High normal alanine aminotransferase is an indicator for better response to antiviral therapy in chronic hepatitis B.

Background: Evidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them. Methods: We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze. Results: ALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden's Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835). Conclusion: Male >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Methods: A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. Results: The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Conclusion: Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007.

Objective: This study aimed to assess the drug susceptibility of clinical isolates of Neisseria gonorrhoeae to spectinomycin, ceftriaxone and azithromycin. Moreover, the temporal trends in the minimum inhibitory concentration (MIC) of five antibiotics from Zhejiang, China, are also in the scope of this study. Methods: A total of 1710 gonococcal clinical strains were collected between 2007 and 2021 from health-care institutions in Zhejiang. The MICs of ceftriaxone, azithromycin, spectinomycin, penicillin and ciprofloxacin were assessed by agar dilution method on 1710 Neisseria gonorrhoeae isolates. Count data were expressed as strains and rates, and MICs distribution was elucidated using descriptive statistics. Results: The total resistance rates of gonococci to azithromycin, spectinomycin, penicillin and ciprofloxacin in this study were 19.3%, 0.3%, 75.4% and 99.7%, respectively. Conclusion: The in vitro results showed a high prevalence of resistance to ciprofloxacin and penicillin. Azithromycin resistance rate has exceeded 5%, suggested a high prevalence of resistance. Ceftriaxone and spectinomycin are suggested based on this study for the treatment of Neisseria gonorrhoeae in Zhejiang.

Assessment of the effectiveness of parent-targeted interventions for the use of child restraint systems: a systematic review and meta-analysis.

Background: It is essential to implement parent-targeted interventions to increase the use of child restraint systems (CRS) and thus reduce the injuries and deaths of children due to motor vehicle collisions. To optimize future intervention designs, this meta-analysis sought to quantify the effects of parent-targeted interventions and explore potential intervention moderators. Methods: Studies met inclusion criteria if they included a parents-targeted intervention that focused on increasing CRS use for children, published from the inception of the databases to January 2022, were systematically retrieved from the PubMed, Embase, Cochrane library, Web of Science, Sinomed, Wanfang, and CNKI databases. Next, 2 researchers independently screened the retrieved articles, evaluated their quality according to the Cochrane Tool, and extracted the data. Finally, Stata12.0 was used for the meta-analysis. Heterogeneity was examined with I2, stratified analyses, and meta-regression. Results: Of the 1,690 articles retrieved, 9 studies, comprising 22,329 parents of children aged 0-12 years, were ultimately included in the analysis. The results of the meta-analysis showed that the CRS use rate of the intervention group was 1.62 times higher than that of the control group [95% confidence interval (CI): 1.25-2.11, Z=3.616, P<0.001], indicating the positive effect of parent-targeted interventions on promoting the use of CRS. The subgroup analysis found that interventions guided by behavioral theories increased the use of CRS (odds ratio: 1.44, 95% CI: 1.27-1.63, n=5). The difference in the use of CRS between the groups in the studies that were not guided by theories was not statistically significant, indicating that interventions guided by behavioral theories may be the source of the heterogeneity. Risk of bias was low in most studies. Conclusions: It is necessary to conduct interventions with parents to increase the use of CRS. The effects on CRS use appear to differ depending on whether the interventions are guided by behavioral theories. In-depth research needs to be conducted to explore the characteristics of the interventions, especially those guided by different behavioral theories, to reduce child vehicle injuries.

Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure.

Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d-galactosamine induced acute liver failure via inhibition of TLR4 pathway.

Splenic CD11c(low)CD45RB(high) dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure.

Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF.

Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1.

High mobility group box 1 (HMGB1) has been widely reported to mediate damage caused by inflammatory responses. The aim of our study is to investigate the role of HMGB1 in endotoxin tolerance (ET) alleviating inflammation of acute liver failure (ALF) rats and its possible signaling mechanism. To mimic ET, male Sprague-Dawley rats were pretreated with low dose of lipopolysaccharide (LPS) (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent ALF induction. ALF was induced by intraperitoneal administration of D-GalN/LPS. ET induced by LPS pretreatment significantly improved the survival rate of ALF rats. Moreover, after ALF induction, ET+ALF rats exhibited lower serum enzyme (ALT, AST and TBiL) levels, lower production of inflammatory cytokines (IL-6, TNF-a and HMGB1) and more minor liver histopathological damage than ALF rats. ET+ALF rats showed enhanced expression levels of HMGB1, decreased levels of STAT1 and p-STAT1, augmented expression of SOCS1 in liver tissues than ALF rats. These results indicated that ET induced by low-dose LPS pretreatment may alleviate inflammation and liver injury in experimental acute liver failure rats mainly through inhibition of hepatic HMGB1 translocation and release.

Isoniazid-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Presenting as Acute Eosinophilic Myocarditis.

It has been reported that hypereosinophilic syndrome may be induced by antituberculosis drugs. We herein report the case of a 43-year-old man who had been on antituberculosis drugs for two months to treat tuberculous meningitis. During therapy, he suffered from drug rash with eosinophilia and systemic symptoms (DRESS) presenting as acute eosinophilic myocarditis, as confirmed on a histopathologic examination. According to the patient's medication history, clinical features and accessory examination findings, the eosinophilic myocarditis was thought to be possibly induced by isoniazid. Although further investigations are needed to confirm causality, isoniazid may be added to the list of drugs with the potential to cause DRESS syndrome.

LPS pretreatment ameliorates D-galactosamine/lipopolysaccharide-induced acute liver failure in rat.

Acute liver failure (ALF) remains an extremely poor prognosis and high mortality; with no effective treatments. The endotoxin tolerance (ET) phenotype has been reported to exhibit protective activities in several sepsis models. We now investigated the effects and underlying intraperitoneal injection of the same volume of pyrogen-free 0.9% sodium chloride instead of LPS for five consecutive days before D-GalN/LPS injection in rats. The serum levels of TNF-α, IL-6, ALT, AST and TBiL from ET + ALF group and ALF group were measured at different time points. Our results showed that ET + ALF group markedly reduced the serum levels of TNF-α, IL-6, ALT, AST and TBiL and histological features in the ET + ALF group were improved significantly. Furthermore, LPS pre-treatment inhibited D-GalN/LPS-induced NF-κB activation, Bax activation, signal transducer and activator of transcription-1 (STAT1) and signal transducer and activator of transcription-3 (STAT3) activities. LPS pre-treatment also significantly enhance the expression of suppressors of cytokine signaling 1 (SOCS1) and suppressors of cytokine signaling 3 (SOCS3). Our experimental data indicated that ET might alleviate D-GalN/LPS-induced ALF by inhibiting the inflammatory response, inactivation of STAT1 and STAT3 and up-regulation of SOCS1 and SOCS3.

A case of multiple macronodular hepatic tuberculosis difficult to differentiate from hepatocellular carcinoma with intrahepatic metastasis: CT-guided fine needle aspiration biopsy confirmed the diagnosis.

Multiple macronodular hepatic tuberculosis is difficult to be differentiated from hepatocellular carcinoma with intrahepatic metastasis in clinical practice, especially when hepatitis B with or without liver cirrhosis coexists with it. Herein, we report a 30-year-old man with a 10-year history of hepatitis B and a family medical history of hepatocellular carcinoma related with hepatitis B that was finally diagnosed as multiple macronodular hepatic tuberculosis. Abdominal B-mode ultrasonography (US) and plain computed tomography (CT) revealed multiple unequal-sized nodules in the liver. CT-guided fine needle aspiration biopsy (FNAB) of the liver demonstrated a caseating granuloma with lymphocytes, multinucleate giant cells and epithelioid cells compatible with the diagnosis of tuberculosis and no hepatoma cells were detected. Thus, the diagnosis of hepatic tuberculosis was confirmed and hepatocellular carcinoma with intrahepatic metastasis was excluded.

[The study on the role of SOCS1 and SOCS3 in the livers of endotoxin tolerance rats].

OBJECTIVE: To explore the mechanism of endotoxin tolerance(ETT) through observing the gene expression of SOCS1 and SOCS3 in the livers of ETT rats. METHODS: SD male rats were divided randomly into acute liver failure model group (ALF group) and ETT group. LPS 0.1 mg/kg (ETT group) or normal saline (ALF group) was administered five consecutive intraperitoneal injections at 24 h intervals, then, the two groups were treated with intraperitoneal injection of D-GalN 800 mg/Kg and LPS 8 microg/rat 24 h later. Liver histopathology and fine structure of rats were observed by HE staining and electron microscope. The TNF-alpha level were estimated by ELISA, the concentrations of endotoxin were determined by tachypleus amebocyte lysate and the gene expressions of SOCS1 and SOCS3 in the liver were measured by RT-PCR at 0, 2, 6, 12, 24 and 48 h after the injection of D-GalN/LPS. RESULTS: D-GalN/LPS induced acute liver injury was attenuated significantly in ETT group. The concentrations of endotoxin and the TNF-alpha level were evidently lower in the ETT group than those in the ALF group (endotoxin: 6 h: 1.11 +/- 0.38 vs 0.74 +/- 0.22, 24 h: 1.12 +/- 0.24 vs 0.86 +/- 0.21, all P < 0.05, 12 h: 1.88 +/- 0.35 vs 0.62 +/- 0.16, 48 h: 1.10 +/- 0.13 vs 0.84 +/- 0.19, all P < 0.01; TNF-alpha: 6 h: 86.9 +/- 12.6 vs 70.0 +/- 12.8, P < 0.05, 12 h: 77.0 +/- 18.1 vs 48.8 +/- 12.8, 24 h: 63.8 +/- 9.2 vs 39.1 +/- 5.7, 48 h: 53.2 +/- 8.3 vs 38.2 +/- 9.9, all P < 0.01). In the ALF group, the expressions of SOCS-1 and SOCS-3 were obviously higher than those in the controls and reached peak at 12th hours and 6th hours respectively. The gene expression of SOCS1 and SOCS3 in the liver in ETT group were increased significantly and much higher than those in ALF groups. (SOCS1: 6 h: 0.955 +/- 0.186 vs 1.349 +/- 0.390, 48 h: 0.766 +/- 0.145 vs 0.970 +/- 0.205, all P < 0.05, 2 h: 0.554 +/- 0.164 vs 0.841 +/- 0.175, 12 h: 1.130 +/- 0.181 vs 1.888 +/- 0.573, 24 h: 0.990 +/- 0.212 vs 1.550 +/- 0.439, all P < 0.01; SOCS3: 6 h: 0.914 +/- 0.054 vs 1.039 +/- 0.109, 12 h: 0.781 +/- 0.044 vs 0.863 +/- 0.063, all P < 0.05, 2 h: 0.681 +/- 0.139 vs 0.898 +/- 0.058, 24 h: 0.700 +/- 0.065 vs 0.811 +/- 0.055, all P < 0.01). CONCLUSIONS: LPS pretreatment can induce endotoxin tolerance of rats, inhibited the level of TNF-alpha and endotoxin. The up-regulation of SOCS1 and SOCS3 gene expression may be one of the possible mechanisms responsible for endotoxin tolerance.

[Changes of plasma cytokines in patients with severe hepatitis treated with a probiotic preparation].

OBJECTIVE: To study the changes of plasma cytokines in patients with severe hepatitis treated with a probiotic preparation. METHODS: One hundred twelve patients with severe hepatitis treated with a basic regimen were randomly divided into a probiotic preparation treatment group and a control group. Their plasma cytokines such as tumor necrosis factor alpha, interleukin-2, interleukin-6, interleukin-10, were determined by conventional techniques. RESULTS: Clinical symptoms of 84.5% of the treatment group were obviously improved. The treatment effectiveness in this group was better than that in the control group (X2=8.888). It showed that liver functions were significantly improved compared to those of the control group . After the probiotic preparation therapy, there were significant decreases in the concentrations of TNFa and IL-6. TNFa and IL-6 in the treatment group and in the control group were (109.4+/-14.7) pg/ml vs (128.7+/-18.8) pg/ml and (84.3+/-20.1) pg/ml vs (109.1+/-18.7) pg/ml respectively. However, the concentrations of IL-10 and IL-2 in the treatment group increased obviously: IL-2 was (59.8+/-12.2) pg/ml vs (47.1+/-6.7) pg/ml and IL-10 was (30.6+/-6.6) pg/ml vs (22.5+/-6.1) pg/ml. CONCLUSION: The probiotic preparation treatment effectively reduces the TNFa and IL-6 and increases the concentrations of IL-10 and IL-2 in the blood of the patients with severe hepatitis.