The genomic distribution map of human papillomavirus in Western China.

Human papillomavirus (HPV) has been confirmed as the causative agent for cervical cancer. In this study, a total of 301 880 women were recruited from four different regions of Western China, with 301 880 exfoliated cervical cell samples collected from women for DNA isolation and purification. The HPV genotype was tested by polymerase chain reaction. The overall HPV prevalence rate, high-risk (HR) HPV infection rate, low-risk (LR) HPV infection rate and mixed HPV infection rate was 18.24%, 79.14%, 12.56% and 8.30%, respectively. The four most common HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49%, 19.93%, 14.54% and 10.01%, respectively. In LR HPV genotype, HPV-6 ranked the highest (28.17%), followed by HPV-81 (9.09%) and HPV-11 (3.78%). HPV genotype subgroup analysis also showed that single-type infection was the most common (77.26%) among HPV-positive individuals. Among multi-infection genotypes, double infection was the most common with frequencies of 76.04%. The overall prevalence of HPV is high in Western China, whose distribution demonstrates different patterns across different ages and regions. Viral genotypes HPV 53, 6 were frequently detected in this population, which is worth of significant clinical attention.

Ginsenoside Rg1 alleviates acute liver injury through the induction of autophagy and suppressing NF-κB/NLRP3 inflammasome signaling pathway.

Background: Severe hepatitis is a common cause of chronic or acute liver disease and autophagy might play an important role in cellular response to inflammation and injury. It has been reported that Ginsenoside-Rg1 (G-Rg1) has strong hepatoprotective effects for acute liver injury, but its protective mechanisms have not yet been elucidated. This study aims to explore the detailed molecular mechanisms of G-Rg1 on acute liver injury via autophagy. Methods: The role of G-Rg1 by autophagic induction was studied in the mouse model of acute liver injury which induced by carbon tetrachloride (CCl4). Liver function, inflammatory reaction and apoptosis were detected when autophagy has been inhibited by 3-MA or stimulated by RPA. MCC950 and ATP were applied to investigate the role of NLRP3 inflammasome in acute liver injury. The differential expression of NF-κB, NLRP3 inflammasome, caspase 1, caspase 3, IL-1ß, IL-18, LC3-I, LC3-II, Beclin-1, PINK1 and Parkin have been detected by the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results: G-Rg1 could decrease ALT, AST, TNF-α, IL-1ß and IL-6 in mice with CCl4-induced acute liver injury. The change of autophagy and apoptosis after the treatment of 3-MA or RPA demonstrated that the autophagy played a key role in the protective effect of G-Rg1 in acute liver injury. The enhancement of G-Rg1 promoted-autophagy resulted in the significant decrease in NF-κB, NLRP3 inflammasome, caspase 1, caspase 3, IL-1ß and IL-18, which suggesting that NF-κB/NLRP3 inflammasome signaling pathway was associated with the autophagy induced by G-Rg1 in acute liver injury. Conclusion: G-Rg1 ameliorated acute liver injury via the autophagy, which may be related to NF-κB/NLRP3 inflammasome signaling pathway.

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Risk factors for the exacerbation of patients with 2019 Novel Coronavirus: A meta-analysis.

Many studies have reported the risk factors for exacerbations in patients with 2019 novel coronavirus (2019-nCoV). This study aims to perform the meta-analysis of risk factors for the exacerbation of the novel coronavirus-infected pneumonia (NCIP). PubMed, Embase and Google scholar have been searched. We included the cohort studies involving risk factors for the exacerbation of NCIP. This meta-analysis compared the risk factors of patients between intensive care (ICU) group and non-ICU group. Two cohort studies were included in this study. After comparing the patients between intensive care (ICU) group and non-ICU group, several important factors were found to significantly increase the risk of exacerbations in patients with NCIP, and they included hypertension (RR=2.34; 95% CI=1.21 to 4.51; P=0.01), cardiovascular diseases (RR=2.28; 95% CI=1.13 to 4.58; P=0.02), COPD (RR=7.65; 95% CI=1.24 to 47.13; P=0.03), dyspnea (RR=2.89; 95% CI=2.05 to 4.08; P<0.00001), myalgia or fatigue (RR=1.24; 95% CI=1.01 to 1.52; P=0.04), but several factors such as gender, Huanan Seafood Wholesale Market exposure, diabetes, chronic liver disease, malignancy, fever, cough, expectoration, headache and diarrhoea appeared to have no obvious effect on the exacerbation of pneumonia. In addition, as the exacerbation of pneumonia, some complications had the high probability to occur according to the meta-analysis of acute respiratory distress syndrome (ARDS) (RR=13.95; 95% CI=6.20 to 31.41; P<0.00001), shock (RR=24.29; 95% CI=4.66 to 126.69; P=0.0002), acute cardiac injury (RR=10.32; 95% CI=3.05 to 34.96; P=0.0002) and acute kidney injury (RR=5.90; 95% CI=1.32 to 26.35; P=0.02) between two groups. Several risk factors were confirmed to significantly improve the risk of exacerbation in patients with NCIP, which was very important for the exacerbation prediction and treatment of these patients.

Effect and mechanism of ginsenoside Rg1-regulating hepatic steatosis in HepG2 cells induced by free fatty acid.

Ginsenoside Rg1 (G-Rg1) is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases including nonalcoholic fatty liver disease (NAFLD). But there is a lack of literature reporting the effect of G-Rg1 on lipid metabolism balance in NAFLD. We investigated the effect and mechanism of G-Rg1 on lipid metabolism in vitro. We found that G-Rg1 decreased the levels of TG, TC, and MDA, and increased activity of SOD. Results of RT-PCR and western blotting showed that supplementation with G-Rg1 downregulated the expression of PPAR γ, FABP1, FATP2/5, CD36, SREBP1 c, and FASN, while the expression of PPAR ɑ, CPT1, ACOX1, MTTP, and ApoB100 was upregulated, after induction by a free fatty acid. Taken together, we conclude that G-Rg1 inhibits lipid synthesis and lipid uptake, and enhances lipid oxidation and lipid export to reduce hepatic steatosis of HepG2 cells by regulating PPAR ɑ and PPAR γ expression.

Potential risk factors for case fatality rate of novel coronavirus (COVID-19) in China: A pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVE: Since the first case of the pneumonia caused by 2019 novel coronavirus (COVID-19) is found in Wuhan, there have been more than 70,000 cases reported in China. This study aims to perform the meta-analysis of risk factors for the case fatality rate (CFR) of the 2019 novel coronavirus (COVID-19). DESIGN AND METHODS: We have searched PubMed, Google scholar and medRxiv for the cohort studies involving risk factors for the CFR of COVID-19. This meta-analysis compares the risk factors of CFR between fatal patients and non-fatal patients. RESULTS: Two cohort studies are included in this study. After comparing the patients between fatal cases and non-fatal cases, several important factors are found to significantly increase the CFR in patients with COVID-19, and include the age ranging 60-70 (OR = 1.85; 95% CI = 1.62 to 2.11; P < .00001) and especially≥70 (OR = 8.45; 95% CI = 7.47 to 9.55; P < .00001), sex of male (OR = 1.88; 95% CI = 1.30 to 2.73; P = .0008), occupation of retirees (OR = 4.27; 95% CI = 2.50 to 7.28; P < .00001), and severe cases (OR = 691.76; 95% CI = 4.82 to 99,265.63; P = .01). As the advancement of early diagnosis and treatment, the CFR after January 21 (or 22), 2020 is substantially decreased in COVID-19 than before (OR = 0.21; 95% CI = 0.19 to 0.24; P < .00001). CONCLUSIONS: Several factors are confirmed to significantly improve the CFR in patients with COVID-19, which is very important for the treatment and good prognosis of these patients.

Comparison of Minimally Invasive and Open Transforaminal Lumbar Interbody Fusion for Lumbar Disc Herniation: A Retrospective Cohort Study.

BACKGROUND This cohort study compared the efficacy and safety of minimally invasive versus open transforaminal lumbar interbody fusion (Mis-TLIF versus Open-TLIF) for lumbar disc herniation with radiculopathy. MATERIAL AND METHODS From July 2016 to September 2017, we recruited 37 patients suffering from lumbar disc herniation with radiculopathy. Seventeen patients underwent Mis-TLIF (Mis group) and 20 patients underwent Open-TLIF (Open group). Baseline characteristics were similar between the 2 groups before surgery. We compared postoperative clinical and radiological outcomes between the 2 groups. RESULTS Compared to patients in the Open group, patients in the Mis group has significantly less intraoperative hemorrhage, drainage fluid, time to go, and hospital stay after surgery, but had longer operation times (P<0.05). These 2 groups had similar postoperative hemoglobin reduction and drain removal time. In addition, the postoperative back and leg pain and intervertebral height reduction at 3 months after surgery in the Mis group were remarkably lower than those in the Open group. There was no significant difference in postoperative Oswestry disability index (ODI) or intervertebral height change immediately after surgery and at 1 month postoperatively between the 2 groups. CONCLUSIONS Mis-TLIF shows some benefits in lumbar disc herniation compared to Open-TLIF in terms of intraoperative hemorrhage, drainage fluid, time to go, hospital stay after surgery, and postoperative back and leg pain.

[Effect and mechanism of ginsenoside Rg1 as an alcoholic hepatitis treatment in a rat model].

OBJECTIVE: To observe the effect of Rgl treatment on prognosis of alcoholic hepatitis using a rat model. METHODS: Female Sprague-Dawley rats were radomly divided into four groups:unmodeled control, untreated model, Rgl-treated model, and dexamethasone (DXM)-treated model. The model groups were generated by intragastric injection of alcohol. The unmodeled control group was given an equal dosage of normal saline by the same route. After model establishment, the Rg1 treatment group and the DXM treatment group were administered a 120-hour treatment of Rgl or DXM; the unmodeled controls were administered normal saline on the same schedule. All rats were then fasted for 120 hours and venous blood samples were collected for detection of serum aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TBil), albumin (Alb), tumor necrosis factor-alpha (TNFat) and interleukin 6 (IL-6). Markers of liver inflammation were measured by immunohistochemistry, western blotting, and real-time quantitative reverse transcription PCR. Fat and apoptosis indices were assessed by hematoxylin-eosin staining and TUNEL assay, respectively. The t-test and F test were used for statistical analyses. RESULTS: The model group showed remarkably more liver steatosis (over one-third of the tissue) than the unmodeled control group, indicating proper establishment of alcoholic liver disease in the modeled rats. The AST, ALT, TBil, and IL-6 levels were significantly higher in the untreated model group than in the Rgl-treated group and the DXM-treated group. The values were significantly different between the Rg1-treated group and the DXM-treated group:ALT, 69.19+/-8.00 U/L vs.102.88+/-5.16 U/L; TBil, 0.36+/-0.07 µmol/L vs.1.20+/-0.18 µmol/L; IL-6, 126.50+/-6.50 U/ml vs.169.19+/-7.68 U/ml; TNFa, 268.31+/-13.19 µg/L vs.318.94+/-7.87 µg/L (all P less than 0.05). Expression of caspase3 and caspase8 was significantly higher in the model group than in the Rgltreated group and the DXM-treated group (both P<0.05). The apoptosis index was significantly lower in the Rgltreated group and the DXM-treated group than in the model group (both P<0.05). The mRNA and protein expression of caspase3, caspase8 and NF-kB were significantly lower in the Rgl-treated group and the DXM-treated group than in the model group (allP less than 0.05), and the levels of all were significantly lower in the Rgl-treated group cornered to the DXM-treated group (all P<0.05). Conehision In rats with alcoholic hepatitis, Rg1 can significantly relieve pathological injury, improve liver function by blocking the apoptotic pathway, and inhibit release of inflammatory cytokines.

Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

USP9X-mediated NRP1 deubiquitination promotes liver fibrosis by activating hepatic stellate cells.

Liver fibrosis is a complex fibrotic process that develops early in the course of cirrhosis and is caused by chronic liver damage. The activation of hepatic stellate cells is primarily responsible for the fibrosis process. Studies show that NRP1 influences HSC motility and migration. However, whether NRP1 regulates HSC activation remains unknown. C57BL/6 male mice (6-8 weeks old) were intraperitoneally injected with 10% CCl4 in olive oil (5 µl/g body weight) every three days for four weeks to create an animal model of liver fibrosis. Control mice received olive oil (5 µl/g body weight). Different assays such as immunohistochemistry, immunostaining, Western blotting, qRT-PCR, immunoprecipitation, immunoprecipitation, and GST pull-down assays, and in vivo and in vitro ubiquitination assays were conducted. We found that NRP1 expression was significantly elevated both in mouse and human fibrotic livers, mainly in activated HSCs at the fibrotic foci. NRP1 promoted HSC activation via the cytokine TGF-ß1, VEGFA, and PDGF-BB. Moreover, USP9X was found to be a critical deubiquitinating enzyme for the stability and high activity of NRP1 and NRP1 deubiquitination mediated by USP9X enhanced HSC activation and liver fibrosis. NRP1 deubiquitination mediated by USP9X enhances HSC activation, implying that targeting NRP1 or USP9X potentiates novel options in the treatment of liver fibrosis.

Runx2 activates hepatic stellate cells to promote liver fibrosis via transcriptionally regulating Itgav expression.

BACKGROUNDS AND AIMS: As a central event during liver fibrosis, hepatic stellate cells (HSC) have been thought to be a potential therapeutic target for liver fibrosis. Previous studies have shown that runt-related transcription factor 2 (Runx2) is associated with the development of non-alcoholic fatty liver disease, while its specific role in HSC activation and hepatic fibrosis remains elusive. APPROACH AND RESULTS: In this study, we found that Runx2 expression was significantly upregulated in human liver fibrosis with different aetiologies. Runx2 expression was also gradually elevated in mouse liver during fibrosis, and Runx2 was mainly expressed in the activated HSC. Knockdown of Runx2 in HSC markedly alleviated CCl4 -induced, 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced or methionine-choline deficient (MCD)-induced liver fibrosis, while hepatic overexpression of Runx2 via HBAAV-Runx2 or VA-Lip-Runx2 injection exacerbated CCl4 -induced liver fibrosis. In vitro analysis demonstrated that Runx2 promoted HSC activation and proliferation, whereas Runx2 knockdown in HSC suppressed these effects. RNA-seq and Runx2 ChIP-seq analysis demonstrated that Runx2 could promote integrin alpha-V (Itgav) expression by binding to its promoter. Blockade of Itgav attenuated Runx2-induced HSC activation and liver fibrosis. Additionally, we found that cytokines (TGF-ß1, PDGF, EGF) promote the expression and nuclear translocation of Runx2 through protein kinase A (PKA) in HSC. CONCLUSIONS: Runx2 is critical for HSC activation via transcriptionally regulating Itgav expression during liver fibrosis, and may be a promising therapeutic target for liver fibrosis.

T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing.

Background: Hepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients. Methods: The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR. Result: 11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong. Conclusion: TEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.

What contributes to the re-positive nucleic acid test results for the omicron variant of SARS-CoV-2 in the shelter cabin hospital in Shanghai, China?

Background: Despite the increasing reports of re-positive SARS-CoV-2 cases after recovery and discharge from hospitals, our knowledge remains very limited regarding the contributing factors of re-positivity and its roles in the transmission and epidemiology of the Omicron variant. Methods: In this retrospective study, re-positivity is defined as the positive nucleic acid result (Ct < 35) following two consecutive negative results during hospitalization. A total of 751 patients from Shanghai Shelter Cabin Hospital were enrolled and divided with a ratio of about 1:2 into the re-positivity group and the non-re-positivity group. Patients required three consecutive negative results daily as the de-isolation criterion. The follow-up time of discharged patients lasted five weeks. Univariate regression analysis was used to compare variables between the re-positivity and non-re-positivity groups, and the single re-positivity and multiple re-positivity groups, with P < 0.05 defined as the statistical significance of differences. Subsequently, variables with P < 0.2 were subjected to multivariate logistic regression analysis to investigate the odds ratio (OR) of re-positivity and the influencing factors of re-positivity of the Omicron variant. Results: The re-positivity group had a higher proportion of males (68.1% vs 58.1%, p = 0.000), a higher education level (31.9% vs 12.7%, p = 0.007), a longer hospitalization duration (13 days vs 8 days, p = 0.000), and a higher Convidecia vaccination rate (6.0% vs 2.4%, p = 0.011). Further multivariable analysis showed male (OR = 2.168, p = 0.000), Convidecia vaccination (OR = 2.634, p = 0.014), hospitalization duration (OR = 2.146, p = 0.000) and education level (OR = 1.595, p = 0.007) were associated with re-positivity. The average rate of re-positivity was 25% during hospitalization and decreased to 0.4% among discharged patients. Re-positivity was more common in the period with a larger number of hospitalized patients and in larger wards with a larger number of patients. Conclusion: A large number of hospitalized patients, large-sized wards, and gender are significant contributing factors to re-positivity. Division of the shelter cabin hospital into small independent wards and requirement of three consecutive results daily as the de-isolation criterion might be more beneficial to the control and prevention of the spread of the Omicron variant.

Skeletal muscle mass index as a predictor of long-term cirrhosis onset in young non-cirrhotic males with acute-on-chronic liver failure.

Background: The relationship between skeletal muscle mass index (SMI) and cirrhosis incidence in patients with non-cirrhotic acute-on-chronic (ACLF) has not been clarified. This study aimed to assess the predictive value of SMI on the incidence of long-term cirrhosis in male non-cirrhotic ACLF patients. Materials and methods: Male ACLF patients who were free of liver cirrhosis were retrospectively included in this study. Univariate and multivariate logistic analyses were conducted to determine the risk factors for the long-term (1-year) development of cirrhosis. The receiver operating characteristic curves (ROC) were used to assess the ability of SMI levels to predict the incidence of cirrhosis. Restricted triple spline (RCS) described the dose-response relationship between SMI and the risk of cirrhosis. Subgroup analysis was stratified by age (≤ 40 years and > 40 years). Results: A total of 230 subjects were included in this study, of whom 45.2% (104/230) were diagnosed with cirrhosis within 360 days. Patients who progressed to cirrhosis had a lower SMI [46.1 ± 6.9 versus 49.2 ± 6.5 cm2/m2, P = 0.001] and a higher proportion of sarcopenia (19.2% versus 6.3%, P = 0.003). In multivariate logistic regression, SMI remained a protective agent against 360-days progression to cirrhosis in males with ACLF after adjustment (OR 0.950, 95% CI: 0.908-0.994, P < 0.05). SMI exerted a non-linear dose-dependent effect on the risk of cirrhosis. The area under the ROC curve (AUC) for the L3-SMI to predict the incidence of cirrhosis in male non-cirrhotic ACLF patients was 0.636 (P < 0.001). We observed significant differences in SMI among male ACLF patients in different age groups. Further subgroup analysis by age revealed that lower SMI was associated with the 1-year incidence of cirrhosis in male ACLF patients aged less than 40 years (OR 0.908, 95% CI: 0.842-0.979, P < 0.05), whereas SMI did not affect the 1-year risk of cirrhosis in older subjects (age > 40 years). Conclusion: A higher SMI represents an independent protective factor for developing long-term cirrhosis in male ACLF patients who do not experience cirrhosis, especially in those under 40 years of age.

Causal roles of circulating adiponectin in osteoporosis and cancers.

Circulating adiponectin has some association with the risk of osteoporosis and cancers, but their causal relationships remains elusive. Mendelian randomization (MR) study was used to explore the causal roles of circulating adiponectin in osteoporosis and cancers by using genome-wide association studies (GWASs) associated with circulating adiponectin, osteoporosis and cancers. Fifteen single nucleotide polymorphisms (SNPs) were used as instrumental variables for circulating adiponectin. Genetic predisposition to high circulating adiponectin was strongly associated with low femoral neck bone mineral density (FN-BMD, beta-estimate: -0.015, 95% CI: -0.023 to -0.006, SE: 0.004, P-value = 0.001), low forearm BMD (FA-BMD, beta-estimate: -0.027, 95% CI: -0.050 to -0.004, SE: 0.012, P-value = 0.023) and increased risk of breast cancer (beta-estimate: 0.011, 95% CI: 0.001 to 0.022, SE: 0.005, P-value = 0.031). There was limited evidence of the associations between circulating adiponectin and other outcomes (i.e. lumbar spine BMD [LS-BMD], colorectal cancer, liver cancer, lung cancer, bone cancer and prostate cancer). This study provides robust evidence that high circulating adiponectin is causally associated with low FN-BMD, low FA-BMD and increased risk of breast cancer, which may provide new insight to prevent and treat osteoporosis and breast cancer.

CYP2E1-dependent upregulation of SIRT7 is response to alcohol mediated metastasis in hepatocellular carcinoma.

Long-term alcohol use is a confirmed risk factor of liver cancer tumorigenesis and metastasis. Multiple mechanisms responsible for alcohol related tumorigenesis have been proposed, including toxic reactive metabolite production, oxidative stress and fat accumulation. However, mechanisms underlying alcohol-mediated liver cancer metastasis remain largely unknown. We have previously demonstrated that SIRT7 regulates chemosensitivity by altering a p53-dependent pathway in human HCC. In the current study, we further revealed that SIRT7 is a critical factor in promoting liver cancer metastasis. SIRT7 expression is associated with disease stage and high SIRT7 predicts worse overall and disease-free survival. Overexpression of SIRT7 promotes HCC cell migration and EMT while knockdown of SIRT7 showed opposite effects. Mechanistically, we found that SIRT7 suppresses E-Cadherin expression through FOXO3-dependent promoter binding and H3K18 deacetylation. Knockdown of FOXO3 abolished the suppressive effect of SIRT7 on E-cadherin transcription. More importantly, we identified that alcohol treatment upregulates SIRT7 and suppresses E-cadherin expression via a CYP2E/ROS axis in hepatocytes both in vitro and in vivo. Antioxidant treatment in primary hepatocyte or CYP2E1-/- mice fed with alcohol impaired those effects. Reducing SIRT7 activity completely abolished alcohol-mediated promotion of liver cancer metastasis in vivo. Taken together, our data reveal that SIRT7 is a pivotal regulator of alcohol-mediated HCC metastasis.

The influence of zinc supplementation on metabolic status in gestational diabetes: a meta-analysis of randomized controlled studies.

INTRODUCTION: Zinc supplementation has emerged as an important approach to improve metabolic status in gestational diabetes. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of zinc supplementation to improve metabolic status for gestational diabetes. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of zinc supplementation (or its combination) versus placebo on metabolic status of gestational diabetes are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model. RESULTS: Five RCTs involving 263 patients are included in the meta-analysis. Compared with control intervention for gestational diabetes, zinc supplementation is associated with significantly reduced FPG (std. MD = -0.52; 95% CI = -0.82 to -0.21; p = .0008), insulin (std. MD = -0.68; 95% CI = -0.98 to -0.37; p < .0001), HOMA-IR (std. MD = -0.77; 95% CI = -1.08 to -0.45; p < .00001), and increased QUICKI (std. MD = 0.58; 95% CI = 0.28-0.89; p = .0002) as well as zinc change (std. MD = 0.90; 95% CI = 0.58-1.21; p < .00001), but has no remarkable influence on LDL-cholesterol (std. MD = -0.13; 95% CI = -0.43-0.17; p = .40), and total cholesterol (std. MD = -0.28; 95% CI = -0.63-0.07; p = .11). CONCLUSIONS: Zinc supplementation is effective to decrease FPG, insulin, HOMA-IR and improve QUICKI in gestational diabetes, but has no significant impact on LDL-cholesterol and total cholesterol.

The efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia: a meta-analysis of randomized controlled studies.

INTRODUCTION: The efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia remains controversial. We conduct a systematic review and meta-analysis to explore the influence of intravenous fluid supplementation on treatment efficacy of neonatal hyperbilirubinemia. METHODS: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia. This meta-analysis is performed using the random-effect model. RESULTS: Six RCTs are included in the meta-analysis. Overall, compared with control group for neonatal hyperbilirubinemia, intravenous fluid supplementation is associated with decreased TSB at 8 h (std. MD = -0.82; 95% CI = -1.46 to -0.17; p = .01), 12 h (std. MD = -0.46; 95% CI = -0.81 to -0.10; p = .01), 24 h (std. MD = -0.47; 95% CI = -0.78 to -0.16; p = .003) and 36 h (std. MD = -0.37; 95% CI = -0.73 to -0.02; p = .04), as well as reduced incidence of exchange transfusion (RR = 0.29; 95% CI = 0.14-0.59; p = .0006), but has no significant impact on duration of phototherapy (std. MD = -0.34; 95% CI = -0.88-0.21; p = .22). CONCLUSIONS: Intravenous fluid supplementation can provide additional benefits for the treatment of neonatal hyperbilirubinemia.

Hepatoprotection by Ginsenoside Rg1 in alcoholic liver disease.

Alcoholic hepatitis (AH) has caused serious mortality to the world's population. Despite tremendous efforts to reduce disease burden, effective treatments for this disease are still lacking. Ginsenoside Rg1 (G-Rg1) has been reported to be hepatoprotective in several liver injury models. However, therapeutic potential of this drug in AH has not been tested. In this study, using a chronic ethanol-feeding model, we found that ethanol-fed mice presented clinical indicators of liver injury, such as elevated serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (Tbil), as well as development of hepatic steatosis. Upon treatment with G-Rg1, animals showed marked decreases in serum biochemical parameters, as well as improvement in liver histology. Mechanistically, G-Rg1 blocked the induction of cytochrome P4502E1 (CYP2E1), and prevented the generation of reactive oxygen species (ROS), mitochondria damage, as well as hepatocellular apoptosis. As a result, NLRP3 inflammasome activation was inhibited, which subsequently suppressed the production of active caspase-1 and inflammatory cytokines. Our data has demonstrated a hepatoprotective role for G-Rg1 in AH, and identified potential drugable pathways to improve disease outcomes. These findings may have significant implications for developing novel therapies for inflammatory liver diseases.

Systematic Influence of Circulating Bilirubin Levels on Osteoporosis.

Observational studies report some association between circulating bilirubin levels and osteoporosis, but it is unknown if this association is causal or confounded. In this two-sample Mendelian randomization (MR) study, we included a large genome-wide association study (GWAS) associated with total bilirubin levels among 317,639 people, a large meta-analysis to identify genetic variants associated with bone mineral density (BMD) estimated by heel quantitative ultrasound (eBMD) among 426,824 individuals and fracture among 1.2 million individuals. The results revealed that circulating bilirubin levels had no causal influence on eBMD (beta-estimate: 0.004, 95% confidence interval [CI]: -0.019 to 0.028, SE:0.012, P-value=0.705) or the risk of fracture (beta-estimate: -0.009, 95% CI: -0.035 to 0.017, SE:0.013, P-value=0.488), which were both confirmed by multiple sensitivity analyses. Our results confirm that circulating bilirubin levels have no causal role in eBMD or the incidence of fracture, indicating that circulating bilirubin levels is unlikely to be a causal risk factor for osteoporosis or fracture.