Cryoablation is a less prevalent percutaneous ablative therapy for hepatocellular carcinoma （HCC）, and current evidence about its usefulness is limited. We report our experience in treating 1595 HCC cases with percu...Cryoablation is a less prevalent percutaneous ablative therapy for hepatocellular carcinoma （HCC）, and current evidence about its usefulness is limited. We report our experience in treating 1595 HCC cases with percutaneous cryoablation to give a comprehensive profile about the effectiveness, safety and long-term outcome of this therapy. From January 2003 to December 2013, 1595 patients with 2313 HCC nodules were ablated with 2958 cryoablation sessions in our center. Complete ablation was achieved in 1294 patients for 1893 nodules with a mean diameter of 3.4 ＋ 2.2 cm. The complete ablation rate was 81.2%, 99.4%, 94.4%, and 45.6% in all tumors, tumors 〈 3 cm, tumors 〈 5 cm, and tumors 〉 5 cm, respectively. Major complications were observed after 80 （3.4%） of the 2958 cryoablations and minor complications were observed after 330 cryoablations with no treatment-related deaths. After a median follow-up of 33.4 months, 937 patients developed different types of recurrence. The 5- and 10-year overall survival was 25.7% and 9.2%, respectively. Cryoablation showed reliable safety and efficacy and should be considered as a promising technique, particularly when a large zone of ablation is required.展开更多
Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most mal...Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.展开更多
目的探讨临床药师在参与新生儿万古霉素治疗药物监测(therapeutic drug monitoring,TDM)临床实践中发挥的作用,为医师调整给药方案提供参考。方法采用回顾性分析方法,收集符合条件的新生儿31例,对其一般情况、病原学检查、血药浓度监测...目的探讨临床药师在参与新生儿万古霉素治疗药物监测(therapeutic drug monitoring,TDM)临床实践中发挥的作用,为医师调整给药方案提供参考。方法采用回顾性分析方法,收集符合条件的新生儿31例,对其一般情况、病原学检查、血药浓度监测结果、影响血药谷浓度的因素、药物疗效及药品不良反应(adverse drug reaction,ADR)等结果进行统计分析。结果31例患儿中,新生儿脓毒血症占46.34%;病原学检查88.00%为革兰阳性菌,其中多重耐药菌占77.27%。初次血药谷浓度监测范围在10~20μg·mL-1的患儿仅占32.26%,医师采纳临床药师干预建议后谷浓度的达标率提高至83.33%(P<0.05);给药间隔与血药谷浓度呈负相关(P<0.05)。本次研究万古霉素治疗有效率80.65%,且未发生万古霉素相关ADR。结论万古霉素在TDM下治疗由革兰阳性菌引起的新生儿重症感染疗效确切,但经验性用药后血药谷浓度达标率低,医师采纳临床药师干预建议、减少给药间隔可显著提高血药谷浓度,为医师调整给药方案提供了参考。展开更多
Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expr...Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.展开更多
Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85%of all cancer cases in the country.Several g...Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85%of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.展开更多
Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative researc...Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.展开更多
China.In this study,we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019(COVID-19)in the Beijing region.Methods:In this retrospective study,we enrolled inpatients...China.In this study,we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019(COVID-19)in the Beijing region.Methods:In this retrospective study,we enrolled inpatients admitted for COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital in Beijing between November 10,2022,and January 30,2023.Demographic and clinical features and treatment outcomeswere comprehensively analyzed.We used logistic regression and linear regression analyses to explore the risk factors associated with disease severity and time of nucleic acid conversion,respectively.Results:A total of 1010 hospitalized patients with COVID-19 were enrolled.The median age was 43.0 years(interquartile range,28.0–63.0),and patients aged<60 years and≥60 years comprised 71.2%and 28.8%of total included patients,respectively.The clinical classification of mild(74.6%,753/1010),moderate(21.0%,212/1010),severe(2.7%,27/1010),and unidentified(1.8%,18/1010)was separately recorded;1005 patients were discharged,and 5 patients died in the hospital.The outbreak of the emerging epidemic witnessed an evident increase in the proportion of moderate(42.9%vs.16.4%)and severe(10.3%vs.1.1%)cases after December 7,2022.Patients with a moderate/severe classification had higher levels of procalcitonin,IL-6,serum ferritin,C-reactive protein,lactic dehydrogenase,serum urea nitrogen,and D-dimer and lower counts of CD4+T,CD8+T,and B cells(all P<0.001).Multivariable regression analysis revealed that increased odds of disease severity were associated with the following factors:age≥60 years,IL-6>7 pg/mL,lactic dehydrogenase level>245 U/L,cough,and fever at admission.Age≥80 years and chronic lung diseasewere independent risk factors in the nonmild group in elderly patients.In addition,the duration for nucleic acid to turn negativewas approximately 5.0 d(interquartile range,3.0–7.0).Prolonged time of nucleic acid conversion was associated with age≥60 years,serum urea nitrogen level>8.2 mmol/L,neutrophil count>7×10^(9)展开更多
Prime editing is a revolutionary gene-editing method that is capable of introducing insertions,deletions and base substitutions into the genome.However,the editing efficiency of Prime Editor(PE)is limited by the DNA r...Prime editing is a revolutionary gene-editing method that is capable of introducing insertions,deletions and base substitutions into the genome.However,the editing efficiency of Prime Editor(PE)is limited by the DNA repair process.Here,we show that overexpression of the flap structure-specific endonuclease 1(FEN1)and the DNA ligase 1(LIG1)increases the efficiency of prime editing,which is similar to the dominant negative mutL homolog 1(MLH1dn).In addition,MLH1 is still the dominant factor over FEN1 and LIG1 in prime editing.Our results help to further understand the relationship of proteins involved in prime editing and envisage future directions for the development of PE.展开更多
Dear Editor,The ongoing COVID-19 pandemic has resulted in over 25.0 million confirmed cases and over 840,000 deaths globally.As the third severe respiratory disease outbreak caused by the coronavirus,COVID-19 has led ...Dear Editor,The ongoing COVID-19 pandemic has resulted in over 25.0 million confirmed cases and over 840,000 deaths globally.As the third severe respiratory disease outbreak caused by the coronavirus,COVID-19 has led to much larger infected populations and coverage of geographic areas than SARS and MERS.Such high prevalence of infection has raised significant concerns about the emergence and spread of escape variants,which may evade human immunity and eventually render candidate vaccines and antibody-based therapeutics ineffective.Indeed,some naturally mutated SARS-CoV or MERS-CoV strains from the sequential outbreaks were reported to resist neutralization by the antibodies isolated during the first outbreak1,2.展开更多
Objective:Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor(MAPKi)resistance,which is one of the most common forms of resistance that has emerged in many types of cancers.Here,we...Objective:Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor(MAPKi)resistance,which is one of the most common forms of resistance that has emerged in many types of cancers.Here,we aimed to systematically identify the genetic interactions underlying MAPKi resistance,and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi resistance.Methods:We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi,and validated 3 genetic combinations through competitive growth,cell viability,and spheroid formation assays.We next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic combinations.We also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation,Western blot,qRTPCR,and immunofluorescence assays.Results:We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance(ITGB3+IGF1R,ITGB3+JNK,and HDGF+LGR5).We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi exposure.Specifically,we discovered a novel protein complex,HDGF-LGR5,that adaptively responded to MAPKi to enhance cancer cell stemness,which was up-or downregulated by the inhibitors of ITGB3+JNK or ITGB3+IGF1R.Conclusions:Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells.ITGB3-+IGF1R-targeting drugs(cilengitide+linsitinib)could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex,which enhanced cancer stemness during MAPKi stress.展开更多
The coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is threatening public health.The human angiotensin-converting enzyme 2(ACE2)has a remarkably high affinity b...The coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is threatening public health.The human angiotensin-converting enzyme 2(ACE2)has a remarkably high affinity binding to SARS-CoV-2.This study explored whether certain populations,including obese and cancer patients,are susceptible to SARS-CoV-2.The expression pattern of ACE2 in normal and tumor tissues of cancer patients was compared by the search for network database and re-analysis of pubic data.The level of ACE2 expression in normal adipose tissue was higher than that in normal lung tissue,which indicated the adipose tissue might be vulnerable to SARS-CoV-2;the levels of ACE2 expressed by adipocytes and adipose progenitor cells were similar between non-obese individuals and obese individuals(BMI>29),but obese individuals have more adiposes so as to increase the number of ACE2-expressing cells;the expression of ACE2 in tumor tissues posed by five different types of cancers increased significantly compared with that in adjacent tissues.Therefore,we proposed the following hypothesis:the obese individuals and five types of cancer patients might have a higher risk of SARS-CoV-2 infection,which might become the target population of SARS-CoV-2 infection in the future.展开更多
Dear Editor,COVID-19(Coronavirus Disease 2019)is a disease caused by the single-stranded sense RNA virus SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),which has caused a global public health crisis.1 How...Dear Editor,COVID-19(Coronavirus Disease 2019)is a disease caused by the single-stranded sense RNA virus SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),which has caused a global public health crisis.1 However,so far no effective serum marker has been found as a biomarker for COVID-19 diagnosis,except that viral nucleic acid detection is an effective evidence of SARS-CoV-2 infection.展开更多
Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer ...Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer includes two major types： hepatocellular carcinoma （HCC, about 80%） and cholangiocarcinoma （CCA, about 15%）. Many etiological factors contribute to HCC development, such as hepatitis B virus （HBV）, hepatitis C virus （HCV）, aflatoxin B1 （AFB1）, alcohol, and metabolic diseases3. By contrast, the major risk factors for CCA are liver flukes （Opisthorchis viverrini and Clonorchis sinensis） and primary sclerosing cholangitis4,展开更多
目的评估万古霉素早产儿治疗药物监测(Therapeutic Drug Monitoring,TDM)及用药情况,分析万古霉素在早产儿重症感染治疗过程中进行TDM的必要性。方法采用回顾性分析方法,制定相应标准,按标准收集2016—2018年南京医科大学附属无锡妇幼...目的评估万古霉素早产儿治疗药物监测(Therapeutic Drug Monitoring,TDM)及用药情况,分析万古霉素在早产儿重症感染治疗过程中进行TDM的必要性。方法采用回顾性分析方法,制定相应标准,按标准收集2016—2018年南京医科大学附属无锡妇幼保健院早产儿34例,统计分析其基本情况、血培养、痰培养等相关病原学检查、药敏试验结果、血药浓度结果、化验室指标、药物疗效及药品不良反应(Adverse Drug Reaction,ADR)等结果。结果统计分析的34例病儿中,诊断以新生儿脓毒血症为主(48.94%),病原学送检率100%,阳性检出率76.47%,22例(占83.33%)为革兰阳性菌感染,药敏试验结果均显示对万古霉素敏感;监测范围在10~20μg/mL的初次血药谷浓度病儿极少(仅占26.47%),而通过临床药师合理干预可大大提高谷浓度的达标率(占76.92%),差异有统计学意义(P<0.05)。经万古霉素治疗后有效率达85.29%,复查病儿的各项指标较前有明显好转[降钙素原(PCT)为(0.86±0.28)比(0.31±0.43)ng/mL,尿素(Urea)为(5.39±3.91)比(2.24±1.35)mmol/L,血肌酐(Cr)为(64.24±20.44)比(34.43±9.82)μmol/L,胱抑素C(CysC)为(1.85±0.55)比(1.29±0.28)mg/L、天冬氨酸氨基转移酶(AST)为(43.72±25.03)比(25.03±11.01)IU/L,均P<0.05];未检测到万古霉素引起的耳肾损害等ADR。结论万古霉素治疗早产儿感染,特别是革兰阳性菌引起的重症感染效果明确。进行TDM可以实现早产儿万古霉素治疗个体化,使早产儿用药更加安全有效。展开更多
Dear Editor,The rapid emerge nee and persistence of the pan demic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had enormous impacts on global health and the economy.Effective vaccines again...Dear Editor,The rapid emerge nee and persistence of the pan demic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19)pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).展开更多
文摘Cryoablation is a less prevalent percutaneous ablative therapy for hepatocellular carcinoma （HCC）, and current evidence about its usefulness is limited. We report our experience in treating 1595 HCC cases with percutaneous cryoablation to give a comprehensive profile about the effectiveness, safety and long-term outcome of this therapy. From January 2003 to December 2013, 1595 patients with 2313 HCC nodules were ablated with 2958 cryoablation sessions in our center. Complete ablation was achieved in 1294 patients for 1893 nodules with a mean diameter of 3.4 ＋ 2.2 cm. The complete ablation rate was 81.2%, 99.4%, 94.4%, and 45.6% in all tumors, tumors 〈 3 cm, tumors 〈 5 cm, and tumors 〉 5 cm, respectively. Major complications were observed after 80 （3.4%） of the 2958 cryoablations and minor complications were observed after 330 cryoablations with no treatment-related deaths. After a median follow-up of 33.4 months, 937 patients developed different types of recurrence. The 5- and 10-year overall survival was 25.7% and 9.2%, respectively. Cryoablation showed reliable safety and efficacy and should be considered as a promising technique, particularly when a large zone of ablation is required.
基金funding support from the National Natural Science Foundation of China(Grant Nos.81672467,81702773,81702389,and 81672368)the Major National R&D Project(Grant Nos.2018ZX10723204,2018ZX10302205,and 2018ZX09J18107)the Natural Science Foundation of Beijing(Grant No.7172207)。
文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.
文摘目的探讨临床药师在参与新生儿万古霉素治疗药物监测(therapeutic drug monitoring,TDM)临床实践中发挥的作用,为医师调整给药方案提供参考。方法采用回顾性分析方法,收集符合条件的新生儿31例,对其一般情况、病原学检查、血药浓度监测结果、影响血药谷浓度的因素、药物疗效及药品不良反应(adverse drug reaction,ADR)等结果进行统计分析。结果31例患儿中,新生儿脓毒血症占46.34%;病原学检查88.00%为革兰阳性菌,其中多重耐药菌占77.27%。初次血药谷浓度监测范围在10~20μg·mL-1的患儿仅占32.26%,医师采纳临床药师干预建议后谷浓度的达标率提高至83.33%(P<0.05);给药间隔与血药谷浓度呈负相关(P<0.05)。本次研究万古霉素治疗有效率80.65%,且未发生万古霉素相关ADR。结论万古霉素在TDM下治疗由革兰阳性菌引起的新生儿重症感染疗效确切,但经验性用药后血药谷浓度达标率低,医师采纳临床药师干预建议、减少给药间隔可显著提高血药谷浓度,为医师调整给药方案提供了参考。
基金supported by the National Natural Science Foundation of China Fund Project(82272956).
文摘Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.
基金funded by the National Natural Science Foundation of China(No.82272956).
文摘Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85%of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.
基金This study was supported by funding from the Science Technology and Innovation Committee of Shenzhen Municipality(Grant No.2019N002)Capital's Funds for Health Improvement and Research(Grant No.Z181100001718075).
文摘Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.
基金supported by the National Natural Science Foundation of China(82370019)the Emergency Key Program of Guangzhou Laboratory(EKPG21-30-4)+1 种基金the National Key Research and Development Plan(2022YFC2304404,2022YFC2304803)the Military Emergency Research Project on COVID-19(BWS20J006).
文摘China.In this study,we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019(COVID-19)in the Beijing region.Methods:In this retrospective study,we enrolled inpatients admitted for COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital in Beijing between November 10,2022,and January 30,2023.Demographic and clinical features and treatment outcomeswere comprehensively analyzed.We used logistic regression and linear regression analyses to explore the risk factors associated with disease severity and time of nucleic acid conversion,respectively.Results:A total of 1010 hospitalized patients with COVID-19 were enrolled.The median age was 43.0 years(interquartile range,28.0–63.0),and patients aged<60 years and≥60 years comprised 71.2%and 28.8%of total included patients,respectively.The clinical classification of mild(74.6%,753/1010),moderate(21.0%,212/1010),severe(2.7%,27/1010),and unidentified(1.8%,18/1010)was separately recorded;1005 patients were discharged,and 5 patients died in the hospital.The outbreak of the emerging epidemic witnessed an evident increase in the proportion of moderate(42.9%vs.16.4%)and severe(10.3%vs.1.1%)cases after December 7,2022.Patients with a moderate/severe classification had higher levels of procalcitonin,IL-6,serum ferritin,C-reactive protein,lactic dehydrogenase,serum urea nitrogen,and D-dimer and lower counts of CD4+T,CD8+T,and B cells(all P<0.001).Multivariable regression analysis revealed that increased odds of disease severity were associated with the following factors:age≥60 years,IL-6>7 pg/mL,lactic dehydrogenase level>245 U/L,cough,and fever at admission.Age≥80 years and chronic lung diseasewere independent risk factors in the nonmild group in elderly patients.In addition,the duration for nucleic acid to turn negativewas approximately 5.0 d(interquartile range,3.0–7.0).Prolonged time of nucleic acid conversion was associated with age≥60 years,serum urea nitrogen level>8.2 mmol/L,neutrophil count>7×10^(9)
基金National Natural Science Foundation of China(32171413,61721003)the Basic Research Program of Tsinghua National Lab for Information Science and Technology and the Science,Technology and Innovation Commission of Shenzhen Municipality(KCXFZ202002011006448).
文摘Prime editing is a revolutionary gene-editing method that is capable of introducing insertions,deletions and base substitutions into the genome.However,the editing efficiency of Prime Editor(PE)is limited by the DNA repair process.Here,we show that overexpression of the flap structure-specific endonuclease 1(FEN1)and the DNA ligase 1(LIG1)increases the efficiency of prime editing,which is similar to the dominant negative mutL homolog 1(MLH1dn).In addition,MLH1 is still the dominant factor over FEN1 and LIG1 in prime editing.Our results help to further understand the relationship of proteins involved in prime editing and envisage future directions for the development of PE.
基金This work was supported by grants from the National Key R&D Program of China(2019YFA0904400)National Natural Science Foundation of China(81822027,81630090)+1 种基金National Megaprojects of China for Major Infectious Diseases(2018ZX10301403,2018ZX10101003)the staff from Core Facility of Microbiology and Parasitology,Shanghai Medical College,Fudan University.
文摘Dear Editor,The ongoing COVID-19 pandemic has resulted in over 25.0 million confirmed cases and over 840,000 deaths globally.As the third severe respiratory disease outbreak caused by the coronavirus,COVID-19 has led to much larger infected populations and coverage of geographic areas than SARS and MERS.Such high prevalence of infection has raised significant concerns about the emergence and spread of escape variants,which may evade human immunity and eventually render candidate vaccines and antibody-based therapeutics ineffective.Indeed,some naturally mutated SARS-CoV or MERS-CoV strains from the sequential outbreaks were reported to resist neutralization by the antibodies isolated during the first outbreak1,2.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.31471255,31771483,81171515,31670991,and 61721003)the National Key Research and Development Program(Grant Nos.2017YFC0908400 and 2017YFC0908401).
文摘Objective:Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor(MAPKi)resistance,which is one of the most common forms of resistance that has emerged in many types of cancers.Here,we aimed to systematically identify the genetic interactions underlying MAPKi resistance,and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi resistance.Methods:We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi,and validated 3 genetic combinations through competitive growth,cell viability,and spheroid formation assays.We next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic combinations.We also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation,Western blot,qRTPCR,and immunofluorescence assays.Results:We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance(ITGB3+IGF1R,ITGB3+JNK,and HDGF+LGR5).We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi exposure.Specifically,we discovered a novel protein complex,HDGF-LGR5,that adaptively responded to MAPKi to enhance cancer cell stemness,which was up-or downregulated by the inhibitors of ITGB3+JNK or ITGB3+IGF1R.Conclusions:Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells.ITGB3-+IGF1R-targeting drugs(cilengitide+linsitinib)could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex,which enhanced cancer stemness during MAPKi stress.
基金This work was funded by Medical Big Data and AIR&D Project of General Hospital(2019MBD-001 and 2019MBD-025)Youth Foundation of Chinese PLA General Hospital(QNF19040)+1 种基金National Science Foundation of China(81902495)National Science and Technology Major Project(2018ZX10723204).
文摘The coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is threatening public health.The human angiotensin-converting enzyme 2(ACE2)has a remarkably high affinity binding to SARS-CoV-2.This study explored whether certain populations,including obese and cancer patients,are susceptible to SARS-CoV-2.The expression pattern of ACE2 in normal and tumor tissues of cancer patients was compared by the search for network database and re-analysis of pubic data.The level of ACE2 expression in normal adipose tissue was higher than that in normal lung tissue,which indicated the adipose tissue might be vulnerable to SARS-CoV-2;the levels of ACE2 expressed by adipocytes and adipose progenitor cells were similar between non-obese individuals and obese individuals(BMI>29),but obese individuals have more adiposes so as to increase the number of ACE2-expressing cells;the expression of ACE2 in tumor tissues posed by five different types of cancers increased significantly compared with that in adjacent tissues.Therefore,we proposed the following hypothesis:the obese individuals and five types of cancer patients might have a higher risk of SARS-CoV-2 infection,which might become the target population of SARS-CoV-2 infection in the future.
基金This study was supported by the Major Research plan of the National Natural Science Foundation of China(82030044)the China Ministry of Science and Technology(2020YFA0707801).
文摘Dear Editor,COVID-19(Coronavirus Disease 2019)is a disease caused by the single-stranded sense RNA virus SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),which has caused a global public health crisis.1 However,so far no effective serum marker has been found as a biomarker for COVID-19 diagnosis,except that viral nucleic acid detection is an effective evidence of SARS-CoV-2 infection.
基金supported,in part,by the Precision Medical Research Program from Ministry of Science and Technology of China(Grant No.YL 2017YFC0908400)National Science and Technology Major Project for Infectious Disease and Funding(Grant No.YL 17-163-12-ZT-005-095-01)+2 种基金Science and Technology Commission in Ministry of National Defense of China(Grant No.YL 17-163-12-ZT-005-095-01)Xinwei Wang was supported by the intramural research program of the Center for Cancer Research,National Cancer Institute of the United StatesJunfang Ji was supported by the Thousand Young Talents Plan of China,National Natural Science Foundation of China(Grant No.81672905)
文摘Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer includes two major types： hepatocellular carcinoma （HCC, about 80%） and cholangiocarcinoma （CCA, about 15%）. Many etiological factors contribute to HCC development, such as hepatitis B virus （HBV）, hepatitis C virus （HCV）, aflatoxin B1 （AFB1）, alcohol, and metabolic diseases3. By contrast, the major risk factors for CCA are liver flukes （Opisthorchis viverrini and Clonorchis sinensis） and primary sclerosing cholangitis4,
文摘目的评估万古霉素早产儿治疗药物监测(Therapeutic Drug Monitoring,TDM)及用药情况,分析万古霉素在早产儿重症感染治疗过程中进行TDM的必要性。方法采用回顾性分析方法,制定相应标准,按标准收集2016—2018年南京医科大学附属无锡妇幼保健院早产儿34例,统计分析其基本情况、血培养、痰培养等相关病原学检查、药敏试验结果、血药浓度结果、化验室指标、药物疗效及药品不良反应(Adverse Drug Reaction,ADR)等结果。结果统计分析的34例病儿中,诊断以新生儿脓毒血症为主(48.94%),病原学送检率100%,阳性检出率76.47%,22例(占83.33%)为革兰阳性菌感染,药敏试验结果均显示对万古霉素敏感;监测范围在10~20μg/mL的初次血药谷浓度病儿极少(仅占26.47%),而通过临床药师合理干预可大大提高谷浓度的达标率(占76.92%),差异有统计学意义(P<0.05)。经万古霉素治疗后有效率达85.29%,复查病儿的各项指标较前有明显好转[降钙素原(PCT)为(0.86±0.28)比(0.31±0.43)ng/mL,尿素(Urea)为(5.39±3.91)比(2.24±1.35)mmol/L,血肌酐(Cr)为(64.24±20.44)比(34.43±9.82)μmol/L,胱抑素C(CysC)为(1.85±0.55)比(1.29±0.28)mg/L、天冬氨酸氨基转移酶(AST)为(43.72±25.03)比(25.03±11.01)IU/L,均P<0.05];未检测到万古霉素引起的耳肾损害等ADR。结论万古霉素治疗早产儿感染,特别是革兰阳性菌引起的重症感染效果明确。进行TDM可以实现早产儿万古霉素治疗个体化,使早产儿用药更加安全有效。
基金This work was supported by the National Key Research and Development Plan of China(grant numbers:2018YFE0200400 and 2017YFA0504801)the Fundamental Research Funds for the Central Universities,Nankai University(grant numbers ZB19100123,63191212 and 63191316)+1 种基金ShanghaiTech University Shanghai In stitute for Adva need Immuno chemical Studies(SIAIS)research fundingRussian Scientific Foundation(grant number 17-74-30019).
文摘Dear Editor,The rapid emerge nee and persistence of the pan demic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19)pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).
