Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia:a randomized controlled study

BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin treatment.Geraniol acetate(Gefarnate)is an anti-ulcer drug.It was reported that geraniol might participate in lipid metabolism through a variety of pathways.The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia.METHODS In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,respectively.At baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were tested.RESULTS After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant difference.CONCLUSIONS The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia.This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis:A network meta-analysis

BACKGROUND Diabetic gastroparesis(DGP)is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them.The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine(TCM)decoctions that have been shown to be effective in treating the disease.There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice.AIM To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference.METHODS PubMed,EMBASE,Cochrane Library,Web of Science,China National Knowledge Infrastructure,The China Biology Medicine DVD,Wanfang,and CQVIP were searched from inception to September 17,2022,to collect randomized controlled trials(RCTs)about TCM decoctions for DGP.Clinical effects and symptom scores were the primary outcomes.Additionally,we assessed motilin(MOT),somatostatin(SS),gastrin(GAS),gastric emptying rate,gastric emptying time,and adverse drug events as secondary outcomes.RESULTS A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included.The results of network meta-analysis(NMA)and surface under the cumulative ranking curve showed that with western medicine(WM)as a common control,the Banxia Xiexin Decoction(BXXD)+WM was most effective in clinical effects and enhancing early satiety scores;the Simo decoction(SMD)+WM was most effective in improving nausea and vomiting scores and anorexia scores,bloating scores;the Chaishao Liujunzi Decoction(CSLJD)was most effective in MOT,the Zhishi Xiaopi Decoction(ZSXPD)was most effective in SS and upgrading emptying rate;the Jianpi Xiaozhi Decoction was most effective in GAS;the CSLJD+WM was most effective in improving gastric emptying time.CONCLUSION These NMA results suggest that the BXXD+WM and SMD+WM may be one of the potential optimal treatments.Due to various limitations,further large-sample,double-blind,multi-center randomized RCTs are needed.

Traditional Chinese medicine in the treatment of high incidence diseases in cold areas: the thrombotic diseases

Thrombotic diseases are the leading causes of death worldwide,especially in cold climates.Traditional Chinese medicine(TCM)-based therapies have gained increasing popularity worldwide,but also raised some concerns about its efficacy,safety profile and exact mechanisms.TCM has been traditionally used in the management of thrombosis and convincingly proven effective in modifying thrombosis progression,particularly the platelet function,coagulation system and fibrinolytic system.This review article focuses on TCM regulation of thrombosis with brief discussion on the fundamental aspects and relevant background information for better understanding of the subject.In addition to its antithrombotic effects,we will dive insight into the cellular and molecular mechanisms of TCM as pharmacological regulators of platelet aggregation,coagulation,and fibrinolysis.With increasing awareness and understanding of the benefits and potentials of TCM,TCM products will in no doubt gain its broader applications in the treatment of thrombosis and associated disorders,which in turn will deepen our understanding of its pharmacological and molecular mechanisms.Finally,current review provides a perspective view on the future directions to TCM research on thrombosis.

Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring

Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in offspring.The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring.Adult female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before pregnancy.They we re continued on diets during pregnancy and la ctation.Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage.Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the plasma.After ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet.In brain tissue,there was no difference in ischemic damage volume.When protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet.Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke outcomes.This study emphasizes the importance of maternal diet and the impact it can have on offspring health.

Unveiling metabolic flux changes during acute cold exposure

Controlling energy expenditure during acute cold exposure is a fundamental aspect of metabolic dynamics in organisms.However,prior studies on cold-induced thermogenesis faced limitations,primarily focusing on brown adipose tissue(BAT)and lacking precise in vivo flux measurements.This editorial aims to highlight the recent research by Bornstein et al.providing a comprehensive and quantitative insight into the intricate alterations in metabolic flux that drive this phenomenon[1].

Association between SLC2A9 Genetic Variants and Risk of Hyperuricemia in a Uygur Population

This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population,the Uygurs in Xinjiang,China.According to our inclusion and exclusion criteria,Uygur adults from Xinjiang constituted the study population.There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls.Five single nucleotide polymorphisms within SLC2A9(rs938557,rs7679916,rs7349721,rsl3101785,and rs 13137343)were selected with the HapMap dataset and TaqMan assays.We found that,in normouricemia group,rs938557 was significantly correlated with uric acid(β=11.39±3.74,P=0.0024)adjusting for age,gender and BMI;rs7679916 and rsl3137343 were marginally associated with uric acid concentration(β=5.77±3.O9,P=0.0626;p=-5.99±3.08,P=0.0520).In the hyperuricemia group,no SNP was found to possibly influence uric acid concentration.None of these SNPs showed significant association with hyperuricemia after controlling for age,gender and BMI.There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples.In turn,some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.

Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome

Objective:Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events.Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome plays an important role in the development of hypertension.Tranilast(TR),an inhibitor of NLRP3,provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent.This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions.Methods and results:Sprague Dawley(SD)rats were exposed to moderate cold temperature(4±1℃),and then were randomized to receive TR or vehicle for 3 weeks,while the control group was raised under rat room temperature(RT,23±1℃).We found that cold exposure substantially increased blood pressure,NLRP3 inflammasome level,and fibrosis in aorta,which were reversed by TR.Conclusion:TR has an anti-hypertensive property in cold environment,and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis.These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

iTRAQ-based analysis of 17β-estradiol induced proteome in Chinese tongue sole Cynoglossus semilaevis

The phenomenon of sex dimorphism prevails among many fi sh species. It has attracted the general research interest due to its close relationship to fi sh growth and thus aquaculture productivity. In Chinese tongue sole ( Cynoglossus semilaevis ), 17β-estradiol (E2) can be used reportedly to induce the feminization of fi sh, although the detailed regulatory network remained elusive. We treated the tongue sole fry before sex diff erentiation with E2 (10 and 30 μg/L) to identify potential targets of E2 in Chinese tongue sole. The E2 treatment indeed induced genetic male fi sh sex-reversal to phenotypic female. Using an iTRAQ-based comparative proteomic analysis, 409 proteins that diff erentially expressed after E2 induction were identifi ed, including 259 up-regulated and 150 down-regulated proteins. Furthermore, 19 diff erentially expressed proteins identifi ed in the comparative proteomic analysis were selected to assess their transcription and eight of them exhibited the same tendency. Functions of the eight proteins included mainly nucleotide and protein binding. Interestingly, a far upstream element-binding protein 3-like isoform exhibited the signifi cant upregulation both at transcription and translation levels after E2 treatment. This work identifi ed a set of candidate proteins for E2 response and deepened our understanding of E2 regulatory mechanism.

Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1^(-/-))and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAPinduced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1^(-/-)mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p4503a11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Double-blinded,randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia

Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.

Exosome-based small RNA delivery:Progress and prospects

RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.

Effects of Shengmai Yin(生脉饮)on pulmonary and cardiac function in coronavirus disease 2019 convalescent patients with cardiopulmonary symptoms:a randomized,double blind,multicenter control trial

OBJECTIVE:To evaluate the efficacy and safety of Shengmai Yin(生脉饮,SMY)on visual analogue scale(VAS)for cardiopulmonary symptoms in coronavirus disease 2019(COVID-19)convalescent patients.METHODS:In this randomized,double blind and multicenter controlled trial,a total of 200 COVID-19 convalescent patients who with cardiopulmonary symptoms were enrolled from three medical centers in Hubei,China.These patients were randomized divided into trial group and the control group,100 patients in each one,SMY and its placebo were applied to respectively,for two weeks.VAS of clinical symptoms included shortness of breath,hidrosis,chest distress,palpitation,and dry cough was performed at 0,1,2 weeks.Decrease in VAS of 30%or more was defined as effective,and a reduction in VAS of 0 was defined as curative.RESULTS:A total of 192 completed the study.The VAS of TCM symptoms showed there was no difference in baseline between the two groups.The VAS in both groups was down-regulated,and there was no significant difference in VAS and cure rates at the first and second week between the two groups.There was no significant difference in breath,hidrosis,palpitation,and dry cough between the two groups but SMY treatment for two weeks has remarkable therapeutic effects in chest distress than placebo.CONCLUSIONS:SMY could effectively ameliorate the symptoms of chest distress,and improve the quality of life of the COVID-19 convalescent patients.

CircRNA DICAR as a novel endogenous regulator for diabetic cardiomyopathy and diabetic pyroptosis of cardiomyocytes

In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM.

Key regulators of intestinal stem cells:diet,microbiota,and microbial metabolites

Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic reactions in the body.Evidence suggests that intestinal stem cells(ISCs),which are phenotypic precursors of various intestinal epithelial cells,play a significant role in the regulation of intestinal barrier function and homeostasis.The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs.As a result,the effects exerted by dietary factors,intestinal microbiomes,and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed.This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota,related metabolites,and ISCs,with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body.Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19

Traditional Chinese medicine(TCM)has played an important role in the prevention and treatment of Coronavirus disease 2019(COVID-19)epidemic in China.The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment.According to a series of evidence-based studies,TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups.For patients with mild and moderate forms of COVID-19,TCM can relieve the related signs and symptoms,shorten the period of nucleic-acid negative conversion,and reduce conversion rate to the severe form of the disease.For COVID-19 patients with severe and critical illnesses,TCM can improve inflammatory indicators and blood oxygen saturation,shorten the hospital stay,and reduce the mortality rate.During recovery,TCM can improve patients’symptoms,promote organ function recovery,boost the quality of patients’life,and reduce the nucleic-acid repositive conversion rate.A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects,immune regulation,and protection of organ function via a multicomponent,multitarget,and multipathway approach.

Ticagrelor versus clopidogrel in East Asian patients with acute coronary syndrome:A meta-analysis

Objective:There exist conflicting data on the efficacy and safety of ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome(ACS).We performed a meta-analysis to evaluate whether ticagrelor or clopidogrel produces better outcomes for East Asian patients with ACS.Methods:We searched for randomized controlled trials reporting associations between ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome in PubMed,EMBASE,web of science and Cochrane central register of controlled trials.Results:Ten studies involving 3715 participants were qualified for our analysis.The major adverse cardiovascular events(MACE)were significantly decreased in patients with ticagrelor treatment compared to those with clopidogrel(risk ratio[RR]:0.61;95%confidence interval[CI]:0.38-0.98;P=0.042).There was no significant difference in all-cause death(RR:0.89;95%CI:0.61-1.29;P=0.540),cardiovascular death(RR:0.86;95%CI:0.58-1.27;P=0.451),myocardial infarction(RR:0.91;95%CI:0.65-1.27;P=0.575)and stroke(RR:0.77;95%CI:0.44-1.36;P=0.372)between ticagrelor and clopidogrel.Ticagrelor was associated with a significantly higher risk of bleeding compared to clopidogrel(RR:1.71;95%CI:1.37-2.13;P=0.000).Conclusion:The present meta-analysis demonstrates that ticagrelor reduced the incidence of MACE in ACS patients from East Asia compared with clopidogrel.However,it increased the risk of bleeding.

Effectiveness of Xiaoyao capsule(逍遥丸)on sleep disorders and mood disturbance in patients in recovery from coronavirus disease 2019:a randomized controlled trial

OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19.Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization.The patients received either Xiaoyao capsule(experimental group)or a placebo Xiaoyao capsule(control group)for 2 weeks.The improvements in the Traditional Chinese Medicine(TCM)syndrome scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep were compared between the two groups.RESULTS:The TCM syndrome pattern scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment(P>0.05).CONCLUSIONS:Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.

评价散寒化湿颗粒与奈玛特韦-利托那韦对照治疗轻型/中型新型冠状病毒感染有效性和安全性的随机、开放、多中心临床研究

Sanhan Huashi granules(SHG)demonstrated therapeutic effects against coronavirus disease 2019(COVID-19)in observational studies.In order to compare the effectiveness and safety of SHG and nirmatrelvir–ritonavir in treating adults with mild-to-moderate COVID-19,we conducted a randomized,activecontrolled,open-label,multi-center trial conducted between February and July in 2023.The patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir–ritonavir group.A total of 400participants were randomized,among which 200 participants ultimately received SHG and 198 received nirmatrelvir–ritonavir.The primary outcome was time to sustained clinical recovery through day 28.SHG significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir–ritonavir(6.0(95%CI,5.0 to 6.0)vs.8.0(95%CI,6.0 to 9.0)d;P=0.001),particularly for individual symptoms including fever,sore throat,cough and fatigue.No participants in either group died and incidence of severe COVID-19 showed no difference between two groups.Participants who received nirmatrelvir–ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG(46.4%(95%CI,39.1 to 53.7)vs.65.6%(95%CI,58.3 to 72.4);P<0.001).Most adverse events were mild in both groups.In summary,SHG was superior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19,despite a lower virus clearance rate observed after 5 d of treatment(Chinese Clinical Trial Registry Identifier:Chi CTR2300067872).

Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3

Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction(TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II(AngII). Emodin upregulated expression of metastasis associated protein 3(MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis;in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis via upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis.