Utilizing bioinformatics for integrated analysis of multiple genes in the diagnosis and pathogenesis of metastatic pheochromocytoma and paraganglioma

Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.

Application of artificial intelligence in the prediction of immunotherapy efficacy in hepatocellular carcinoma:Current status and prospects

Artificial Intelligence(AI)has increased as a potent tool in medicine,with promising oncology applications.The emergence of immunotherapy has transformed the treatment terrain for hepatocellular carcinoma(HCC),offering new hope to patients with this challenging malignancy.This article examines the role and future of AI in forecasting the effectiveness of immunotherapy in HCC.We highlight the potential of AI to revolutionize the prediction of therapy response,thus improving patient selection and clinical outcomes.The article further outlines the challenges and future research directions in this emerging field.

Clinical Assessment of the Use of Propinox Hydrochloride and Scopolamine Hydrochloride in the Treatment of Abdominal Colic: A Retrospective, Comparative Study

Objectives: The purpose of this study was to evaluate and compare the use of propinox hydrochloride and scopolamine hydrochloride in patients presenting abdominal colic (abdominal pain), in terms of treatment efficacy and tolerability. Material & Methods: This was an analytical, retrospective, comparative study based on hospital records of outpatients treated at Serviço de Clínica Médica do Hospital das Clínicas Costantino Otaviano (HCTCO) and at Santa Casa de Misericórdia do Rio de Janeiro, from 1988-1998. Subjects were divided into two groups: patients from Group 1 were treated with propinox hydrochloride, while patients from Group 2 were treated with scopolamine hydrochloride. Statistical analysis was performed using GraphPad Prism version 5.0. For comparison of categorical variables, we used the chi-squared or Fisher’s test, while continuous variables were analyzed using ANOVA or the Student’s T test. Results: A total of 1042 subjects were included, of which 525 were allocated to Group 1 and 517 to Group 2. Mean treatment duration was 9.166 days (±4.208) in Group 1 and 8.795 days (±5.052) in Group 2, with no statistically significant difference in treatment duration between the two groups (p = 0.198). All subjects in Group 1 were treated with propinox 10 mg (2 coated tablets, three times per day) while all subjects in Group 2 were treated with scopolamine hydrochloride 10 mg (2 coated tablets, three times per day). There were no statistically significant between-group differences in weight, BMI, heart rate, and respiratory rate at pre- and post-treatment;with the exception of higher post-treatment systolic blood pressure in Group 1, blood pressure measures also remained homogenous. Adverse events were reported among both treatment groups with no significant between-group difference in incidence (p = 0566). At pretreatment, pain intensity was more severe in Group 1 (p = 0.0257), while at post-treatment, there was no statistically significant difference between the two treatment groups (p = 0.895). There was a statistically significant improvement in pain intensity within both treatment groups (χ2 = 631.4;df = 3;p < 0.0001 for Group 1 and χ2 = 554.3;df = 3;p < 0.0001 for Group 2). Conclusion: The results obtained in this study indicate a therapeutic equivalence between propinox hydrochloride and scopolamine hydrochloride. Both treatments demonstrated good efficacy and tolerability in the treatment of abdominal colic pain, in the population evaluated.

亚太地区慢性乙型肝炎治疗共识(2012最新版)

自2008年至今,有大量关于慢性HBV感染的自然史和治疗的最新数据不断涌现。其中包括慢性HBV感染的无症状感染者,以社区为基础的队列研究,HBV基因型的作用,非药物诱导的自然HBV变异型毒株,无创性肝纤维化评估方法的应用,HBsAg定量在临床中的应用,更有效的新治疗药物和新治疗方案等等。来自亚太地区的专家审查和评估了相关数据,并共同商讨了近年来报道的最有意义的发现,基于此,对2008年版的亚太地区慢性乙型肝炎治疗共识进行修订,同时对2008年版治疗指南定义的关键词组进行了修订。修订后的指南包括以下几方面内容:一般治疗,肝纤维化评价适应证,何时开始治疗或停药,初始抗病毒治疗药物的选择,如何监测治疗中和治疗后的患者。关于特殊人群的治疗建议中包括了对妊娠妇女,已发生耐药,合并其他病毒感染,肝功能失代偿,接受免疫抑制治疗、化疗,肝移植或肝细胞癌患者的具体治疗建议。

Influence of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis

AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mortality, pathological changes of mesenteric lymph nodes, expression levels of NF-kB, P-selectin, Bax, Bcl-2 and caspase-3 protein and changes in apoptotic indexes in lymph nodes were observed at 3, 6 and 12 h after operation. The blood levels of endotoxin, superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1) in blood were determined. RESULTS: SOD content, expression of Bax protein and apoptotic index were significantly higher in the treated group than in the model group at different time points (P < 0.05 or P < 0.01). Other blood-detecting indexes and histopathological scores of mesenteric lymphnodes were lower in the treated than in the model group (P < 0.05, P < 0.01 or P < 0.01). NF-kB protein expression was negative in all groups. Comparing P-selectin and caspase-3 expression levels among all three groups, there was no marked difference between the model and treated group. CONCLUSION: Dexamethasone can protect mesen-teric lymph nodes. The mechanism may be by reducing the content of inflammatory mediators in the blood and inducing lymphocyte apoptosis.

Sarcopenia and non-alcoholic fatty liver disease:Is there a relationship?A systematic review

AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) in adult patients with sarcopenia.METHODS Randomized clinical trials,cross-sectional or cohort studies including adult patients(over 18 years) with sarcopenia were selected.The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients.In the screening process,44 fulltext articles were included in the review and 41 studies were excluded.RESULTS Three cross-sectional studies were included.The authors attempted to perform a systematic review,but due to the differences between the studies,a qualitative synthesis was provided.The diagnosis of NAFLD was made by non-invasive methods(image methods or any surrogate markers) in all three evaluated studies.All the studies suggested that there was an independent association between sarcopenia and NAFLD.CONCLUSION Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.

Cytomegalovirus enteritis mimicking Crohn's disease in a lupus nephritis patient:A case report

Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.

Technologies for repairing peripheral nerve injury Progress in domestic and foreign investigations

OBJECTIVE： Studies on the repair of peripheral nerve injury have achieved great progresses in recent years.Clinical nerve repair prefers microsurgery, while fundamental researches focus on tissue engineering and gene therapy. Recently, microencapsulation technique rises up as a new treatment therapy. This article mainly summarized the repairing techniques referred above, in order to make the basis for further research.DATA SOURCES： A computer-based online search of Pubmed database was undertaken to identify articles about injury and repair of peripheral nerve published in English between January 1997 and May 2007 using the key words of ＂peripheral nerve, injury, repair＂. At the same time, Chinese relative articles were searched in China National Knowledge Infrastructure （CNKI） using the same key words in Chinese.STUDY SELECTION： The data were primarily checked, and the references after each literature were looked up, and the articles focused on the injury and repair of peripheral nerve were selected. Those published in kola-magazine in recent 5 years were in priority for the articles with similar contents. Repetitive studies or Meta analysis were excluded.DATA EXTRACTION： Totally 144 articles were collected, and 30 literatures were selected as most relative reference literatures, and the other 114 articles were excluded due to old or repeated researches. Among the 30 selected articles, 6 focused on the surgical treatment for peripheral nerve injury, 10 on tissue engineering and Schwann cell, 3 on microencapsulation technology, 5 on gene therapy, 2 on immunosuppresant and 4 on neurotrophic factors.DATA SYNTHESIS： The technologies for repairing peripheral nerve injury are developing with time, also have been successfully combined with tissue engineering and gene therapy techniques which are advanced nowadays. As the researches go further, immunodepression factors have attracted more and more attentions,microencapsulation technology and gene therapy repair also go into the view of researchers. The main aim of technique referred above is to recover the physiological structure and function as much as possible. However,the clinical applications have a long way to go for the series of restrictions from the problems of rejection, etc.The clinical repair of peripheral nerve injury still mainly depends on microscopic neurorrhaphy and nerve grafting at present, whereas the satisfying repair techniques are waiting for more professional researches.CONCLUSION： Restricted by techniques, microsurgery repair is still the first choice for peripheral nerve injury. Microencapsulation technique and gene therapy offer a new direction for peripheral nerve repair;tissue engineering gains great success in animal experiment together have wide prospect on clinical application, many problems wait for solution though, they will be point of following researches.

MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes

BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable screening biomarker of liver cirrhosis(LC)and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease.MicroRNA(miRNA)is considered a key player in HCC and T2DM,and it might be a hidden culprit in diabetes-associated HCC,making it a promising reliable prognostic tool.AIM To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.METHODS Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing;then,RT-qPCR was used to validate significantly altered miRNAs between the two groups.Candidate miRNAs were tested in serum samples of 200 T2DM patients,270 LC patients,200 HCC patients,and 225 healthy control subjects.Additionally,receiver operating characteristic(ROC)analysis,with area under the curve(AUC),was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients(LC+T2DM).RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LCpositive T2DM patients.Two miRNAs(miR-34a,miR-221)were significantly upregulated and five miRNAs(miR-16,miR-23-3p,miR-122-5p,miR-198,miR-199a-3p)were significantly down-regulated in HCC compared to LC patients.Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients,as it could identify HCC with high diagnostic accuracy in diabetic LC patients(AUC=0.993)and in diabetic nonmalignant patients(AUC=0.961).CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients.The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.

Meta-analysis of serum copper and heart failure

OBJECTIVE The purpose of this study is to clarify the association between Cu levels and heart failure(HF)using a meta-analysis approach.METHODS We searched articles in the Pub Med,EMbase,CNKI,Wanfang,VIP and CBM Database published as of August 2016.The case control study on the relationship between serum copper levels and HF were collected and read and extracted by two independent researchers.A Meta analysis was conducted using Stata 12.0 software.RESULTS A total of twenty-one eligible articles,including 893 HF and 654 control subjects,were enrolled.The Meta analysis showed that serum copper levels in HF were higher than control group[SMD=0.881,95%CI:(0.487,1.264),Z=4.5,P<0.001].The sensitivity analysis indicated that the results were reliable.Begg′s tests did not find the existence of publication bias.CONCLUSION This metaanalysis indicates that there is a significant association between high Cu serum level and HF.

The Effects of Prey Items Diversity and Digestible Materials in Stomach on Digestive Tract Length in Hylarana guentheri

Difference in environmental condition shapes variation in digestive tract length in evolutionary process.In particular,environmental difference results in variation in food resource among different habitats,and thereby affecting energy intake and energy allocation.The digestive theory predicts that animals foraging high indigestible materials of stomach contents can promote the increased gut dimensions.Here,we studied variation in digestive tract and gut length across six Hylarana guentheri populations at different altitudes and latitudes to test the prediction of the digestive theory.We found that altitude and latitude did not affect variation in relative size of digestive tract and gut among populations.We also found that relative size of digestive tract and gut did not be correlated with diversity of prey items,but negatively correlated with proportion of digestible materials.Our findings suggest that individuals foraging less digestible materials display relatively longer digestive tract than individuals foraging more digestible materials.

Non-cytotoxic nanoparticles re-educating macrophages achieving both innate and adaptive immune responses for tumor therapy

Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metastasis.Here,we develop a nanomedicine that can re-educate M2 polarized macrophages to restore their anti-tumor activities.The nanomedicine has a core-shell structure to co-load IPI549,a PI3Kγinhibitor,and CpG,a Toll-like receptor 9 agonist.Specifically,the hydrophobic IPI549 is self-assembled into a pure drug nano-core,while MOF shell layer is coated for CpG encapsulation,achieving extra-high total drugs loading of 44%.Such nanosystem could facilitate intracellular delivery of the payloads but without any cytotoxicity,displaying excellent biocompatibility.After entering macrophages,the released IPI549 and CpG exert a synergistic effect to switch macrophages from M2 to M1 phenotype,which enables anti-tumor activities via directly engulfing tumor cells or excreting tumor killing cytokines.Moreover,tumor antigens released from the dying tumor cells could be effectively presented by the re-educated macrophages owing to the up-regulation of various antigen presenting mediators,resulting in infiltration and activation of cytotoxic T lymphocytes.As a result,the nanosystem triggers a robust antitumor immune response in combination with PD-L1 antibody to inhibit tumor growth and metastasis.This work provides a non-cytotoxic nanomedicine to modulate tumor immune microenvironment by reprograming macrophages.

Exosomes Derived from Hydroquinone-transformed Human Bronchial Epithelial Cells Inhibited Recipient Cell Apoptosis by transferring miR-221

Objective Although benzene is a confirmed environmental carcinogen,the mechanism of its carcinogenicity remains largely unclear.The suggested oncogene,miR-221,is elevated and plays important roles in various tumors,but its role in benzene-induced carcinogenesis remains unknown.Methods In the present study,we constructed hydroquinone(HQ,a representative metabolite of benzene with biological activity)-transformed malignant cell line(16 HBE-t)and analyzed the level of miR-221 in it with qRT-PCR.Exosomes from 16 HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation,characterized by transmission electron microscopy and laser scanning confocal microscope,and then transfected into 16 HBE cells.The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.Results The amount of miR-221 in 16 HBE-t was significantly increased compared with controls.When recipient cells ingested exosomes derived from 16 HBE-t,miR-221 was increased,and apoptosis induced by HQ was inhibited.Blocking miR-221 in 16 HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.Conclusion Exosomal miR-221 secreted by 16 HBE-t inhibits apoptosis induced by HQ in normal recipient cells.

Changes of the F-wave in the acute phase of permanent spinal cord ischaemic injury predict spinal cord function in animal models of rabbits

Objective:to explore the changes of the F-wave in the posterior tibial nerve of rabbits after different levels of lumbar spinal cord ischaemic injury and its correlation with motor function and the extent of lumbar spinal cord pathological damage.Methods:thirty New Zealand rabbits were randomly divided into 6 groups.The control group(n=5)was used to exclude the influence of anaesthesia and surgery on the F-wave.Different levels of lumbar arteries were ligated in the five experimental groups(n=5).The F-wave was recorded to observe the changes in the acute phase of spinal cord ischaemia.The correlation between the changes of the F-wave in the acute reversible phase and the motor function of the spinal cord was analysed.Motor functions were assessed after surgery and 2 d after vascular ligation.The specimens were taken 2 d after ligation for histopathologic observation.Results:the results for the control group indicated that anaesthesia and surgery did not affect the F-wave results.There was no statistically significant difference in the F-wave amplitudes and latency before and after ligation in the 1 and 2 level ligation groups.The F-wave changed immediately after ligation in the 3,4 and 5 ligation groups.The latency of the F-wave gradually extended,the amplitude of the F-wave gradually reduced.The amplitude variations of the F-wave were positively correlated with the motor function 2 d after ligation,there was a statistically significant difference.With the increase in the number of vascular ligation,the degree of destruction of the motor neurons in the anterior horn of the spinal cord in the pathological specimens increased.Conclusion:the F-waves in the posterior tibial nerve of rabbits were found to be sensitive to the lumbar spinal cord ischaemic injury and specific to predict motor function.

Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants

Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.

Antigenic characterization of SARS-CoV-2 Omicron subvariants XBB.1.5,BQ.1,BQ.1.1,BF.7 and BA.2.75.2

Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurprisingly,these new subvariants are quickly gaining prevalence worldwide.In fact,some of them have outcompeted BA.5 in the USA according to CDC’s national genomic surveillance data in which,as of 6th February 2023,XBB.1.5,BQ.1.1,BQ.1,XBB and BF.7 have achieved a dominance of 66.4%,19.9%,7.3%,2.3%and 0.5%in the USA,as compared to 0.5%for BA.5.In this report,using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors,we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5 in comparison to other Omicron sub-lineages.XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts.By comparing the differential neutralization profiles,we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees

Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.

Hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts

In heart disease, transforming growth factor-β1 （TGF-β1） converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide （HzS） sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 （10 ng mL-1） for 24 h with or without sodium hydrosul- fide （NariS, 100 μmol L-1, 30 min pretreatment） treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.

Ursodeoxycholic acid as adjuvant treatment to phototherapy for neonatal hyperbilirubinemia:a systematic review and meta‑analysis

Background Neonatal hyperbilirubinemia is observed in most newborns,and 5–15%of neonates require phototherapy.Phototherapy is efective but often prolongs hospitalization and has both short-term and potential long-term harms.The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid(UDCA)combined with phototherapy in neonatal hyperbilirubinemia.Methods A literature search was conducted on September 1,2021;590 studies were screened,and 17 full texts were assessed by two authors.We included randomized controlled trials with or without placebo intervention.Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration.We calculated mean diferences with 95%confdence intervals(CI).Results Six studies with 880 neonates were included.Of these studies,only two used a placebo-controlled double-blinded design.The overall risk of bias was high in one and moderate in four of the included studies.The mean decrease in the total bilirubin level during the frst 24 hours was 2.06 mg/dL(95%CI 0.82–3.30;six studies)greater in the UDCA treatment group.The phototherapy duration was 19.7 hours(95%CI 10.4–29.1;fve studies)shorter in the UDCA treatment group.Conclusions We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment.Further studies are needed to confrm the efcacy,acute and long-term outcomes,and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.