Objective To investigate the potential role of plasma adiponectin concentration in predicting the response of patients with depression to electroconvulsive therapy(ECT).Methods This study enrolled depressive patients scheduled for ECT at the First Hospital of Shanxi Medical University between January 2022 and March 2024.Patients were categorized as either ECT responders(>50%reduction)or non-responders(≤50%reduction)based on post-ECT reduction rate of the 24-item Hamilton depression scale(HAMD)scores from baseline.Plasma adiponectin levels were measured in all patients before their first ECT treatment.To identify predictors of ECT response in patients with depression,the predictive value of plasma adiponectin was evaluated using receiver operating characteristic(ROC)curve analysis.Results A total of 80 patients with depression were enrolled including 44 in the ECT-responsive group and 36 in the non-responsive group.The plasma adiponectin level was significantly higher in the responsive group than in the non-responsive group[5.67(3.64,10.55)μg/mL vs.4.01(2.59,5.04)μg/mL,P=0.002].Pearson correlation analysis revealed a significant positive correlation between plasma adiponectin levels and the HAMD reduction rate(r=0.300,P=0.007).Multivariate logistic regression analysis showed that plasma adiponectin was independently associated with the response to ECT in patients with depression(OR=1.218,95%CI:1.009-1.470,P=0.040).Furthermore,ROC curve analysis demonstrated that the area under the curve(AUC)for adiponectin in predicting ECT response was 0.748(95%CI:0.583-0.813).Conclusion Pretreatment plasma adiponectin may serve as a potential biomarker for predicting response to ECT in patients with depression.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Background and purpose:In recent years,chimeric antigen receptor T(CAR-T)cell therapy has achieved breakthrough progress in cancer treatment.γδ T cells,with their non-major histocompatibility complex(MHC)-restricted antigen recognition,broad antitumor activity,and low risk of graft-versus-host disease(GVHD),have garnered significant interest in CAR-γδ T cell therapy.However,critical challenges including suboptimal in vitro expansion and low viral transduction efficiency severely hinder the research and clinical application of CAR-γδ T cells.This study aimed to establish an efficient platform for preparing CAR-γδ T cells by optimizing the in vitro expansion conditions of γδ T cells and refining lentiviral transduction strategies.Methods:We first optimized the expansion protocol for γδ T cells by screening various cytokine combinations and the concentrations of individual cytokines within combination,and evaluating cell purity,viability,fold expansion,and expressions of cytotoxicity and exhaustion markers to identify the optimal culture conditions.Subsequently,the transduction conditions for CAR-γδ T cells were improved by determining the optimal activation duration of γδ T cells prior to gene transfer,as well as the optimal multiplicity of infection(MOI)for lentiviral transduction.Finally,CAR-γδ T cells were successfully generated using the optimized protocol,and their cytotoxic activity against target cells was validated via calcein-release assay and flow cytometry,with a preliminary assessment of the potential risk of GVHD induction.Results:Experimental data demonstrated that,compared with the interleukin(IL)-2-only culture,the IL-2+IL-7+IL-15 combination significantly enhanced the expansion capacity of γδ T cells(876.50±238.35-fold vs 1 627.50±472.15-fold),cell purity(73.67%±1.53%vs 90.69%±2.00%),and cell viability(63.01%±7.05%vs 89.00%±3.61%).It also increased the expression of the cytotoxicity marker CD16(4.20%±1.73%vs 14.66%±0.58%)and reduced the expression of the exhaustion marker programmed death-1(PD-1)(35.67%±6.26%vs 21.10%±6.49%).A cytokine concentration gradient orthogonal assay further identified 10 ng/mL IL-7 and 10 ng/mL IL-15 as the optimal concentrations within the IL-2+IL-7+IL-15 combination.Gene transduction performed 96-120 h after activation using a multiplicity of infection(MOI)of 5-10 resulted in the highest transduction efficiency for CAR-γδ T cells(96 h:12.87%±4.35%;120 h:11.37%±2.35%).CAR-γδ T cells generated using the optimized system exhibited specific cytotoxic effects against tumor cells expressing the target antigen,and no evidence of GVHD induction was observed.Conclusion:CAR-γδ T cells produced using the IL-2+IL-7(10 ng/mL)+IL-15(10 ng/mL)regimen combined with a 96-120 h activation period prior to transduction using a multiplicity of infection(MOI)of 5-10 significantly outperformed conventional methods in terms of expansion efficiency,cell purity,and transduction efficiency.The synergistic antitumor effects mediated by both natural immune receptors and CAR-specific recognition,along with the initial absence of GVHD risk,provide critical technical support for the clinical translation of CAR-γδ T cell therapy,establishing a solid theoretical and practical foundation.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Objective To investigate whether Piceatannol(PIC)improves diabetic retinopathy(DR)mediated by microglial polarization and to elucidate the underlying molecular mechanisms.Methods Network pharmacology and bioinformatics were used to analyze the common targets of DR,PIC,and microglia.Human retinal vascular endothelial cells(HRVECs)were cultured in vitro and randomly divided into the NG-HRVECs group,HG-HRVECs group,and HG+PIC-HRVECs group.Cell viability was assessed by the CCK-8 assay,apoptosis was detected by the TUNEL assay,and the concentrations of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured using ELISA kits.BV-2 cells were cultured in vitro and randomly divided into the NG-BV-2 group,HG-BV-2 group,HG+PIC-BV-2 group,HG+Si-NC-BV-2 group,HG+Si-CXCR4-BV-2 group,and HG+Ibrutinib-BV-2 group.The levels of arginase-1(Arg-1)and inducible ni-tric oxide synthase(iNOS)were measured using ELISA kits.Furthermore,conditioned medium(CM)from BV-2 cells of each group was collected to treat HRVECs,after which the viability,apoptosis rate,and TNF-α and IL-6 concentrations of the HRVECs were measured.A DR rat model was established and intervened with PIC to investigate the ameliorative effects of PIC on retinal pathology.Results Bioinformatics analysis identified CXCR4 as the key target of this study.Compared with the NG-HRVECs group,the apoptosis rate and the concentrations of TNF-α and IL-6 were increased in the HG-HRVECs group.Compared with the HG-HRVECs group,the HG+PIC-HRVECs group showed a decreased apoptosis rate and reduced concentrations of TNF-α and IL-6(all P＜0.05).Compared with the NG-BV-2 group,the HG-BV-2 group ex-hibited decreased Arg-1 levels and increased iNOS levels.Compared with the HG-BV-2 group,the HG+PIC-BV-2,HG+Si-CXCR4-BV-2,and HG+Ibrutinib-BV-2 groups all showed increased Arg-1 levels and decreased iNOS levels(all P＜0.05).Compared with the NG-BV-2-CM group,the HG-BV-2-CM group led to decreased viability,increased apoptosis rate,and in-creased concentrations of TNF-α and IL-6 in HRVECs.In contrast,the HG+PIC-BV-2-CM,HG+Si-CXCR4-BV-2-CM,and HG+Ibrutinib-BV-2-CM groups reversed the effects induced by HG-BV-2-CM on HRVECs(all P＜0.05).Animal experiment results showed that compared with DR model rats,rats treated with different doses of PIC exhibited significantly ameliora-ted retinal histopathological damage,and the protein expressions of Arg-1,iNOS,CXCR4,and p-BTK were reversed.Con-clusion PIC ameliorates DR progression mediated by microglial polarization by inhibiting the CXCR4/BTK pathway.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

In recent years, idiopathic macular hole (IMH) surgery has a very high success rate due to the development of small-gauge vitrectomy, while the recovery of visual acuity is not satisfactory.Current studies have found that continuity of retinal blood vessels in the macular area and changes in retinal and choroidal perfusion are closely related to the formation and healing of MH, and have a significant impact on the visual prognosis in IMH patients.This article reviews the research progress on variations of parameters for retinal and choroidal vessels in IMH patients, as well as their relationship with visual prognosis.For retinal parameters, the changes in the foveal avascular zone, superficial and deep capillary plexus density, paracentral intraretinal cystoid spaces, retinal vessels position are discussed.Relevant research related to choroidal blood flow perfusion changes and the effects of different surgical methods on macular perfusion in patients with IMH are summarized to provide basis for further understanding the etiology and prognosis of IMH.

Objective To investigate whether Piceatannol(PIC)improves diabetic retinopathy(DR)mediated by microglial polarization and to elucidate the underlying molecular mechanisms.Methods Network pharmacology and bioinformatics were used to analyze the common targets of DR,PIC,and microglia.Human retinal vascular endothelial cells(HRVECs)were cultured in vitro and randomly divided into the NG-HRVECs group,HG-HRVECs group,and HG+PIC-HRVECs group.Cell viability was assessed by the CCK-8 assay,apoptosis was detected by the TUNEL assay,and the concentrations of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured using ELISA kits.BV-2 cells were cultured in vitro and randomly divided into the NG-BV-2 group,HG-BV-2 group,HG+PIC-BV-2 group,HG+Si-NC-BV-2 group,HG+Si-CXCR4-BV-2 group,and HG+Ibrutinib-BV-2 group.The levels of arginase-1(Arg-1)and inducible ni-tric oxide synthase(iNOS)were measured using ELISA kits.Furthermore,conditioned medium(CM)from BV-2 cells of each group was collected to treat HRVECs,after which the viability,apoptosis rate,and TNF-α and IL-6 concentrations of the HRVECs were measured.A DR rat model was established and intervened with PIC to investigate the ameliorative effects of PIC on retinal pathology.Results Bioinformatics analysis identified CXCR4 as the key target of this study.Compared with the NG-HRVECs group,the apoptosis rate and the concentrations of TNF-α and IL-6 were increased in the HG-HRVECs group.Compared with the HG-HRVECs group,the HG+PIC-HRVECs group showed a decreased apoptosis rate and reduced concentrations of TNF-α and IL-6(all P＜0.05).Compared with the NG-BV-2 group,the HG-BV-2 group ex-hibited decreased Arg-1 levels and increased iNOS levels.Compared with the HG-BV-2 group,the HG+PIC-BV-2,HG+Si-CXCR4-BV-2,and HG+Ibrutinib-BV-2 groups all showed increased Arg-1 levels and decreased iNOS levels(all P＜0.05).Compared with the NG-BV-2-CM group,the HG-BV-2-CM group led to decreased viability,increased apoptosis rate,and in-creased concentrations of TNF-α and IL-6 in HRVECs.In contrast,the HG+PIC-BV-2-CM,HG+Si-CXCR4-BV-2-CM,and HG+Ibrutinib-BV-2-CM groups reversed the effects induced by HG-BV-2-CM on HRVECs(all P＜0.05).Animal experiment results showed that compared with DR model rats,rats treated with different doses of PIC exhibited significantly ameliora-ted retinal histopathological damage,and the protein expressions of Arg-1,iNOS,CXCR4,and p-BTK were reversed.Con-clusion PIC ameliorates DR progression mediated by microglial polarization by inhibiting the CXCR4/BTK pathway.

Objective: To investigate the scientific research capacity building of administrative offices of Centers for Disease Control and Prevention (CDCs) across 31 provinces (autonomous regions, municipalities), the Xinjiang Production and Construction Corps, and 5 separately listed cities in China, so as to provide the reference for improving the positioning of office functions and promoting the enhancement of scientific research capabilities. Methods: A self-administered questionnaire survey was conducted among heads and staff members of administrative offices in 37 CDCs. Data on office setup, general information, staffing, scientific research incentive measures and outputs were collected and analyzed. Results: The 37 administrative offices of the CDCs had an average authorized staffing size of 12 personnel. There were 17 of them setting independently allocated budgets. A total of 511 staff members were surveyed, comprising 238 males and 273 females, resulting in a male-to-female ratio of 0.87∶1. In terms of educational attainment, the majority held bachelor's degrees (225 individuals, 44.03%) or master's degrees and above (157 individuals, 30.72%). Professional technical personnel constituted the main occupational category, 302 individuals accounting for 59.10%. Intermediate professional titles were most common, 138 individuals accounting for 27.00%. From 2021 to 2023, a total of 68 research incentive measures have been implemented, and 579 personnel have received further training. These offices cumulatively led or participated in 80 scientific research projects and published 253 papers. Sixteen offices reported 10 and above scientific research outputs. These offices generally exhibited higher proportions of independently allocated budgets, greater numbers of senior professional titles, more staff with master's degrees or above, more implemented research incentive measures, and higher frequencies of staff further trainings. Conclusions The staff in the administrative offices of CDCs generally have a high level of educational attainment and include a significant number of professional technical personnel. However, their scientific research capacity remains relatively underdeveloped. It is recommended to conduct targeted professional training and research-focused lectures to enhance research literacy, leverage the strengths of multidisciplinary backgrounds, and promote cross-departmental and cross-institutional scientific research activities.