AIM:To determine the therapeutic effect of lamivudine in late pregnancy for the interruption of motherto-child transmission(MTCT) of hepatitis B virus(HBV).METHODS:Studies were identified by searching available databa...AIM:To determine the therapeutic effect of lamivudine in late pregnancy for the interruption of motherto-child transmission(MTCT) of hepatitis B virus(HBV).METHODS:Studies were identified by searching available databases up to January 2011.Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials(RCTs) with lamivudine treatment in late pregnancy,and newborns or infants whose serum hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg) or HBV DNA had been documented.The relative risks(RRs) for interruption of MTCT as indicated by HBsAg,HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval(CI) to estimate the efficacy of lamivudine treatment.RESULTS:Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis.The overall RR was 0.43(95% CI,0.25-0.76;8 RCTs;Pheterogeneity = 0.04) and 0.33(95% CI,0.23-0.47;6 RCTs;Pheterogeneity = 0.93) indicated by newborn HBsAg or HBV DNA.The RR was 0.33(95% CI,0.21-0.50;6 RCTs;Pheterogeneity = 0.46) and 0.32(95% CI,0.20-0.50;4 RCTs;Pheterogeneity = 0.33) indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth.The RR(lamivudine vs hepatitis B immunoglobulin) was 0.27(95% CI,0.16-0.46;5 RCTs;Pheterogeneity = 0.94) and 0.24(95% CI,0.07-0.79;3 RCTs;P heterogeneity = 0.60) indicated by newborn HBsAg or HBV DNA,respectively.In the mothers with viral load < 106 copies/mL after lamivudine treatment,the efficacy(RR,95% CI) was 0.33,0.21-0.53(5 RCTs;Pheterogeneity = 0.82) for the interruption of MTCT,however,this value was not significant if maternal viral load was > 106 copies/mL after lamivudine treatment(P = 0.45,2 RCTs),as indicated by newborn serum HBsAg.The RR(lamivudine initiated from 28 wk of gestation vs control) was 0.34(95% CI,0.22-0.52;7 RCTs;Pheterogeneity = 0.92) and 0.33(95% CI,0.22-0.50;5 RCTs;Pheterogeneity = 0.86) indicated by newborn HBsAg or HBV DNA.The incidence of adverse effects of lamivudine was not higher in the mothers than in controls(P = 0.97).Only one study reported side effects of lamivudine in newborns.CONCLUSION:Lamivudine treatment in HBV carriermothers from 28 wk of gestation may interrupt MTCT of HBV efficiently.Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT.HBV MTCT might be interrupted efficiently if maternal viral load is reduced to < 106 copies/mL by lamivudine treatment.展开更多
AIM: To examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/ catenin complex and...AIM: To examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/ catenin complex and clinicopathologic parameters of HCC patients. METHODS: An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS: Reduced expression of E-cadherin, α-, β-, γ-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively). A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively). In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P =0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with α-, β-, γ-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION: Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.展开更多
AIM:To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma(ICC) . METHODS:An immunohistochemical study of E-cadherin and P120 catenin was...AIM:To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma(ICC) . METHODS:An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS:The expression of E-cadherin and P120 was reduced in 27 cases(64.3%) and 31 cases(73.8%) ,respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade(χ2 = 9.333,P = 009 and χ2 = 11.71,P = 0.003) ,TNM stage(χ2= 8.627,P = 0.035 and χ2 = 13.123,P = 0.004) ,intrahepatic metastasis(χ2= 7.292,P = 0.007 and χ2 = 4.657,P = 0.041,respectively) and patients' survival(χ2= 6.351,P = 0.002 and χ2 = 4.023,P = 0.000,respectively) . In addition,the expression of P120 was in concordance with that of E-cadherin(χ2 = 13.797,P = 0.000) ,indicating that the expression of P120 may be dependent on that of E-cadherin. Finally,only P120 expression was found to be an independent prognostic factor in Cox regression model(r = 0.088,P = 0.049) . CONCLUSION:Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markersfor predicting tumor invasion,metastasis and patients' survival,but only P120 is an independent prognostic factor for ICC.展开更多
Background: Hepatocellular carcinoma(HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells(LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase(ACLY), ...Background: Hepatocellular carcinoma(HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells(LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase(ACLY), as a key enzyme for de novo lipogenesis, has been reported to be upregulated in various tumors. However, its expression and role in HCC and LTICs remain unknown. Methods: The expressions of ACLY in HCC tissues were detected by quantitative real-time PCR(q RT-PCR), Western blotting and immunohistochemistry. Kaplan-Meier curves and Chi-square test were used to determine the clinical significance of ACLY expression in HCC patients. A series of assays were performed to determine the function of ACLY on stemness, migration and invasion of HCC cells. Luciferase reporter assay, Western blotting and immunoprecipitation were used to study the regulation of the Wnt/β-catenin signaling by ACLY. Rescue experiments were performed to investigate whether β-catenin was the mediator of ACLY-regulated stemness and migration in HCC cells. Results: ACLY was highly expressed in HCC tissues and LTICs. Overexpression of ACLY was significantly correlated with poor prognosis, progression and metastasis of HCC patients. Knockdown of ACLY remarkably suppressed stemness properties, migration and invasion in HCC cells. Mechanistically, ACLY could regulate the canonical Wnt pathway by affecting the stability of β-catenin, and Lys49 acetylation of β-catenin might mediate ACLY-regulated β-catenin level in HCC cells. Conclusions: ACLY is a potent regulator of Wnt/β-catenin signaling in modulating LTICs stemness and metastasis in HCC. ACLY may serve as a new target for the diagnosis and treatment of HCC.展开更多
Background: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor in- cluding hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the ...Background: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor in- cluding hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the association of Six2 with clinical pathological characteristics. Methods: The expressions of Six2 in HCC tumor, para-tumor tissue and portal vein tumor thrombus (PVTT) were detected by tissue microarray technique, immunohistochemistry, real-time RT-PCR and West- ern blotting. Chi-square and Kaplan-Meier analysis were used to analyze the correlation between Six2 expression and prognosis of HCC patients. Lentivirus mediated Six2 knockdown, spheroid formation as- say, proliferation assay and subcutaneous tumor implantation were performed to determine the function of Six2. Results: In 274 HCC samples, Six2 was strongly expressed. Kaplan-Meier analysis revealed that high ex- pression of Six2 was correlated with a shorter overall survival (OS) and disease-free survival (DFS). More- over, Six2 expression was associated with sex, alpha-fetoprotein, tumor size and portal vein invasion. Six2 was highly expressed in PVTT. Six2 knockdown inhibited HCC cell lines proliferation, migration, and self-renewal in vitro and in vivo. In addition, low-expression of Six2 weakened TGF-β induced Smad4 activation and epithelial-mesenchymal transition in HCC cell lines. Conclusions: Elevated Six2 expression in HCC tumor patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-β/Smad signal pathway.展开更多
Background:Transarterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)are commonly used to treat intrahepatic recurrent liver cancers.However,there is no informa-tion regarding their effe...Background:Transarterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)are commonly used to treat intrahepatic recurrent liver cancers.However,there is no informa-tion regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma(ICC)after resection.Methods:A total of 275 patients with localized recurrent ICC who received either TACE(n=183)or PMCT(n=92)were studied.A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT.Prognostic factors for TACE and PMCT were identified respectively.Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values.Results:Both TACE and PMCT provided curativeness in partial patients(5-year overall survival:21.4%and 6.1%,respectively),but TACE provided better survival benefit in both overall patients(hazard ratio[HR]=0.71;95%confidence interval[CI]:0.50–0.97;P=0.034)and propensity score matching analysis(HR=0.69;95%CI:0.47–0.98;P=0.041).Independent prognostic factors for TACE were tumor size>5 cm,poor differentiation,and major resection,whereas poor differentiation,hepatitis B virus infection,cholelithiasis,and lymph node metastasis were identified for PMCT.Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70,respectively.Conclusions:TACE provided better survival benefits compared to PMCT.However,there was a disparity in prognostic factors,suggesting evaluation of the two nomograms may be supportive in modality selection.Further prospective validation studies are required for the results to be applied in clinical medicine.展开更多
Phenolic compounds are widely present in domestic and industrial sewage and have serious environmental hazards.Electrochemical oxidation(EO)is one of the most promising methods for sewage degradation because of its hi...Phenolic compounds are widely present in domestic and industrial sewage and have serious environmental hazards.Electrochemical oxidation(EO)is one of the most promising methods for sewage degradation because of its high efficiency,environmental compatibility,and safety.In this work,we present an in-depth overview of the mechanism and factors affecting the degradation of phenolic compounds by EO.In particular,the effects of treatment of phenolic compounds with different anode materials are discussed in detail.The non-active anode shows higher degradation efficiency,less intermediate accumulation,and lower energy consumption than the active anode.EO combined with other treatment methods(biological,photo,and Fenton)presents advantages,such as low energy consumption and high degradation rate.Mean-while,the remaining drawbacks of the EO process in the phenolic compound treatment system have been discussed.Furthermore,future re-search directions are put forward to improve the feasibility of the practical application of EO technology.展开更多
Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometr...Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometry by time-of-flight(CyTOF)to establish the immune profile of peripheral blood mononuclear cells(PBMCs)on the single-cell level at indicated time points before,during,and after chemotherapy.Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters.Tissue microarrays(TMAs)were used for prognostic evaluation.A total of 20 ICC patients treated with gemcitabine(GEM)were enrolled in our study,including eight cases with good response(R)and 12 cases with non-response(NR).Tremendous changes in PBMC composition,including an increased level of CD4/CD8 double-positive T cells(DPT),were observed after chemotherapy.Patients with higher level of CD4^(+)CD45RO^(+)CXCR3^(+)T cells before treatment had a favorable response to chemotherapy.Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy,which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.展开更多
Objective To investigate the genetic causes of sudden sensorineural hearing loss(SSNHL)patients in China.This study focused on analyzing variations of coding sequence of common genes related to deafness,revealing the ...Objective To investigate the genetic causes of sudden sensorineural hearing loss(SSNHL)patients in China.This study focused on analyzing variations of coding sequence of common genes related to deafness,revealing the molecular pathogenesis of sudden deafness from a genomics perspective,discovering molecular markers associated with the onset of deafness,and then supplying prevention to high-risk populations,classifying disease according to accurate etiology,and choosing a much more precision therapy.Methods We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital.In this study,mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo.Results We identified 51 cases of unilateral sudden deafness,including 2 cases of low-mid frequency hearing impairment,18 cases of mid-high frequency hearing loss,11 cases of flat-type hearing loss,and 20 cases of all frequency hearing loss.Among the 51 cases,8(15.69%)cases of GJB2 heterozygous variations,1(1.96%)case of GJB3 heterozygous variations,5(9.8%)cases of SLC26A4 heterozygous variations,2(3.92%)cases of COCH heterozygous variations,14(27.45%)cases of CDH23 heterozygous variations,14(27.45%)cases of OTOF heterozygous variations,1(1.96%)case of SLC17A8 heterozygous variations and 2(3.92%)cases of KCNE1 heterozygous variations.No mtDNA gene variations were identified.Conclusion SSNHL has some relationship with hereditary in Chinese population,but its complex genetic pathogenic mechanisms need further study.展开更多
On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of...On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC. Additionally, sex hormones can also affect HBV-related HCC by inducing epigenetic changes. The evidence that both morphology and function of the human liver are affected by sex hormones was found over 60 years ago. However,the underlying molecular mechanism largely remains to be elucidated. This review focuses mainly on the molecular mechanisms behind the sex difference in HCC associated with HBV and other factors. In addition, several potential treatment and therapeutic strategies for inflammation-driven HCC will be introduced in this review.展开更多
基金supported by the National Natural Science Foundation of China(No.51674021)the Major Science and Technology Innovation Project of Shandong Province,China(No.2019JZZY010358)。
基金the financial supports from the National Natural Science Foundation of China (Nos. 52004194, 51874219)the China Postdoctoral Science Foundation (No. 2019M662733)。
基金Supported by National Natural Science Foundation of China,No. 81025015 and No. 30921006
文摘AIM:To determine the therapeutic effect of lamivudine in late pregnancy for the interruption of motherto-child transmission(MTCT) of hepatitis B virus(HBV).METHODS:Studies were identified by searching available databases up to January 2011.Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials(RCTs) with lamivudine treatment in late pregnancy,and newborns or infants whose serum hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg) or HBV DNA had been documented.The relative risks(RRs) for interruption of MTCT as indicated by HBsAg,HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval(CI) to estimate the efficacy of lamivudine treatment.RESULTS:Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis.The overall RR was 0.43(95% CI,0.25-0.76;8 RCTs;Pheterogeneity = 0.04) and 0.33(95% CI,0.23-0.47;6 RCTs;Pheterogeneity = 0.93) indicated by newborn HBsAg or HBV DNA.The RR was 0.33(95% CI,0.21-0.50;6 RCTs;Pheterogeneity = 0.46) and 0.32(95% CI,0.20-0.50;4 RCTs;Pheterogeneity = 0.33) indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth.The RR(lamivudine vs hepatitis B immunoglobulin) was 0.27(95% CI,0.16-0.46;5 RCTs;Pheterogeneity = 0.94) and 0.24(95% CI,0.07-0.79;3 RCTs;P heterogeneity = 0.60) indicated by newborn HBsAg or HBV DNA,respectively.In the mothers with viral load < 106 copies/mL after lamivudine treatment,the efficacy(RR,95% CI) was 0.33,0.21-0.53(5 RCTs;Pheterogeneity = 0.82) for the interruption of MTCT,however,this value was not significant if maternal viral load was > 106 copies/mL after lamivudine treatment(P = 0.45,2 RCTs),as indicated by newborn serum HBsAg.The RR(lamivudine initiated from 28 wk of gestation vs control) was 0.34(95% CI,0.22-0.52;7 RCTs;Pheterogeneity = 0.92) and 0.33(95% CI,0.22-0.50;5 RCTs;Pheterogeneity = 0.86) indicated by newborn HBsAg or HBV DNA.The incidence of adverse effects of lamivudine was not higher in the mothers than in controls(P = 0.97).Only one study reported side effects of lamivudine in newborns.CONCLUSION:Lamivudine treatment in HBV carriermothers from 28 wk of gestation may interrupt MTCT of HBV efficiently.Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT.HBV MTCT might be interrupted efficiently if maternal viral load is reduced to < 106 copies/mL by lamivudine treatment.
文摘AIM: To examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/ catenin complex and clinicopathologic parameters of HCC patients. METHODS: An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS: Reduced expression of E-cadherin, α-, β-, γ-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively). A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively). In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P =0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with α-, β-, γ-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION: Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.
文摘AIM:To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma(ICC) . METHODS:An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS:The expression of E-cadherin and P120 was reduced in 27 cases(64.3%) and 31 cases(73.8%) ,respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade(χ2 = 9.333,P = 009 and χ2 = 11.71,P = 0.003) ,TNM stage(χ2= 8.627,P = 0.035 and χ2 = 13.123,P = 0.004) ,intrahepatic metastasis(χ2= 7.292,P = 0.007 and χ2 = 4.657,P = 0.041,respectively) and patients' survival(χ2= 6.351,P = 0.002 and χ2 = 4.023,P = 0.000,respectively) . In addition,the expression of P120 was in concordance with that of E-cadherin(χ2 = 13.797,P = 0.000) ,indicating that the expression of P120 may be dependent on that of E-cadherin. Finally,only P120 expression was found to be an independent prognostic factor in Cox regression model(r = 0.088,P = 0.049) . CONCLUSION:Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markersfor predicting tumor invasion,metastasis and patients' survival,but only P120 is an independent prognostic factor for ICC.
基金supported by grants from the National Natu-ral Science Foundation of China (81972779)Ministry of Education (MOE) Key Laboratory on signaling Regulation and Targeting Therapy of Liver Cancer,and Shanghai Key Laboratory of Hepato-biliary Tumor Biology,Chinese National Key Project (2018ZX10723204-006-003)。
文摘Background: Hepatocellular carcinoma(HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells(LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase(ACLY), as a key enzyme for de novo lipogenesis, has been reported to be upregulated in various tumors. However, its expression and role in HCC and LTICs remain unknown. Methods: The expressions of ACLY in HCC tissues were detected by quantitative real-time PCR(q RT-PCR), Western blotting and immunohistochemistry. Kaplan-Meier curves and Chi-square test were used to determine the clinical significance of ACLY expression in HCC patients. A series of assays were performed to determine the function of ACLY on stemness, migration and invasion of HCC cells. Luciferase reporter assay, Western blotting and immunoprecipitation were used to study the regulation of the Wnt/β-catenin signaling by ACLY. Rescue experiments were performed to investigate whether β-catenin was the mediator of ACLY-regulated stemness and migration in HCC cells. Results: ACLY was highly expressed in HCC tissues and LTICs. Overexpression of ACLY was significantly correlated with poor prognosis, progression and metastasis of HCC patients. Knockdown of ACLY remarkably suppressed stemness properties, migration and invasion in HCC cells. Mechanistically, ACLY could regulate the canonical Wnt pathway by affecting the stability of β-catenin, and Lys49 acetylation of β-catenin might mediate ACLY-regulated β-catenin level in HCC cells. Conclusions: ACLY is a potent regulator of Wnt/β-catenin signaling in modulating LTICs stemness and metastasis in HCC. ACLY may serve as a new target for the diagnosis and treatment of HCC.
基金supported by grants from the State Key Project for Liver Cancer(2017ZX10203206)the National Key Research and Development Program(2017YFC0906900)+2 种基金the National Natural Science Foundation of China(813700 6 6,81670516)the Funds for Creative Research Groups of China(81521091)the Precision Medicine Project of Second Military Medical University(2017JZ30)
文摘Background: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor in- cluding hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the association of Six2 with clinical pathological characteristics. Methods: The expressions of Six2 in HCC tumor, para-tumor tissue and portal vein tumor thrombus (PVTT) were detected by tissue microarray technique, immunohistochemistry, real-time RT-PCR and West- ern blotting. Chi-square and Kaplan-Meier analysis were used to analyze the correlation between Six2 expression and prognosis of HCC patients. Lentivirus mediated Six2 knockdown, spheroid formation as- say, proliferation assay and subcutaneous tumor implantation were performed to determine the function of Six2. Results: In 274 HCC samples, Six2 was strongly expressed. Kaplan-Meier analysis revealed that high ex- pression of Six2 was correlated with a shorter overall survival (OS) and disease-free survival (DFS). More- over, Six2 expression was associated with sex, alpha-fetoprotein, tumor size and portal vein invasion. Six2 was highly expressed in PVTT. Six2 knockdown inhibited HCC cell lines proliferation, migration, and self-renewal in vitro and in vivo. In addition, low-expression of Six2 weakened TGF-β induced Smad4 activation and epithelial-mesenchymal transition in HCC cell lines. Conclusions: Elevated Six2 expression in HCC tumor patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-β/Smad signal pathway.
基金This work was supported by the National Natural Science Foundation of China(No.11804196 and No.11904210)the Project funded by China Postdoctoral Science Foundation(No.2018M642689)the Open Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates,(South China University of Technology)(No.2019B030301003).
基金supported by grants from the National Natural Science Foundation of China(81902939)Startup Fund for Young Teacher from Shanghai Jiaotong University(KJ3-0214-18-0022).
文摘Background:Transarterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)are commonly used to treat intrahepatic recurrent liver cancers.However,there is no informa-tion regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma(ICC)after resection.Methods:A total of 275 patients with localized recurrent ICC who received either TACE(n=183)or PMCT(n=92)were studied.A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT.Prognostic factors for TACE and PMCT were identified respectively.Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values.Results:Both TACE and PMCT provided curativeness in partial patients(5-year overall survival:21.4%and 6.1%,respectively),but TACE provided better survival benefit in both overall patients(hazard ratio[HR]=0.71;95%confidence interval[CI]:0.50–0.97;P=0.034)and propensity score matching analysis(HR=0.69;95%CI:0.47–0.98;P=0.041).Independent prognostic factors for TACE were tumor size>5 cm,poor differentiation,and major resection,whereas poor differentiation,hepatitis B virus infection,cholelithiasis,and lymph node metastasis were identified for PMCT.Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70,respectively.Conclusions:TACE provided better survival benefits compared to PMCT.However,there was a disparity in prognostic factors,suggesting evaluation of the two nomograms may be supportive in modality selection.Further prospective validation studies are required for the results to be applied in clinical medicine.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.52025041 and 51974021)the Fundamental Research Funds for the Central Universities(No.FRF-TP-19-004B2Z),and the Beijing Excellent Talents Foundation.
文摘Phenolic compounds are widely present in domestic and industrial sewage and have serious environmental hazards.Electrochemical oxidation(EO)is one of the most promising methods for sewage degradation because of its high efficiency,environmental compatibility,and safety.In this work,we present an in-depth overview of the mechanism and factors affecting the degradation of phenolic compounds by EO.In particular,the effects of treatment of phenolic compounds with different anode materials are discussed in detail.The non-active anode shows higher degradation efficiency,less intermediate accumulation,and lower energy consumption than the active anode.EO combined with other treatment methods(biological,photo,and Fenton)presents advantages,such as low energy consumption and high degradation rate.Mean-while,the remaining drawbacks of the EO process in the phenolic compound treatment system have been discussed.Furthermore,future re-search directions are put forward to improve the feasibility of the practical application of EO technology.
基金This work was supported by the National Research Program of China(2017YFA0505803 and 2017YFC0908100)the State Key Project for Infectious Diseases(2018ZX10732202-001)+2 种基金National Natural Science Foundation of China(81790633,81672860,61922047,81422032,and 81902412)National Natural Science Foundation of Shanghai,China(17ZR143800)National Science Foundation for Distinguished Young Scholars of China(81702298).
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometry by time-of-flight(CyTOF)to establish the immune profile of peripheral blood mononuclear cells(PBMCs)on the single-cell level at indicated time points before,during,and after chemotherapy.Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters.Tissue microarrays(TMAs)were used for prognostic evaluation.A total of 20 ICC patients treated with gemcitabine(GEM)were enrolled in our study,including eight cases with good response(R)and 12 cases with non-response(NR).Tremendous changes in PBMC composition,including an increased level of CD4/CD8 double-positive T cells(DPT),were observed after chemotherapy.Patients with higher level of CD4^(+)CD45RO^(+)CXCR3^(+)T cells before treatment had a favorable response to chemotherapy.Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy,which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.
基金supported by the National Natural Science Foundation of China(No.81830028,No.81900950 and No.81900951).
文摘Objective To investigate the genetic causes of sudden sensorineural hearing loss(SSNHL)patients in China.This study focused on analyzing variations of coding sequence of common genes related to deafness,revealing the molecular pathogenesis of sudden deafness from a genomics perspective,discovering molecular markers associated with the onset of deafness,and then supplying prevention to high-risk populations,classifying disease according to accurate etiology,and choosing a much more precision therapy.Methods We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital.In this study,mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo.Results We identified 51 cases of unilateral sudden deafness,including 2 cases of low-mid frequency hearing impairment,18 cases of mid-high frequency hearing loss,11 cases of flat-type hearing loss,and 20 cases of all frequency hearing loss.Among the 51 cases,8(15.69%)cases of GJB2 heterozygous variations,1(1.96%)case of GJB3 heterozygous variations,5(9.8%)cases of SLC26A4 heterozygous variations,2(3.92%)cases of COCH heterozygous variations,14(27.45%)cases of CDH23 heterozygous variations,14(27.45%)cases of OTOF heterozygous variations,1(1.96%)case of SLC17A8 heterozygous variations and 2(3.92%)cases of KCNE1 heterozygous variations.No mtDNA gene variations were identified.Conclusion SSNHL has some relationship with hereditary in Chinese population,but its complex genetic pathogenic mechanisms need further study.
基金supported by the State Key Project for Liver Cancer(2012ZX10002009)National Natural Science Foundation of China(81301811,81521091,81422032,81272212,81672860,81372674,and 91529303)+1 种基金Science Foundation of Shanghai(134119a3700)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12010201)
文摘On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC. Additionally, sex hormones can also affect HBV-related HCC by inducing epigenetic changes. The evidence that both morphology and function of the human liver are affected by sex hormones was found over 60 years ago. However,the underlying molecular mechanism largely remains to be elucidated. This review focuses mainly on the molecular mechanisms behind the sex difference in HCC associated with HBV and other factors. In addition, several potential treatment and therapeutic strategies for inflammation-driven HCC will be introduced in this review.
