Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

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.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To establish a prediction model for symptomatic radiation pneumonitis (SRP) after radiotherapy for thoracic cancer based on a longitudinal cohort and dose interval variations.Methods:Clinical data of 587 patients who received thoracic radiotherapy in Department of Radiotherapy of Yunnan Cancer Hospital from July 2022 to June 2023 were retrospectively analyzed. The National Cancer Institute common terminology criteria for adverse events (CTCAE) version 5.0 was used to grade radiation pneumonitis, and clinical factors, traditional independent dosimetric characteristics and dose interval variation characteristics were collected. Features used to predict the occurrence of SRP were screened using genetic algorithms and analyzed the correlation between the selected features and SRP occurrence. Predictive models for SRP occurrence were established using the selected features and evaluated, and the optimal predictive model was visualized using a column chart.Results:The incidence of SRP was 35.94%. Five clinical factors, seven independent dosimetric features and six dose interval variation features were screened out by genetic algorithms to effectively predict the occurrence of SRP. The area under ROC curve (AUC) of clinical factors combined with traditional independent dosimetric factors and dose interval variation factors was 76%. The AUC of clinical factors combined with traditional independent dosimetric factors and that of clinical factors combined with dose interval variation factors was 69% and 67%, respectively. The addition of the characteristics of dose interval variation factors significantly improved the effectiveness of the prediction model.Conclusions:The supplement of the characteristics of dose interval variation factors can significantly improve the performance of the SRP prediction model for thoracic tumors after radiotherapy. The SRP prediction model based on dose interval variations can effectively predict the occurrence of SRP.

Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.

Epidural labor analgesia aims to provide effective medical services to alleviate labor pain in parturients, while adhering to the principles of voluntary participation and clinical safety. In 2018, Peking Union Medical College Hospital(PUMCH)became one of the first pilot units for labor analgesia in China, and has achieved satisfactory results in high-quality development of labor analgesia. This article mainly introduces the achievements and experience of labor analgesia at PUMCH, including: (1) prioritizing maternal and infant safety, arranging personnel rationally, and developing standardized treatment processes through multidisciplinary collaboration to ensure safe and comfortable childbirth; (2) leveraging the hospital's comprehensive capabilities in emergency treatment, and improving collaborative rescue plans for critically ill parturients and newborns; (3) implementing advanced teaching methods to effectively train and conduct simulated drills for labor analgesia and rescue of critically ill parturients; (4) conducting patient education and informative lectures to help parturients acquire a scientific understanding of labor analgesia. We hope that this experience can provide reference and inspiration for other hospitals.

Objective:To explore the characteristics of hippocampal subfield volume changes in bipolar disorder (BD) patients with childhood trauma and investigate the correlation between these volume changes and the severity of depressive symptoms.Methods:A total of 112 BD patients in the depressive phase and 62 healthy controls (HC) were recruited from April 2019 to April 2024. All participants were assessed using 17-item Hamilton depression scale (HAMD-17), Hamilton anxiety scale (HAMA), and the childhood trauma questionnaire (CTQ). Based on CTQ scores, BD patients were divided into two groups: the BD with childhood trauma group (BD-CT group, n=51) and the BD without childhood trauma group (BD-nCT group, n=61). T1-weighted magnetic resonance imaging (MRI) scans of the brain were collected for all participants, and hippocampal subfield volumes were segmented using FreeSurfer software.SPSS 26.0 software and Rv 4.1.1 software were used for data analysis.Generalized linear models were used to compare volume differences among three groups. Partial correlation analysis was performed to examine the relationship between the hippocampal subfield volumes showing significant differences and HAMD scores. Results:Significant differences were observed among the three groups in the left CA3(221.49(185.83, 243.02), 194.02(163.53, 226.19), 227.39(200.65, 247.47)), left CA4(261.68(240.89, 285.45), 236.86(210.76, 264.78), 269.75(244.90, 286.03)), left granule cell layer of the dentate gyrus (GC-ML-DG)(307.84(283.35, 328.85), 277.92(249.51, 308.25), 315.39(285.18, 330.25)), and left molecular layer(586.72(549.38, 635.25), 548.16(500.34, 605.24), 602.15(557.63, 637.13)) (Wald χ2=12.81-17.60, all P<0.05). The BD-CT group had significantly smaller volumes in the left CA3, left CA4, left GC-ML-DG, and left molecular layer compared to the BD-nCT group (all P<0.05). The BD-CT group also showed significantly smaller volumes in the left CA3, left CA4, and left GC-ML-DG compared to the HC group (all P<0.05). The volumes of left CA3 ( r=-0.33), left CA4 ( r=-0.31), left GC-ML-DG ( r=-0.31), and left molecular layer ( r=-0.28) regions were negatively correlated with HAMD scores (all P<0.05, Bonferroni correction). Conclusion:BD patients with childhood trauma exhibit reduced volumes in the left hippocampus subfields, including left CA3, left CA4, left GC-ML-DG and left molecular layer.These volume reductions are negatively correlated with the severity of depression.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.