Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarte...Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.展开更多
Background:Hepatocellular carcinoma(HCC)remains a significant global health challenge.While firstline treatments with immune checkpoint inhibitors(ICIs)have improved patient outcomes,the selection of effective second-...Background:Hepatocellular carcinoma(HCC)remains a significant global health challenge.While firstline treatments with immune checkpoint inhibitors(ICIs)have improved patient outcomes,the selection of effective second-line therapies remains unclear.This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.Methods:Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies,alone or combined with ICIs were enrolled.Clinical data were collected,and propensity score matching(PSM)was used to ensure comparability between treatment groups.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and treatment-related adverse events.The study was registered at www.chictr.org.cn(ChiCTR2400091318).Results:A total of 149 patients were included:113 in the combination therapy group(Rego-ICI group)and 36 in the regorafenib monotherapy group(Rego group).After PSM,the Rego-ICI group showed significantly improved OS[19.0 vs.11.0 months,hazard ratio(HR)=0.426,95%confidence interval(CI):0.235–0.772,P=0.005]and PFS(4.0 vs.3.0 months,HR=0.539,95%CI:0.337–0.863,P=0.010)compared to the Rego group.Differences in ORR and DCR were not statistically significant(ORR:19.4%vs.9.7%,P=0.226;DCR:64.2%vs.48.4%,P=0.139),but the Rego-ICI group showed better disease control.Regorafenib plus ICI improved both OS and PFS with no new safety signals.Conclusions:The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments.These findings support the potential of regorafenib plus ICIs as an effective second-line therapy.展开更多
Perihilar cholangiocarcinoma(pCCA)and intrahepatic cholangiocarcinoma(iCCA)are highly malignant neoplasms with a 5-year overall survival rate of approximately 30%[1,2].Surgical resection remains the only potentially c...Perihilar cholangiocarcinoma(pCCA)and intrahepatic cholangiocarcinoma(iCCA)are highly malignant neoplasms with a 5-year overall survival rate of approximately 30%[1,2].Surgical resection remains the only potentially curative treatment,yet only one-fifth of patients are eligible for resection at initial diagnosis[3].Threedimensional(3D)reconstruction technology provides precise preoperative visualization of complex hilar anatomy,significantly enhancing surgical planning and outcomes[4].Recent advances in 3D reconstruction technology have enhanced preoperative planning by providing precise anatomical mapping of tumor-vessel relationships and biliary variations[4,5].Therefore,this report describes a case of left iCCA successfully resected with biliary reconstruction guided by 3D visualization.展开更多
BACKGROUND In-depth comparative investigations in terms of clinical efficacies of liver tumor microwave ablation(MWA)and laparoscopic hepatectomy(LH),which are both important treatment modalities for liver neoplasms,h...BACKGROUND In-depth comparative investigations in terms of clinical efficacies of liver tumor microwave ablation(MWA)and laparoscopic hepatectomy(LH),which are both important treatment modalities for liver neoplasms,have been limited in patients diagnosed with primary small liver cancer(PSLC).AIM To compare and analyze the clinical efficacy of liver tumor MWA and LH for PSLC.METHODS This study retrospectively analyzed the medical records of 123 patients with PSLC admitted to Xuzhou Central Hospital from January 2015 to November 2022 and categorized them based on treatment modalities into the LH and MWA groups.The LH group,consisting of 61 cases,received LH,and the MWA group,which included 62 cases,underwent liver tumor MWA.Basic data and various periop-erative indicators were compared between the two groups,including changes in liver function indicators[alanine aminotransferase(ALT),glutamic aminotrans-ferase(AST),and total bilirubin(TBIL)]pre-and post-treatment,and efficacy and postoperative complications were analyzed.RESULTS No statistically significant difference was observed between the two groups in terms of age,gender,tumor diameter,liver function Child-Pugh classification and number of tumors,body mass index,and educational status(P>0.05).The overall effective rate was higher in the MWA group than in the LH group(98.39%vs 88.52%)(χ2=4.918,P=0.027).The MWA group exhibited less operation time,intraoperative bleeding,defecation time,and hospital stay than the LH group(P<0.05).No difference was found in liver function indicators between the two groups pre-treatment(P>0.05),and ALT,AST,and TBIL levels decreased in both groups post-treatment,with the MWA group demonstrating lower levels(P<0.05).The MWA and LH groups exhibited postoperative complication rates of 4.84%and 19.67%,respectively,with statistically significant differences between the two groups(P=0.012,χ2=6.318).CONCLUSION MWA is more effective in treating PSLC,and it promotes faster postoperative recovery for patients,and more security improves liver function and reduces postoperative complications compared to LH.展开更多
Ischemia-reperfusion injury(IRI)remains an unavoidable challenge in liver surgery,with macrophages playing a critical role in its pathogenesis.However,the mechanisms by which macrophages regulate the pathogenesis of I...Ischemia-reperfusion injury(IRI)remains an unavoidable challenge in liver surgery,with macrophages playing a critical role in its pathogenesis.However,the mechanisms by which macrophages regulate the pathogenesis of IRI are not well understood.Through a target-guided screening approach,we identified a small 3 k Da peptide(Sj DX5-271)from various schistosome egg-derived peptides that induced M2 macrophage polarization.SjDX5-271 treatment protected mice against liver IRI by promoting M2 macrophage polarization,and this protective effect was abrogated when the macrophages were depleted.Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages from the SjDX5-271 treatment group.We further identified that SjDX5-271 promoted M2 macrophage polarization by inhibiting the TLR4/My D88/NF-κB signaling pathway and alleviated hepatic inflammation in liver IRI.Collectively,SjDX5-271 exhibited some promising therapeutic effects in IRI and represented a novel therapeutic approach,potentially applicable to other immune-related diseases.The current study demonstrates the potential of new biologics from the parasite,enhances our understanding of host-parasite interplay,and provides a blueprint for future therapies for immunerelated diseases.展开更多
Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to ...Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.展开更多
Background:Skin photoaging is a physiological or pathological process caused by multiple factors.Developing anti-skin photoaging drugs is a hot topic in cosmetology research fields.The purpose of this study was to exp...Background:Skin photoaging is a physiological or pathological process caused by multiple factors.Developing anti-skin photoaging drugs is a hot topic in cosmetology research fields.The purpose of this study was to explore the therapeutic effect of Dendrobium officinale(D.officinale)on skin aging.Methods:The ingredients of D.officinale were detected by UHPLC-Q-TOF/MS.The targets of D.officinale were screened by Swiss Target Prediction database.GeneCards,NCBI,and OMIM databases were utilized to find out the targets associated with skin photoaging.Overlapping targets of D.officinale and skin photoaging were obtained by Venn analysis.The ingredient-disease target network and protein-protein interaction network were constructed by using the STRING database and Cytoscape software.The key compounds and hub genes were obtained by analyzing networks.The DAVID database was applied for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the overlapping targets.Autodock Vina software was used to simulate molecular docking and the results were visualized using Pymol.Finally,the skin photoaging models of cells and mice were established to validate the results predicted by network pharmacology.Results:In D.officinale,a total of 59 compounds and 595 targets were detected,of which 59 proteins were intersectional with skin photoaging targets.The top 10 active ingredients(Dendrophenol,Herbacetin,Lyoniresinol,Trans-ferulaldehyde,Naringenin,and so on)and 8 hub genes(AKT1,TNF,VEGFA,MAPK3,CASP3,MMP9,CTNNB1,and EGFR)were identified.All the key active compounds could bind well with core protein targets(binding energy<-5 kcal/mol).The potential therapeutic targets were related to the response to reactive oxygen species,collagen catabolic process,extracellular matrix organization,and apoptotic process,mainly.We also found that D.officinale could enhance the cell viability and activity of anti-oxidases,reduce reactive oxygen species and MMP9 levels,and stable mitochondrial membrane potential.Furthermore,D.officinale could alleviate skin photoaging injury and reduce malondialdehyde level in mice.Conclusion:D.officinale alleviated skin photoaging via regulating oxidative stress,apoptosis,and collagen catabolic process.展开更多
BACKGROUND Inflammatory cytokines are associated with cancer prognosis,but their specific role in cholangiocarcinoma remains poorly understood.The lymphocyte to C-reactive protein ratio(LCR),a novel inflammatory-nutri...BACKGROUND Inflammatory cytokines are associated with cancer prognosis,but their specific role in cholangiocarcinoma remains poorly understood.The lymphocyte to C-reactive protein ratio(LCR),a novel inflammatory-nutritional biomarker,has demonstrated predictive value in gastrointestinal cancers;however,its clinical relevance in cholangiocarcinoma has not been investigated.AIM To validate the LCR as an independent prognostic factor for overall survival(OS),surgical site infection(SSI),and length of hospital stay in patients with resectable cholangiocarcinoma.METHODS We conducted a retrospective analysis of 76 patients with cholangiocarcinoma who underwent radical surgery between 2008 and 2013.The preoperative LCR was calculated as the lymphocyte count divided by C-reactive protein level,using a cutoff value of 180.Univariate and multivariate logistic regression analyses were performed to evaluate factors associated with SSI and hospitalization duration,while Kaplan-Meier survival curves and Cox proportional hazards models were used to assess predictors of OS.RESULTS Patients in the low LCR group was significantly associated with several adverse clinical outcomes:A shorter median OS(14.93 months vs 46.67 months;P=0.022);a 4.5-fold increased risk of prolonged hospitalization(P=0.007);and a higher incidence of SSI(odds ratio=4.41,P=0.045).Multivariate analysis confirmed that LCR was an independent predictor of OS[hazard ratio(HR)=3.204,P=0.002],SSI,and hospitalization duration.Additionally,R0 resection(HR=3.546,P=0.002)and advanced tumor-node-metastasis stage(HR=2.016,P=0.035)were identified as independent prognostic factors for OS.CONCLUSION In this retrospective study,preoperative LCR is a cost-effective and practical biomarker that independently predicts OS,postoperative complications,and hospitalization duration in patients with resectable cholangiocarcinoma,thereby facilitating more precise patient stratification.展开更多
AIM:To compare the outcomes between doubleguidewire technique(DGT) and transpancreatic precut sphincterotomy(TPS) in patients with difficult biliary cannulation.METHODS:This was a prospective,randomized study conducte...AIM:To compare the outcomes between doubleguidewire technique(DGT) and transpancreatic precut sphincterotomy(TPS) in patients with difficult biliary cannulation.METHODS:This was a prospective,randomized study conducted in single tertiary referral hospital in Korea.Between January 2005 and September 2010.A total of 71 patients,who bile duct cannulation was not possible and selective pancreatic duct cannulation was achieved,were randomized into DGT(n = 34) and TPS(n = 37) groups.DGT or TPS was done for selective biliary cannulation.We measured the technical success rates of biliary cannulation,median cannulation time,and procedure related complications.RESULTS:The distribution of patients after randomization was balanced,and both groups were comparable in baseline characteristics,except the higher percentage of endoscopic nasobiliary drainage in the DGT group(55.9% vs 13.5%,P < 0.001).Successful cannulation rate and mean cannulation times in DGT and TPS groups were 91.2% vs 91.9% and 14.1 ± 13.2 min vs 15.4 ± 17.9 min,P = 0.732,respectively.There was no significant difference between the two groups.The overall incidence of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis was 38.2% vs 10.8%,P < 0.011 in the DGT group and the TPS group;post-procedure pancreatitis was significantly higher in the DGT group.But the overall incidence of post-ERCP hyperamylasemia was no significant difference between the two groups;DGT group vs TPS group:14.7% vs 16.2%,P < 1.0.CONCLUSION:When free bile duct cannulation was difficult and selective pancreatic duct cannulation was achieved,DGT and TPS facilitated biliary cannulation and showed similar success rates.However,post-procedure pancreatitis was significantly higher in the DGT group.展开更多
AIM： To investigate the role of SMYD3 in hepatocellular carcinoma （HCC） development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS： Expression of SMYD3 in HCC ...AIM： To investigate the role of SMYD3 in hepatocellular carcinoma （HCC） development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS： Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference （RNAi） was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZl CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS： SMYD3 over-expression in HCC was associated with RIZl hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de- methylated RIZl CpG promoter （P 〈 0.01） and increased RIZl mRNA expression （P 〈 0.01）. Consequently, SMYD3 down-expression with RIZl de-methylation strongly inhibited hepatoma cell growth （MTT inhibitory rates： Pgenesil-1-s1 60.95%± 7.97%, Pgenesil-1-s2 72.14% ± 9.68% vs Pgenesil-1-hk 6.89% ± 4.12%, P 〈 0.01） and migration （Pgenesil-1-s1 4.24% ± 1.58%, Pgenesil- 1-s1 4.87% ± 0.73% vs Pgenesil-1 19.03% ± 4.63%, Pgenesil-1-hk 19.95% ±5.21%, P 〈 0.01） and induced apoptosis （FCM subG1 phase Pgenesil-1-s1 19.07% ＋ 1.78%, Pgenesil-1-s2 17.68% ± 2.36% vs Pgenesil-1 0.47% ± 0.12%, Pgenesil-1-hk 1.46% ± 0.28%, P 〈 0.01. TUNEL-positive cells： Pgenesil-1-s1 40.24%± 5.18%, Pgenesil-1-s2 38.48% ± 4.65% vs Pgenesil-1 2.1B% - 1.34%, Pgenesil-1-hk 2.84%± 1.22%, P 〈 0.01） in HepG2 cells. CONCLUSION： These results demonstrate that SMYD3plays a critical role in the carcinogenesis and progression of HCC, The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZl CpG promoter hypermethylation.展开更多
AIM To assess the antiviral effects of hepatitis B virus(HBV) S gene-specific anti-gene locked nucleic acid(LNA) in transgenic mice.METHODS Thirty HBV transgenic mice were acclimatized to laboratory conditions and pos...AIM To assess the antiviral effects of hepatitis B virus(HBV) S gene-specific anti-gene locked nucleic acid(LNA) in transgenic mice.METHODS Thirty HBV transgenic mice were acclimatized to laboratory conditions and positive for serum HBV surface antigen(HBs Ag) and HBV DNA, were randomly divided into 5 groups(n = 7), including negative control(blank control, unrelated sequence control), positive control(lamivudine, anti-sense-LNA), and anti-gene-LNA experimental group. LNA was injected into transgenic mice by tail vein while lamivudine was administeredby gavage. Serum HBV DNA and HBs Ag levels were determined by fluorescence-based PCR and enzymelinked immune sorbent assay, respectively. HBV S gene expression amounts were assessed by reverse transcription polymerase chain reaction. Positive rates of HBsA g in liver cells were evaluated immunohistochemistry.RESULTS Average rate reductions of HBs Ag after treatment on the 3 rd, 5 th, and 7 th days were 32.34%, 45.96%, and 59.15%, respectively. The inhibitory effect of antigene-LNA on serum HBs Ag peaked on day 7, with statistically significant differences compared with pretreatment(0.96 ± 0.18 vs 2.35 ± 0.33, P < 0.05) and control values(P < 0.05 for all). Average reduction rates of HBV DNA on the 3 rd, 5 th, and 7 th days were 38.55%, 50.95%, and 62.26%, respectively. This inhibitory effect peaked on the 7 th day after treatment with anti-gene-LNA, with statistically significant differences compared with pre-treatment(4.17 ± 1.29 vs 11.05 ± 1.25, P < 0.05) and control values(P < 0.05 for all). The mR NA levels of the HBV S gene(P < 0.05 for all) and rates of HBsA g positive liver cells(P < 0.05 for all) were significantly reduced compared with the control groups. Liver and kidney function, and histology showed no abnormalities. CONCLUSION Anti-gene-LNA targeting the S gene of HBV displays strong inhibitory effects on HBV in transgenic mice, providing theoretical and experimental bases for gene therapy in HBV.展开更多
Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immun...Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR.However,immunosuppressive agents negatively impact the immune system of the patients,causing them to suffer from serious complications,such as chronic infection and malignant tumors.Therefore,a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant(OT)is essential for developing better treatment options and improving patient outcomes.This article reviews the role of immune cells in OTR and organ transplant tolerance(OTT),including the novel cell therapies that are currently under clinical trials for transplant recipients.展开更多
Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the targe...Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.展开更多
Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to pred...Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.展开更多
This article reports on a retrospective analysis on 121 patients and a prospectivestudy on 21 patients with acute cholangitis of severe type(ACST)for a study on the timing se-lection of emergency operation for ACST.Tw...This article reports on a retrospective analysis on 121 patients and a prospectivestudy on 21 patients with acute cholangitis of severe type(ACST)for a study on the timing se-lection of emergency operation for ACST.Twenty two clinical,biological,etiologic,pathologicand operative variables were analyzed.Simple regression revealed 11 factors with prognosticsignificance,but multivariate analysis detected only 6 factors with independent significance inpredicting mortality(age,mean blood pressure,generalized peritonitis,serum albumin-globin ra-tio,blood culture,and the number of failed organs and systems).The results indicate that theclinical principles of treatment for ACST should be the combination of medical and surgicaltreatment.Active conservative treatment is practically applicable to the majority of ACST,espe-cially,those with short history and few complication.Prognostic mathematical model of ACSTdoes good for its timing selection of emergency operation.A critical level of 0.40 is determinedto be the discriminant score for emergency bile duct drainage.The model seems to have advan-tages over the traditional method.展开更多
BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patie...BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.展开更多
The prognosis for patients diagnosed with hepatocellular carcinoma with bile duct tumor thrombus(HCCBDTT)remains dismal,and there are presently no universally accepted treatment guidelines to address this complex cond...The prognosis for patients diagnosed with hepatocellular carcinoma with bile duct tumor thrombus(HCCBDTT)remains dismal,and there are presently no universally accepted treatment guidelines to address this complex condition.Long-term outcomes of liver transplantation(LT)for HCC-BDTT patients are unclear,and whether LT is a proper therapeutic option for HCC-BDTT patients remains to be determined.Therefore,we design a clinical trial to evaluate whether LT can improve recurrence-free survival(RFS)and overall survival(OS)in HCC-BDTT patients.This is an open-labeled,single-arm,prospective,multicenter and real-world study aiming to assess the survival outcomes of HCC-BDTT patients in LT.Patients will be enrolled based on histological confirmation of HCC with BDTT.The study is planned to take 4 years,2 years for enrollment and 2 years for follow-up.We anticipate that LT confers beneficial survival outcomes for HCC-BDTT patients,specifically in terms of the pivotal parameters,such as RFS and quality of life.Upon successful completion of the trial,we will extend our monitoring over a longer follow-up time to accurately estimate important indicators such as OS.We expect that this study provides substantial evidence to refine treatment guidelines through thorough data analysis,ultimately contributing to better patient outcomes and advancing our understanding of the disease.展开更多
Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1.At this N/P ...Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1.At this N/P ratio,the transfection efficiency in the hepatoma cells was the highest with a slow release effect.Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation,and can target the transfection into hepatoma cells by combination with galactose and biotin receptors.The transfection rate was inhibited by the competition of galactose and biotin.Bio-GC nanomaterials were imported into cells’cytoplasm by their receptors,followed by the imported exogenous gene transfected into the cells.Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice,by carrying the gene through the blood to the hepatoma tissue.Taken together,bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation,improving the rate of transfection in hepatoma cells,and transporting the gene into the cytoplasm in vitro and in vivo.Therefore,they are efficient hepatoma-targeting gene carriers.展开更多
To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].Howe...To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].展开更多
Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischem...Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischemia/reperfusion(RIR)model.Methods:Small-animal PET imaging in vivo was performed with ^(18)F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.Results:We found that the average standardized uptake value(SUV_(average))of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group(P<0.05).We also found that glucose uptake in different cortical subregions including the left auditory cortex,right medial prefrontal cortex,right para cortex,left retrosplenial cortex,right retrosplenial cortex,and right visual cortex was significantly increased in the RIR group(P<0.05),but there was no significant difference in the SUV_(avcrage) of right auditory cortex,left medial prefrontal cortex,left para cortex,and left visual cortex between the two groups.Conclusion:The ^(18)F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.展开更多
基金supported by grants from the National Natural Science Foundation of China(91959203,82272836 and 82373017)。
文摘Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.
基金supported by a grant from the Zhongda Hospital Affiliated to Southeast University,Jiangsu Province High-Level Hospital Construction Funds(No.YKK24270)。
文摘Background:Hepatocellular carcinoma(HCC)remains a significant global health challenge.While firstline treatments with immune checkpoint inhibitors(ICIs)have improved patient outcomes,the selection of effective second-line therapies remains unclear.This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.Methods:Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies,alone or combined with ICIs were enrolled.Clinical data were collected,and propensity score matching(PSM)was used to ensure comparability between treatment groups.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and treatment-related adverse events.The study was registered at www.chictr.org.cn(ChiCTR2400091318).Results:A total of 149 patients were included:113 in the combination therapy group(Rego-ICI group)and 36 in the regorafenib monotherapy group(Rego group).After PSM,the Rego-ICI group showed significantly improved OS[19.0 vs.11.0 months,hazard ratio(HR)=0.426,95%confidence interval(CI):0.235–0.772,P=0.005]and PFS(4.0 vs.3.0 months,HR=0.539,95%CI:0.337–0.863,P=0.010)compared to the Rego group.Differences in ORR and DCR were not statistically significant(ORR:19.4%vs.9.7%,P=0.226;DCR:64.2%vs.48.4%,P=0.139),but the Rego-ICI group showed better disease control.Regorafenib plus ICI improved both OS and PFS with no new safety signals.Conclusions:The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments.These findings support the potential of regorafenib plus ICIs as an effective second-line therapy.
基金supported by grants from the National Natural Science Foundation of China(82170412)Shanghai Municipal Science and Technology Commission Clinical Innovation Research Special Project(23Y11905400).
文摘Perihilar cholangiocarcinoma(pCCA)and intrahepatic cholangiocarcinoma(iCCA)are highly malignant neoplasms with a 5-year overall survival rate of approximately 30%[1,2].Surgical resection remains the only potentially curative treatment,yet only one-fifth of patients are eligible for resection at initial diagnosis[3].Threedimensional(3D)reconstruction technology provides precise preoperative visualization of complex hilar anatomy,significantly enhancing surgical planning and outcomes[4].Recent advances in 3D reconstruction technology have enhanced preoperative planning by providing precise anatomical mapping of tumor-vessel relationships and biliary variations[4,5].Therefore,this report describes a case of left iCCA successfully resected with biliary reconstruction guided by 3D visualization.
文摘BACKGROUND In-depth comparative investigations in terms of clinical efficacies of liver tumor microwave ablation(MWA)and laparoscopic hepatectomy(LH),which are both important treatment modalities for liver neoplasms,have been limited in patients diagnosed with primary small liver cancer(PSLC).AIM To compare and analyze the clinical efficacy of liver tumor MWA and LH for PSLC.METHODS This study retrospectively analyzed the medical records of 123 patients with PSLC admitted to Xuzhou Central Hospital from January 2015 to November 2022 and categorized them based on treatment modalities into the LH and MWA groups.The LH group,consisting of 61 cases,received LH,and the MWA group,which included 62 cases,underwent liver tumor MWA.Basic data and various periop-erative indicators were compared between the two groups,including changes in liver function indicators[alanine aminotransferase(ALT),glutamic aminotrans-ferase(AST),and total bilirubin(TBIL)]pre-and post-treatment,and efficacy and postoperative complications were analyzed.RESULTS No statistically significant difference was observed between the two groups in terms of age,gender,tumor diameter,liver function Child-Pugh classification and number of tumors,body mass index,and educational status(P>0.05).The overall effective rate was higher in the MWA group than in the LH group(98.39%vs 88.52%)(χ2=4.918,P=0.027).The MWA group exhibited less operation time,intraoperative bleeding,defecation time,and hospital stay than the LH group(P<0.05).No difference was found in liver function indicators between the two groups pre-treatment(P>0.05),and ALT,AST,and TBIL levels decreased in both groups post-treatment,with the MWA group demonstrating lower levels(P<0.05).The MWA and LH groups exhibited postoperative complication rates of 4.84%and 19.67%,respectively,with statistically significant differences between the two groups(P=0.012,χ2=6.318).CONCLUSION MWA is more effective in treating PSLC,and it promotes faster postoperative recovery for patients,and more security improves liver function and reduces postoperative complications compared to LH.
基金supported by the National Natural Science Foundation of China(Grant No.81971965)。
文摘Ischemia-reperfusion injury(IRI)remains an unavoidable challenge in liver surgery,with macrophages playing a critical role in its pathogenesis.However,the mechanisms by which macrophages regulate the pathogenesis of IRI are not well understood.Through a target-guided screening approach,we identified a small 3 k Da peptide(Sj DX5-271)from various schistosome egg-derived peptides that induced M2 macrophage polarization.SjDX5-271 treatment protected mice against liver IRI by promoting M2 macrophage polarization,and this protective effect was abrogated when the macrophages were depleted.Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages from the SjDX5-271 treatment group.We further identified that SjDX5-271 promoted M2 macrophage polarization by inhibiting the TLR4/My D88/NF-κB signaling pathway and alleviated hepatic inflammation in liver IRI.Collectively,SjDX5-271 exhibited some promising therapeutic effects in IRI and represented a novel therapeutic approach,potentially applicable to other immune-related diseases.The current study demonstrates the potential of new biologics from the parasite,enhances our understanding of host-parasite interplay,and provides a blueprint for future therapies for immunerelated diseases.
文摘Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.
文摘Background:Skin photoaging is a physiological or pathological process caused by multiple factors.Developing anti-skin photoaging drugs is a hot topic in cosmetology research fields.The purpose of this study was to explore the therapeutic effect of Dendrobium officinale(D.officinale)on skin aging.Methods:The ingredients of D.officinale were detected by UHPLC-Q-TOF/MS.The targets of D.officinale were screened by Swiss Target Prediction database.GeneCards,NCBI,and OMIM databases were utilized to find out the targets associated with skin photoaging.Overlapping targets of D.officinale and skin photoaging were obtained by Venn analysis.The ingredient-disease target network and protein-protein interaction network were constructed by using the STRING database and Cytoscape software.The key compounds and hub genes were obtained by analyzing networks.The DAVID database was applied for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the overlapping targets.Autodock Vina software was used to simulate molecular docking and the results were visualized using Pymol.Finally,the skin photoaging models of cells and mice were established to validate the results predicted by network pharmacology.Results:In D.officinale,a total of 59 compounds and 595 targets were detected,of which 59 proteins were intersectional with skin photoaging targets.The top 10 active ingredients(Dendrophenol,Herbacetin,Lyoniresinol,Trans-ferulaldehyde,Naringenin,and so on)and 8 hub genes(AKT1,TNF,VEGFA,MAPK3,CASP3,MMP9,CTNNB1,and EGFR)were identified.All the key active compounds could bind well with core protein targets(binding energy<-5 kcal/mol).The potential therapeutic targets were related to the response to reactive oxygen species,collagen catabolic process,extracellular matrix organization,and apoptotic process,mainly.We also found that D.officinale could enhance the cell viability and activity of anti-oxidases,reduce reactive oxygen species and MMP9 levels,and stable mitochondrial membrane potential.Furthermore,D.officinale could alleviate skin photoaging injury and reduce malondialdehyde level in mice.Conclusion:D.officinale alleviated skin photoaging via regulating oxidative stress,apoptosis,and collagen catabolic process.
基金Supported by National Natural Science Foundation of China,No.82170412.
文摘BACKGROUND Inflammatory cytokines are associated with cancer prognosis,but their specific role in cholangiocarcinoma remains poorly understood.The lymphocyte to C-reactive protein ratio(LCR),a novel inflammatory-nutritional biomarker,has demonstrated predictive value in gastrointestinal cancers;however,its clinical relevance in cholangiocarcinoma has not been investigated.AIM To validate the LCR as an independent prognostic factor for overall survival(OS),surgical site infection(SSI),and length of hospital stay in patients with resectable cholangiocarcinoma.METHODS We conducted a retrospective analysis of 76 patients with cholangiocarcinoma who underwent radical surgery between 2008 and 2013.The preoperative LCR was calculated as the lymphocyte count divided by C-reactive protein level,using a cutoff value of 180.Univariate and multivariate logistic regression analyses were performed to evaluate factors associated with SSI and hospitalization duration,while Kaplan-Meier survival curves and Cox proportional hazards models were used to assess predictors of OS.RESULTS Patients in the low LCR group was significantly associated with several adverse clinical outcomes:A shorter median OS(14.93 months vs 46.67 months;P=0.022);a 4.5-fold increased risk of prolonged hospitalization(P=0.007);and a higher incidence of SSI(odds ratio=4.41,P=0.045).Multivariate analysis confirmed that LCR was an independent predictor of OS[hazard ratio(HR)=3.204,P=0.002],SSI,and hospitalization duration.Additionally,R0 resection(HR=3.546,P=0.002)and advanced tumor-node-metastasis stage(HR=2.016,P=0.035)were identified as independent prognostic factors for OS.CONCLUSION In this retrospective study,preoperative LCR is a cost-effective and practical biomarker that independently predicts OS,postoperative complications,and hospitalization duration in patients with resectable cholangiocarcinoma,thereby facilitating more precise patient stratification.
文摘AIM:To compare the outcomes between doubleguidewire technique(DGT) and transpancreatic precut sphincterotomy(TPS) in patients with difficult biliary cannulation.METHODS:This was a prospective,randomized study conducted in single tertiary referral hospital in Korea.Between January 2005 and September 2010.A total of 71 patients,who bile duct cannulation was not possible and selective pancreatic duct cannulation was achieved,were randomized into DGT(n = 34) and TPS(n = 37) groups.DGT or TPS was done for selective biliary cannulation.We measured the technical success rates of biliary cannulation,median cannulation time,and procedure related complications.RESULTS:The distribution of patients after randomization was balanced,and both groups were comparable in baseline characteristics,except the higher percentage of endoscopic nasobiliary drainage in the DGT group(55.9% vs 13.5%,P < 0.001).Successful cannulation rate and mean cannulation times in DGT and TPS groups were 91.2% vs 91.9% and 14.1 ± 13.2 min vs 15.4 ± 17.9 min,P = 0.732,respectively.There was no significant difference between the two groups.The overall incidence of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis was 38.2% vs 10.8%,P < 0.011 in the DGT group and the TPS group;post-procedure pancreatitis was significantly higher in the DGT group.But the overall incidence of post-ERCP hyperamylasemia was no significant difference between the two groups;DGT group vs TPS group:14.7% vs 16.2%,P < 1.0.CONCLUSION:When free bile duct cannulation was difficult and selective pancreatic duct cannulation was achieved,DGT and TPS facilitated biliary cannulation and showed similar success rates.However,post-procedure pancreatitis was significantly higher in the DGT group.
基金National Natural Science Foundation of China, No 30200273 & 30672067
文摘AIM： To investigate the role of SMYD3 in hepatocellular carcinoma （HCC） development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS： Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference （RNAi） was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZl CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS： SMYD3 over-expression in HCC was associated with RIZl hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de- methylated RIZl CpG promoter （P 〈 0.01） and increased RIZl mRNA expression （P 〈 0.01）. Consequently, SMYD3 down-expression with RIZl de-methylation strongly inhibited hepatoma cell growth （MTT inhibitory rates： Pgenesil-1-s1 60.95%± 7.97%, Pgenesil-1-s2 72.14% ± 9.68% vs Pgenesil-1-hk 6.89% ± 4.12%, P 〈 0.01） and migration （Pgenesil-1-s1 4.24% ± 1.58%, Pgenesil- 1-s1 4.87% ± 0.73% vs Pgenesil-1 19.03% ± 4.63%, Pgenesil-1-hk 19.95% ±5.21%, P 〈 0.01） and induced apoptosis （FCM subG1 phase Pgenesil-1-s1 19.07% ＋ 1.78%, Pgenesil-1-s2 17.68% ± 2.36% vs Pgenesil-1 0.47% ± 0.12%, Pgenesil-1-hk 1.46% ± 0.28%, P 〈 0.01. TUNEL-positive cells： Pgenesil-1-s1 40.24%± 5.18%, Pgenesil-1-s2 38.48% ± 4.65% vs Pgenesil-1 2.1B% - 1.34%, Pgenesil-1-hk 2.84%± 1.22%, P 〈 0.01） in HepG2 cells. CONCLUSION： These results demonstrate that SMYD3plays a critical role in the carcinogenesis and progression of HCC, The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZl CpG promoter hypermethylation.
基金Supported by National Natural Science Foundation of China,No.81460123Guangxi Graduate Innovation Program,No.201601005Guangxi Clinic Medicine Research Center of Hepatobiliary Disease,No.AD17129025
文摘AIM To assess the antiviral effects of hepatitis B virus(HBV) S gene-specific anti-gene locked nucleic acid(LNA) in transgenic mice.METHODS Thirty HBV transgenic mice were acclimatized to laboratory conditions and positive for serum HBV surface antigen(HBs Ag) and HBV DNA, were randomly divided into 5 groups(n = 7), including negative control(blank control, unrelated sequence control), positive control(lamivudine, anti-sense-LNA), and anti-gene-LNA experimental group. LNA was injected into transgenic mice by tail vein while lamivudine was administeredby gavage. Serum HBV DNA and HBs Ag levels were determined by fluorescence-based PCR and enzymelinked immune sorbent assay, respectively. HBV S gene expression amounts were assessed by reverse transcription polymerase chain reaction. Positive rates of HBsA g in liver cells were evaluated immunohistochemistry.RESULTS Average rate reductions of HBs Ag after treatment on the 3 rd, 5 th, and 7 th days were 32.34%, 45.96%, and 59.15%, respectively. The inhibitory effect of antigene-LNA on serum HBs Ag peaked on day 7, with statistically significant differences compared with pretreatment(0.96 ± 0.18 vs 2.35 ± 0.33, P < 0.05) and control values(P < 0.05 for all). Average reduction rates of HBV DNA on the 3 rd, 5 th, and 7 th days were 38.55%, 50.95%, and 62.26%, respectively. This inhibitory effect peaked on the 7 th day after treatment with anti-gene-LNA, with statistically significant differences compared with pre-treatment(4.17 ± 1.29 vs 11.05 ± 1.25, P < 0.05) and control values(P < 0.05 for all). The mR NA levels of the HBV S gene(P < 0.05 for all) and rates of HBsA g positive liver cells(P < 0.05 for all) were significantly reduced compared with the control groups. Liver and kidney function, and histology showed no abnormalities. CONCLUSION Anti-gene-LNA targeting the S gene of HBV displays strong inhibitory effects on HBV in transgenic mice, providing theoretical and experimental bases for gene therapy in HBV.
基金supported by grants from the National Natural Science Foundation of China(81971495 and 91442117)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-035)+2 种基金the National Science Foundation of Jiangsu Province(BRA2017533 and BK20191490)the State Key Laboratory of Reproductive Medicine(SKLRM-K202001)the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials。
文摘Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR.However,immunosuppressive agents negatively impact the immune system of the patients,causing them to suffer from serious complications,such as chronic infection and malignant tumors.Therefore,a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant(OT)is essential for developing better treatment options and improving patient outcomes.This article reviews the role of immune cells in OTR and organ transplant tolerance(OTT),including the novel cell therapies that are currently under clinical trials for transplant recipients.
基金supported by grants from the National Natural Science Foundation of China (82070676)Jiangsu Provincial Medi-cal Innovation Center (CXZX202203)Jiangsu Provincial Medi-cal Key Laboratory (ZDXYS202201)。
文摘Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.
基金Supported by the Research Fund of Beijing Tsinghua Changgung Hospital,No.12021C11016.
文摘Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.
基金Supported by the National Natural Science Foundation of China
文摘This article reports on a retrospective analysis on 121 patients and a prospectivestudy on 21 patients with acute cholangitis of severe type(ACST)for a study on the timing se-lection of emergency operation for ACST.Twenty two clinical,biological,etiologic,pathologicand operative variables were analyzed.Simple regression revealed 11 factors with prognosticsignificance,but multivariate analysis detected only 6 factors with independent significance inpredicting mortality(age,mean blood pressure,generalized peritonitis,serum albumin-globin ra-tio,blood culture,and the number of failed organs and systems).The results indicate that theclinical principles of treatment for ACST should be the combination of medical and surgicaltreatment.Active conservative treatment is practically applicable to the majority of ACST,espe-cially,those with short history and few complication.Prognostic mathematical model of ACSTdoes good for its timing selection of emergency operation.A critical level of 0.40 is determinedto be the discriminant score for emergency bile duct drainage.The model seems to have advan-tages over the traditional method.
文摘BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.
基金supported by grants from the National Key Research and Development Program of China(2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(92159202)+3 种基金the National Natural Science Foundation of China(82300743)the Zhejiang Provincial Natural Science Foundation of China(LQ23H160044)the Key Research&Development Plan of Zhejiang Province(2024C03051)Ningbo Top Medical and Health Research Program(2024020818)。
文摘The prognosis for patients diagnosed with hepatocellular carcinoma with bile duct tumor thrombus(HCCBDTT)remains dismal,and there are presently no universally accepted treatment guidelines to address this complex condition.Long-term outcomes of liver transplantation(LT)for HCC-BDTT patients are unclear,and whether LT is a proper therapeutic option for HCC-BDTT patients remains to be determined.Therefore,we design a clinical trial to evaluate whether LT can improve recurrence-free survival(RFS)and overall survival(OS)in HCC-BDTT patients.This is an open-labeled,single-arm,prospective,multicenter and real-world study aiming to assess the survival outcomes of HCC-BDTT patients in LT.Patients will be enrolled based on histological confirmation of HCC with BDTT.The study is planned to take 4 years,2 years for enrollment and 2 years for follow-up.We anticipate that LT confers beneficial survival outcomes for HCC-BDTT patients,specifically in terms of the pivotal parameters,such as RFS and quality of life.Upon successful completion of the trial,we will extend our monitoring over a longer follow-up time to accurately estimate important indicators such as OS.We expect that this study provides substantial evidence to refine treatment guidelines through thorough data analysis,ultimately contributing to better patient outcomes and advancing our understanding of the disease.
基金Funded by the Scientific Research Project of Shanghai Municipal Health Commission(No.201940430)。
文摘Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1.At this N/P ratio,the transfection efficiency in the hepatoma cells was the highest with a slow release effect.Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation,and can target the transfection into hepatoma cells by combination with galactose and biotin receptors.The transfection rate was inhibited by the competition of galactose and biotin.Bio-GC nanomaterials were imported into cells’cytoplasm by their receptors,followed by the imported exogenous gene transfected into the cells.Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice,by carrying the gene through the blood to the hepatoma tissue.Taken together,bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation,improving the rate of transfection in hepatoma cells,and transporting the gene into the cytoplasm in vitro and in vivo.Therefore,they are efficient hepatoma-targeting gene carriers.
基金The study was supported by grants from the National Natural Science Foundation of China(81871259,81971495,82070675,81530048,82200731 and 81570562)the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].
基金supported by grants from Hubei Provincial Natural Science Foundation of China(No.2019CFB805)National Natural Science Foundation of China(No.81670240 and No.81873467).
文摘Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischemia/reperfusion(RIR)model.Methods:Small-animal PET imaging in vivo was performed with ^(18)F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.Results:We found that the average standardized uptake value(SUV_(average))of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group(P<0.05).We also found that glucose uptake in different cortical subregions including the left auditory cortex,right medial prefrontal cortex,right para cortex,left retrosplenial cortex,right retrosplenial cortex,and right visual cortex was significantly increased in the RIR group(P<0.05),but there was no significant difference in the SUV_(avcrage) of right auditory cortex,left medial prefrontal cortex,left para cortex,and left visual cortex between the two groups.Conclusion:The ^(18)F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.
