Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

Aim To explore the effect of berberine (B E) on RSV infected HEp-2 cells and the related mechanism. Methods HEp-2 cells were infected with RSV and treated with BE. Cell viability was assessed using the CCK-8 assay. Protein expression levels of NLRP3, ASC, caspase-1, PINK1, Parkin, Beclinl, p62, LC3 I,LC3 II,and BNIP3 in HEp-2 cells were detected by Western blot. The secretion level of IL-1 p in HEp-2 cells was measured using ELISA. Apoptosis rate and mitochondrial membrane potential of HEp-2 cells were examined by flow cytometry. Mitochondrial ROS (mtROS) in HEp-2 cells was detected through MitoSOX staining. Colocalization of mitochondria and autophagosomes in HEp-2 cells was investigated using immunofluorescence staining. Cyclosporin A was used for validation experiments. Results BE could significantly improve the activity of RSV-infected HEp-2 cells,reduce the apoptosis rate (P < 0. 05), and decrease the activation level of NLRP3 inflammasomes and IL-lp level (P <0. 05); BE improved mitochondrial function by increasing mitochondrial membrane potential and ATP levels,and reduced mtROS. BE significantly promoted the colocalization of mitochondria-autophagosome in RSV infected cells, inducing PINK1/ Parkin and BNIP3 to mediate mitochondrial autophagy; cyclosporine A aggravated RSV infection. Conclusions BE has protective effects on HEp-2 cells infected by RSV. The mechanism may be related to the inhibitory effect of BE on the production of mtROS and the activation of NLRP3 inflammasomes by inducing PINK1/ Parkin and BNIP3-mediated mitochondrial autophagy.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the relationship between the status of infarct related artery(IRA)occlusion and thrombus types in patients with non-ST-segment elevation myocardial infarction(NSTEMI)using optical coherence tomography(OCT).Methods A total of 170 NSTEMI patients who underwent emergency percutaneous coronary intervention at Henan Provincial People1s Hospital from October 2021 to August 2023 and underwent OCT examination were included in the study.Among them,83 cases were in the total occlusion group and 87 cases were in the non-total occlusion group.The baseline characteristics,coronary angiography findings,and OCT results of the patients were compared and analyzed.Results Compared with the non-total occlusion group,the patients in the total occlusion group were more younger(P=0.013),the proportion of male was higher(P=0.026),and the proportion of patients with hypertension(P=0.010)and diabetes(P=0.033)was lower.In the total occlusion group,left circumflex artery(LCX)served as the main IRA,whereas in the non-total occlusion group,left anterior descending(LAD)was the predominant IRA(P=0.012);In addition,there was a significantly higher occurrence of rentrop grade Ⅱ～Ⅲ in the total occlusion group compared to the non-total occlusion group(P=0.022).The OCT results showed that in most cases,the total occlusion group was caused by plaque rupture events(P=0.014),mainly red/mixed thrombus(P＜0.001);The non-total occlusion group was more commonly associated with plaque erosion events(P=0.014),with white thrombus being the main cause(P＜0.001).Conclusions Total occlusion of infarct-related artery in NSTEMI patients often occurs in the LCX,and the patient is more younger,the thrombus type is mainly red/mixed thrombus,while non-total occlusion lesions are mainly white thrombus.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Methamphetamine abuse is a major public health problem in the world,and in recent years,methamphetamine is also the most abused synthetic drug in China.The neurotoxic or addiction mechanism of methamphetamine has not been fully clarified,and there is still a lack of specific withdrawal methods and drugs for methamphetamine abuse.Mitochondria are not on-ly the organelles to which methamphetamine directly produces toxic effects,but also participate in regulating the neurotoxic damage process of methamphetamine.Mitochondrial quality is the regulatory basis for maintaining mitochondrial homeostasis and is regulated by three main mechanisms,which are mitochon-drial biogenesis,mitochondrial dynamic,and mitophagy.This review summarizes the research progress of mitochondrial quality control in methamphetamine-induced neurotoxicity,which may provide theoretical support for further research on the mechanism of methamphetamine neurotoxicity and development the mito-chondria-targeting drugs.

Objective To construct trajectory models of care-seeking patterns for type 2 diabetes mellitus(T2DM)patients,analyze the influencing factors of different trajectories,and explore the fasting blood glucose control levels of T2DM patients with different trajectories.Methods A retrospective cohort study was carried out on 18088 T2DM patients who had health records and been involved in the diabetic management in Community Health Service Center of Minhang District,Shanghai from 2006 to 2009.Starting from Jan 1,2010,participants were followed up until Dec 31,2019,with complete follow-up information.Group-based trajectory modelling(GBTM)was employed to identify and construct the fluctuation trajectory of fasting blood glucose in the patients.Bayesian information criterion(BIC),average posterior probability(AvePP)and other evaluation indicators were used to select the optimum subgroup number model.Then the differences in demographic characteristics,health status,family history,fasting blood glucose,BMI,etc were compared among different categories.Multinational logistic regression model was constructed to explore the influencing factors of different fluctuation trajectories.Cox regression analysis was used to examine the relationship between the long-term trajectories of care-seeking patterns and fasting blood glucose control level.Results Using GBTM analysis,we constructed the optimal Model 4 to categorize 18088 T2DM patients with community health records into five distinct trajectory subgroups:continuous non-attendance group(22.29%),low-level increasing group(15.09%),high-level slowly decreasing group(14.18%),high-level rapidly decreasing group(14.90%),and continuous regular attendance group(33.54%).With the continuous regular attendance group serving as the reference,gender,age,place of residence,baseline comorbidity of hypertension,baseline fasting plasma glucose level,and BMI were found to influence the community attendance trajectories of T2DM patients(P<0.05).After adjusting for confounding factors,Cox regression analysis revealed that compared to the continuous non-attendance group,the low-level increasing group,high-level slowly decreasing group,and continuous regular attendance group had better glycemic control,with HRs of 0.37(95%CI:0.34-0.39),0.72(95%CI:0.67-0.78),and 0.78(95%CI:0.73-0.84),respectively.The glycemic control level in the high-level rapidly decreasing group was comparable,with an HR of 1.06(95%CI:0.99-1.12).Conclusion Based on the optimal model,the community medical treatment trajectories of T2DM patients showed different dynamic characteristics.Factors such as gender,residence,hypertension,and weight loss may influence these varying trajectories.Regular community visits and follow-up may help control blood glucose levels.