INTRODUCTION AND OBJECTIVES:Congestive hepatopathy (CH) is a hepatic vascular disease that results in chronic liver congestion, which can lead to liver fibrosis. New uses of metformin have been discovered over the years. However, the function of metformin in congestive liver fibrosis is not yet fully understood. This study aimed to investigate the effect of metformin on liver fibrosis in a mouse model of CH. MATERIALS AND METHODS:Partial ligation of the inferior vena cava (pIVCL) was used to establish a mouse model of liver congestion. Metformin (0.1%) was added to the daily drinking water of the animals, and the effect of metformin on liver tissue was studied after 6 weeks. Hepatic stellate cells (HSCs) were also stimulated with CoCl2 to investigate the inhibitory impact of metformin on the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) pathway. RESULTS:Metformin attenuated liver congestion; decreased the expression of collagen, fibronectin, α-smooth muscle actin (α-SMA), and HIF-1α; and ameliorated liver fibrosis in pIVCL mice. The proliferation and migration of HSCs were inhibited by metformin in vitro, which prevented α-SMA expression and restrained HSC activation. The expression levels of phosphorylated-mTOR, HIF-1α, and vascular endothelial growth factor were also decreased. CONCLUSIONS:Metformin inhibits CH-induced liver fibrosis. Functionally, this beneficial effect may be the result of inhibition of HSC activation and of the mTOR/HIF-1α signaling pathway.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant tumors in the world. In recent years, more and more inhibitors against gene targets have been found to be beneficial to survival. However, the function of homo-sapiens histone H3 associated protein kinase (GSG2) in HCC has not been completely understood. METHODS The expression of GSG2 in HCC tissues was detected by immunohistochemical staining. The lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown GSG2 expression in HCC cell lines Hep3B2.1-7 and SK-HEP-1. Cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively, and flow cytometry assay was used to investigate the cell apoptosis in vitro. Mice xenograft model was constructed to detect the functions of GSG2 on tumor growth in vivo. Human Apoptosis Antibody Array was conducted to find the possible mechanism. RESULTS GSG2 was overexpressed in HCC tissues compared with adjacent normal tissues. The knockdown of GSG2 had the functions of inhibiting the progression of HCC, including inhibiting cell proliferation and colony formation and promoting cell apoptosis. Compared with shCtrl group, the shGSG2 group expressed higher apoptotic genes such as caspase 3, caspase 8, Fas and FasL, while lower IGF1, Bcl2 and Bcl-w. CONCLUSIONS Our study showed that knockdown of GSG2 suppresses the tumor growth in vitro and vivo. Therefore, GSG2 might play an oncogenic role in HCC.

Objective:To explore the mechanism of mTOR/HIF-1α signaling pathway in Budd-Chiari syndrome (B-CS) liver fibrosis.Methods:Twenty male C57 mice were randomly divided into Sham operation group (Sham), sham operation+ rapamycin (Sham+ Ra) group, B-CS group, B-CS+ rapamycin (B-CS+ Ra) Group, 5 in each group. The B-CS mouse model was constructed by partial ligation of the inferior vena cava(IVC) at the posterior segment of the liver; IVC was not ligated in the Sham group. Mice in Sham+ Ra and B-CS+ Ra groups were intraperitoneally injected with rapamycin (2 mg/kg, 5% DMSO solution preparation) every other day, Sham group and B-CS group were injected with the same dose of 5% DMSO solution.After 6 weeks, samples were taken, and part of the liver tissue was used to make paraffin sections for hematoxylin-eosin (HE) and Sirus Red staining to observe the pathological changes, and immunohistochemical staining to detect the expression of α-SMA and Fibrinogen in liver tissues; Protein and RNA were extracted from fresh liver tissue, and Western-blot was used to detect α-SMA, Fibrinogen, p-mTOR, mTOR, HIF-1α, Collagen I, and VEGF protein levels. Real-time fluorescent quantitative PCR was used to detect mTOR, HIF-1α, CollagenⅠ, VEGF mRNA levels.Measurement data were expressed as mean±standard deviation ( ± s), and the comparison between groups was performed by one-way ANOVA test. Results:The results of pathological staining showed that in the B-CS group, there was severe congestion around the central vein of the liver and sinusoids, widening of the sinus space, and increased collagen deposition, indicating that this study successfully established a mouse B-CS liver fibrosis model. The expression levels of fibrosis indicators α-SMA and Collagen I protein, mTOR pathway related indicators p-mTOR and HIF-1α protein, and microthrombus indicator Fibrinogen protein in the Sham group were 0.027±0.012, 0.337±0.008, 0.138±0.024, 0.296±0.113, 0.733±0.192; B-CS group were 0.986±0.001, 0.927±0.055, 0.936±0.044, 1.693±0.443, 1.612±0.068, and the differences were statistically significant ( P<0.05). The expression levels of B-CS+ Ra group were 0.707±0.078, 0.311±0.024, 0.332±0.094, 0.254±0.117, 0.569±0.075, which were statistically significant compared with B-CS group ( P<0.05). Conclusions:The mTOR/HIF-1α signaling pathway is significantly activated in mouse B-CS liver fibrosis. This pathway may participate in the development of liver fibrosis by regulating microthrombosis.

Objective:To study the factors influencing short-term prognosis of patients with Budd-Chiari syndrome (B-CS) presenting with upper gastrointestinal bleeding and to assess the predictive value of platelet-albumin-bilirubin score (PALBI) on death within 30 d in these patients.Methods:A retrospective study was conducted on 74 patients with B-CS who presented with upper gastrointestinal bleeding and were treated at the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020. There were 51 males and 23 females, with age of (46.5±11.1) years old. These patients were divided into the survival group ( n=58) and the death group ( n=16) according to the disease outcomes up to 30 d of follow-up. Factors influencing short-term deaths of these patients were analyzed, and the predictive values of PALBI, ALBI, CTP and MELD scores on short-term prognosis of the patients were assessed. The receiver operating characteristic (ROC) curves were plotted, and the areas under the curve (AUC) were calculated and compared. Results:The differences between patients in the survival and death groups for white blood cell, platelet, PALBI score, PALBI classification, ALBI score, CTP score, MELD score, and presence or absence of hepatic encephalopathy were significantly different (all P<0.05). Multivariate logistic regression analysis showed that CTP score≥10 or CTP grade C ( OR=1.669, 95% CI: 1.048-2.661), and PALBI score >-2.09 or PALBI grade 3 ( OR=5.245, 95% CI: 2.128-12.924) were independent risk factors for predicting death within 30 days. The areas under the ROC curves for PALBI, ALBI, CTP and MELD score were 0.89, 0.72, 0.77 and 0.76, with the cut-off values of -1.92, -1.60, 8.50 and 13.60, respectively. The differences between the PALBI score and ALBI, CTP scores were significantly different ( P<0.05). Conclusion:The PALBI score showed a positive predictive value on short-term prognostic assessment of patients with B-CS presenting with upper gastrointestinal bleeding. It was comparable to the effect of the MELD score but was significantly better than the ALBI and CTP scores.

Objective:To investigate the clinical treatment options for cavernous transformation of portal vein (CTPV).Methods:Data of 65 CTPV patients receiving invasive treatment and followed up at the First Affiliated Hospital of Zhengzhou University between Apr 2011 and Apr 2021 were collected. Patients were divided into four groups based on different treatment option, 24 patients were treated with transjugular intrahepatic portosystemic stent-shunt (TIPS) and 11 patients with splenopneumopexy, while 22 patients underwent splenectomy and devascularization , 8 were treated by endoscopic variceal ligation . The difference of postoperative upper gastrointestinal bleeding and hepatic encephalopathy between the four groups were analyzed,Results:There were no difference between four groups in sex, age, preoperative serum aspartate aminotransferase, total bilirubin, albuminand Child-Turcotte-Pugh grade. The incidence of hepatic encephalopathy in the TIPS group was 33.3%±9.6%、46.5%±10.3% and 64.4%±13.1% in half year, 1 year, and 3 years , respectively. Postoperative hepatic encephalopathy rate was higher in TIPS group( χ2=31.191, P=0.000). Three patients in the TIPS group developed upper gastrointestinal hemorrhage within 6 months after the operation, and postoperative upper gastrointestinal bleeding rate was higher in splenopneumopexy group( χ2=7.542, P=0.006), Conclusion:The clinical treatment options for CTPV patients are complicated ,we should make individual treatment options depend on the etiology, clinical symptoms and site of blood flow obstruction.

Background: Hepatocellular carcinoma (HCC) is the main type of primary liver cancer and shows a heavy burden worldwide. Its recurrence and mortality rate are still uncontrolled by the usage of present treatments. More attention has been focused on exploring specific genes that play important roles in HCC procession, and the function of DEP domain containing 1B (DEPDC1B) in HCC has not been researched. Methods: Immunohistochemical staining was used to detect the expression level of DEPDC1B in tumor tissues and adjacent normal tissues. After DEPDC1B and CDK1 knockdown in cell lines HEP3B2.1-7 and SK-HEP-1, MTT assay and colony formation assay was used to detect cell growth, flow cytometry assay was used to investigate cell apoptosis and cell cycle, wound-healing assay and Transwell assay were used to examine the tumor cell migration. Moreover, a xenograft model was constructed to research functions of DEPDC1B in tumor growth in vivo. Results: The results show that DEPDC1B knockdown inhibit the progression of HCC, through inhibiting cell proliferation, migration, colony formation, leading to G2 phase arrest, and promoting cell apoptosis in vitro, and CDK1 was selected for further mechanic research according to the results of Human GeneChip prime view. The results of recovery experiment displayed that the functions of DEPDC1B on HCC progression were mediated by CDK1. DEPDC1B knockdown can also inhibit tumor growth in vivo. Conclusions: The study confirmed that DEPDC1B knockdown restrains the tumor growth in vitro and vivo, and it can interact with CDK1 and rescued by CDK1. The study suggested that DEPDC1B was as a potential therapeutic target involved in HCC growth and progression.

目的 分析布-加综合征(B-CS)合并下腔静脉(IVC)血栓病人介入开通后的复发情况,并探讨其危险因素.方法 回顾性分析2015年10月至2020年10月在郑州大学第一附属医院接受介入治疗的79例B-CS合并IVC血栓病人临床资料并进行随访,使用Kaplan-Meier法计算术后复发率并绘制复发曲线,对影响复发的危险因素进行Cox回归分析.结果 42例病人于首次术后出现复发,6个月、1年、2年、3年、5年的累积复发率分别为24.3％、32.5％、51.0％、56.5％、69.7％.36例复发病人再次接受了介入治疗,其中14例IVC阻塞病人二次术后6个月、1年、2年的累积复发率分别为7.1％、15.6％、26.1％;另外22例合并血栓形成的病人二次术后累计复发率为14.3％、33.3％、38.9％.多因素Cox回归分析显示IVC阻塞段长度、A类副肝静脉数目、口服抗凝药类别、血小板计数、血清白蛋白、New Clichy指数是病人复发的独立危险因素(P值均＜0.01).结论 B-CS合并IVC血栓的介入术后复发率较高并受多种因素影响,定期复查、尽早干预能够改善病人预后.

Objective: To examine the effect of thrombolytic therapy of Budd-Chiari syndrome (B-CS) with inferior vena cava (IVC) thrombosis, and the prognosis factors of it. Methods: The clinical data of 67 patients of B-CS with IVC thrombosis treated in the Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2020 were analyzed retrospectively. There were 30 males and 37 females. The age was (47.7±11.1) years(range: 18 to 72 years). All patients received catheter directed thrombolysis, and the thrombolysis process, complications and outcomes were analyzed. All patients received IVC balloon angioplasty after thrombolytic therapy. The t test, χ2 test, Mann-Whitney U test were used for univariate analysis of the prognosis factors of thrombolysis effects, while unconditional Logistic regression model were used for multivariate analysis. Results: In the 67 patients, 47 cases succerssed in thrombolytic therapy. The successful rates of thrombolysis at 1-, 2-, 3- and 4-week were 9.0%, 29.9%, 64.2% and 70.1%, respectively. The rates of thrombolytic catheter-related infection at 1-, 2-, 3- and 4-week were 1.5%, 4.5%, 14.9% and 31.3%, respectively. No serious complications such as symptomatic and acute pulmonary embolism occurred during perioperative period of IVC balloon angioplasty. Univariate analysis showed that differences in thrombus length ((36.7±18.1) mm vs. (52.0±16.4) mm, t=-3.234, P=0.002), Child-Pugh classification (class A/B/C: 37/8/2 vs. 10/8/2, Z=-2.310, P=0.021) and pre-opening IVC proportion (68.1% (32/47) vs. 35.0% (7/20), χ²=6.313, P=0.012) were statistically significant. The thrombus length (OR=0.948, 95%CI: 0.913 to 0.984, P=0.005), pre-opening IVC (OR=5.451, 95%CI: 1.469 to 20.228, P=0.011) were independent prognosis factors of thrombolytic effect. Conclusions: Thrombolytic therapy for B-CS with IVC thrombosis were satisfactory, and the thrombolysis duration should be confined within 3 weeks. IVC balloon angioplasty is safe and effective for patients failing in thrombolysis, and pre-opening IVC is an important method to improve the thrombolytic effect.

BACKGROUND Primary hepatic neuroendocrine tumors (PHNETs), a group of neuroendocrine neoplasms, are extremely rare. There are only few case reports about PHNETs in the literature. The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches. AIM To discuss the clinical characteristics, diagnosis, and treatment of PHNETs and risk factors related to survival. METHODS We retrospectively analyzed the clinical data, imaging features, immunohistochemistry data, and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1, 2014 to November 15, 2019. Finally, survival analysis was performed to identify the risk factors for survival. RESULTS The main symptoms and signs included intermittent abdominal pain (19 patients, 47.5%) and bloating (8 patients, 20.0%). The positive rates of tested tumor markers were recorded as follows: Carbohydrate antigen 19-9 (CA19-9) (6 patients, 15.0%), CA72-4 (3 patients, 7.5%), carcinoembryonic antigen (7 patients, 17.5%), and alpha-fetoprotein (6 patients, 15.0%). Immunohistochemical staining results showed positivity for Syn in 38 (97.4%) of 39 patients, for chromogranin A in 17 (65.4%) of 26 patients, for CD56 in 35 (94.6%) of 37 patients, for AE1/AE3 in 28 (87.5%) of 32 patients, and for Ki-67 in all 40 (100.0%) patients. The overall survival rate was significantly related to the tumor grade, AE1/AE3, and Ki-67. No significant correlation was found between other parameters (age, gender, tumor number, tumor size, metastasis, and treatment) and overall survival. CONCLUSION Higher grade, negative AE1/AE3, and higher Ki-67 are associated with a worse survival rate. Kinds of treatment and other parameters have no significant influence on overall survival.

巴德-吉亚利综合征(Budd-Chiari syndrome,B-CS),又称布-加综合征,是一种严重的肝脏血管疾病,因肝静脉和(或)肝后段下腔静脉狭窄或节段性闭塞导致肝脏淤血,其慢性进展可能导致肝细胞癌的发生.在B-CS治疗的发展过程中,外科手术曾作为主要手段,随着介入技术的不断成熟和肝细胞癌诊疗领域的进展,B-CS相关肝癌的诊治方案也更加多样,对不同分型B-CS、不同期别肝细胞癌的诊疗已形成多学科协作的个体化 、规范化 、精准化模式.此文通过总结近年来B-CS及肝细胞癌诊疗领域的进展,并结合病例诊治的经验,对B-CS合并HCC的综合诊治进行讨论.

不稳定型心绞痛(UAP)系非ST段抬高性急性冠状动脉综合征(NSTACS)中最常见者,其本身即为不稳定性血栓性事件.因此,尽早进行有效干预,阻断血栓进展极为重要.循征医学证明,UAP药物治疗的核心为抗栓,其中抗凝治疗更为重要.

目的:观察地尔硫(艹卓)静脉内给药治疗高血压急症临床疗效.方法:本院急诊和住院的重度高血压病人38例(男性20例,女性18例,年龄62 a±s 9 a)用地尔硫NFDA1针剂10～20 mg加25 %葡萄糖注射液40 mL静脉推注.观察用药后10,30,60,120 min血压、心率变化情况.结果:用药后10 min血压开始下降(收缩压下降了1.5 kPa±0.3 kPa; 舒张压下降了0.61 kPa±0.24 kPa),30 min后收缩压、舒张压明显下降,心率减慢,1～2 h降至正常或安全水平,总有效率达到95 %.结论:地尔硫NFDA1静脉内注射治疗高血压急症起效快,疗效好.