h after an intratympanic injection of gadolinium to grade the presence of endolymphatic hydrops. Among the 13 patients with hydrops confirmed by preoperative MRI, vestibular hydrops had no significant change in all patients; cochlear hydrops became negative in 2 patients, and remained unchanged in the other 11 patients after surgery. Definite vertigo attacks were substantially controlled in one patient and completely controlled in 12 patients during a follow-up period of 8-34 months after surgery. The hearing levels were improved in 3 patients, remained unchanged in 7 patients, and decreased in 3 patients. In conclusion, endolymphatic sac surgery does not always alleviate endolymphatic hydrops in patients with Meniere＇s disease. Relief from vertigo cannot always be attributed to the remission of hydrops. A change in hearing levels cannot be explained by hydrops status alone.
基金This work was supported by funds from the National Natural Science Foundation of China(31972474,31471157)the Open Fund of State Key Laboratory of Tea Plant Biology and Utilization(SKLTOF20150103).
文摘A high-quality genome is the basis for studies on functional,evolutionary,and comparative genomics.The majority of attention has been paid to the solution of complex chromosome structures and highly repetitive sequences,along with the emergence of a new‘telomere-to-telomere(T2T)assembly’era.However,the bioinformatic tools for the automatic construction and/or characterization of T2T genome are limited.Here,we developed a user-friendly web toolkit,quarTeT,which currently includes four modules:AssemblyMapper,GapFiller,TeloExplorer,and CentroMiner.First,AssemblyMapper is designed to assemble phased contigs into the chromosome-level genome by referring to a closely related genome.Then,GapFiller would endeavor to fill all unclosed gaps in a given genome with the aid of additional ultra-long sequences.Finally,TeloExplorer and CentroMiner are applied to identify candidate telomere and centromere as well as their localizations on each chromosome.These four modules can be used alone or in combination with each other for T2T genome assembly and characterization.As a case study,by adopting the entire modular functions of quarTeT,we have achieved the Actinidia chinensis genome assembly that is of a quality comparable to the reported genome Hongyang v4.0,which was assembled with the addition of manual handling.Further evaluation of CentroMiner by searching centromeres in Arabidopsis thaliana and Oryza sativa genomes showed that quarTeT is capable of identifying all the centromeric regions that have been previously detected by experimental methods.Collectively,quarTeT is an efficient toolkit for studies of large-scale T2T genomes and can be accessed at http://www.atcgn.com:8080/quarTeT/home.html without registration.
基金supported by a grant from National Key Science and Technology Research&Development Plan in China,No.2016YFC1101500the National Natural Science Foundation of China,No.11672332
文摘Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels：（1） polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury.（2） Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers.（3） Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.
基金This work was supported by Changbai Mountain Scholars,Jilin Provincial government to YY.
文摘Objective:We aimed to investigate the value of threedimensional(3D)T1 volumetric isotropic turbo spin echo acquisition(VISTA)in the diagnosis of cervical artery dissection(CAD).Methods:We prospectively included patients who were suspected as having a CAD within 1 month of onset.For T1 VISTA,the diagnosis of the dissection was based on the presence of intramural high-signal,intimal flap,double lumen and aneurysmal dilation.The final diagnosis of dissection was based on the clinical history,physical examination,and all of the imaging tests.Results:A total of 46 patients were included in this study.The final diagnosis of CAD was made for 21 patients.Diagnosis of dissection was made for 20 of the 21 patients after assessing T1 VISTA.A definitive diagnosis of dissection was not made for 5 patients(including 3 patients with digital subtraction angiography)before the T1 VISTA examination.The sensitivity and specificity for T1 VISTA were 95.2%(95%CI,76.2%to 99.9%)and 100%(95%CI,86.3%to 100%),respectively.The agreement between the two researchers for T1 VISTA for diagnosis of CAD was very good(k=0.91).For patients without acute artery occlusion,all of them had a definite conclusion with or without dissection by T1 VISTA(n=29).However,for 17 patients with acute artery occlusion,the possibility of dissection could not be excluded for 6 of them by T1 VISTA(p=0.001).Conclusions:3D T1 VISTA at 3.0 Tesla was useful in the diagnosis of acute CAD.However,for some patients with total occlusion of the artery without typical imaging features of dissection,the unequivocal distinction between intramural haematoma and intraluminal thrombus may be not adequate by T1 VISTA alone.Future studies should investigate whether a follow-up scan,a contrast-enhanced imaging or an optimal VISTA technique could be useful.
基金supported financially by the Hainan Provincial Natural Science Foundation of China(No.2018CXTD344)the Central Public-Interest Scientific Institution Basal Research Fund for the Chinese Academy of Tropical Agricultural Sciences(Nos.1630032017074 and 1630032017024).
文摘Proanthocyanidins(PAs),also known as“condensed tannins”,are colorless metabolites produced through the flavonoid pathway that are involved in stress resistance in plants.Because PAs are involved in the anthocyanin biosynthetic pathway,they play a role in the modification of pigmentation conferred by anthocyanins in ornamental organs.In this study,we isolated the gene and functionally characterized an R2R3-MYB transcription factor(TF),AaMYB3,and a basic helix-loop-helix TF,AabHLH1,from Anthurium andraeanum(Hort.),a typical tropical flower.AaMYB3 is primarily expressed in the spathe and negatively correlates with anthocyanin accumulation.A complementation test in an Arabidopsis tt8 mutant showed that AabHLH1 successfully restores the PA-deficient seed coat phenotype.The ectopic overexpression of AaMYB3 alone or its coexpression with AabHLH1 in transgenic tobacco resulted in light pink or even pale-pink corolla limbs by reducing their anthocyanin levels and greatly enhancing their accumulation of PAs.This overexpression of the anthurium TF genes upregulated the late anthocyanin enzymeencoding genes(NtDFR and NtANS)and the key PA genes(NtLAR and NtANR)in transgenic tobacco.The interaction between AaMYB3 and the AabHLH1 protein was confirmed using yeast two-hybrid(Y2H)and bimolecular fluorescence complementation(BiFC)assays.In the developing red spathes of the cultivars“Vitara”and“Tropical”,the expression of AaMYB3 was closely linked to PA accumulation,and AaMYB3 was coexpressed with AaCHS,AaF3H,AaDFR,AaANS,AaLAR,and AaANR.The expression pattern of AabHLH1 was similar to that of AaF3′H.Our results suggest that AaMYB3 and AabHLH1 are involved in the regulation of PA biosynthesis in anthurium and could potentially be used to metabolically engineer PA biosynthesis in plants.
