Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.

Objective To investigate the feasibility of the spatiotemporal filtering model in analysis of reported schistosomiasis cases, so as to provide insights into analysis of complicated data pertaining to schistosomiasis control. Methods Demographic and epidemiological data of reported schistosomiasis cases in Anhui Province from 1997 to 2010 were collected from Anhui Provincial Center for Disease Control and Prevention, and the annual prevalence of Schistosoma japonicum human infections was calculated. The meteorological data were captured from meteorological stations in counties (cities, districts) of Anhui Province where schistosomiasis cases were reported from 1997 to 2010 at the National Meteorological Information Center, including monthly average air temperature and precipitation. Meteorological data were interpolated using the inverse-distance weighting method, and the annual average air temperature and annual precipitation were calculated in each county (city, district). The centroid of the county (city, district) where schistosomiasis cases were reported was extracted using the software ArcGIS 10.0, and the Euclidean distance from each centroid to the Yangtze River was calculated as the distance between that county (city, district) and the Yangtze River. The global Moran’s I of the prevalence of S. japonicum human infections in Anhui Province for each year from 1997 to 2010 were calculated to analyze the spatial autocorrelation. A spatial weight matrix was constructed using Rook adjacency, and a first-order temporal weight matrix was built to quantify the relationship between disease changes over time. Subsequently, a spatiotemporal structure matrix was constructed. A negative binomial model was built based on the spatiotemporal structure matrix and data pertaining to reported schistosomiasis cases, and a linear model was created between the residual of the model and candidate set feature vectors to determine the optimal subset composition of the spatiotemporal filter through stepwise regression. Then, a spatio-temporal filtering model was constructed using the negative binomial model. Negative binomial models, Bayesian spatial models, and Bayesian spatiotemporal models were constructed and compared with the spatiotemporal filtering model to validate the performance of the spatiotemporal filtering model, and cross-validation was conducted for each model. The goodness of fit was evaluated using the deviance information criterion (DIC) and Watanabe-Akaike information criterion (WAIC), and the effectiveness of model validation was assessed using mean squared error (MSE), while the accuracy of assessment results was assessed using coefficients and their 95% confidence intervals (CI), and the computational efficiency was assessed based on the running time of the model. The four feature vectors with the largest Moran’s I values were selected to identify regions with autocorrelation through their schematic diagrams to investigate the differences in spatiotemporal patterns of specific regions. Results Of all models created, the spatiotemporal filtering model exhibited the highest goodness of fit (DIC = 3 240.70, WAIC = 3 257.80), the best model validation effectiveness (MSE = 42 617.52), and the runtime was 3.18 s, exhibiting the optimal performance. Across all modeling results, the distance from the Yangtze River showed a negative correlation with the number of reported schistosomiasis cases (coefficient values = −4.93 to −3.78, none of the 95% CIs included 0), and annual average air temperature or average precipitation posed no significant effects on numbers of reported schistosomiasis cases (both of the 95% CIs included 0). Schematic diagrams of feature vectors showed that the transmission of schistosomiasis might be associated with water systems in Anhui Province, and localized clustering patterns were primarily concentrated in the northern and western parts of schistosomiasis-endemic areas in the province. Conclusion The spatiotemporal filtering model is an effective spatiotemporal analysis characterized by simple modeling, user-friendly operation, accurate results and good flexibility, which may serve as an efficient alternative to conventional complex spatiotemporal models for data analysis in schistosomiasis researches.

S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg²⁺ improved the enzyme activity. The enzyme kinetic analysis showed that the K_m and k_cat/K_m of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics* ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Cysteine/biosynthesis* ; Mixed Function Oxygenases/metabolism* ; Schizosaccharomyces pombe Proteins/metabolism* ; Oxygenases/metabolism* ; Kinetics

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.

Objective:To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma.Methods:Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children′s Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed.Results:The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group ( P<0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions:There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

Objective:To explore the relationship between depressive symptoms and filial piety in adult-child caregivers of disabled elderly,and the mediating effect of mutuality on the relationship.Methods:Totally 383 adult-child caregivers were assessed with the Center for Epidemiological Studies Depression Scale(CES-D),Dual Filial Piety Scale(DFPS)and Mutuality Scale(MS).The SPSS macro program Process was used to test the mediation model.Results:The CES-D scores were negatively correlated with the reciprocal filial piety scores and the MS scores(r=-0.49,-0.48,Ps＜0.01)and positively correlated with the authoritarian filial piety scores(r=0.37,P＜0.01).The MS scores were positively correlated with the reciprocal filial piety scores(r=0.76,P＜0.01),and negatively correlated with the authoritarian filial piety scores(r=-0.84,P＜0.01).Reciprocal filial piety scores were negatively associated with CES-D scores(β=-0.67).In addition,MS scores partly mediated the relationship between reciprocal filial piety scores and CES-D scores,the value of mediating effect was 22.89％.Conclusion:The depressive symptoms are correlated with filial piety and mutuality among adult-child caregivers of disabled eld-erly.

OBJECTIVE To investigate the distribution and regulation of G-quadruplex(G4)in enzymes related to glycolysis.METHODS The sequences of the transcription start site(TSS)region upstream of 1500 bp to the 5'-Untranslated region in 200 enzymes and their subtypes in glycolysis were selected for bioinformatics analysis.Related enzymes in glycolysis containing putative G-quadru-plex-forming sequences(PQSs)were identified.Circular Dichroism and Native polyacrylamide gel elec-trophoresis were used to verify the formation of G4.The ExonucleaseⅠhydrolysis assay was used to validate the stability of the formed G4 under 0,0.5,2,8,16,and 32 min.A reporter gene plasmid was constructed by inserting specific fragments of the related enzymes before the luciferase expression sequence.The dual-luciferase reporter assay system validate the expression level of luciferase to assess the impact of G4 on promoter activity.Real-time quantitative PCR was performed to validate the transcriptional regulatory role of G4 by detecting the mRNA levels of luciferase.RESULTS ①Bioin-formatics analysis showed that out of the 200 glycolysis-related enzymes,12 contained PQSs.Based on the analysis of the length and structure of PQSs,aldolase A(ALDOA)and phosphoglycerate mutase 2(PGAM2)proved to be able to form stable G4.② ALDOA and PGAM2 had the maximum positive absorption peak at 260 nm and maximum negative absorption peak at 240 nm.Both of them could form a G4 at the same time.③After digestion with ExonucleaseⅠ,ALDOA and PGAM2 showed no significant hydrolysis and demonstrated the stability of G4 structures.However,both of them could be gradually hydrolyzed after mutations in their PQSs.④ After PQS mutation of ALDOA and PGAM2,the mRNA levels and expression of downstream luciferase of ALDOA were significantly increased(P<0.05,P<0.01),while PGAM2 was significantly decreased(P<0.05,P<0.01).CONCLUSION The gene sequences of glycolysis-related enzymes and their subtypes contain a large number of PQSs.ALDOA and PGAM2 can form stable G4 and perform transcriptional regulatory functions.

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:Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis.Methods:We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University.Results:The median age at onset was 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and 13 patients had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P＜0.05). Conclusions:SMMN-FGT has a relatively good clinical prognosis, and even advanced patients can benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions are seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.