Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Abstract: Objective　To find out the existing problems and provide reference for further improving the quality of report information by analyzing the report cards of COVID-19 and the positive report cards of primary screening reported in Ningxia. Methods　All COVID-19 case cards from 2020 to 2021 and initial screening positive cards were derived from the Chinese Information System for Disease Control and Prevention according to final review date. The timeliness of case reporting, timeliness of case review, completeness and accuracy of the case cards were analyzed. Results　In Ningxia, the first case of COVID-19 was reported on January 20, 2020, and as of December 31, 2021, 122 confirmed cases and 4 symptomatic infected cases were reported. In 2021, the timely reporting rate of COVID-19 was 98.00%, which increased by 8.24% compared with 2020 (90.54%). Compared with 2020, the average time limit for diagnosis to reporting of COVID-19 in 2021 was shortened by 83.12%; in 2021, the timely review rate of COVID-19 was 100.00%, which increased by 13.84% compared with 2020 (87.84%). Compared with 2020, the time from reporting to final review was shortened by 98.91%. In 2021, the timely rate of positive reports in COVID-19 in Ningxia was 90.00%, among which the timely rate of reports by county (district) nucleic acid detection institutions was the highest (92.31%), followed by municipal (91.67%) and autonomous region (81.82%). Conclusions　At the beginning of the epidemic in 2020, the timeliness of COVID-19 in Ningxia was poor, and through the implementation of measures such as technical training, supervision and inspection to continuously optimize the staffing of medical institutions and disease control institutions, the timeliness of reporting COVID-19 in Ningxia in 2021 was substantially improved, but there were still some weak links. In the future work, technical guidance and training should be carried out for weak links, and efforts should be made to improve the quality of reports.

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (C_T50)>4 MIC and 9 cases with trough concentration>MIC, both C_T50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r²=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC_{0-24 h}) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC_{0-24 h}, lower elimination rate constant and clearance rate.
Female ; Male ; Humans ; Child ; Child, Preschool ; Infant ; Anti-Bacterial Agents/therapeutic use* ; Vancomycin/therapeutic use* ; Bayes Theorem ; Extracorporeal Membrane Oxygenation ; Prospective Studies ; Sepsis/drug therapy*

Objective:To predict the potential molecular mechanism of Yangxue Antai Fang in treating prethrombolic state of recurrent spontaneous abortion （RSA-PTS）. Method:The chemical constituents and drug targets of Yangxue Antai Fang were collected by Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP V2.0）. RSA-PTS disease target information was collected by TCMIP V2.0 and improved by Online Mendelian Inheritance in Man （OMIM） database. The interaction of these targets was analyzed and key target network was constructed. Gene ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were further performed. Finally， Cytoscape 3.5.1 was used to build up a multidimensional network of TCM-ingredient-target-pathway. The levels of absorption， distribution， metabolism， excretion and toxicity （ADMET） of the main components in the network were analyzed. Result:A total of 310 chemical constituents and 975 targets were collected from 8 TCMs in Yangxue Antai Fang. A total of 143 targets of RSA-PTS were obtained. A total of 243 core targets were obtained by the interrelationship analysis of drug and disease targets. The analysis of the top 100 core targets showed that these targets might participate in treating RSA-PTS by affecting biological processes related to thrombosis， such as blood coagulation， platelet activation， positive regulation of angiogenesis and so on. Pathway analysis showed that these targets were mainly concentrated in complement and coagulation cascades， platelet activation， estrogen signaling pathway， thyroid hormone signaling pathway， etc. Multidimensional network analysis in combination with ADMET level showed that 14 components （leonurine， paeonol， vanillin， and so on） may play a therapeutic role in RSA-PTS by affecting coagulation factors Ⅱ （F2）， plasminogen （PLG） and estrogen receptor 1 （ESR1） proteins involved in complement and coagulation cascades， platelet activation， thyroid hormone signaling pathway and others. Conclusion:The main chemical constituents in Yangxue Antai Fang may improve RSA-PTS by regulating complement and coagulation cascades， blood coagulation， platelet activation and other biological processes.