OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

Aim To investigate the regulatory mecha-nism of butin on the proliferation,migration,cycle blockage and pyroptosis related inflammatory factors in human fibroblast-like synoviocytes of rheumatoid arthri-tis(HFLS-RA).Methods Cell proliferation,migra-tion and invasion were studied using cell migration and invasion assays.Cell cycle was detected by flow cytom-etry,and the expression of the pyroptosis-associated in-flammatory factors IL-1β,IL-18,caspase-1 and caspase-3 was detected by ELISA,RT-qPCR and West-ern blot.Results Migration and invasion experiments showed that the cell proliferation rate of the butin group was lower than that of the blank control group(P＜0.05).Cell cycle analysis demonstrated that in the G0/G1 phase,the DNA expression was elevated in the medium and high-dose groups of butin(P＜0.05),while in the G2 and S phases,the DNA expression was reduced in the medium and high-dose groups of butin(P＜0.05).The results of ELISA,RT-qPCR and Western blot assay revealed that the expression of IL-1β,IL-1 8,caspase-1,and caspase-3 decreased in the butin group compared with the IL-1β+caspase-3 in-hibitor group(P＜0.05).Conclusions Butin inhib-its HFLS-RA proliferation by inhibiting the synthesis of inflammatory vesicles by caspase-1 in the pyroptosis pathway,thereby reducing the production and release of inflammatory factors such as IL-1β and IL-18 down-stream of the pathway,and also inhibits HFLS-RA pro-liferation by exerting a significant blocking effect in the G1 phase,which may be one of the potential mecha-nisms of butin in the treatment of RA.

Objective To mine valid information in public databases through bioinformatics analysis and machine learning models and to identify candidate genes related to preeclampsia,so as to improve the accuracy of early diagnosis and provide targets for pathogenesis,diagnosis and treatment research.Methods The RNA-seq datasets of placental tissue samples of preeclampsia patients and healthy pregnant women were retrieved from the Gene Expression Omnibus,and the gene expression matrix was obtained after data download,quality control,comparison and quantification through bioinformation analysis.The differentially expressed genes were screened by DESeq2 1.38.3,the enrichment pathway was determined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes,the co-expression network was constructed using weighted gene co-expression network analysis(WGCNA),and the machine learning prediction model was established by random forest algorithm.Results A total of 49 common differentially expressed genes were screened from placental tissue samples of 156 pregnant women(70 preeclampsia patients and 86 healthy pregnant women)in 4 datasets and they were significantly enriched in extracellular regions,positive regulation pathway of follicle-stimulating hormone secretion,hormone activity pathway,and cytokine-cytokine receptor interaction pathway,etc.The 49 differentially expressed genes were categorized into 7 co-expression modules by WGCNA,and key modules highly related to preeclampsia were identified.Six candidate key genes(fms related receptor tyrosine kinase 1[FLT1],pappalysin 2[PAPPA2],protein phosphatase 1 regulatory inhibitor subunit 1C[PPP1R1C],myosin ⅦB[MYO7B],long intergenic non-protein coding RNA 2009[LINC02009],and inhibin subunit α[INHA])were screened.The random forest model based on these 6 key genes had good predictive value for preeclampsia(area under curve was 0.978).Conclusion Preeclampsia may be associated with genes for hormone secretion,immune response,angiogenic factors,pregnancy-associated plasma proteins,and inhibin,and these genes may be candidate diagnostic markers of preeclampsia.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective:To construct an early postoperative frailty prevention nursing program for elderly patients with enterostomy, so as to provide a basis for formulating targeted nursing programs.Methods:The overall research period was from July to October 2022. Guided by the frailty integration model and cross-cultural nursing theory, the content framework indicators of the early postoperative frailty prevention nursing program for elderly patients with enterostomy were initially constructed through literature research, semi-structured interviews, and combined with the results of the previous cross-sectional survey. A total of 20 gastroenterostomy and nursing experts from 10 ClassⅢ hospitals in 7 provinces and municipalities were selected through the purposive sampling. Delphi method was used to carry out 2 rounds of consultation with 20 experts to determine the early postoperative frailty prevention nursing program for elderly patients with enterostomy.Results:In the 2 rounds of expert consultations, the effective response rates of the questionnaire were all 100% (20/20), the expert authority coefficients were all 0.95, and the Kendall's W were 0.23 and 0.32 respectively ( P<0.05). The coefficient of variation of indicators at all levels ranged from 0.050 to 0.167. The final early postoperative frailty prevention nursing program for elderly patients with enterostomy included 5 first-level indicators, 23 second-level indicators, and 63 third-level indicators. Conclusions:The early postoperative frailty prevention nursing program for elderly patients with enterostomy is scientific and necessary, and can provide a theoretical basis for nurses to implement frailty prevention and nursing for elderly patients.

Objectives:To explore the correlation between mitral annulus calcification(MAC)and recurrence of atrial fibrillation(AF)after radiofrequency ablation. Methods:The study included 785 patients with AF who underwent radiofrequency ablation in Beijing Anzhen Hospital from January 1,2019 to December 31,2020.According to the recurrence of AF after operation,patients were divided into recurrence group and non-recurrence group.Univariate Cox regression model was used to analyze the risk factors associated with AF recurrence,and multivariate Cox regression model was used to evaluate the influence of MAC on AF recurrence. Results:The average follow-up was(16±10)months.190 patients(24.2%)in the recurrence group,595(75.8%)patients in the non-recurrence.Patients in the recurrence group were older,had a higher proportion non-paroxysmal AF,a higher proportion of MAC,moderate/severe mitral regurgitation and larger left atrial diameter(LAD),and higher CHA2DS2-VASc score(all P<0.001).Univariate analysis showed that MAC was a risk factor of AF recurrence after radiofrequency ablation(HR=2.530,95%CI:1.639-3.907,P<0.001).After adjusting for age and sex,MAC remained significantly associated with an increased risk of AF recurrence after radiofrequency ablation(HR=1.52,95%CI:1.14-2.17,P<0.001).After multivariate adjustment for age,sex,non-paroxysmal AF,hypertension,diabetes,LAD,moderate/severe mitral regurgitation,and CHA2DS2-VASc score,MAC remained as an independent risk factor of AF recurrence(HR=1.48,95%CI:1.13-1.95,P=0.001). Conclusions:MAC is significantly associated with an increased risk of AF recurrence after radiofrequency ablation.

Abstract: Objective　To analyze the epidemiological characteristics and related factors of norovirus in Guangxi from 2015 to 2020, and to provide scientific recommendations for norovirus prevention and control. Methods The foodborne diseases surveillance data were collected from 11 sentinel hospitals through the National Foodborne Disease Monitoring and Reporting System from 2015 to 2020. R software with version 4.0.3 was used for descriptive and statistical analysis, including epidemic curve, chi-square test, and trend chi-square and so on. Logistic regression was used to analyze norovirus-related factors, OR values and 95% confidence intervals were calculated respectively with the statistical test level of P<0.05. Results There were 1 008 norovirus cases detected, with a detection rate of 12.75% (1 008/7 903). Children with age less than 5 years (OR=1.43, 95%CI: 1.13-1.82) and patients at age 20-45 (OR=1.45, 95%CI: 1.13-1.87) were high risk population. The detection rate was higher in autumn (OR=1.29, 95%CI: 1.08-1.53) but lower in summer (OR=0.67, 95%CI: 0.55-0.80). In addition, the tourist area (Guilin City) presented a higher detection rate than other areas (OR=1.41, 95%CI: 1.10-1.80). Aquatic products (OR=1.40, 95%CI: 1.03-1.91), meat and dairy products (OR=1.31, 95%CI: 1.06-1.61) were high-risk foods for norovirus infection. The prevention and control policies of COVID-19 can reduce the possibility of norovirus by 61% (OR=0.39, 95%CI: 0.31-0.49) showed a declining trend (Trend χ2=85.33, P<0.001). In addition, prolonged visit time can lead to 19%-23% decrease in the detection rate of norovirus (OR24-48 hours=0.81, 95%CI: 0.70-0.95; OR>48 hours=0.77, 95%CI: 0.63-0.93). Conclusions　The epidemic of norovirus presented seasonal and regional distribution in Guangxi with a declining detection rate trend in diarrhea patients during recent 6 years. Young children were high-risk population in infection norovirus. The intake of seafood can increase the risk of norovirus infection. The prevention and control policies of COVID-19 can sharply decrease the possibility of infection norovirus. The monitoring of key foods such as seafood should be strengthened, and the early screening of suspected cases should be taken. The norovirus monitoring should be improved to ensure the health of the population.