ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Objective To investigate the role of SLC7A11-mediated disulfidptosis in regulating the functional heterogeneity of cancer-associated fibroblasts (CAFs) and remodeling the immune microenvironment in ovarian cancer (OC). Methods Utilizing an integrative multi-omics framework, we synchronized transcriptomic data from TCGA and GEO with high-resolution single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. We employed CellChat interactome algorithms to map disulfidptosis-related gene expression profiles across various cellular hierarchies. The mechanistic link between SLC7A11 and SPP1 was further examined via qPCR assays under glucose-deprived, disulfidptosis-inducing conditions. Results SLC7A11 was identified as a crucial regulator of disulfidptosis, exhibiting significant overexpression in OC tissues. Elevated SLC7A11 levels were positively correlated with advanced FIGO stages, increased tumor burden, and resistance to immune checkpoint blockade. scRNA-seq profiling identified a distinct CAF lineage (CAF1/CAF5) characterized by a robust disulfidptosis signature. This subpopulation was associated with epithelial-mesenchymal transition and an immunosuppressive niche via the SPP1-CD44 signaling axis. In situ spatial mapping suggested the localized amplification of SPP1-mediated signaling at the CAF-tumor cell interface, forming high-intensity interactomes with ITGAV, ITGB1, and CD44. Metabolic stress induced by glucose starvation significantly altered the transcriptional profiles of SLC7A11 and SPP1. Notably, the glucose starvation-induced upregulation of NRF2 mRNA in fibroblasts was effectively mitigated by NRF2 knockdown or treatment with the disulfidptosis inhibitor 2-mercaptoethanol. Conclusion SLC7A11-mediated disulfidptosis may activates a subset of CAFs, which may contribute to remodeling the tumor microenvironment and suppressing anti-tumor immunity through the secretion of SPP1.

Objective To investigate mortality risk factors and characterize pathogen distribution and antimicrobial resistance patterns in intensive care unit(ICU)patients with suspected infection following surgery.Methods A total of 65 hospitals in 16 provinces in China from July 1,2021,to December 31,2022.Clinical data were collected for surgical patients transferred to the ICU with suspected infection.Data included demographics[sex,age,underlying conditions(hypertension,diabetes,cardiovascular/cerebrovascular disease,hematologic disease)],surgical site,infection site,microbiological results with susceptibility testing,drug resistance and acute physiology and chronic health evaluationⅡ(APACHEⅡ)scores and the length of hospital stays.Patients were stratified by prognosis into death group and survial group,by drug resistance status into resistant and non-resistant groups.Univariate and multivariate Logistic regression identified risk factors for mortality and antimicrobial resistance.Draw the receiver operator characteristic curve(ROC curve)to evaluate the predictive value of each risk factor for patient prognosis and drug resistance occurrence.Results A total of 677 patients with suspected postoperative infection in the ICU were enrolled.There were 96 deaths and 591 survivors.① Analysis of risk factors affecting prognosis:univariate analysis showed that compared with the survival group,the patients in the had a higher APACHEⅡscore,the proportion of patients with previous cerebrovascular disease,surgery sites in the abdomen,chest,brain,pelvis,limbs,other areas,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,Gram-positive bacterial infection(Candida),fungal infection,multi-drug resistant bacterial infection was higher,and the length of hospital stay was shorter(all P<0.05).Multivariate Logistic regression analysis identified higher APACHEⅡscore[odds ratio(OR)=1.15,95%confidence interval(95%CI)was 1.11-1.20],pulmonary infection(OR=4.07,95%CI was 2.05-8.11),bloodstream infection(OR=2.61,95%CI was 1.52-4.51),and urinary tract infection(OR=2.20,95%CI was 1.01-4.42)were independent risk factors for prognosis(all P<0.05).The ROC curve analysis showed that the death risk prediction model established based on the above independent risk factors had certain predictive value for the prognosis of ICU postoperative patients with suspected infection,area under the curve(AUC)=0.820,95%CI was 0.770-0.860,P<0.05.②Regarding antimicrobial resistance:250 patients developed resistance and 427 did not.Univariate analysis showed compared with the non-resistant group,the APACHEⅡscore,the proportion of patients with cerebrovascular diseases,hematological diseases,surgeries at chest,brain,limbs,other sites,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,intracranial infection,Gram-negative bacillus infection,and Gram-positive cocci infection(Staphylococcus epidermidis,Staphylococcus aureus,Enterococcus faecalis),and the mortality rate in the resistant group were significantly higher,the proportion of patients with surgeries at abdominal cavity,pelvic cavity and abdominal cavity infection were significantly lower,and the length of hospital stay was significantly longer(all P<0.05).Multivariate Logistic regression analysis bloodstream infection(OR=4.00,95%CI was 2.22-7.19),urinary tract infection(OR=3.25,95%CI was 1.47-7.17),Klebsiella pneumoniae infection(OR=2.23,95%CI was 11.22-44.02),Acinetobacter baumannii infection(OR=48.12,95%CI was 20.10-115.17),Pseudomonas aeruginosa infection(OR=34.06,95%CI was 13.00-89.25),Escherichia coli infection(OR=24.97,95%CI was 10.55-59.13),Stenotrophomonas maltophilia infection(OR=19.04,95%CI was 3.30-109.96),and Staphylococcus aureus infection(OR=13.48,95%CI was 4.57-39.78)were independent risk factors for resistance(all P<0.01).The ROC curve analysis showed that the predictive model for drug resistance established based on the above independent risk factors had certain predictive value for drug resistance in adult patients with suspected infections after surgery in the ICU.The AUC=0.920,95%CI was 0.890-0.940,P<0.05.Conclusion Higher APACHEⅡscores and the presence of pulmonary,bloodstream,or urinary tract infections were associated with increased mortality in ICU patients with suspected postoperative infection.Patients with bloodstream or urinary tract infections,or infections caused by Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Escherichia coli,Stenotrophomonas maltophilia,or Staphylococcus aureus,had significantly higher odds of developing antimicrobial resistance.

Objective:To analyze the intercomparision result of personal dose monitoring and gross alpha/beta detection capability between the disease control and prevention institutions at provincial, municpal and county levels during 2022-2024, in order to provide a reference for radiation detection capability and policy making of these institutions in China.Methods:Data on personal dose monitoring and gross alpha/beta detection, obtanied from the 2022-2024 radiation detection capability intercomparison between the disease control and prevention institutions at different levels, were recorded. Both the qualification rates (including excellence) and excellence rates of all the institutions at all evels from 2022 to 2024 were analyzed using SPSS 22.0.Results:From 2022 to 2024, the number of participating institutions at all levels showed an overall upward trend, increasing from 262 to 430, with particularly notable growth at the municipal level. In the 2024 gross α/β detection capability intercomparison, the non-qualification rate in municipal-level institutions was significantly higher than in county-level institutions ( χ2=10.53, P < 0.05). The qualification rate (including excellence) of the municipal-level gross alpha/beta detection in 2022 and 2024 were lower than in 2023( χ2=29.93, P < 0.01). Among all regions, the 2024 personal dose monitoring intercomparison result showed that the qualification rate (including excellence) in East China was higher than in Southwest and Northwest China ( χ2=15.62, P <0.01). East China also outperformed Northwest China ( χ2=16.21, P <0.01). In the 2022 gross alpha/beta detection capability intercomparison, the qualification rate (including excellent performance) in East China and South China was higher than in Northwest China ( χ2=23.76, 11.22, P<0.01). Overall, East China showed relatively higher qualification rate in intercomparison result of both personal dose monitoring and radiation detection (including excellence), while Northwest China showed lower qualification rates (including excellence). Conclusions:Although the radiation detection capability of disease control and prevention institutions at all levels has improved in recent years, there are still insufficience of detection capabilities at some municipal- and county-level laboratories and even unbalance between different regionas. Policy support should prioritize underdeveloped areas, such as municipal- and county-level institutions and the Northwest, and enhance the technical proficiency and quality management of laboratory personnel.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

In this work,with tris(4-aminophenyl)amine(TAPA)and 1,3,5-tris(4-formylphenyl)benzene(TFPB)as monomers,an imine-type porous organic polymer,TAPA-TFPB,was synthesized using a simple method under the catalysis of acetic acid.The material TAPA-TFPB was used as solid-phase extraction adsorbent and combined with ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry(UHPLC-QTOF-MS)to establish a detection method for four kinds of nitrofuran metabolites(NFMs)residues in meat samples.The parameters of the adsorbent dosage,the pH value and volume of sample,and the type and volume of washing and eluent solvents were optimized,respectively.Under the optimal extraction conditions,low detection limits(0.11-1.60 μg/kg)were achieved for four kinds of NFMs.At three different spiked levels,the intra-day and inter-day precisions(Relative standard deviations)were 2.8% -10.9% and 4.3% -16.2%,respectively,and the spiked recoveries were 72.0% -107.2%.The results showed that the method chould be used for efficient extraction and analysis of trace NFMs residues in meat samples,indicating that TAPA-TFPB was a kind of promising SPE adsorbent.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

Objective To construct a competency evaluation model for forensic practitioners,providing a reference for their training and assessment.Methods Based on the iceberg and onion models of com-petency,and with reference to Spencer's Competency Dictionary,literature research was conducted and focus group interviews were employed to preliminarily construct core indices and measurement items for evaluating the competency of forensic practitioners.The Delphi method was applied for two rounds of expert consultation to further refine the competency evaluation index system.The analytic hierarchy process(AHP)was used to calculate the weights of the indices.Results A competency evaluation model for forensic practitioners was constructed,consisting of 7 core indices,encompassing forensic skills,identification service capabilities,and the ability to apply relevant legal knowledge and 49 mea-surement items.The weights of the core indices and measurement items were determined.Conclusion The constructed competency evaluation model for forensic practitioners is scientifically sound and inno-vative,and has unique characteristics of forensic medicine compared with other medical models.