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Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 491-502页

作者： Yi-Fan Lv Bing Zhu Ming-Ming Meng Yi-Fan Wu Cheng-Bin Dong Yu Zhang Bo-Wen Liu Shao-Li You Sa Lv Yong-Ping Yang Fu-Quan Liu Liver disease Minimally Invasive Diagnosis and treatment Center Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Liver Vascular disease Diagnosis and treatment Center The Fifth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100039China

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)placement is a procedure that can effectively treat complications of portal hypertension,such as variceal bleeding and refractory ascites.However,there have been no specific studies on predicting long-term survival after TIPS placement.AIM To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS.METHODS A retrospective analysis was conducted on a cohort of 224 patients who un-derwent TIPS implantation.Through univariate and multivariate Cox regression analyses,various factors were examined for their ability to predict survival at 6 years after TIPS.Consequently,a composite score was formulated,encompassing the indication,shunt reasonability,portal venous pressure gradient(PPG)after TIPS,percentage decrease in portal venous pressure(PVP),indocyanine green retention rate at 15 min(ICGR15)and total bilirubin(Tbil)level.Furthermore,the performance of the newly developed Cox(NDC)model was evaluated in an in-ternal validation cohort and compared with that of a series of existing models.RESULTS The indication(variceal bleeding or ascites),shunt reasonability(reasonable or unreasonable),ICGR15,post-operative PPG,percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement.The NDC model incorporated these parameters and successfully identified patients at high risk,exhibiting a notably elevated mortality rate following the TIPS procedure,as observed in both the training and validation cohorts.Additionally,in terms of predicting the long-term survival rate,the performance of the NDC model was significantly better than that of the other four models[Child-Pugh,model for end-stage liver disease(MELD),MELD-sodium and the Freiburg index of post-TIPS survival].CONCLUSION The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis,help identify high-risk patients and guide follow-up management after TIPS impla

关键词： Transjugular intrahepatic portosystemic shunt Long-term survival Predictive model

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The key mediator of diabetic kidney disease:Potassium channel dysfunction

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Genes & diseases 2024年第4期11卷 188-200页

作者： Jia Guo Chaojie Zhang Hui Zhao Yufan Yan Zhangsuo Liu Nephrology Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Key Laboratory of Precision Diagnosis and treatment for Chronic Kidney disease in Henan Province ZhengzhouHenan 450052China Research Center for Kidney disease ZhengzhouHenan 450052China

Diabetic kidney disease is a leading cause of end-stage renal disease,making it a global public health concern.The molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex pathogenesis.Thus,exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney disease.lon channels are important proteins that maintain the physiological functions of cells and organs.Among ion channels,potassium channels stand out,because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell excitability.Certain potassium channel abnormalities have been found to be closely related to diabetic kid-ney disease progression and genetic susceptibility,such as KATp,Kca,Kir,and Kv.In this review,we summarized the roles of different types of potassium channels in the occurrence and devel-opment of diabetic kidney disease to discuss whether the development of DKD is due to potas-sium channel dysfunction and present new ideas for the treatment of DKD.

关键词： Channel dysfunction Diabetic kidney disease End-stage renal disease lon channel Potassium

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Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer

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World Journal of Clinical Cases 2024年第4期12卷 700-720页

作者： Zi-Zheng Wu Yuan-Jun Wei Tong Li Jie Zheng Yin-Feng Liu Meng Han Diagnosis and treatment Center The First Hospital of QinhuangdaoQinhuangdao 066000Hebei ProvinceChina Department of General Surgery Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina Breast disease Diagnosis and treatment Center The First Hospital of QinhuangdaoHebei Medical UniversityQinhuangdao 066000Hebei ProvinceChina Breast disease Diagnosis and treatment Center Chengde Medical CollegeChengde 067000Hebei ProvinceChina

BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered

关键词： Breast cancer Prognosis Gene signature The Cancer Genome Atlas The Gene Expression Omnibus

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Effects of dual antiplatelet therapy de-escalation on the prognosis of acute coronary syndrome patients at high risk of ischemia who underwent percutaneous coronary intervention

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Chinese Medical Journal 2024年第6期137卷 746-748页

作者： Jingyao Wang Yachao Li Mengjie Lei Yanli Yang Haiyan Gao Xiangjin Wang Lei An Haili Zhou Xue Sun Cairong Li Zhigang Zhao Zengming Xue Department of Cardiology Langfang People’s HospitalHebei Medical UniversityLangfang Core Laboratory of Precision Treatment of Coronary Artery DiseaseLangfangHebei 065000China

To the Editor:Current guidelines recommend that for patients with acute coronary syndrome(ACS)undergoing percutaneous coronary intervention(PCI),dual antiplatelet therapy(DAPT),preferably involving powerful P2Y_(12) receptor inhibitors,including ticagrelor or prasugrel,should be used for at least 12 months.^([1–3])However,there is a lack of relevant evidence regarding the feasibility of de-escalation treatment and specific DAPT treatment regimens for ACS patient populations with high ischemic risk.

关键词： coronary patients acute

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Surgical treatment of inflammatory bowel disease:From the gastroenterologist’s stand-point

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1235-1254页

作者： John K Triantafillidis Inflammatory Bowel disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece Hellenic Society of Gastrointestinal Oncology Haidari 12461AthensGreece

treatment of ulcerative colitis(UC)and Crohn’s disease(CD)represents,in the majority of cases,a real challenge to the gastroenterologist’s abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and experience.During the last two decades,our pharmaceutical arsenal was significantly strengthened,especially after the introduction of the so-called biological agents,drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the disease.However,colectomy is still necessary for some patients with severe UC although smaller compared to the past,precisely because of the improvements achieved in the available conservative treatment.Nevertheless,surgeries to treat colon dysplasia and cancer are increasing to some extent.At the same time,satisfactory improvements in surgical techniques,the pre-and post-operative care of patients,as well as the selection of the appropriate time for performing the surgery have been noticed.Regarding patients with CD,the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their disease.On the other hand,the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel in situ as possible.This article discusses the indications for surgical management of UC patients from the gastroenterologist’s point of view,the results of the emerging new techniques such as transanal surgery and robotics,as well as alternative operations to the classic ileo-anal-pouch anastomosis.The author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant literature.The self-evident is emphasized,that is,to achieve an excellent therapeutic result in patients with severe inflammatory bowel disease in today’s era;t

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease Surgery treatment Ileo-anal-pouch anastomosis Indications Techniques

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Essential oils improve nursery pigs' performance and appetite via modulation of intestinal health and microbiota

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Animal Nutrition 2024年第1期16卷 174-188页

作者： Bi-Chen Zhao Tian-Hao Wang Jian Chen Bai-Hao Qiu Ya-Ru Xu Jin-Long Li College of Veterinary Medicine Northeast Agricultural University Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine Northeast Agricultural University Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal disease Prevention and treatment Northeast Agricultural University

Optimal intestinal health and functionality are essential for animal health and performance,and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control mechanisms.Given the potential of essential oil (EO) in improving animal performance and improving feed palatability,we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and microbiota.Cinnamaldehyde (100 mg/kg),carvacrol (100 mg/kg),and their mixtures(including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol) were supplemented into the diets of 240 nursery pigs for 42 d,and data related to performance were measured.Thereafter,the influence of EO on intestinal health,appetite and gut microbiota and their correlations were explored.EO supplementation increased (P<0.05) the body weight,average daily gain (ADG) and average daily feed intake (ADFI) of piglets,and reduced (P<0.05) diarrhea rates in nursery pigs.Furthermore,EO increased (P<0.05) the intestinal absorption area and the abundance of tight junction proteins,and decreased (P<0.05) intestinal permeability and local inflammation.In terms of intestinal development and the mucus barrier,EO promoted intestinal development and increased (P<0.05) the number of goblet cells.Additionally,we found that piglets in the EO-supplemented group had upregulated (P<0.05) levels of transporters and digestive enzymes in the intestine,which were significantly associated with daily gain and feed utilization.In addition,EO supplementation somewhat improved appetite in nursery pigs,increased the diversity of the gut microbiome and the abundance of beneficial bacteria,and there was a correlation between altered bacterial structure and appetite-related hormones.These findings indicate that EO is effective in promoting growth performance and nutrient absorption as well as in regulating appetite by improving intestinal health and bacterial structure.

关键词： Nursery pig Essential oil Intestinal health Appetite Microbiota

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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast disease Prevention and treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and treatment of Breast disease Jinan 250033China Department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

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Biomedical and Environmental Sciences 2024年第2期37卷 187-195页

作者： LIU Jia Jia SU Qiu Dong YI Yao SHEN Li Ping BI Sheng Li National Institute for Viral disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

关键词： Anti-OX40 antibody Hepatitis B core virus-like particles Tumor Combination therapy

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Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1821-1832页

作者： Xu Ren Yong-Ping Qu Chun-Lan Zhu Xiao-Hong Xu Hong Jiang Yi-Xia Lu Hong-Peng Xue Digestive disease Hospital of Heilongjiang Provincial Hospital Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Digestive Endoscopy Center of Heilongjiang Provincial Hospital Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Second Department of Gastroenterology Digestive Disease Hospital of Heilongjiang Provincial Hospitaland Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Department of Pathology Heilongjiang Provincial HospitalHarbin 150001Heilongjiang ProvinceChina

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous growth.Currently reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages.We have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010.AIM To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of IPNB.METHODS Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included.PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with electrocautery.The primary outcome was its feasibility,indicated by technical success.The secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and safety.RESULTS Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were included.Low-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,respectively.Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB.All five patients achieved technical success of PTCS-BP.Four patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors.All four patients with mucin-

关键词： Intraductal papillary neoplasm of the bile duct Percutaneous transhepatic cholangioscopy Biliary polypectomy Feasibility Efficacy

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Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1514-1531页

作者： Yong Pan Yi-Ru Zhang Ling-Yun Wang Li-Na Wu Ying-Qiu Ma Zhou Fang Shi-Bo Li Department of Infectious disease Zhoushan HospitalWenzhou Medical UniversityZhoushan 316021Zhejiang ProvinceChina State Key Laboratory for the Diagnosis and treatment of Infectious diseases The First Affiliated Hospital of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Infectious disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

关键词： Hepatocellular carcinoma Competitive endogenous RNA Molecular mechanism Prognosis Biomarker

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