Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Objective:To evaluate the accuracy of the oral healthcare information provided by different large language models (LLM) to explore their feasibility and limitations in the application of oral auxiliary, treatment and health consultation.Methods:This study designed eight items comprising 47 questions in total related to the diagnosis and treatment of oral diseases [to assess the performance of LLM as an artificial intelligence (AI) medical assistant], and five items comprising 35 questions in total about oral health consultations (to assess the performance of LLM as a simulated doctor). These questions were answered individually by the five LLM models (Erine Bot, HuatuoGPT, Tongyi Qianwen, iFlytek Spark, ChatGPT). Two attending physicians with more than 5 years of experience independently rated the responses using the 3C criteria (correct, clear, concise), and the consistency between the raters was assessed using the Spearman rank correlation coefficient, and the Kruskal-Wallis test and Dunn post hoc test were used to assess the statistical differences between the models. Additionally, this study used 600 questions from the 2023 dental licensing examination to evaluate the time taken to answer, scores, and accuracy of each model.Results:As an AI medical assistant, LLM can assist doctors in diagnosis and treatment decision-making, with an inter-evaluator Spearman coefficient of 0.505 ( P<0.01). As a simulated doctor, LLM can carry out patient popularization, with an inter-evaluator Spearman coefficient of 0.533 ( P<0.01). The 3C scores of each model as an AI medical assistant and a simulated doctor were respectively: 2.00 (1.00, 3.00) and 2.00 (2.00, 3.00) points of Erine Bot, 1.00 (1.00, 2.00) and 2.00 (1.00, 2.00) points of HuatuoGPT, 2.00 (1.00, 2.00) and 2.00 (1.00, 3.00) points of Tongyi Qianwen, 2.00 (1.00, 2.00) and 2.00 (1.75, 2.25) points of iFlytek Spark, 3.00 (2.00, 3.00) and 3.00 (2.00, 3.00) points of ChatGPT (full score of 4 points). The Kruskal-Wallis test results showed that, as an AI medical assistant or a simulated doctor, there were statistically differences in the 3C scores among the five large language models (all P<0.001). The average score of the 5 LLMs on the dental licensing examination was 370.2, with an accuracy rate of 61.7% (370.2/600) and a time consumption of 94.6 min. Specifically, Erine Bot took 115 min, scored 363 points with an accuracy rate of 60.5% (363/600), HuatuoGPT took 224 min and scored 305 points with an accuracy rate of 50.8% (305/600), Tongyi Qianwen took 43 min, scored 438 points with an accuracy rate of 73.0% (438/600), iFlytek Spark took 32 min, scored 364 points with an accuracy rate of 60.7% (364/600), and ChatGPT took 59 min, scored 381 points with an accuracy rate of 63.5% (381/600). Conclusions:Based on the evaluation of LLM′s dual roles as an AI medical assistant and a simulated doctor, ChatGPT performes the best, with basically correct, clear and concise answers, followed by Erine Bot, Tongyi Qianwen and iFlytek Spark, with HuatuoGPT lagging behind significantly. In the dental licensing examination, all the 4 LLM, except for HuatuoGPT, reach the passing level, and the time consumpution for answering is significantly reduced compared to the 8 h required for the exam regulations in all of the five models. LLM has the feasibility of application in oral auxiliary, treatment and health consultation, and it can help both doctors and patients obtain medical information quickly. Howere, their outputs carry a risk of errors (since the 3C scoring results do not reach the full marks), so prudent judgment should be exercised when using them.

Objective:To investigate the protective effect of a composite hydrogel against hydrogen peroxide(H2O2)-induced oxidative stress injury in the cardiomyocytes,and to clarify its possible mechanism.Methods:The mice were subcutaneously injected with 100 μL of hydrogel.After normal feeding for 1,14,and 28 d,the mice were sacrificed.Tissue samples were collected and subjected to HE staining to observe the histocompatibity of the hydrogel.The primary cardiomyocytes isolated from 1-day-old SD rats were used to establish an oxidative stress injury model.The primary cardiomyocyties were divided into control,H2O2 and H2O2+Hydrogel groups.The primary cardiomyocytes in control group were cultured normally,the primary cardiomyocytes in H2O2 group were treated with 200 μmol·L-1 H2O2 for 24 h,and the primary cardiomyocytes in H2O2+Hydrogel group were incubated with 1 g·L-1 composite hydrogel and 200 μmol·L-1 H2O2 for 24 h.The viabilities of cardiomyocytes in various groups were assessed by cell counting kit-8(CCK-8)method.Dihydroethidium(DHE)and 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining were used to assess the reactive oxygen species(ROS)levels in the cells.The expressions of filamentous actin(F-actin)in the cells in various groups were detected by phalloidin fluorescence staining;the expressions of connexin 43(Cx43)and cardiac troponin T(cTnT)proteins in the cardiomyocytes in various groups were detected by immunofluorescence method.The apoptotic rates of cardiomyocytes in various groups were assessed with TUNEL staining method.The expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in the cardiomyocytes in various groups were assessed by Western blotting method.Results:The HE staining results showed that the inflammatory cells around the implanted hydrogel were less infiltrated,and the inflammatory reaction of subcutaneous implantation was less.Compared with control group,the viability of cardiomyocytes in H2O2 group was significantly decreased(P＜0.05),the level of ROS in the cells was increased(P＜0.05),the expression levels of Cx43,cTnT and F-actin proteins in the cells were decreased(P＜0.001),the apoptosis rate of cardiomyocytes were decreased(P＜0.01),the expression level of Bcl-2 protein in the cells was increased(P＜0.001),and the expression level of Bax protein was decreased(P＜0.01).Compared with H2O2 group,the viability of cardiomyocytes was significantly increased(P＜0.05),the level of ROS in the cells was decreased(P＜0.01),the expression levels of cTnT,Cx43 and F-actin proteins were increased(P＜0.01),the apoptotic rate of cardiomyocytes were significantly decreased(P＜0.001),the expression level of Bcl-2 protein in the cells were decreased(P＜0.01),and the expression level of Bax protein was increased(P＜0.01).Conclusion:Hydrogel may promote the expression of cardiomyocyte-related proteins by scavenging ROS in the environment and inhibit the cardiomyocyte apoptosis to achieve the protective effect on the cardiomyocytes under oxidative stress.

AIM:This study aims to investigate the expression and prognostic value of ubiquitin-conjugating enzyme E2C(UBE2C)in hepatocellular carcinoma(HCC),and to explore its impact on cancer stemness and the regulato-ry mechanisms.METHODS:(1)The TCGA and GEO databases were used to analyze UBE2C mRNA expression levels in HCC tissues and their correlation with prognosis using bioinformatics techniques,and these findings were further vali-dated in postoperative specimens from 107 HCC patients.The GEPIA database was used to analyze the correlation be-tween UBE2C and steroid receptor coactivator(SRC).(2)The CCK8,colony formation,wound healing,and spheroid formation assays were used to assess the effects of UBE2C on HCC cell proliferation,migration,and stemness.The inter-action between UBE2C and signal transducer and activator of transcription 3(STAT3),as well as its regulatory mecha-nism,was examined by Western blot and co-immunoprecipitation assays.(3)The subcutaneous xenograft model in nude mice was employed to validate the role of UBE2C in tumor growth in vivo.RESULTS:(1)Bioinformatics analysis re-vealed that UBE2C expression was significantly up-regulated in HCC tissues compared with adjacent normal tissues(P<0.05 in TCGA,and P<0.01 in GEO).Consistently,analysis of HCC specimens confirmed that high UBE2C expression was associated with shortened overall survival and disease-free survival of HCC patients(P<0.05).Furthermore,analysis using the GEPIA database revealed a positive correlation between UBE2C and SRC(P<0.01).(2)In vitro experiments demonstrated that UBE2C significantly promotes the proliferation and migration of HCC cells.Based on these findings,we presumed that UBE2C may regulate the phosphorylation of STAT3 at the Y705 site by modulating SRC activity,thereby in-fluencing the stemness characteristics of tumor cells.(3)In vivo experiments further confirmed that UBE2C inhibition sig-nificantly suppressed tumor growth.CONCLUSION:The UBE2C promoted proliferation and migration of HCC cells and regulated the stemness of HCC cells by interacting with STAT3.

Depression is a common mental illness that has a negative impact on patient quality of life,as well as representing a serious economic burden to society.The strategy of interfering with depression based on signaling pathways has recently attracted widespread attention.The cAMP pathway is an important cellular signaling pathway that plays a key role in the pathogenesis of and interventions for depression.In this review,we addresses recent studies on cAMP pathway-based interventions in depression,to provide a theoretical basis for regulating the cAMP pathway and its cascade mechanism in depression.

Objective:To explore the clinical characteristics and healthcare burden in patients with McCune-Albright syndrome (MAS).Methods:A cross-sectional study was conducted at the Children′s Hospital, Zhejiang University School of Medicine. Clinical and healthcare burden data were systematically collected through structured questionnaires in 164 children with MAS from February 2022 to May 2023. According to the clinical characteristics, patients were categorized into 3 groups: monosymptomatic, bisymptomatic and trisymptomatic groups. Patients were also divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Comparative analyses of clinical characteristics and healthcare burden were conducted across age, sex, and symptom categories.Results:The cohort comprised 59 males (36.0%) and 105 females (64.0%) with an age of 4.6 (2.0, 7.4) years. Age stratification revealed 117 cases (71.3%) aged 0-<7 years, 29 cases (17.7%) aged 7-<10 years, and 18 cases (11.0%) aged 10-<18 years. Among monosymptomatic (67 cases, 40.9%), the cohort comprised 32 females (47.8%) and 35 males (52.2%), predominantly presenting with fibrous dysplasia (57 cases, 85.1%). This subgroup showed peak prevalence in the 0-<7 years age range (29 cases (50.9%)). The bisymptomatic cohort (56 cases, 34.1%) consisted of 39 females (69.6%) and 17 males (30.4%), predominantly manifesting fibrous dysplasia with skin hyperpigmentation (25 cases, 44.6%). Peak prevalence occurred in the 0-<7 years subgroup(16 cases (64.0%)). The trisymptomatic cohort (41 cases, 25.0%) consisted of 34 females (82.9%) and 7 males (17.1%), with peak prevalence occurring in the 0-<7 years subgroup (36 cases (87.8%)). The diagnostic journey analysis revealed 94 cases (57.3%) required 1-3 referrals, and 34 cases (20.7%) necessitated >3 referrals from symptom onset to definitive diagnosis. Healthcare expenditure analysis revealed 69 families (42.1%) incurred direct medical costs of 10 000-100 000 CNY, with 11 families (6.7%) exceeding >100 000 CNY. Direct non-medical costs reached of 10 000-100 000 CNY for 62 families (37.8%) and >100 000 CNY for 4 families (2.4%). Productivity loss affected 58 families (35.4%) at 10 000-100 000 CNY and 8 families (4.9%) above 100 000 CNY during the study period.Conclusion:MAS requires increased attention to skeletal manifestations, especially in children aged 0-<7 years. Moreover, the significant financial burden on families necessitates a society-wide support system.

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

Objective:To construct a Harvard cancer index-based risk predictive model for perioperative venous thromboembolism (VTE) in elderly patients with femoral neck fracture and assess its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 610 elderly patients with femoral neck fracture admitted to Peking Union Medical College Hospital between January 2013 and December 2022, including 193 males and 417 females, aged 60-99 years [(77.3±9.0)years]. The patients were divided into VTE group ( n=125) and non-VTE group ( n=485) according to occurrence of VTE during the perioperative period. The two groups were compared in terms of gender, age, body mass index, smoking status, alcohol consumption, time from fracture to admission, surgical waiting time, comorbidities, perioperative electrolyte disorders, past or present history of malignancy, past history of deep vein thrombosis (DVT) or pulmonary embolism (PE), and preoperative use of oral anticoagulants. Univariate analysis and multivariable stepwise Logistic regression analysis were conducted to evaluate and identify independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. A perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed using the Harvard cancer index: (1) assigning a risk score to each variable according to the corresponding conversion criteria of the Harvard cancer index and risk score, based on the magnitude of their ORs; (2) determining the exposure rate of each risk factor based on the population distribution observed in this study; (3) calculating the average population risk score; (4) computing the individual VTE risk score; (5) deriving the ratio (X) of each individual ′s VTE risk score to the population average. Based on the Harvard cancer index classification criteria for disease risk levels, individual VTE risk categories were determined. The predictive performance of the risk stratification was evaluated by comparing the incidence of VTE across different risk levels. The predictive performance of the model was evaluated based on sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC). The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) test and internal validation was performed using the bootstrap resampling method with 1000 iterations. Results:Univariate analysis showed that gender, age, time from fracture to admission, surgical waiting time, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, history of DVT or PE, and preoperative use of oral anticoagulant drug were moderately associated with the occurrence of VTE in elderly patients with femoral neck fracture ( P<0.10). Multivariable stepwise logistic regression analysis demonstrated that female gender ( OR=2.26, 95% CI 1.34, 3.80, P<0.01), time from fracture to admission>1 day ( OR=3.70, 95% CI 2.24, 6.12, P<0.01), surgical waiting time>70 hours ( OR=2.06, 95% CI 1.29, 3.30, P<0.01), previous cerebral infarction ( OR=3.78, 95% CI 1.04, 13.76, P<0.05), stroke within the past month ( OR=11.57, 95% CI 1.21, 110.44, P<0.05), Alzheimer′s disease ( OR=3.26, 95% CI 1.12, 9.49, P<0.05), primary Parkinson ′s syndrome ( OR=3.47, 95% CI 1.22, 9.85, P<0.05), previous hysterectomy with bilateral adnexectomy ( OR=4.75, 95% CI 2.09, 10.80, P<0.01), perioperative electrolyte disorders ( OR=2.73, 95% CI 1.39, 5.35, P<0.01), and preoperative oral anticoagulant use ( OR=3.86, 95% CI 1.18, 12.67, P<0.05) were significantly associated with the occurrence of perioperative VTE in elderly patients with femoral neck fracture. Based on the above 10 risk factors, a perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed with the Harvard cancer index. The formula was as follows: X=[10×(female gender)+25×(time from fracture to admission>1 day)+10×(surgical waiting time>70 hours)+25×(previous cerebral infarction)+50×(stroke within the past month)+25×(Alzheimer′s disease)+25×(primary Parkinson′s disease)+25×(previous hysterectomy with bilateral adnexectomy)+10×(perioperative electrolyte disorders)+25×(preoperative use of oral anticoagulant drug)]/33. Individualized VTE risk was classified into five levels: very low, low, moderate, high, and very high, with corresponding VTE rates of 4.8%, 11.8%, 14.9%, 32.3%, and 73.5%, respectively ( χ2=87.71, P<0.01). The VTE risk predictive model demonstrated an AUC of 0.74 (95% CI 0.69, 0.79, P<0.01), with a sensitivity of 63.2% and specificity of 74.8%. The H-L goodness-of-fit test indicated satisfactory model calibration ( P>0.05). The internal validation with the bootstrap method confirmed that the AUC remained 0.74. Conclusions:Female gender, time from fracture to admission>1 day, surgical waiting time>70 hours, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, and preoperative use of oral anticoagulant drug are independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. Based on these factors, the perioperative VTE risk predictive model constructed using the Harvard cancer index demonstrates good clinical predictive value. Individualized VTE risk stratification can effectively identify high-, intermediate-, and low-risk populations, providing a valuable reference for tailoring anticoagulant prophylaxis strategies and enhancing postoperative surveillance.

Spinal cord injury represents a severe central nervous system trauma characterized by prolonged treatment duration, limited neural regeneration, and delayed functional recovery, greatly affecting patients′ quality of life. The impaired neural tissue struggles to recover effectively due to both the hostile microenvironment and its own compromised state. Current clinical interventions, including early reduction, laminectomy decompression, and intravenous or intrathecal methylprednisolone administration, fail to simultaneously modulate the microenvironment and improve the neural status. Zinc, a trace element abundant in the central nervous system, plays a critical role in gene expression regulation, synaptic plasticity, and neuronal activity. Clinical evidences have indicated that lower serum zinc concentration in patients with spinal cord injury correlates with poorer outcomes and animal experiments have also demonstrated the neuroprotective effects of zinc. In fact, zinc supplementation therapy has not yet been developed into a mature clinical protocol. Besides, related animal studies still lack comprehensive understanding. To this end, the authors reviewed the biological characteristics of zinc, its administration routes, neuroprotective effects and mechanisms in the management of spinal cord injury, aiming to provide references for future basic research and clinical practice.

Spinal cord injury is a highly disabling central nervous system disorder whose pathological progression is closely associated with blood-spinal cord barrier (BSCB) disruption. Physical trauma to the spine or spinal cord may compromise BSCB integrity, triggering secondary damage including spinal edema, hemorrhage, oxidative stress, and excessive inflammatory responses. For the pivotal role of protecting the spinal cord microenvironment, the repair of BSCB is crucial in the treatment of spinal cord injury. Although present studies have explored BSCB repair strategies such as biological factor regulation, biomaterial applications, and traditional Chinese medicine interventions, most studies focus on improving the overall barrier function and fail to systematically elucidate how these strategies target the core functional units of BSCB, namely the endothelial cells and their junction structures, to achieve functional and structural restoration of the barrier. Therefore, the authors reviewed the composition and key repair targets of BSCB, along with research advances in BSCB repair strategies based on endothelial cells and junction structures, aiming to provide insights for basic research and clinical treatment of spinal cord injury.