MicroRNA-124 (miR-124) is related to liver injury due to chronic hepatitis B (CHB) and hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, the mechanism whereby miR-124 regulates liver inflammation remains unknown. In this study, we show that serum miR-124 serves as a compensatory predictive factor for organ failure and the 28-day prognosis of patients with HBV-ACLF. Moreover, within a mouse model of concanavalin A-induced acute liver injury, miR-124 is highly expressed in Kupffer cells. Overexpression of miR-124 significantly decreases interleukin-6 (IL-6) secretion, and relieves pathological liver necrosis to a great extent. Mechanistically, miR-124 directly targets the 3′-untranslated region of signal transducer and activator of transcription 3 (STAT3) and inhibits IL-6/STAT3 signaling, which reduces pro-inflammatory Kupffer cell polarization. Collectively, our findings suggest that miR-124 can potentially serve as a predictive biomarker for HBV-ACLF prognosis and may represent a promising therapeutic target for relieving severe liver injury resulting from cytokine storms.

Coagulation and fibrinolysis disorders are major prognostic factors in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Here, we aimed to clarify the role of disseminated intravascular coagulation (DIC) scores in predicting HBV-ACLF patient prognosis. We assessed the DIC score from HBV-ACLF patients at Huashan Hospital in Shanghai, China from June 2013 to May 2021 and evaluated it in relation to short-term mortality, clinical course, and infection. A novel prognostic scoring model was proposed based on DIC scores. A total of 163 transplant-free HBV-ACLF patients were enrolled. DIC scores were higher in non-survivors than survivors (6 vs. 4, P = 0.000) and were independently associated with short-term mortality [hazard ratio (HR): 1.397, 95% confidence interval (95% CI): 1.040-1.875, P = 0.026]. DIC scores were associated with ACLF grade, clinical course, and infection. Moreover, they were correlated with model for end-stage liver disease (MELD) scores (r = 0.521, P < 0.001). The area under the receiver operating curve (auROC) of CLIF-C OF-DICs [a novel prognostic score based on age, DIC score, and Chronic liver failure-consortium organ function score (CLIF-C OFs)] for 90-day mortality was 0.936, which was higher than six other generic prognostic scoring models. These results were confirmed in a validation cohort (n = 82). In conclusion, elevated DIC score is associated with poor prognosis in HBV-ACLF patients, and can be used jointly with CLIF-C OFs to improve the accuracy of prognosis prediction.

The pathogenesis of liver in patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) remains largely unknown. We aimed to elucidate the molecular mechanism underlying the pathogenesis of liver in HBV-ACLF patients by using multiple approaches including transcriptome analysis. We performed transcriptomic sequencing analysis on the liver of HBV-ACLF patients (n = 6), chronic hepatitis B (n = 6), liver cirrhosis (n = 6) and normal control (n = 5), then explored the potential pathogenesis mechanism in liver specimen from another 48 subjects and further validated the molecular and cellular mechanisms using THP-1 cells. RNA-sequencing data analysis indicated that, among the genes up-regulated in HBV-ACLF, genes related to inflammatory response and chemotaxis accounted for a large proportion of the total DEGs. A number of key chemokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8) and NF-ĸB pathway were identified to be robust in the liver samples from HBV-ACLF patients. Interestingly, cylindromatosis (CYLD) was found to be downregulated in the liver of HBV-ACLF patients, in line with the well-established role of CYLD in regulating most of the chemokines and pro-inflammatory cytokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8, IL-6, IL-1β) via inhibition of NF-ĸB. Indeed, the knockdown of CYLD resulted in sustained activation of NF-ĸB in macrophages and enhanced chemokines and inflammatory cytokines production, which in turn enhanced chemotactic migration of neutrophil, monocyte, T lymphocytes, and NK cell. In conclusions, down-regulated CYLD aggravated inflammatory cell chemotaxis through enhancing NF-κB activation in HBV-ACLF patients, thereby participating in the pathogenesis of HBV-ACLF injury.

目的 对非公立医疗机构助力上海市入境医疗旅游发展的情况进行探讨.方法 回顾性地分析2016-2018年上海市非公立医疗机构收治外籍住院患者的数量、地域分布、疾病构成、手术分级、疾病转归等,并与同期公立医疗机构收治外籍住院患者的情况进行比较.结果 在入境医疗旅游领域,非公立医疗机构具有效率优势和国际化优势,但仍需提升医疗技术、服务品质、品牌美誉度等.结论 非公立医疗机构应通过高质量的诊疗水平和优质的国际化服务管理模式不断提升自身的竞争力,充分利用当前的利好政策,助力上海市入境医疗旅游的发展.

阿米巴感染性肠炎是一种较少见的胃肠道感染性疾病，临床症状表现为不同程度的腹痛、腹泻伴血便，暴发型阿米巴肠病为其最严重的并发症，病死率高。本文回顾性分析复旦大学附属华山医院收治的1例以转移性右下腹痛表现起病，最终确诊为暴发型阿米巴肠病患者的临床资料和治疗过程，并结合国内外文献分析该病临床特点、影像学表现、病理特点及治疗。

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a dynamic but reversible disease. We aimed to clarify whether the change in Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) grade in HBV-ACLF patients can be used to predict prognosis, and to explore the appropriate conditions for performing urgent liver transplantation. We assessed the COSSH-ACLF grades of HBV-ACLF patients at different time points from June 2013 to May 2019 at Huashan Hospital in Shanghai, China, and analyzed the relationship between the change in grade and patient prognosis. A total of 207 HBV-ACLF patients were enrolled, of which 79 underwent urgent liver transplantation. Their COSSH-ACLF grades were calculated at diagnosis, 3–7 days after diagnosis, and on the final day. Most of the final ACLF grades were consistent with their corresponding grades at days 3–7 after diagnosis (62.5%), while only 44.5% were in accordance with the initial grades at diagnosis. In patients who had a poor prognosis (initial ACLF-3 and ACLF-2 or -3 at days 3–7), the 28-day survival rate was 93.3% in those who underwent transplantation and 6.8% in those who did not (P < 0.0001). However, in patients who had a good prognosis (ACLF-0 or ACLF-1 at days 3–7), the 28-day survival rate was 100% in transplanted patients and 91.5% in non-transplanted patients (P = 0.236). Reevaluation of the COSSH-ACLF grade 3–7 days after diagnosis could potentially show an indication for urgent liver transplantation.

The aim of the present study was to investigate the predictive value of baseline serum microRNA (miRNA)-125b for nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). A total of 66 patients with Be antigen (HBeAg)-positive CHB received NAs therapy for 144 weeks. Serum miRNA-125b levels were measured at the baseline, while hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) and alanine aminotransferase (ALT) levels were measured throughout treatment. Stepwise logistic regression analysis was performed to identify predictors of treatment response. The results indicated that baseline serum miR-125b (OR=4.377; P=0.006), HBsAg (OR=0.120; P=0.010), ALT >5× upper limit of normal (ULN; OR=11.726; P=0.018) and undetectable HBV DNA at week 24 (OR=7.828; P=0.021) were independent predictors of complete response (CR) at 144 weeks (CR is defined as HBV DNA <500 IU/ml and HBeAg seroconversion). The baseline serum miRNA-125b combined with baseline HBsAg level yielded an area under the receiver-operating curve of 0.852 in discriminating CR and non-CR at 144 week. The combination of baseline miRNA-125b ≥1.7 and ALT >5× ULN had a positive predictive value 80% for CR at 144 weeks. The combination of baseline miRNA-125b ≥1.7 and HbsAg ≤4.4 (log10 IU/ml) had a negative predictive value of CR at 144 weeks of 100%. Together, these results suggest that baseline miRNA-125b is a reliable predictor of HBeAg seroconversion following NAs treatment. The present study may be used as a basis for the use of baseline miRNA-125b to optimize treatment prior to NAs therapy.

Aim: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are not free from significant hepatic lesions. Recently, there has been an improved understanding of the clinical significance of quantitative hepatitis B core antibody levels (qAnti-HBc) during CHB management. In this cross-sectional study, we evaluated the utility of qAnti-HBc in identifying significant liver inflammation in CHB patients. Methods: A total of 469 patients (training set, n=363; validation set, n=106) who underwent liver biopsy (LB) were included. The qAnti-HBc levels were quantified and the relationship between histology and serum markers was systematically analyzed. Results: In the training set, qAnti-HBc levels were found to have significant diagnostic value for moderate to severe liver inflammation (>= G2) in all patients (area under the receiver operating characteristic curve [AUROC]=0.768; 95% confidence interval [CI], 0.721-0.810; P<0.001) and in patients with normal or near-normal ALT levels (AUROC=0.767; 95% CI, 0.697-0.828; P<0.001). Our novel index (AC index) for the identification of >= G2 inflammation, which combined the qAnti-HBc and ALT levels, significantly improved diagnostic performance (AUROC=0.813; 95% CI, 0.768-0.852) compared to the use of ALT alone (AUROC=0.779; 95% CI, 0.732-0.821) in all patients. In the validation set, the AC index showed an improved AUROC of 0.890 (95% CI, 0.814-0.942) and 0.867 (95% CI, 0.749-0.943) in all patients and patients with normal ALT levels, respectively. Conclusions: The qAnti-HBc level predicts significant liver inflammation well, even in patients with normal or near-normal ALT levels. Compared with the conventional ALT level, the AC index is a more reliable non-invasive biomarker for significant liver inflammation in CHB patients.

Objective: This study aims to identify the clinical and laboratory features of LAHS and clarify the prognostic factors of HLH. Methods: 67 HLH patients were enrolled. 37 LAHS patients and 30 non-LAHS patients were compared. The diagnostic values of F-18 FDG PET/CT and serum ferritin (SF) levels for distinguishing LAHS from HLH were assessed. The survival data and prognostic significance of PET/CT SUVmax value, SF levels and age in the LAHS group were evaluated. Results: Most LAHS patients had remittent fever with unresponsive to antipyretic drugs and weight loss within six months compared to non-LASH patients (62.16% versus 26.67%, P = 0.0018). The SF levels and PET/CT SUVmax value in LAHS group were significantly higher than those in non-LAHS group (2000 mu g/L versus 632 mu g/L, P = 0.000; 12.03 +/- 7.27 versus 4.47 +/- 2.48, P = 0.000, respectively). Meanwhile, we found that PET/SUV was more than 10 and/or SF was exceed 1000 mu g/L usually occurred in patients with LAHS, which might indicated that PET/CT SUVmax and SF level could be used as potential diagnostic factors of LAHS (AUC 0.819 and AUC 0.950, respectively). In our study, Overall survival (OS) of patients with LAHS was inferior to non-LAHS patients (24.3% versus 53.3%). Furthermore, patients with the advanced disease delayed chemotherapy and the survival was discouraging. In addition, PET/CT SUVmax value and SF level were also associated with poor prognosis. Conclusion: Patients with LAHS had poorer outcome than non-LAHS patients. PET/CT and SF level can be used to make early diagnosis of LAHS, and offer prognostic significance for the patients with secondary HLH.

AbstractCurrent pegylated interferon-&agr; (PEG-IFN) treatment for chronic hepatitis B (CHB) e-antigen (HBeAg)-positive patients are suboptimal, and effective ways of improving PEG-IFN treatment efficacy are needed.This retrospective cohort study compared the efficacy of a PEG-IFN stepwise optimization treatment (PEG-IFN SOT) strategy with that of a 48-week PEG-IFN standard therapy (PEG-IFN ST) in HBeAg-positive CHB patients.A total of 110 patients were included in our study. Of these, 70 received the PEG-IFN SOT and 40 received the PEG-IFN ST (control group). We based the decision whether to add adefovir and/or extend the PEG-IFN–based treatment to 96 weeks on the patients’ 12-week or 24-week early virological response (12W EVR, at least a 2 log10 reduction in HBV DNA copies/mL at week 12; 24W EVR, at least 1 log10 reduction in HBsAg IU/mL or HBsAg <1500 IU/mL at week 24) and their 48-week partial response (48W PR, 1.0 ⩽HBeAg ⩽10.0 S/CO or HBeAg >10.0 S/CO but HBsAg <1000 IU/mL).The HBeAg seroconversion rate 24 weeks post-PEG-IFN treatment was significantly higher in the PEG-IFN SOT than the PEG-IFN ST group (50% vs 22.5%, P = 0.005). The HBsAg clearance rates in the PEG-IFN SOT and ST groups were 10% and 0% (P = 0.04), respectively. Receiving PEG-IFN SOT (OR = 0.26, P = 0.01), ALT × ULN at baseline (OR = 0.74, P = 0.003), and achieving 12 and 24W EVR (OR = 0.29, P = 0.03) were independent factors associated with HBeAg seroconversion.PEG-IFN SOT is a promising strategy for achieving high rates of serological response in HBeAg-positive CHB patients.

Limited research has been conducted on healthcare-associated infective endocarditis (HAIE), although it is of increasing importance. The aim of this study is to compare the epidemiology, clinical characteristics, and prognosis of community-acquired IE (CA-IE) with HAIE and non-nosocomial healthcare-associated IE (NNHCA-IE). A retrospective, consecutive case-series analysis was organized and performed during the 20-year study period in Huashan Hospital, Shanghai, China. A total of 154 patients were enrolled, including 126 (81.8%) who had CA-IE and 28 (18.2%) who had HAIE, among whom 20 (71.4%) had non-nosocomial IE. Patients with HAIE compared to patients with CA-IE had poorer clinical conditions (Charlson comorbidity index >= 2: 35.7% vs. 15.1%, P = 0.012; immunosuppressive therapy: 21.4% vs. 4.0%, P = 0.005), underwent more prosthetic valve replacement (35.7% vs. 7.1%, P < 0.001), had less streptococcus infection (16.7% vs. 51.1%, P = 0.007) but more atypical bacterial infection (50.0% vs. 21.1%, P = 0.017) and poorer outcomes (17.9% vs. 4.0%, P = 0.019). It is noteworthy that the results were quite similar between the comparison of patients with NNHCA-IE and those with CA-IE. Overall, in-hospital mortality was 6.5%. The IE acquisition site and low serum albumin levels (odds ratio (OR): 0.8; P = 0.04) were significantly associated with an increased risk of mortality. Nosocomial IE patients had an 8.3-fold and NNHCA-IE patients had 6.5-fold increase in the risk of mortality compared to CA-IE patients. In conclusion, HAIE and NNHCA-IE have important epidemiological and prognostic implications. Because NNHCA-IE usually occurs in patients residing in the community, it is suggested that these patients should be identified and treated by the community primary care clinical staff as early as possible.