Background and aimsThis research aimed to examine the association between hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and liver inflammation in chronic hepatitis B (CHB) infection patients.MethodsFrom August 2013 to June 2022, CHB patients at Hebei Medical University Third Hospital (Hebei, China) were recruited. Intrahepatic cccDNA was quantified and its association with liver inflammation was analyzed. Liver inflammation was assessed using the Ishak-modified histological activity index (HAI). Biochemical and viral indicators as well as hepatic inflammation biomarkers were monitored.ResultsIn total, 55 CHB patients were enrolled. The average HBV-cccDNA level was markedly elevated in HBeAg+ patients compared to HBeAg patients. Intrahepatic cccDNA levels differed significantly in different liver inflammation groups and showed a positive correlation with the HAI score for hepatic inflammation.ConclusionHBV-cccDNA level was associated with liver inflammation.

Background and ObjectiveGlobal cancer statistics position HCC as the sixth most common malignancy, with mortality rates placing it third. Notably, stress-induced cytoprotective factor CLU is frequently upregulated in HCC, where it has been mechanistically linked to disease progression. Our previous studies demonstrated that CLU is significantly upregulated in the plasma and neoplastic tissues of HCV-induced HCC patients and HCV core protein-expressing HCC cell lines. Our purpose is to elucidate the function and mechanisms of CLU in HCC, particularly in the context of HCV-associated HCC, while also assessing its potential as a drug target.MethodsThe relationship between CLU and genes associated with apoptosis and invasion was analyzed using clinical databases (GEPIA). CLU knockdown-induced alterations in apoptosis and invasion were characterized in HCV core protein-expressing HCC cell lines employing multiple experimental approaches including western blotting, flow cytometry, and transwell assays.ResultsCLU expression was positively correlated with anti-apoptotic and pro-invasive genes in HCC. Significant apoptosis induction was achieved through CLU knockdown, mediated by three key molecular changes: pro-apoptotic genes (BAX, PARP, Caspase3, and Caspase9) were upregulated, the anti-apoptotic gene Bcl2 was downregulated, and AKT phosphorylation was inhibited. Additionally, CLU silencing inhibited cellular invasion by diminishing the expression of matrix metalloproteinase 2 (MMP2), N-cadherin and Vimentin.ConclusionsCLU-mediated regulation of apoptosis and invasion pathways emerges as a critical mechanism in HCC progression according to our data. Our findings demonstrated that CLU is a promising therapeutic target for HCV-associated HCC, providing novel perspectives for developing targeted treatments against this aggressive cancer.

肝细胞癌（HCC）是严重威胁人们健康的高发肿瘤。乙型肝炎病毒（HBV）感染是导致HCC最主要的危险因素，抗病毒治疗可以改善肝功能，预防病毒再激活，降低HCC根治性治疗后的复发率，从而改善HBV 相关HCC患者预后。现报道1例HBV相关HCC患者，在进行抗肿瘤治疗期间，采用恩替卡韦联合艾米替诺福韦抗病毒治疗，实现低病毒血症阴转；减少HBV引起的肝脏损伤并阻止疾病进展，并提供良好的肝功能基础；降低HCC治疗后肿瘤复发风险，延长患者生存时间。

In patients with membranous nephropathy (MN), malignancy may be either the underlying disease or results of immunosuppressive therapy which may also lead to opportunistic infections including the pulmonary cryptococcosis. On CT scan, nodule is the most common feature in pulmonary cryptococcosis and it can mimic lung cancer both clinically and radiologically. Therefore, pulmonary nodular lesions caused by cryptococcosis may be easily misdiagnosed and require unnecessary surgical treatment. As such, we herein presented an isolated subpleural solitary nodule with satellite lesion that closely mimicked lung cancer on both contrast-enhanced computed tomography (CT) scan and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in an MN patient under long-term tacrolimus regimen. Cryptococcosis was ascertained by the finding of oval thick-walled yeast on histopathology of the lung biopsy specimen taken during the Argon-Helium cryotherapy. Further, the pulmonary lesions progressively dissipated after antifungal treatment. Arguably, our experience may help clinicians in general and nephrologists in particular with a better understanding of the cryptococcal infection manifesting as pulmonary nodule(s) in the MN patients and contribute to more efficacious differential diagnosis against the lung cancer.

目的 探讨半乳糖凝集素-3(Gal-3)诱导血管平滑肌细胞增殖及促进大鼠动静脉内瘘(AVF)狭窄发生的作用,并探讨可能机制.方法 取30只AVF大鼠,随机数字法分为AVF组、柑橘果胶组、联合组,每组10只;另取10只大鼠行假手术,设为假手术组.联合组灌胃柑橘果胶生理盐水溶液(含柑橘果胶0.15 mg/kg),尾静脉注射表皮生长因子[细胞外信号调节激酶(ERK)通路激动剂(EGF)](10 μg/kg);柑桔果胶组灌胃柑橘果胶生理盐水溶液(0.15 mg/kg),尾静脉注射等体积PBS;假手术组、AVF组灌胃等量生理盐水,尾静脉注射等体积PBS.每日1次.干预4周.MTT法检测血管平滑肌细胞增殖能力;ELISA法检测血清炎症因子[肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)]水平;ELISA法检测血管组织转化生长因子-β(TGF-β1)、血管内皮细胞生长因子(VEGF)水平;Western blot法检测血管组织p38丝裂原活化蛋白激酶(MAPK)、p-p38 M APK、ERK1/2、p-ERK1/2蛋白表达量.结果 与AVF组比较,柑橘果胶组 24、48、72 h 吸光度值,血清 TNF-α、IL-6 水平,血管组织 TGF-β1、VEGF 水平,p-p38 M APK/p38 M APK、p-ERK1/2/ERK1/2降低(P＜0.05);与柑橘果胶组比较,联合组24、48、72 h吸光度值,血清TNF-α、IL-6水平,血管组织TGF-β1、VEGF 水平,p-p38 MAPK/p38 M APK、p-ERK1/2/ERK1/2 升高(P＜0.05).结论 Gal-3 抑制剂改良柑橘果胶可抑制血管平滑肌细胞增殖及炎症反应,缓解AVF狭窄,并抑制ERK信号通路活性.

Patients with chronic kidney disease are already at an increased risk for pulmonary embolism, since loss of renal function rendered a procoagulant state. Further, malignant tumor is a well-established risk factor for pulmonary thromboembolism. Alternatively, occlusion of the pulmonary vasculature by tumor cells per se and associated thrombi may mimic thromboembolic disease. By comparison, however, report of pulmonary tumor embolism (PTE) in patients on maintenance hemodialysis (MHD) is exceedingly rare. A less vigilant clinician may have otherwise treated this situation as fluid overload or thromboembolic disorder. We herein described in an MHD patient such an unusual case of PTE, which was diagnosed by contrast-enhanced CT and PET/CT. As such, our work may expand the knowledge reserve of dialysis staffs about this rare complication of malignancy.

目的:探讨去整合素金属蛋白酶10(ADAM10)在人动静脉内瘘(AVF)狭窄处血管组织中的表达及其对血管平滑肌细胞(VSMCs)增殖和迁移的影响,并阐明其可能的分子机制.方法:收集42例因AVF狭窄再次接受手术治疗的终末期肾病(ESRD)患者狭窄静脉血管组织(AVF组)及其首次手术的正常静脉血管组织(正常对照组).采用免疫组织化学法检测2组患者静脉血管组织中ADAM10蛋白表达情况,实时荧光定量PCR(RT-qPCR)法检测2组患者静脉血管组织中ADAM10 mRNA表达水平.将VSMCs分为对照组、模型组[脂多糖(LPS)组,给予10 mg·L-1 LPS]、LPS+si-NC组(转染si-NC质粒+10 mg·L-1 LPS)、LPS+si-ADAM10组(转染si-ADAM10质粒+10 mg·L-1 LPS)、LPS+Notch信号通路抑制剂DAPT组(10 mg·L-1 LPS+10μmol·L-1 Notch信号通路抑制剂DAPT)和LPS+si-ADAM10+DAPT组(转染si-ADAM10质粒+10 mg·L-1 LPS+10μmol·L-1 DATP),CCK-8法检测各组细胞增殖活性,Transwell法检测各组迁移细胞数,Western blotting法检测各组细胞中ADAM10、增殖细胞核抗原(PCNA)、基质金属蛋白酶9(MMP-9)、Notch同源蛋白1(Notch1)、Notch细胞内片段(NICD)和发状分裂相关增强子1(Hes1)蛋白表达水平.结果:与正常对照组比较,AVF组患者静脉血管组织中ADAM10蛋白表达量明显增加,ADAM10 mRNA表达水平明显增加(P<0.05).与对照组比较,LPS组细胞增殖活性和迁移细胞数及细胞中ADAM10、PCNA、MMP-9、Notch1、NICD和Hes1蛋白表达水平均明显升高(P<0.05);与LPS组和LPS+si-NC组比较,LPS+si-ADAM10组细胞增殖活性和迁移细胞数及细胞中ADAM10、PCNA、MMP-9、Notch1、NICD和Hes1蛋白表达水平均明显降低(P<0.05).与LPS组比较,LPS+si-ADAM10组和LPS+DAPT组细胞增殖活性和细胞迁移数量及细胞中PCNA、MMP-9、Notch1、NICD和Hes1蛋白表达水平均明显降低(P<0.05);与LPS+si-ADAM10组比较,LPS+si-ADAM10+DAPT组细胞增殖活性和细胞迁移数及细胞中PCNA、MMP-9、Notch1、NICD和Hes1蛋白表达水平均明显降低(P<0.05).结论:ADAM10在人AVF狭窄处血管组织中高表达,沉默ADAM10基因表达可抑制LPS诱导的VSMCs增殖和迁移,其作用机制可能与阻断Notch信号通路有关.

BackgroundWe herein described the coexistence of hemophagocytic lymphohistiocytosis (HLH) and histiocytic necrotizing lymphadenitis, alternatively known as the Kikuchi disease (KD), secondary to hemodialysis catheter-related bloodstream infection (BSI) caused by Corynebacterium striatum.Case presentationA patient on maintenance hemodialysis had developed persistent fever and Corynebacterium striatum was subsequently identified from the culture of both catheter tip and peripheral blood. During mitigation of the BSI, however, his fever was unabated and ensuing workup further found thrombocytopenia, hyperferritinemia, hypertriglyceridemia, low NK cell activity and a surge in serum CD25 levels. Moreover, biopsy of the bone marrow and lymph node detected histopathological evidence of hemophagocytosis and KD, respectively. Upon these abnormalities, the title-bound diagnosis was considered and the patient was eventually recovered from the treatment of dexamethasone instead of antibiotics. Consistently, aberrations in his serum CD25 levels and NK cell activity had subsided two months after discharge.ConclusionsArguably, this encounter offered a unique chance to unravel the principal pathogenic cascade in immunobiology that made the three entities one disease continuum. As such, our work may add new understandings of HLH and/or KD secondary to severe infections in general and excessive release of cytokines in particular among patients with kidney diseases. The resultant early diagnosis is crucial to initiate appropriate treatment and improve the survival of patients with these challenging and potentially life-threatening disorders.

Circular RNA (circRNA) is key regulator of diabetic nephropathy (DN) progression. However, the role of circ_0008529 in DN progression remains to be better deciphered. Cell viability, cell cycle, apoptosis and inflammation were measured by MTS assay, flow cytometry and corresponding assay kits. RT-qPCR was used to assess the expression of circ_0008529, miR-185-5p and SMAD family member 2 (SMAD2). Also, western blotting was performed to measure protein expression. Target relationship was validated by RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation assay. Urinary exosome was isolated using ultracentrifugation method and identified by transmission electron microscopy. Receiver operating characteristic curve was used to analyze the diagnostic value of circ_0008529 in DN patients. Circ_0008529 and SMAD2 were upregulated, while miR-185-5p was downregulated in high glucose (HG)-induced renal tubular HK-2 cells. Under HG treatment, cell viability and cell cycle process were suppressed, while apoptosis, inflammation and extracellular matrix accumulation were enhanced. However, interfering circ_0008529 could attenuate HG-induced effects, and this protection was abated by miR-185 inhibition or SMAD2 re-expression. Mechanically, circ_0008529 and SMAD2 were competing endogenous RNAs for miR-185-5p via target binding, and circ_0008529 regulated SMAD2 expression via miR-185-5p. Notably, circ_0008529 expression was upregulated in urinary exosomes of DN patients, and showed diagnostic value (Sensitivity: 70.21%; Specificity: 86.67%). Circ_0008529 might be a potential target for DN, which regulated DN progression via miR-185-5p/SMAD2 pathway.

BACKGROUND:Thrombosis is one of the main complications leading to the failure of autologous arteriovenous fistula (AVF) for patients with renal failure. Thrombectomy is one of the major therapies to remove thrombi to salvage the AVF and prolong its patency.MATERIALS AND METHODS:Fifty-six patients with AVF thrombosis at the anastomosis were recruited for this study and underwent thrombectomy procedures. Their clinical variables were collected. The vasculature was accessed at the site of the aneurysmal dilatation. Under ultrasound guidance, a scoop thrombectomy procedure was performed by anterograde and retrograde scooping to remove the thrombus using forceps. Then, a sheath was placed in the direct vertical direction. Angioplasty was performed with a balloon to treat the underlying primary arteriovenous stenosis. Patients were followed up for 12 months after surgery. The procedural success, primary and secondary patency rates, and incidence of procedure-related complications were analyzed.RESULTS:There were 2 minor (3.6%) and no major complications. Clinical success was achieved in 55 of the 56 procedures (98.2%). No symptomatic pulmonary embolism or arterial embolization was noted. The primary patency rates at 3, 6, and 12 months were 92.9, 83.8, and 73.3%%, respectively, according to the Kaplan-Meier survival analysis.CONCLUSION:Scoop thrombectomy is a safe procedure with high technical success and a low complication rate, and it is an effective method for patients to receive hemodialysis immediately.

Loss of renal function may render hemodialysis patients more susceptible to infectious diseases, which is the second of all-causes mortality in this population. In addition to infection caused by the classic Klebsiella pneumoniae (cKp), however, hemodialysis staffs are now facing new challenge with growing prevalence of the carbapenem-resistant Kp (CR-Kp) and hypervirulent Kp (hvKp) as they are respectively associated with increased drug-resistance and virulence. We therefore chose to share our recent experience in treating severe infections either caused (cKp, CR-Kp, hvKp) or complicated (CR-hvKp) by these strains in hemodialysis patients. Based upon yet beyond published works, we further came up with the detection of intracranial lesion, novel diagnostic approach using unique biomarkers followed by selection of appropriate antibiotics, management of metastasic abscesses and bracing for the most lethal scenario in the order of cKp, CR-Kp, hvKp and CR-hvKp, respectively. Since reports of complicated hvKp infection in hemodialysis patients were rare, we also discussed in details this clinical entity focusing on its epidemiology, mechanism of increased virulence and involvement of the arteriovenous fistula as insidious source of persistent septicemia. By covering the full spectrum of clinically relevant Kp stains specifically from the viewpoint of nephrology, our work had highlighted the importance of infection control in uremic state and vice versa. As such, it may greatly raise the awareness of dialysis staffs against the challenge of evolving Klebsiella pneumoniae infection in hemodialysis patients and expeditiously reach a higher degree of readiness which was proved to be the key determinant of ultimate survival.

ObjectiveTo investigate the clinical and pathological features of children with glycogen storage disease (GSD). MethodsA retrospective analysis was performed for ten children with GSD who were admitted to the Third Hospital of Hebei Medical University and The Fifth Medical Center of Chinese PLA General Hospital from January 2002 to January 2022, based on medical history, liver biochemistry, and liver biopsy, and population characteristics, clinical manifestations, biochemical parameters, and liver histopathological characteristics were compared and analyzed. ResultsAll ten children had developmental retardation and a short stature, with the manifestations of abnormal liver function, mild weakness, poor appetite, yellow urine, and yellow eyes, and four children had hepatosplenomegaly. Among the ten children, six had the clinical manifestations of hypoglycemia, and one had bilateral gastrocnemius hypertrophy and positive Gower sign. Two children had positive CMV IgG. Liver histopathological manifestations included diffuse enlargement of hepatocytes, light cytoplasm, and small nucleus in the middle like plant cells, with or without fibrous tissue proliferation. ConclusionMost patients with GSD have developmental retardation and abnormal aminotransferases, and liver pathological examination shows specific pathological features.

ObjectiveTo summarize the clinical features of patients with Wilson’s disease (WD). MethodsA retrospective analysis was performed for the clinical data of 83 patients with WD who were admitted to The Third Hospital of Hebei Medical University from April 2013 to August 2021, including clinical manifestations, Imaging examinations, laboratory examinations, liver histopathological examinations, and ATP7B gene testing results. The patients were divided into groups based on different clinical types. A one-way analysis of variance was used for comparison between groups. ResultsThe youngest age was 3 years for the 83 patients with WD, among whom 39 (46.99%) had an age of ≤18 years, with a mean age of 21.16±14.87 years for all 83 patients. Of all patients, 63.86% had liver-type WD, 31 patients (37.35%) had developed liver cirrhosis at the time of consultation, and 5 patients (62%) attended the hospital due to acute or acute-on-chronic liver failure. Of all patients, 62(74.69%) were positive for corneal K-F ring, and the positive rate of K-F ring was 66.04% in the patients with liver-type WD. Among the 83 patients, 79(95.18%) had a reduction in blood ceruloplasmin, and 73(87.95%) had an increase in 24-hour urine copper. The liver histopathological results of 25 patients showed varying degrees of inflammation, fibrosis, steatosis, and copper particle deposition in liver tissue. The ATP7B gene testing results of 25 patients showed that c.2333G＞T/p.R778L of exon 8 was the most common mutation site. ConclusionMost patients with WD have the manifestation of liver diseases, and the examinations of corneal K-F ring, serum ceruloplasmin, and 24-h urine copper have their own limitations. Liver pathology and ATP7B gene testing can be performed when it is unable to make a confirmed diagnosis.

Loss of renal function may render hemodialysis patients more susceptible to infectious diseases, which is the second of all-causes mortality in this population. In addition to infection caused by the classic Klebsiella pneumoniae (cKp), however, hemodialysis staffs are now facing new challenge with growing prevalence of the carbapenem-resistant Kp (CR-Kp) and hypervirulent Kp (hvKp) as they are respectively associated with increased drug-resistance and virulence. We therefore chose to share our recent experience in treating severe infections either caused (cKp, CR-Kp, hvKp) or complicated (CR-hvKp) by these strains in hemodialysis patients. Based upon yet beyond published works, we further came up with the detection of intracranial lesion, novel diagnostic approach using unique biomarkers followed by selection of appropriate antibiotics, management of metastasic abscesses and bracing for the most lethal scenario in the order of cKp, CR-Kp, hvKp and CR-hvKp, respectively. Since reports of complicated hvKp infection in hemodialysis patients were rare, we also discussed in details this clinical entity focusing on its epidemiology, mechanism of increased virulence and involvement of the arteriovenous fistula as insidious source of persistent septicemia. By covering the full spectrum of clinically relevant Kp stains specifically from the viewpoint of nephrology, our work had highlighted the importance of infection control in uremic state and vice versa. As such, it may greatly raise the awareness of dialysis staffs against the challenge of evolving Klebsiella pneumoniae infection in hemodialysis patients and expeditiously reach a higher degree of readiness which was proved to be the key determinant of ultimate survival.

Acute kidney injury (AKI) is a common complication of sepsis and increase morbidity and mortality. Long non-coding RNA (LncRNA) GAS6-AS2 was related to inflammation and apoptosis in different diseases by regulating miRNAs and downstream genes, but its role in AKI remains unclear. Thus, we speculated that GAS6-AS2 might function in sepsis-related AKI via regulating target genes. Here, LPS or CLP was used to establish in vitro or in vivo sepsis-related AKI model. The interactions between GAS6-AS2 and miR-136-5p, and miR-136-5p and OXSR1, were validated by luciferase reporter assay, RNA pull-down, or RIP assay. Cell apoptosis was determined by flow cytometry, Western blotting, or IHC. The kidney injury was evaluated by H&E staining. The expression of GAS6-AS2, miR-136-5p, and OXSR1 was determined by qRT-PCR or Western blotting. We found that GAS6-AS2 was up-regulated in LPS-treated HK2 cells and the CLP-induced rat model. In vitro, GAS6-AS2 knockdown decreased cleaved caspase-3 and bax expression and increased bcl-2 expression. The levels of TNF-α, IL-1β, and IL-6 were reduced by GAS6-AS2 down-regulation. GAS6-AS2 knockdown ameliorated oxidative stress in the cells, as indicated by the reduced ROS and MDA levels and the elevated SOD level. In vivo, GAS6-AS2 down-regulation decreased urinary NGAL and Kim-1 levels and serum sCr and BUN levels, and H&E proved that the kidney injury was alleviated. GAS6-AS2 knockdown also reduced apoptosis, inflammation, and oxidation induced by CLP in vivo. Mechanically, GAS6-AS2 sponged miR-136-5p which targeted OXSR1. Overall, lncRNA GAS6-AS2 knockdown has the potential to ameliorate sepsis-related AKI, and the mechanism is related to miR-136-5p/OXSR1 axis.

Non-alcoholic steatohepatitis (NASH) has no approved therapy. The farnesoid X nuclear receptor (FXR) agonist obeticholic acid (OCA) has shown promise as a drug for NASH, but can adversely affect plasma lipid profiles. Therefore, the present study aimed to investigate the effects and underlying mechanisms of OCA in combination with simvastatin (SIM) in a high-fat diet (HFD)-induced model of NASH. C57BL/6J mice were fed with a HFD for 16 weeks to establish the NASH model. The mice were randomly divided into the following five groups: HFD, HFD + OCA, HFD + SIM, HFD + OCA + SIM and control. After 16 weeks, the mice were sacrificed under anesthesia. The ratios of liver weight to body weight (Lw/Bw) and of abdominal adipose tissue weight to body weight were calculated. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, triglycerides and low-density lipoprotein were measured. Liver sections were stained with hematoxylin and eosin. The protein levels of FXR, small heterodimeric partner (SHP) and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) in the liver were detected by western blotting, while the mRNA levels of FXR, SHP, CYP7A1, bile salt export pump, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), sterol regulatory element binding protein-1 (SREBP1) and fatty acid synthase (FASN) were examined by reverse transcription-quantitative polymerase chain reaction. The administration of OCA with or without SIM reduced the liver inflammation score compared with those of the HFD and HFD + SIM groups, with no significant difference between the HFD + OCA and HFD + OCA + SIM groups. The steatosis score followed similar trends to the inflammation score. In HFD-fed mice, OCA combined with SIM prevented body weight gain compared with that in HFD and HFD + OCA groups, and reduced the Lw/Bw ratio compared with that in the HFD and HFD + SIM groups. In addition to preventing HFD-induced increases of ALT and AST, the combination of OCA and SIM reduced the mRNA levels of IL-6, TNF-α, SREBP1 and FASN. On the basis of these results, it may be concluded that the strategy of combining OCA with SIM represents an effective pharmacotherapy for NASH.

Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus. Accumulating studies suggest that the deregulation of circular RNA (circRNA) is involved in DN pathogenesis. This study aimed to investigate the role of circSMAD4 in DN models. Methods Mice were treated with streptozotocin to establish DN models in vivo. Mouse glomerulus mesangial cells (SV40-MES13) were treated with high glucose to establish DN models in vitro. The expression of circSMAD4, miR-377-3p and bone morphogenetic protein 7 ( BMP7 ) mRNA was measured by quantitative real-time PCR (qPCR). The releases of inflammatory factors were examined by ELISA. The protein levels of fibrosis-related markers, apoptosis-related markers and BMP7 were checked by western blot. Cell apoptosis was monitored by flow cytometry assay. The predicted relationship between miR-377-3p and circSMAD4 or BMP7 was validated by dual-luciferase reporter assay or pull-down assay. Results CircSMAD4 was poorly expressed in DN mice and HG-treated SV40-MES13 cells. HG induced SV40-MES13 cell inflammation, extracellular matrix (ECM) deposition and apoptosis. CircSMAD4 overexpression alleviated, while circSMAD4 knockdown aggravated HG-induced SV40-MES13 cell injuries. MiR-377-3p was targeted by circSMAD4, and miR-377-3p enrichment partly reversed the effects of circSMAD4 overexpression. BMP7 was a target of miR-377-3p, and circSMAD4 regulated BMP7 expression by targeting miR-377-3p. MiR-377-3p overexpression aggravated HG-induced injuries by suppressing BMP7 . Conclusion CircSMAD4 alleviates HG-induced SV40-MES13 cell inflammation, ECM deposition and apoptosis by relieving miR-377-3p-mediated inhibition on BMP7 in DN progression.

Objective: To clarify the clinical efficacy of Yiqi Huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis. Methods: An open, positive-drug, parallel-controlled study method was applied. A total of 207 cases of liver fibrosis with chronic hepatitis B and C diagnosed with liver biopsy and transient elastography were selected. According to the principle of syndrome differentiation in traditional Chinese medicine, self-made Yiqi Huoxue recipe (n = 127) and Fuzheng Huayu capsule (n = 80) were used for the treatment course of 24-48 weeks. Change score of TCM symptom, liver biochemistry, liver stiffness measurement (LSM), and noninvasive liver fibrosis index [aspartate transaminase to platelet ratio index (APRI), and fibrosis-4 score (FIB-4)] were compared between the two groups to evaluate the therapeutic effect of Yiqi Huoxue recipe on liver fibrosis. Results: Yiqi Huoxue recipe group and Fuzheng Huayu capsule group baseline LSM, APRI and FIB-4 was compared, and there was no statistically significant difference between them (P > 0.05). Yiqi Huoxue recipe and Fuzheng Huayu capsule received patients had improved symptom scores to a certain extent. Hepatic facies, discomfort over liver area, and soreness and weakness of waist and knees (P < 0.05) was significantly improved in Yiqi Huoxue recipe than Fuzheng Huayu capsule. Liver biochemical indicators (ALT, AST, GGT, ALP) had gradually relapsed with the extension of treatment duration and the normalization rate between the two groups after 24 to 48 weeks had reached 100% vs. 100%, 100% vs. 93.8%, 96.8% vs. 92.3% and 87.5% vs. 81.8%. After 12 weeks of treatment, APRI values ​​of both groups had significantly reduced, and after 48 weeks of treatment, LSM values of both groups had significantly improved. Moreover, Yiqi Huoxue recipe FIB-4 score was significantly improved after 48 weeks of treatment, and the difference was statistically significant compared to Fuzheng Huayu capsule group (P < 0.05). After treatment, LSM, APRI, and FIB-4 total effectiveness in the two groups were 80.0% vs. 63.6%, P = 0.046; 68.4% vs. 52.0%, P = 0.052; 68.4% vs. 62.0%, P = 0.437, respectively. LSM total effectiveness was significantly higher in Yiqi Huoxue recipe treated group than Fuzheng Huayu capsule group. Conclusion: Traditional Chinese medicine Yiqi Huoxue decoction can be used as an optimal treatment for liver fibrosis of chronic viral hepatitis.

Methods Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis.