To investigate whether the presence of baseline portal vein thrombosis (PVT) and its anatomical subtypes influence long-term outcomes in cirrhotic patients with esophagogastric variceal bleeding (EGVB) undergoing technically successful transjugular intrahepatic portosystemic shunt (TIPS). This retrospective cohort study included 140 cirrhotic EGVB patients who underwent successful TIPS between 2017 and 2024. Patients were stratified into groups with (n = 52) and without baseline PVT (n = 88) based on cross-sectional imaging. PVT was subclassified into simple (main trunk only) and mixed (extending to branches/mesenteric veins) types. The primary composite endpoint included all-cause mortality, variceal rebleeding, or shunt dysfunction. Kaplan–Meier analysis and multivariable Cox regression were performed. Median follow-up was 1286 days. Composite endpoint events occurred in 59 patients (42.1

BACKGROUND:Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS:A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS:PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION:Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING:A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Background The diagnosis of hepatocellular carcinoma (HCC) often experiences latency, ultimately leading to unfavorable patient outcomes due to delayed therapeutic interventions. Our study is designed to develop and validate a model that employs triple-phase computerized tomography (CT)-based deep learning radiomics and clinical variables for early warning of HCC in patients with cirrhosis. Methods We studied 1858 patients with cirrhosis primarily from the PreCar cohort (NCT03588442) between June 2018 and January 2020 at 11 centres, and collected triple-phase CT images and laboratory results 3-12 months prior to HCC diagnosis or non-HCC final follow-up. Using radiomics and deep learning techniques, early warning model was developed in the discovery cohort (n = 924), and then validated in an internal validation cohort (n = 231), and an external validation cohort from 10 external centres (n = 703). Findings We developed a hybrid model, named ALARM model, which integrates deep learning radiomics with clinical variables, enabling early warning of the majority of HCC cases. The ALARM model effectively predicted short-term HCC development in cirrhotic patients with area under the curve (AUC) of 0.929 (95% confidence interval 0.918-0.941) in the discovery cohort, 0.902 (0.818-0.987) in the internal validation cohort, and 0.918 (0.898-0.961) in the external validation cohort. By applying optimal thresholds of 0.21 and 0.65, the high-risk (n = 221, 11.9%) and medium-risk (n = 433, 23.3%) groups, which covered 94.4% (84/89) of the patients who developed HCC, had significantly higher rates of HCC occurrence compared to the low-risk group (n = 1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P < 0.001). Furthermore, ALARM also demonstrated consistent performance in subgroup analysis.Interpretation The novel ALARM model, based on deep learning radiomics with clinical variables, provides reliable estimates of short-term HCC development for cirrhotic patients, and may have the potential to improve the precision in clinical decision-making and early initiation of HCC treatments. Funding This work was supported by National Key Research and Development Program of China (2022YFC2303600, 2022YFC2304800), and the National Natural Science Foundation of China (82170610), Guangdong Basic and Applied Basic Research Foundation (2023A1515011211). Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Additional file 2: Table S3: Detail information of 345 HCC patients in training cohort. Table S4: Detail information of 344 LC patients in training cohort. Table S5: Detail information of 151 HCC patients in test cohort. Table S6: Detail information of 145 LC patients in test cohort. Table S7: Detail information of 112 HCC patients in validation cohort. Table S8: Detail information of 88 LC patients in validation cohort.

Background & Aims: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. Methods: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. Results: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP-> aMAP-2-> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). Conclusions: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

目的 探讨尿液中23种金属浓度与精液质量参数的关联性.方法 招募394名育龄男性,收集精液和尿液样本,使用电感耦合等离子体质谱联用仪(inductively coupled plasma-mass spectrometry,ICP-MS)检测尿液中23种金属浓度,对每种尿液金属浓度四分位数分组(0.05).结论 尿液中锌和铅浓度与精子前向运动活力、精子总活力和精子存活率呈负相关,尿液中锑浓度与精子正常形态率呈负相关.

Abstract Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

先天性肝纤维化（CHF）是一种罕见的与胆管板畸形相关的肝内胆管遗传发育障碍疾病，无特异性临床表现，易误诊或漏诊。现报道1例误诊为肝硬化并发食管胃底静脉曲张破裂出血患者在行经颈静脉肝内门体分流术（TIPS）治疗时发现，最后经病理学检查确诊为CHF患者的临床资料，以期提高CHF的诊治水平。

There is no specific treatment for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). It is not clear when transjugular intrahepatic portosystemic shunt (TIPS) should be implemented in PA-HSOS patients. This study aimed to evaluate the timing of TIPS using total bilirubin (TBIL) as a measure, and to investigate efficacy of TIPS. We retrospectively analyzed the medical records of 10 PA-HSOS patients, among whom 4 patients had received TIPS (TIPS group), and the remaining patients were assigned to the internal medicine group. In the TIPS group, the TBIL level before TIPS was 84.4 ± 45.2 µmol/L (> 3 mg/dL), and TBIL levels were increased to different degrees after TIPS. With the extension of time, serum TBIL levels gradually decreased, and no liver failure occurred. With regards to the short-term outcomes, 3 patients recovered, 1 developed chronic illness and 0 died in the TIPS group. Moreover, 0 patients recovered, 5 developed chronic illness and 1 died in the internal medicine group. The rank sum test of group design revealed significant differences in clinical outcomes (P = 0.02). It was suggested that when the internal medicine effect of PA-HSOS patients is poor, TIPS should be considered, which is no trestricted to the limit of 3 mg/dL TBIL. It was also found TIPS effectively promote the recovery of liver function and reduce the occurrence of chronicity.

目的 评定原子荧光光谱法测定尿中锑含量的测量不确定度.方法 采用GBZ/T302-2018《尿中锑的测定原子荧光光谱法》测定尿中锑含量,依据JJF 1059.1-2012《测量不确定度评定与表示》和GB/T27420-2018《合格评定生物样本测量不确定度评定与表示应用指南》系统评定不确定度,对测定结果进行完整表述.结果 影响尿中锑含量测定结果的不确定度主要来源于锑标准应用液的配制和原子荧光光度仪,尿中锑测定结果最终表述为(7.83±0.22)μg/L(k=2).结论 本次实验系统分析及评定了尿中锑测定的不确定度来源及分量,通过控制样品测定的重要环节可以提高测定结果的准确性,减小不确定度.

Tight junction dysregulation and epithelial damage contribute to intestinal barrier loss in patients with acute liver failure (ALF); however, the regulatory mechanisms of these processes remain poorly understood. The aim of the present study was to investigate the changes of intestinal tight junction and intestinal mucosa in mice with ALF and their mechanisms. In the present study, ALF was induced in mice through an intraperitoneal injection of D-galactosamine and lipopolysaccharide (D-GalN/LPS), and the morphological changes of the liver or small intestine were analyzed using hematoxylin and eosin staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The intestinal tissues and isolated serum were analyzed using western blotting, immunofluorescence staining and ELISA. D-GalN/LPS-induced mice exhibited signs of hepatocyte necrosis, alongside inflammatory cell infiltration into the liver tissue and partial microvilli detachment in the small intestinal mucosa. TEM demonstrated that the intestinal epithelial tight junctions were impaired, whereas SEM micrographs revealed the presence of abnormal microvilli in D-GalN/LPS-induced mice. In addition, the expression levels of phosphorylated (p)-myosin light chain (MLC), MLC kinase (MLCK) and Rho-associated kinase (ROCK) were significantly increased in the D-GalN/LPS-induced mice compared with those in the control mice, whereas the subsequent inhibition of MLCK or ROCK significantly reduced p-MLC expression levels. Conversely, the expression levels of occludin and zonula occludens-1 (ZO-1) were significantly decreased in the D-GalN/LPS-induced mice, and the inhibition of MLCK or ROCK significantly increased occludin and ZO-1 protein expression levels compared with those in the control group. Changes in the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 were similar to the trend observed in p-MLC expression levels. In conclusion, the findings of the present study suggested that in a D-GalN/LPS-induced ALF model, TNF-alpha and IL-6 signaling may increase MLCK and ROCK expression levels, further mediate phosphorylation of MLC, which may result in tight junction dysregulation and intestinal barrier dysfunction.

[目的]比较肝硬化门静脉血栓合并食管胃静脉曲张(gastroesophageal varices,GOV)的患者,经颈静脉肝内门体分流术(transjugular intrahepatic portosystemic shunt,TIPS)或内镜下组织胶联合硬化剂注射术行2级预防后,门静脉血栓的变化.[方法]以肝硬化门静脉血栓合并GOV,接受TIPS 10例(TIPS组)和内镜下组织胶联合硬化剂注射术12例(内镜组)进行2级预防的患者为研究对象,搜集临床资料,比较2组患者门静脉血栓的变化.血栓变化评定为完全溶解、部分溶解、血栓稳定和血栓增加;完全溶解和部分溶解归为有效,血栓稳定和血栓增加归为无效.[结果]术后半年,TIPS组血栓变化有效7例,无效3例,有效率70.0％;内镜组有效0例,无效12例,有效率0％;TIPS组门静脉血栓变化有效率与内镜组相比较,差异有统计学意义(P＜0.05).[结论]肝硬化门静脉血栓合并GOV患者,选择TIPS行2级预防后门静脉血栓改变的有效率优于内镜下组织胶联合硬化剂注射术.

Chromium is an essential element that is required for the normal physiology but can be toxic to humans above a certain level. In spite of growing interest in research on chromium exposure to human health consensus about its effect on human, semen quality has not been achieved. The aim of the present study is to evaluate the impact of chromium exposure on semen parameters. A total of 760 males attending andrology laboratory of Tongji Hospital, Wuhan, for routine semen analysis were enrolled and requested to provide semen and urine samples. The urine level of chromium was evaluated using inductively coupled plasma mass spectrometry (ICP-MS), and computer-assisted semen analysis (CASA) was applied to examine semen parameters. Associations between semen parameters and urinary chromium were analyzed by means of multivariate linear regression analysis. Multivariate analysis showed a negative association between the urinary concentrations of chromium and progressive motility (β = − 0.014, p = 0.040) and total motility (β = − 1.077, p = 0.048), while other semen parameters did not show any statistically significant changes. Urinary chromium could influence semen quality parameters and impair male fecundity.

目的 探讨LINC00176对胃癌细胞增殖、凋亡、迁移和侵袭的影响及潜在的作用机制.方法 miR-NC组(转染miR-NC)、miR-761组(转染miR-761 mimics)、pcDNA3.1组(转染pcDNA3.1)、pcDNA3.1-LINC00176组(转染pcDNA3.1-LINC00176)、si-NC组(转染si-NC)、si-LINC00176组(转染si-LINC00176)、anti-miR-NC组(转染anti-miR-NC)、anti-miR-761组(转染anti-miR-761)、miR-NC+WT-LINC00176组(共转染miR-NC和WT-LINC00176)、miR-NC+MUT-LINC00176组(共转染miR-NC和MUT-LINC00176)、miR-761+WT-LINC00176组(共转染miR-761和WT-LINC00176)、miR-761+MUT-LINC00176组(共转染miR-761和MUT-LINC00176)、pcDNA3.1-LINC00176+miR-NC组(共转染pcDNA3.1-LINC00176和miR-NC)、pcDNA3.1-LINC00176+miR-761组(共转染pcDNA3.1-LINC00176和miR-761)均用脂质体法转染至SGC-7901细胞;采用qRT-PCR检测LINC00176和miR-761的表达水平;CCK-8法检测各组细胞增殖;Transwell检测各组细胞迁移和侵袭;流式细胞术检测各组细胞凋亡;Western印迹检测蛋白表达;双荧光素酶报告基因检测实验检测荧光活性.结果 相较于正常胃黏膜细胞GES-1,胃癌细胞MGC-803、SGC-7901中LINC00176的表达水平显著降低(P<0.05);过表达LINC00176、抑制表达miR-761均可抑制SGC-7901细胞增殖、迁移和侵袭,促进细胞凋亡;抑制Bcl-2、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MPP)-2蛋白表达,促进Bax蛋、E-钙黏蛋白(cadherin)、P21蛋白表达.LINC00176靶向调控miR-761表达.过表达miR-761能逆转LINC00176对胃癌细胞SGC-7901增殖、迁移、侵袭的抑制和凋亡的促进作用.结论 长链非编码RNA LINC00176可抑制胃癌细胞的增殖、迁移和侵袭,促进其凋亡,其机制可能与靶向miR-761基因有关,将可为胃癌的预防和治疗提供新靶点.

[目的]探讨patatin样磷脂酶域3基因(patatin-like phospholipase domain-containing3,PNPLA3)rs139051 C＞T多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)病情进展的影响.[方法]将入院治疗的NAFLD患者130例归入观察组,130例健康志愿者归为对照组,对2组行单核苷酸多态性分型,在共显性和显性模型下评估rs139051C＞T变异与NAFLD的发病、进展的危险因素间的关系.[结果]观察组患者在体质指数、血清胆固醇(cholesterol,TC)、三酰甘油(Triglyceride,TG)、空腹血糖(fasting plasma glucose,FPG)、碱性磷酸酶、谷丙转氨酶(Alanine aminotransferase,ALT)及谷氨酰转肽酶方面均显著高于对照组.rs139051在共显性模型中,相对于正常基因型CC,基因型TC的OR:7.50,95 ％CI=3.00～17.89,基因型TT的OR:3.40,95％CI=1.55～8.05,在对C/T等位基因频率中,等位基因T的变异导致NAFLD患病的OR: 1.99,95％CI=1.20～2.98.在显性模型中,相对于正常基因型CC,TC+ TT基因型,ALT升高、OR(95％CI):2.01 (0.60,7.90);TG:2.23(0.60,9.00);FPG:3.90(1.00,15.12);TC:1.15(0.23,4.15);纤维化积分:4.00(1.14,15.99);肝脏硬度值:5.01(1.22,18.89).[结论]在NAFLD中,TC+ TT基因型与正常CC基因型相比,能增加患病风险,且TC+TT基因型能够增加NAFLD进展危险因素以及肝脏纤维化.

目的 探讨幽门螺杆菌(Helicobacter pylori,Hp)感染对帕金森病患者凝血功能和血小板线粒体呼吸链复合体Ⅰ(Complex Ⅰ)活性的影响.方法 选择2016年12月-2018年12月华中科技大学同济医学院附属武汉中心医院收治的帕金森病患者103例为研究对象,根据是否合并Hp感染分为感染组79例与未感染组24例.测定所有患者凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血酶时间(APTT)和纤维蛋白原(Fib);采用分光光度法测定血小板线粒体Complex Ⅰ活性.结果 两组患者PT差异无统计学意义(P=0.496);感染组TT和APTT分别为(15.89±0.46)s和(26.32±0.89)s低于未感染组,且Fib为(3.98±0.24) g/L高于未感染组(P均＜0.001).感染组血小板线粒体Complex Ⅰ活性为(1.23±0.28) U/ml低于未感染组(P＜0.001).感染组UPDRSⅢ评分和UPDRSⅣ评分分别为(28.40±1.79)分和(3.41±0.37)分高于未感染组;而两组Hoehn-Yahr分级差异无统计学意义(P=0.619).结论 Hp感染导致的凝血功能异常及线粒体功能损伤可能参与了帕金森病的发生,具有一定的临床价值.

Objective: This study aimed to investigate the correlation of Helicobacter pylori (Hp) infection with disease risk and severity of colorectal adenoma, also to explore the association of cytotoxin-associated gene A (CagA) positive (CagA + )- Hp infection with gastrin and ki-67 expressions in colorectal adenoma patients. Methods: There were 1000 colorectal adenoma patients and 1500 controls consecutively enrolled, then Hp infection status was determined by 14 C urea breath test and rapid urease test. Also, serum CagA expression and gastrin expression of colorectal adenoma patients were determined by enzyme-linked immunosorbent assay. Ki-67 expression in adenoma tissue of colorectal adenoma patients was assessed using immunohistochemistry. Results: Hp + rate in colorectal adenoma patients (623 (62.3%)) was more elevated than that in controls (814 (54.3%)). Multivariate logistic regression model analysis disclosed that Hp + was an independent risk factor for colorectal adenoma. Additionally, Hp + was positively associated with tumor size and high-grade intraepithelial neoplasia in colorectal adenoma patients. Also, serum gastrin expression and intratumoral ki-67 expression were higher in Hp + CagA + patients and Hp + CagA − patients compared to Hp − patients, and they were also higher in Hp + CagA + patients compared to Hp + CagA − patients. Conclusion: Hp infection positively associates with higher disease risk and worse disease conditions of colorectal adenoma, and CagA enhances the carcinogenicity of Hp in colorectal adenoma. Keywords Colorectal adenoma , Helicobacter pylori , cytotoxin-associated gene A , gastrin , ki-67

建立了一种超高效液相色谱-串联质谱法(UPLC-MS/MS)快速检测茶叶中高氯酸盐的分析方法.样品经50％乙腈提取,石墨化炭黑(GCB)分散固相萃取净化,采用亲水作用色谱分离,在UPLC-MS/MS的多反应监测(MRM)模式下进行测定.对方法的提取和净化条件进行了系统优化,在优化好条件下,高氯酸盐在0.005～5.0 mg/kg浓度范围内呈现良好的二次曲线关系,相关系数(R2)为0.9998,定量限为0.01 mg/kg.在4种添加浓度(0.005,0.05,0.1,1.0 mg/kg)下的加标回收率在75.2％～95.8％之间,日内和日间相对标准偏差小于10.2％,表明该方法具有很好的准确度和精密度.最后,将所建立的方法用于91个茶叶样品中高氯酸盐的分析,取得了较好的效果.