Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats

AIM: To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved.

New formula for predicting standard liver volume in Chinese adults

AIM To obtain a reference range of morphological indices and establish a formula to accurately predict standard liver volume(SLV) in Chinese adults.METHODS Computed tomography(CT)-estimated total liver volume(CTLV) was determined in 369 Chinese adults. Age,sex,body weight,body height,body mass index,and body surface area(BSA) were recorded using CT. Total splenic volume,portal venous diameter(PVD),splenic venous diameter(SVD),and portal venous cross-sectional area(PVCSA) were also measured by CT. Stepwise multiple linear regression analysis was performed to evaluate the impact of each parameter on CTLV and to develop a new SLV formula. The accuracy of the new formula was compared with the existing formulas in a validation group.RESULTS The average CTLV was 1205.41 ± 257.53 cm3(range,593.80-2250.10 cm3). The average of PVD,SVD and PVCSA was 9.34 ± 1.51 mm,7.40 ± 1.31 mm and 173.22 ± 48.11 mm2,respectively. The CT-estimated splenic volume of healthy adults varied markedly(range,46.60-2892.30 cm3). Sex,age,body height,body weight,body mass index,and BSA were significantly correlated with CTLV. BSA showed the strongest correlation(r = 0.546,P < 0.001),and was used to establish a new model for calculating SLV: SLV(cm3) = 758.259 × BSA(m2)-124.272(R2 = 0.299,P < 0.001). This formula also predicted CTLV more accurately than the existing formulas,but overestimated CTLV in elderly subjects > 70 years of age,and underestimated liver volume when CTLV was > 1800 cm3.CONCLUSION Our new BSA-based formula is more accurate than other formulas in estimating SLV in Chinese adults.

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression.However,the precise molecular mechanisms governing the nuclear import of YAP are not fully understood.In this study,we have uncovered a crucial role of SOX9 in the activation of YAP.SOX9 promotes the nuclear translocation of YAP by direct interaction.Importantly,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP.Additionally,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by PRMT1.YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers.Furthermore,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth.This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients:a randomized,double-blind,placebo-controlled phase 2 trial

Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.

Effects of Low-dose and High-dose Rifaximin in the Treatment of Covert Hepatic Encephalopathy

Background and Aims:Rifaximin is effective in prevent-ing and treating hepatic encephalopathy(HE).This study aimed to investigate the efficacy and safety of different dosages of rifaximin in the treatment of cirrhotic patients with covert HE(CHE).Methods:In this single-center,ran-domized,controlled,open-label study,CHE was diagnosed using a combination of the psychometric HE score and the EncephalApp Stroop test.Cirrhotic patients with CHE were recruited and randomly assigned to low-dose rifaximin 800 mg/day,high-dose rifaximin(1,200 mg/day),and control groups,and were treated for 8 weeks.The sickness impact profile(SIP)scale was used to evaluate the health-relat-ed quality of life(HRQOL)of patients.Forty patients were included in the study,12 were assigned to the low-dose group,14 to the high-dose group,and 14 patients to the control group.Results:The percentage of patients with CHE reversal was significantly higher in both the low-dose(41.67%,5/12)and high-dose(57.14%,8/14)groups than in the control group(7.14%,1/14)at 8 weeks(p=0.037 and p=0.005,respectively).In addition,both doses of ri-faximin resulted in significant improvement of the total SIP score compared with the control group.There were no sig-nificant differences in the CHE reversal rate,total SIP score improvement,and incidence of adverse event between the low-dose and high-dose groups(p>0.05).Conclusions:Low-dose rifaximin reverses CHE and improves HRQOL in cirrhotic patients with comparable effects and safety to high-dose rifaximin.

The presence of NAFLD in nonobese subjects increased the risk of metabolic abnormalities than obese subjects without NAFLD:a population-based cross-sectional study

Background:With lifestyle modification and over-nutrition,the prevalence of nonalcoholic fatty liver disease(NAFLD)has been increasing annually.Here we aimed to assess the updated prevalence of NAFLD,and to evaluate the association of NAFLD with metabolic abnormalities according to gender,body mass index and age.Methods:A population-based cross-sectional study was conducted in Shanghai from December 2016 to July 2017.With a three-stage stratified sampling strategy,3,717 eligible participants were enrolled for the analysis.Results:In total,1,217 subjects(32.7%)had NAFLD.Among them,400(16.3%)of the nonobese and 817(65.0%)of the obese subjects had NAFLD.The prevalence of NAFLD was increased according to the quartiles of age and waist circumference(WC)in the nonobese subjects.Females with nonobese NAFLD had 1.6-,2.6-,2.0-,2.3-and 3.3-fold higher risks for metabolic syndrome,diabetes mellitus,hyperglycemia,hypertriglycerdemia(high TG)and low high-density lipoprotein cholesterol than obese subjects without NAFLD,respectively.Males had comparable metabolic profiles in both groups,except for a 2.0-fold higher risk of high TG in nonobese NAFLD subjects compared with obese subjects without NAFLD.More impressively,the homeostasis metabolic assessment insulin resistance index was comparable between the two groups.Conclusions:The increase of age and WC had significant impact on the risk of NAFLD in nonobese subjects.The presence of NAFLD in nonobese subjects increased the risk of metabolic diseases than obese subjects without NAFLD,especially in female.

The prevalence and associated factors of simple hepatic cysts in Shanghai:a population-based cross-sectional study

To the Editor:Simple hepatic cyst is a common reason for consultation with gastroenterologists and hepatologists.Although most patients have a benign course,some suffer from serious complications,such as intracystic infection,hemorrhage,and even rupture,or symptoms caused by severe oppression of the surrounding tissues and organs.Understanding the prevalence of,and characteristics of,and factors associated with simple hepatic cysts is helpful for better treatment of symptomatic patients.The reported prevalence of the disease varies widely,ranging from 2.5%to 18.0%,and most of them were based on hospital surveys.[1,2,3,4]As an asymptomatic disease in most cases,simple hepatic cysts are usually discovered incidentally on abdominal imaging.Therefore,surveys based on hospital populations cannot represent true prevalence.Furthermore,due to the absence of healthy controls,surveys with hospital populations have been unable to identify associated factors for simple hepatic cysts.[1,2,3,4].

Diagnosis and Treatment Guidelines for Mesenchymal Stem Cell Therapy for Coronavirus Disease 2019(Beijing,2021)

The coronavirus disease 2019(COVID-19)can be caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and has led to millions of deaths among more than 100 million infected people around the world according to the declaration from World Health Organization.Dysregulated immune response of both the innate and adaptive immune systems is subsistent on COVID-19 patients,of which the degree are associated with disease severity,lung damage and long term functional disability.Current treatment options have included antiretroviral drugs,anti-inflammatory factors,antibodies,immune checkpoint inhibitors,and convalescent plasma therapy.More recently,mesenchymal stem cell(MSC)therapy has been explored for the management and control of COVID-19,particularly with the aim of preventing or at least mitigating respiratory co-morbidities.Though the safety and efficacy of stem cell therapy have been validated in multiple phase I–III clinical trials,to date,no standardized stem cell preparation,administration dosage or interval,product QA/QC testing,storage,transportation,or disposal protocols have been established.The present paper proposes a systematic methodology that addresses all the foregoing process steps and evaluation criteria for the efficacious and safe administration of MSCs in the treatment of patients infected with COVID-19.