Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ²=9.719, P=0.008), marital status (χ²=8.496, P=0.014), occupations (χ²=19.462, P<0.001), frequencies of dining out (χ²=5.457, P=0.019), previous Hp test results (χ² =4.131, P=0.042) and test results after treatment (χ²=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.

BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.

Background The mental health problems of employees in administrative organs and public institutions are highly valued.However,there is a lack of understanding regarding the mental health status of employees in provincial and municipal administrative organs and public institutions in Qinghai region.Objective To analyze the anxiety and depression of employees in provincial and municipal administrative organs and public institutions in Qinghai region,so as to provide references for promoting their mental health and intervening in psychological problems.Methods From October 23 to 28,2022,a total of 3 096 employees in provincial and municipal administrative organs and public institutions in Qinghai region were enrolled using stratified cluster sampling technique,and were assessed using Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS).Results A total of 1797(58.04％)employees in municipal and above administrative organs and public institutions in Qinghai region completed a valid questionnaire survey.Depressive symptoms were noted in 579(32.22％).SDS scores yielded statistical difference among the selected employees of different ethnicities,types of job positions and educational levels(F=9.074,101.488,4.477,P<0.01),and the severity of depressive symptoms also demonstrated statistical difference among the selected employees with different ethnicities,educational levels and types of job positions(H=49.196,17.028,160.848,P<0.01).Anxiety symptoms were detected in 711(39.57％)employees.SAS scores exhibited statistical difference among the employees with different genders,ages,ethnicities,educational levels,marital status and types of job positions(t=-4.571,F=6.648,3.950,5.243,12.008,22.253,P<0.01).Statistical differences were also illustrated in the severity of anxiety symptoms among the selected employees with different ages,genders,ethnicities,educational levels,marital status and types of job positions(H=24.361,-3.788,28.365,24.268,25.976,56.204,P<0.01).Conclusion About one-third of employees in municipal and above administrative organs and public institutions in Qinghai region may have symptoms of depression and anxiety.The depression symptoms are more severe among Tibetan people,those with low education levels and ordinary civil servants.The anxiety symptoms are more severe among employees aged 30 and below,those with low education levels,unmarried and those in technical positions.

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

Objective To investigate the effect of Inonotus obliquus extract on Crohn's disease and its mechanism by proteomics technology.Methods Crohn's disease(CD)model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS).A total of 48 SD male rats were randomized into control,model,Inonotus obliquus low-dose(200 mg/kg),medium-dose(400 mg/kg),high-dose(800 mg/kg)groups,and positive control group(mesalazine,225 mg/kg).The disease activity index(DAI)score and the colonic mucosal injury index(CMDI)score were assessed after one week of drug intervention.HE staining was used to observe the histopathological changes in the colon,and ELISA was used to detect the levels of IL-1β,IL-6,and TNF-α in the serum.Proteins were extracted from the colonic tissues of the control group,model group,and Inonotus obliquus high-dose group,and bioinformatics analysis was performed for the proteins identified by quantitative proteomics.Finally,Western blot and RT-qPCR were employed to verify the key proteins.Results Compared with the model group,the DAI,CMDI and HE staining scores were significantly decreased in the medium and high dose groups(P＜0.05 or P＜0.01),as well as the levels of inflammatory factors IL-1β,IL-6 and TNF-αin serum(P＜0.05 or P＜0.01).Proteomic tests showed that there were 199 differentially expressed proteins(DEPs)between the Inonotus obliquus high-dose group and the model group,of which 63 DEPs were related to CD.Bioinformatics analysis showed that these 63 DEPs were mainly involved in NOD-like receptor signaling pathway,calcium signaling pathway,necroptosis,and other pathways.Consistent with proteomic result,expressions of Vdac1 and Trpv2 were confirmed by Western blot and RT-qPCR in colon tissue.Conclusions Inonotus obliquus extract may regulate NOD-like receptor signaling pathway,calcium signaling pathway,and necroptosis by interfering with the expression of Vdac1 and Trpv2,so as to achieve the effect of treating CD.

Objective To analyze the diversity and composition changes of gut fungal communities between mouse model of total parental nutrition(TPN)and normal control mice.Methods After mouse model of TPN was constructed,fresh feces were collected from TPN mice(n=5)and normal control mice(n=5).Internal transcribed spacer(ITS)DNA sequencing was applied to determine intestinal fungi,and then bioinformatics analysis was conducted to identify the differences in fungal diversity,structure,and functional properties between the 2 groups of mice.Results There were significant differences in Alpha diversity(P＜0.05)and Beta diversity(P＜0.01)of intestinal fungi between the 2 groups.In the TPN model group,the relative abundances of Candida,Penicillium,Aspergillus and Talaromyces were obviously reduced(all P＜0.01).LEfSe analysis indicated that the above 4 strains were notably enriched in the normal control mice.Conclusion TPN mice exhibit characteristic changes in the composition of gut fungal flora compared to normal control mice.Dysfunction of gut fungal community may promote the occurrence of TPN related complications,and regulating the balance of gut fungal community may become a new strategy for preventing TPN related complications.

Objective This study aims to investigate the application of symptom group management using a mo-bile health platform in managing heart failure patients during convalescence.Methods The research involved pa-tients with chronic heart failure who were treated at a tertiary A hospital in Qingdao from June 2022 to December 2022.The experimental group consisted of 235 patients who were discharged after treatment in ward A,while the control group consisted of 235 patients who were discharged during the same period in ward B.The experimental group received an mHealth-based symptom clusters management program following routine continuous nursing and the control group was given routine continuous nursing after discharge.6 months after the intervention,the heart function status,self-care level,and quality of life were compared between 2 groups.Results The experimental group ultimately included 232 cases,while the control group ultimately included 225 cases.Furthermore,the cardiac functional status,level of self-care,and quality of life of both the experimental group and the control group showed improvement compared to the pre-intervention period(P＜0.05).The experimental group exhibited significantly better cardiac function status compared to the control group,and the experimental group demonstrated higher levels of self-care confidence,and quality of life relative to the control group(P＜0.05).Conclusion The utilization of a mobile medical platform can enhance the management of heart failure patients'symptom groups,resulting in im-proved disease management efficiency.This platform provides patients with a comprehensive self-management plan,ultimately enhancing their self-management abilities and overall outcomes.

Objective:To investigate the optimal serum antibody titer in acute stage for the diagnosis of Mycoplasma pneumoniae (MP) infection by passive agglutination, and to evaluate the clinical diagnostic value of different antibody titers.Methods:A cross-sectional study.Eighty-eight pairs of clinical serum samples were collected from children with MP infection treated at the Department of Pediatrics in Shengjing Hospital of China Medical University from December 2016 to February 2017 and Children′s Hospital of Baotou in November 2019.The four-fold change of the double serum specific antibody titer was used as the gold standard, and the receiver operating characteristic (ROC) curve was plotted.When detecting the single serum in acute stage, different antibody titers were used as positive criteria to evaluate their clinical application value in the diagnosis of MP infection and find the most appropriate serum antibody titer as the diagnostic cut-off value.Results:(1)When the serum specific antibody titer ≥1∶40 was used as the positive criterion, the sensitivity was 72.9%, the area under the ROC curve was 0.817, and the specificity was 87.5%, which might cause overdiagnosis.When the serum specific antibody titer ≥1∶160 was used as the positive criterion, the specificity was 97.5%, the area under the ROC curve was 0.775, and the sensitivity was 52.1%, which might cause missed diagnosis.When the serum specific antibody titer ≥1∶80 was used as the positive criterion, the sensitivity was 60.4%, the specificity was 97.5%, and the area under the ROC curve was 0.823, overall performing better compared with the said two criteria.(2)After the disease lasted at least 5 days, blood samples were collected.About 72.5% of the children had antibodies, and 60.0% of the children had antibody titers ≥1∶80.Conclusions:(1)When the passive agglutination method is used to detect MP infection, antibody titer ≥1∶80 is recommended as the diagnostic standard.However, in clinical practice, the diagnosis of MP infection depends on clinical and other laboratory test results.(2) It is appropriate to collect blood samples on 5-7 days of illness.If MP infection is clinically suspected, and an antibody titer of 1∶40 is also suggestive, it can perform cooperative diagnosis based on molecular biology lab results or retest at a shorter interval.