ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

Cell ablation has recently emerged as a valuable technique for investigating cell lineage and function during the development of organisms.The nervous system contains diverse cellular populations,whose roles under physiological and pathological conditions are still not fully understood.Various cell ablation methods have been reported to specifically ablate different types of cell populations in the nervous system and have also been used to study cellular functions under physiological conditions as well as the pathogenesis of neurologi-cal system diseases.In this article,we have summarized common cell ablation techniques and focus on their applications in neurobio-logical and neurological system disease research.

Objective To analyze the relationship between changes of CD80, CD86 and Th1/Th2 cytokines and the severity of coxsackievirus A6 (CVA6) hand-foot-mouth disease (HFMD). Methods Among the 380 children with CVA6 HFMD in the 971th Hospital of the People's Liberation Army Navy and the 94th Hospital of the Joint Logistic Support Force were selected from January 2021 to January 2024. According to the disease severity, the children were divided into common group and severe group. The levels of CD80, CD86 and Th1/Th2 cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4)) were compared between the two groups. The ROC curve was used to analyze the evaluation efficiency of CD80, CD86, IFN gamma, and IL-4 levels on the severity of CVA6 HFMD. Multivariate logistic regression analysis was used to analyze the influencing factors of the severity of CVA6 HFMD. Results The levels of CD80, CD86, IFN-γ and IL-4 in the severe group were higher than those in the common group (P<0.05). The AUCs of CD80, CD86, IFN-γ, IL-4 and their combined detection in evaluating severity of CVA6 HFMD were 0.769, 0.717, 0.756, 0.864, and 0.917, respectively. The AUC value and specificity of combined detection were higher than those of single detection of each index (P<0.05). Multivariate logistic regression analysis indicated that age ≤ 3 years old was a risk factors (P<0.05), while time from onset to diagnosis ≤ 3d, duration of fever ≤ 3d, WB ≤ 12×109/L, low expression of CD80, low expression of IFN-γ, and low expression of IL-4 were protective factors (P<0.05). Conclusion CD80, CD86 and Th1/Th2 cytokines (IFN-γ, IL-4) are related to the severity of CVA6 HFMD. Early monitoring of CD80, CD86, IFN-γ and IL-4 levels in children is conducive to understanding their disease progression and guiding physician treatment.

OBJECTIVE To observe the expressions of micro ribonucleic acid-129-5p(miR-129-5p),interleukin-6(IL-6)/signal transducer and activator of transcription 3 gene(STAT3)/helper T cell 17(Th17)signaling path-ways in peripheral blood of the sepsis children complicated with pulmonary infection and analyze the clinical signif-icance.METHODS A total of 123 sepsis children who were complicated with pulmonary infection and were treated in the 971st Hospital of the Navy of The Chinese People's Liberation Army,the 904 Hospital of the Joint Logis-tics Support Force of the People's Liberation Army and Qingdao Women's and Children's Hospital from Jan.2020 to Dec.2023 were assigned as the sepsis complicated with pulmonary infection group,meanwhile,55 sepsis children who were not complicated with pulmonary infection were chosen as the simple sepsis group.The expres-sion levels of miR-129-5p,IL-6 mRNA,STAT3 mRNA and Th17 mRNA in peripheral blood mononuclear cells(PBMCs)were statistically analyzed.Receiver operating characteristics(ROC)curves were drawn to analyze the efficiencies of miR-129-5p and IL-6/STAT3/Th17 pathways in prediction of poor prognosis of the sepsis children with pulmonary infection.RESULTS The miR-129-5p level of the sepsis complicated with pulmonary infection group was lower than that of the simple sepsis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the sepsis complicated with pulmonary infection group were higher than those of the simple sepsis group(all P＜0.05).With the aggravation of illness condition,the miR-129-5p level was reduced,and the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA were elevated(all P＜0.05).The miR-129-5p level of the poor prog-nosis group was lower than that of the favorable prognosis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the poor prognosis group was higher than those of the favorable prognosis group(all P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of miR-129-5p was the largest(0.887)in prediction of the poor prognosis of the sepsis children complicated with pulmonary infection(P＜0.05).CONCLUSION The sepsis children complicated with pulmonary infection show the decline of expression level of peripheral blood miR-129-5p and enhancement of activation degree of IL-6/STAT3/Th17 pathways,which can be used as the indexes for assessment of illness condition and as auxiliary indexes for assessment of prognosis.

OBJECTIVE To explore the expression levels of microribonucleic acid-21(miR-21)and helper T cell(Th)1/Th2 cytokines in peripheral blood of the asthma children complicated with respiratory tract infections of vi-ruses and analyze the significance.METHODS A total of 90 asthma children with respiratory tract infections of vi-ruses(the infection group)and 43 asthma children without respiratory tract infections of viruses(the no infection group)who were treated in the 904th Hospital of the Joint Logistics Support Force of The People's Liberation Ar-my of China were enrolled in the study,and the clinical data were collected from the enrolled patients.The distri-bution of viruses from the children of the infection group was analyzed.The levels of peripheral blood miR-21,Th1 cytokines[interferon-γ(IFN-γ),interleukin(IL)-2]and Th2 cytokines[IL-4,IL-5]were compared between the two groups.The children of the infection group were divided into the mild group,the moderate group and the severe group according to the severity of disease.The levels of the above indexes were compared among the chil-dren with the various degree of illness condition.The association of the illness condition with miR-21,IFN-γ,IL-2,IL-4 and IL-5 was analyzed.RESULTS Respiratory syncytial virus was dominant among the respiratory tract vi-ruses in the infection group,accounting for 32.22％.The levels of IFN-γ and IL-2 of the infection group were low-er than those of the no infection group(P＜0.05),the levels of miR-21,IL-4 and IL-5 of the infection group were higher than those of the no infection group(P＜0.05).The levels of IFN-γ and IL-2 of the severe group were lower than those of the mild group and the moderate group(P＜0.05),while the levels of miR-21,IL-4 and IL-5 of the severe group were higher than those of the mild group and the moderate group(P＜0.05);the levels of IFN-γ and IL-2 of the moderate group were lower than those of the mild group(P＜0.05),and the levels of miR-21,IL-4 andIL-5 of the moderate group were higher than those of the mild group(P＜0.05).Spearman correlation analysis showed that the illness condition of the children was positively correlated with miR-21,IL-4 and IL-5(P＜0.05),which was negatively correlated with IFN-γ and IL-2(P＜0.05).CONCLUSIONS The respiratory tract infections of viruses may aggravate the abnormal rise of peripheral blood miR-21 and the imbalance of Th1/Th2.The above indexes are closely associated with the illness condition of the children.

Objective To investigate the association between intestinal microbiota dysbiosis and colonic polyps,Helicobacter pylori(Hp)infection,and intestinal metaplasia.Methods A total of 200 patients diagnosed with colonic polyps,Hp infection,or both conditions.These patients were classified into three groups:the colonic polyp group(n=90),the Hp infection with intestinal metaplasia group(n=49),and the colonic polyp combined with Hp infection and intestinal metaplasia group(n=61).Additionally,62 individuals who underwent routine health examinations at our hospital during the same period were enrolled as a control group.The study compared gut microbiota imbalances across these groups to investigate the association between intestinal dysbiosis and colonic pol-yps,Hp infection,and the co-occurrence of colonic polyps with Hp-related intestinal metaplasia.Logistic regression analysis was performed to identify risk factors associated with the development of intestinal metaplasia due to Hp infection in patients with colonic polyps.Results Compared to the control group,intestinal flora imbalance was significantly more prevalent in the colorectal polyp group,the Hp infection with intestinal metaplasia group,and the colorectal polyp combined with Hp infection and intestinal metaplasia group(P<0.05).Moreover,intestinal flora imbalance in the colorectal polyp with Hp infection and intestinal metaplasia group was significantly higher than that in both the colorectal polyp group and the Hp infection with intestinal metaplasia group(P<0.05).Regarding exhaled gas levels,H2 and CH4 concentrations were significantly elevated in the groups with colorectal polyps accom-panied by Hp infection and intestinal metaplasia,those with colorectal polyps alone,and those with Hp infection and intestinal metaplasia,compared to the control group(P<0.05).Similarly,exhaled H2S levels were significantly higher in the group with colorectal polyps complicated by Hp infection and intestinal metaplasia than in the control group(P<0.05).Furthermore,exhaled H2 and CH4 levels showed positive correlations with the presence of colorectal polyps,Hp infection with intestinal metaplasia,and colorectal polyps combined with Hp infection and intestinal metaplasia(P<0.05).Exhaled H2S levels were positively correlated with colorectal polyps complicated by Hp infec-tion and intestinal metaplasia(P<0.05).Logistic regression analysis indicated that a history of smoking,atrophic gastritis,peptic ulcer,and intestinal flora imbalance are independent risk factors for Hp infection-associated intesti-nal metaplasia in patients with colorectal polyps(P<0.05).Conclusion Intestinal flora imbalance is associated with colorectal polyps and Hp-induced intestinal metaplasia,suggesting that microbial dysbiosis may represent a potential risk factor for the development of these conditions.

Cell ablation has recently emerged as a valuable technique for investigating cell lineage and function during the development of organisms.The nervous system contains diverse cellular populations,whose roles under physiological and pathological conditions are still not fully understood.Various cell ablation methods have been reported to specifically ablate different types of cell populations in the nervous system and have also been used to study cellular functions under physiological conditions as well as the pathogenesis of neurologi-cal system diseases.In this article,we have summarized common cell ablation techniques and focus on their applications in neurobio-logical and neurological system disease research.

Objective To investigate the association between intestinal microbiota dysbiosis and colonic polyps,Helicobacter pylori(Hp)infection,and intestinal metaplasia.Methods A total of 200 patients diagnosed with colonic polyps,Hp infection,or both conditions.These patients were classified into three groups:the colonic polyp group(n=90),the Hp infection with intestinal metaplasia group(n=49),and the colonic polyp combined with Hp infection and intestinal metaplasia group(n=61).Additionally,62 individuals who underwent routine health examinations at our hospital during the same period were enrolled as a control group.The study compared gut microbiota imbalances across these groups to investigate the association between intestinal dysbiosis and colonic pol-yps,Hp infection,and the co-occurrence of colonic polyps with Hp-related intestinal metaplasia.Logistic regression analysis was performed to identify risk factors associated with the development of intestinal metaplasia due to Hp infection in patients with colonic polyps.Results Compared to the control group,intestinal flora imbalance was significantly more prevalent in the colorectal polyp group,the Hp infection with intestinal metaplasia group,and the colorectal polyp combined with Hp infection and intestinal metaplasia group(P<0.05).Moreover,intestinal flora imbalance in the colorectal polyp with Hp infection and intestinal metaplasia group was significantly higher than that in both the colorectal polyp group and the Hp infection with intestinal metaplasia group(P<0.05).Regarding exhaled gas levels,H2 and CH4 concentrations were significantly elevated in the groups with colorectal polyps accom-panied by Hp infection and intestinal metaplasia,those with colorectal polyps alone,and those with Hp infection and intestinal metaplasia,compared to the control group(P<0.05).Similarly,exhaled H2S levels were significantly higher in the group with colorectal polyps complicated by Hp infection and intestinal metaplasia than in the control group(P<0.05).Furthermore,exhaled H2 and CH4 levels showed positive correlations with the presence of colorectal polyps,Hp infection with intestinal metaplasia,and colorectal polyps combined with Hp infection and intestinal metaplasia(P<0.05).Exhaled H2S levels were positively correlated with colorectal polyps complicated by Hp infec-tion and intestinal metaplasia(P<0.05).Logistic regression analysis indicated that a history of smoking,atrophic gastritis,peptic ulcer,and intestinal flora imbalance are independent risk factors for Hp infection-associated intesti-nal metaplasia in patients with colorectal polyps(P<0.05).Conclusion Intestinal flora imbalance is associated with colorectal polyps and Hp-induced intestinal metaplasia,suggesting that microbial dysbiosis may represent a potential risk factor for the development of these conditions.

OBJECTIVE To observe the expressions of micro ribonucleic acid-129-5p(miR-129-5p),interleukin-6(IL-6)/signal transducer and activator of transcription 3 gene(STAT3)/helper T cell 17(Th17)signaling path-ways in peripheral blood of the sepsis children complicated with pulmonary infection and analyze the clinical signif-icance.METHODS A total of 123 sepsis children who were complicated with pulmonary infection and were treated in the 971st Hospital of the Navy of The Chinese People's Liberation Army,the 904 Hospital of the Joint Logis-tics Support Force of the People's Liberation Army and Qingdao Women's and Children's Hospital from Jan.2020 to Dec.2023 were assigned as the sepsis complicated with pulmonary infection group,meanwhile,55 sepsis children who were not complicated with pulmonary infection were chosen as the simple sepsis group.The expres-sion levels of miR-129-5p,IL-6 mRNA,STAT3 mRNA and Th17 mRNA in peripheral blood mononuclear cells(PBMCs)were statistically analyzed.Receiver operating characteristics(ROC)curves were drawn to analyze the efficiencies of miR-129-5p and IL-6/STAT3/Th17 pathways in prediction of poor prognosis of the sepsis children with pulmonary infection.RESULTS The miR-129-5p level of the sepsis complicated with pulmonary infection group was lower than that of the simple sepsis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the sepsis complicated with pulmonary infection group were higher than those of the simple sepsis group(all P＜0.05).With the aggravation of illness condition,the miR-129-5p level was reduced,and the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA were elevated(all P＜0.05).The miR-129-5p level of the poor prog-nosis group was lower than that of the favorable prognosis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the poor prognosis group was higher than those of the favorable prognosis group(all P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of miR-129-5p was the largest(0.887)in prediction of the poor prognosis of the sepsis children complicated with pulmonary infection(P＜0.05).CONCLUSION The sepsis children complicated with pulmonary infection show the decline of expression level of peripheral blood miR-129-5p and enhancement of activation degree of IL-6/STAT3/Th17 pathways,which can be used as the indexes for assessment of illness condition and as auxiliary indexes for assessment of prognosis.

OBJECTIVE To explore the expression levels of microribonucleic acid-21(miR-21)and helper T cell(Th)1/Th2 cytokines in peripheral blood of the asthma children complicated with respiratory tract infections of vi-ruses and analyze the significance.METHODS A total of 90 asthma children with respiratory tract infections of vi-ruses(the infection group)and 43 asthma children without respiratory tract infections of viruses(the no infection group)who were treated in the 904th Hospital of the Joint Logistics Support Force of The People's Liberation Ar-my of China were enrolled in the study,and the clinical data were collected from the enrolled patients.The distri-bution of viruses from the children of the infection group was analyzed.The levels of peripheral blood miR-21,Th1 cytokines[interferon-γ(IFN-γ),interleukin(IL)-2]and Th2 cytokines[IL-4,IL-5]were compared between the two groups.The children of the infection group were divided into the mild group,the moderate group and the severe group according to the severity of disease.The levels of the above indexes were compared among the chil-dren with the various degree of illness condition.The association of the illness condition with miR-21,IFN-γ,IL-2,IL-4 and IL-5 was analyzed.RESULTS Respiratory syncytial virus was dominant among the respiratory tract vi-ruses in the infection group,accounting for 32.22％.The levels of IFN-γ and IL-2 of the infection group were low-er than those of the no infection group(P＜0.05),the levels of miR-21,IL-4 and IL-5 of the infection group were higher than those of the no infection group(P＜0.05).The levels of IFN-γ and IL-2 of the severe group were lower than those of the mild group and the moderate group(P＜0.05),while the levels of miR-21,IL-4 and IL-5 of the severe group were higher than those of the mild group and the moderate group(P＜0.05);the levels of IFN-γ and IL-2 of the moderate group were lower than those of the mild group(P＜0.05),and the levels of miR-21,IL-4 andIL-5 of the moderate group were higher than those of the mild group(P＜0.05).Spearman correlation analysis showed that the illness condition of the children was positively correlated with miR-21,IL-4 and IL-5(P＜0.05),which was negatively correlated with IFN-γ and IL-2(P＜0.05).CONCLUSIONS The respiratory tract infections of viruses may aggravate the abnormal rise of peripheral blood miR-21 and the imbalance of Th1/Th2.The above indexes are closely associated with the illness condition of the children.