ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy （BQT） on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori （HP） positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT， followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT， followed by 4 weeks of oral probiotic placebo. ¹³C urea breath test was used to evaluate the clinical efficacy， gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention， and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups （P>0.05）. Before the intervention， there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention， patients in the probiotic group had significantly lower pain scores on acid reflux （1.10±0.30 vs 1.35±0.53， P<0.05） and stomach or abdominal hunger than in the placebo group （1.07±0.26 vs 1.30±0.52， P<0.05）. Through the before-and-after comparison of the probiotic group， the scores of abdominal pain （1.24±0.44 vs 1.58±0.71， P<0.05）， stomach or abdominal hunger （1.07±0.26 vs 1.27±0.45， P<0.05） and dry and hard stool （1.24±0.49 vs 1.48±0.75，P<0.05） were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy， but it does not improve the eradication rate of HP.

Ferroptosis is a newly discovered form of cell death that is influenced by iron levels and is triggered by cellular metabolism and excessive lipid peroxidation.Epigenetic regulation plays a crucial role in the development and progression of diseases,making it essential to understand these mechanisms in order to identify potential targets for drug development and clinical treatment.The intersection of ferroptosis and epigenetics has opened up new avenues for research in drug development,offering innovative strategies for combating diseases.Recent studies have shown that epigenetic modifications can impact pathways related to ferroptosis,potentially leading to organ dysfunction.Despite the increasing focus on this relationship,the role of epigenetic regulation in drug development remains largely unexplored.This article explores current research on the interplay between epigenetic regulation and ferroptosis,delving into their regulatory mechanisms and discussing the effects of existing epigenetic modification regula-tors on diseases.Additionally,we highlight ongoing research on epigenetic factors involved in targeting ferroptosis in cancer,providing new insights for the development of cancer treatments.

Sialidosis is a rare autosomal recessive genetic disorder, and has a series of clinical symptoms and signs caused by neuraminidase 1 ( NEU1) gene mutations. This article reviews the etiology, clinical features, diagnoses, treatments and prognoses of sialidosis in order to improve the understanding and diagnosis of this disease and reduce the misdiagnosis of this disease.

Objective:To assess the application value of China consensus on the protocol of early gastric cancer screening in Guangdong province.Methods:A new quantitative scoring system was used in Cantonese residents who underwent early gastric cancer screening from March 2018 to March 2019. According to the scores of initial screening, patients were divided into high-risk, medium-risk and low-risk groups. The detection rates of early gastric cancer, precancerous diseases and precancerous lesions under gastroscopy in each group were compared. Chi-square test was performed for statistical analysis.Results:A total of 545 individuals were selected for gastroscopy, in which 32 cases were classified into high-risk group, 184 into medium-risk group and 329 into low-risk group. The results of gastroscopy examination showed that high-risk group had the highest detection rate of early gastric cancer (12.5%), followed by medium-risk group (1.1%) and low-risk group (0) ( χ2=41.85, P<0.01); the detection rates of precancerous diseases exhibited a similar pattern: high-risk group (60.9%) > medium-risk group (52.4%) > low-risk group (34.3%) ( χ2=18.00, P<0.01). The detection rates of precancerous lesions were 17.9%, 8.8% and 8.8%, respectively, with no significant difference ( χ2=2.58, P=0.28). In terms of the positive rate of endoscopy, high-risk group (71.9%) showed the highest positive rate, followed by medium-risk group (57.1%) and low-risk group (40.1%) ( χ2=21.54, P<0.01). Conclusion:China consensus on the protocol of early gastric cancer screeing is of application value for the screening of early gastric cancer and precancerous lesions in the populations at risk of gastric cancer in Guangdong province.

Objective To evaluate the effect of strengthening nutrition intervention in gravidas with gestational diabetes mellitus (GDM) with WeChat on blood glucose control and pregnant outcomes.Methods A total of 410 gravidas,diagnosed with GDM and treated in the Department of Clinical Nutrition of Shanghai General Hospital from October 2015 to April 2016,were enrolled and randomly divided into two groups (n=205).The control group received traditional nutrition clinic education only,while the intervention group was given strengthened nutrition education through WeChat in addition to traditional education.Blood glucose level and insulin dosage were followed up after one,two and four weeks of intervention.Pregnant outcomes and patient satisfaction were investigated on 42 d after delivery.T test,Chi-square test and non-parametric test were used for statistical analysis.Results (1) Two weeks after the intervention,the average 1-hour postprandial blood glucose in the intervention group was lower than in the control group [(7.46± 1.01) vs (7.68± 1.06) mmol/L,t=2.243,P=0.025].After 4 weeks,both 1-and 2-hour postprandial blood glucose levels of the intervention group were lower than those of the control group [(7.03±0.65) vs (7.33±0.63) mmol/L,t=4.629,P＜0.05;(6.00±0.65) vs (6.21 ±0.62) mmol/L,t=3.153,P＜0.05] and more gravidas achieved euglycemia [79.9％ (151/189) vs 60.8％ (113/186),x2=16.483,P＜0.001].(2) Compared with the control group,the intervention group had a higher vaginal delivery rate [38.7％ (72/186) vs 50.5％ (95/188),x2=5.288,P=0.021] and a lower rate of postpartum complications [9.1％ (17/186) vs 2.1％ (4/188),x2=7.394,P=0.007].All of the gravidas in the intervention group were satisfied with the WeChat intervention except one lost to follow up [99.5％ (203/204)].Conclusions Strengthening nutrition education through WeChat is much more effective than traditional nutritional outpatient education alone in order to achieve a better control of blood glucose and improve pregnant outcomes in GDM women.This intervention is highly acceptable to gravidas and can be further extensively applied in nutrition clinic.

Objective To observe the change of intestinal microflora on the process of nonalcoholic steatohepatitis(NASH),and to explore the synbiotics therapeutic effect on NASH.Methods Rats were administrated with high fat diet to establish NASH model.In the process of NASH rats modeling,the level of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL), fasting blood sugar (FBS) and fasting insulin (FINS) was dynamically tested by automatic biochemical analyzer.The change of main intestinal flora was detected by 16 S rRNA fluorescence quantitative polymerase chain reaction.NAFLD activity score was calculated.HE staining was used to observe the hepaticpathological changes and the TLR4 expression was detected by using enzyme-linked immunosorbent assay and immunohistochemical method.Until the 4th,8th,10th weekin the process of NASH modeling, 10 rats were feeded with synbiotics for 2 weeks, and all of above indicators were tested and observed.Results 1)With the extension of a high-fat diet feeding time, the degree of hepatocyte steatosis obviously increased.NAFLD score was significantly heightened(P<0.01).2)Number of independent activities of rats significantly increased, the serological level of TG, TC, LDL, FBS and FINS were lower significantly after intervention with synbiotics for 2 weeks(P<0.05).3)Synbiotics intervention for two weeks significantly increased the amount of bifidobacterium and lactobacillus and decrease the amount of enterococcus significantly(P<0.05).4)The expression of TLR4 was gradually increased in the process of NASH rats modeling(P<0.05),but decreased after 2 weeks of the synbiotics-intervention (P<0.05).Conclusions Intestinal microecology change is closely related to the development of NASH,therefor, synbiotics could improve the quality of life and biochemical indicators of NASH rats through adjusting intestinal microecology and the expression level of TLR4 protein might been involved.

Objective To investigate the correlation between chronic hepatic diseases and small intestinal inflammation.Methods Patients who received capsule endoscopy in The First Affiliated Hospital of Guangdong Pharmaceutical University were divided into groups of liver cirrhosis,non-alcoholic fatty liver disease(NAFLD),chronic hepatitis and non-hepatic disease according to clinic data from August 2011 to August 2015.The severity of small intestinal mucosal inflammation was graded according to Lewis Scoring system and incidence of small intestinal lesions in different groups and Lewis scores were compared.The liver function was also graded with liver noninvasive scoring systems.Then the correlation between liver function damage and small intestinal lesions was investigated.Results A total of 338 cases were enrolled in the study,including 25 cases of liver cirrhosis,47 cases of NAFLD,20 cases of chronic hepaitis and 246 cases of non-hepatic disease.There were 22 (88.0％),36 (76.6％),12 (60.0％) and 78 (31.7％) cases with lesions in small intestine in the four group respectively with significant differences(P＜0.001).Rate of small intestinal villi edema was significantly higher in liver cirrhosis group,NAFLD group,chronic hepatitis group than that in non-hepatic disease group(all P＜0.017).Small intestinal villi edema was found mainly in the upper and one third of middle parts in small intestine (P =0.033).Lewis scores of liver cirrhosis group (190.80±228.42)and NAFLD group(125.38± 191.31) were higher than those of non-hepatic disease group (42.91±97.69,P=0.021,P =0.034).Forns score,FIB-4 score,NAFLD-FS score and Child-Pugh score were positively correlated with Lewis score (correlation coefficient:0.247,0.244,0.223,0.284respectively,all P＜0.001).Conclusion Chronic hepatic diseases such as liver cirrhosis,NAFLD,chronic hepatitis might be risk factors for small intestinal mucosal inflammation,and the severity of chronic hepatic diseases may be positively correlated with that of small intestinal mucosal lesions.

AIM:To investigate whether angiotensin-(1-7) [Ang-(1-7)] protects H9c2 cardiac cells against high glucose (HG)-induced injury and inflammation by inhibiting the interaction between Toll-like receptor 4 (TLR4) acti-vation and necroptosis .METHODS:The expression levels of receptor-interacting protein 3 ( RIP3;an indicator of necrop-tosis) and TLR4 were determined by Western blot .Cell viability was measured by CCK-8 assay.The activity of lactate de-hydrogenase ( LDH) in the culture medium was measured with a commercial kit .The releases of interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α) were measured by ELISA .The intracellular level of reactive oxygen species ( ROS) was analyzed by 2 ’ , 7 ’-dichlorfluorescein-diacetate ( DCFH-DA ) stating followed by photofluorography .Mitochondrial membrane potential ( MMP) was examined by rhodamine 123 staining followed by photofluorography .RESULTS:After the H9c2 cardiac cells were treated with HG (35 mmol/L glucose) for 24 h, the expression of RIP3 was obviously increased . Co-treatment of the cells with 30μmol/L TAK-242 (an inhibitor of TLR4) attenuated the up-regulation of RIP3 induced by HG.Furthermore, the expression of TLR4 was significantly increased after the cells were exposed to HG for 24 h, and co-treatment of the cells with 100μmol/L necrostatin-1 ( Nec-1;a specific inhibitor of necroptosis ) and HG for 24 h attenua-ted the up-regulation of TLR4 expression induced by HG .Moreover, 1μmol/L Ang-(1-7) simultaneously blocked the up-regulation of the RIP3 and TLR4 induced by HG.On the other hand, co-treatment of the cells with 1μmol/L Ang-(1-7), 30 μmol/L TAK-242 or 100 μmol/L Nec-1 and HG for 24 h attenuated HG-induced injuries and inflammatory response , leading to the increase in the cell viability , and the decreases in the activity of LDH , ROS generation , MMP loss as well as the releases of IL-1βand TNF-α.CONCLUSION:Ang-(1-7) protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the interaction between TLR 4 activation and necroptosis .

AIM:To investigate whether the opening of ATP-sensitive K+(KATP) channels protects H9c2 car-diac cells against high glucose ( HG)-induced injury and inflammation by inhibiting the Toll-like receptor 4 ( TLR4 )/nu-clear factor-κB ( NF-κB) pathway.METHODS:The protein levels of TLR4 and NF-κB p65 were determined by Western blot.The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA.The cell viabil-ity was measured by CCK-8 assay.Mitochondrial membrane potential (MMP) was examined by rhodamine 123 (Rh 123) staining followed by photofluorography.The intracellular levels of reactive oxygen species ( ROS) were detected by 2′, 7′-
dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography.The number of apoptotic cells was ob-served by Hoechst 33258 nuclear staining followed by photofluorography.RESULTS: After the H9c2 cardiac cells were treated with HG (35 mmol/L glucose) for 24 h, the protein levels of TLR4 and phosphorylated NF-κB p65 ( p-NF-κB p65) were significantly increased.Pretreatment of the cells with 100 μmol/L diazoxide ( DZ, a KATP channel opener) for 30 min before exposure to HG considerably blocked the up-regulation of the TLR4 and p-NF-κB protein levels induced by HG.Moreover, co-treatment of the cells with 30 μmol/L TAK-242 (an inhibitor of TLR4) obviously inhibited the HG-in-duced up-regulation of the p-NF-κB p65 protein level.On the other hand, pretreatment of the cells with 100 μmol/L DZ had a clear myocardial protection effect, which attenuated the HG-induced cytotoxicity, inflammatory response, mitochon-drial damage, oxidative stress and apoptosis, evidenced by an increase in the cell viability, and decreases in the levels of IL-1βand TNF-α, MMP loss, ROS generation and the number of apoptotic cells.Similarly, co-treatment of H9c2 cardiac cells with 30μmol/L TAK-242 or 100μmol/L PDTC ( an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries and inflammation induced by HG.CONCLUSION: The opening of KATP channels protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the TLR4/NF-κB pathway.

Aim To investigate the role of ATP-sensi-tive potassium channels-Akt pathway in exogenous hy-drogen sulfide( H2 S) inhibiting the high glucose( HG)-induced injury in H9c2 cardiac cells. Methods The expression level of Akt protein was tested by Western blot assay. The cell viability was measured by cell counter kit-8(CCK-8 assay). The number of apoptotic cells was tested by Hoechst 33258 nuclear staining fol-lowed by photofluorography. The intracellular levels of reactive oxygen species ( ROS ) were detected by DCFH-DA staining followed by photofluorography. Mi-tochondrial membrane potential ( MMP ) was examined by JC-1 staining followed by photofluorography. Results H9c2 cells were treated with 35 mmol·L-1 glucose (high glucose, HG) for 0 ~24 h respectively. After treating for 3 h, the expression level of phosphorated ( p )-Akt protein began to be obviously reduced, the maximum reduced expression level was observed after the cells were exposed to HG for 24 h. Pretreatment of the cells with 50 μmol · L-1 pinacidil ( Pin, a KATP channel opener) or 400 μmol·L-1 NaHS( a donor of H2 S) prior to exposure to HG considerably blocked the down regulation of p-Akt expression level induced by HG. However, pretreatment with 1 mmol · L-1 KATP channel blocker glibenclamide( Gli) obviously attenua-ted the inhibitory effect of NaHS on HG-induced down-regulation of p-Akt expression level. On the other hand, the protective effects of NaHS against the HG-induced cardiomyocyte injury were markedly blocked by 30 μmol·L-1 Ly294002(an inhibitor of Akt), as indicated by the decrease in cell viability and MMP dissipation as well as the increases in the number of apoptotic cells and ROS generation. Conclution KATP channels-Akt pathway mediates the protective effect of H2 S against the HG-induced cardiac injury.