OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Aim To investigate the dynamic changes of neuronal cells at different time points following acute cerebral ischemia-reperfusion injury by establishing a model of brain ischemia-reperfusion injury.Methods Thirty male Sprague-Dawley(SD)rats were ran-domly divided into six groups:sham group and cere-bral ischemia-reperfusion injury(IR)groups at differ-ent time points.Focal cerebral ischemia-reperfusion injury model was established using the middle cerebral artery occlusion(MCAO)technique.The Longa sco-ring method was used to assess neurobehavioral scores in rats.After successful model preparation,routine paraffin sections were made,and TUNEL staining and immunohistochemistry staining with NeuN antibody were performed to observe cell apoptosis and neuronal cell survival,respectively.Immunohistochemistry stai-ning was also performed to investigate the changes in glial fibrillary acidic protein(GFAP)as a marker for astrocytes,ionized calcium-binding adapter molecule 1(IBA-1)as a marker for microglia,and CD31 as a marker for endothelial cells at different time points.Results No significant changes were observed in neu-ronal cells of the sham group at different time points.In the cerebral ischemia-reperfusion injury groups,cell apoptosis was activated at IR3h and increased in quan-tity with morphological damage as time progressed.Ne-uN+neurons showed signs of ischemic injury after IR3h,with abnormal cell morphology.From 12 h,Ne-uN+neurons decreased in a time-dependent manner and reached their peak severity at 24 h.GFAP+astro-cytes decreased significantly after IR3h,while poorly labeled GFAP+astrocytes increased at IR 6 h and al-most disappeared in the infarcted area at 24 h and 48 h.The number of IBA-1+microglia-positive cells de-creased at IR3h,and their volume increased at IR6h.Microglial cell death was observed in the infarcted area at IR12h.CD31+endothelial cells around the infarc-ted cortex and striatum increased significantly after IR3h and persisted until 48 h.Conclusions After cerebral ischemia-reperfusion injury,the number of ap-optotic cells increases with the prolongation of time,and NeuN+neurons exhibit the most severe damage at 24 h.GFAP+astrocytes and microglial cells gradually die over time.The number of CD31+endothelial cells increases significantly around the infarcted cortex and striatum after 3 h of reperfusion and persists until 48 h.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective:To investigate the prevalence of frailty among elders aged ≥60 years in the Beijing community and analyze the risk factors of frailty.Methods:This is a cross-sectional study. A total of 1936 older persons in Baizhifang Community in Beijing were included between May and September 2023. Their frailty was evaluated by Fried Frailty Phenotype Scale. Mini Nutritional Assessment-Short Form (MNA-SF), Short Physical Performance Battery (SPPB), and Geriatric Depression Scale (GDS) were used to evaluate nutritional status, physical function, and depression, respectively. The prevalence and risk factors of frailty among the elderly in the community were analyzed.Results:A total of 168 individuals met the criteria for frailty, and the prevalence of frailty was 8.7%. Compared to the non-frail group, the frail group was predominantly female (71.4% vs 62.2%; χ 2=5.59, P=0.018), older [(72.1±6.6) vs (69.9±6.0) ages; t=-5.25, P<0.001], unmarried (1.8% vs 0.8%; χ 2=8.60, P=0.014), with lower education levels (10.7% vs 3.5%; χ 2=23.38, P<0.001), poorer self-assessed health (22.6% vs 6.5%; χ 2=69.80, P<0.001), lower MNA-SF scores [(12.2±2.2) vs (13.0±1.4) scores; t=6.29, P<0.001], lower SPPB scores [(8.4±1.9) vs (10.2±1.6) scores; t=14.62, P<0.001], higher GDS scores [(4.0±3.8) vs (1.9±2.1) scores; t=-11.48, P<0.001], and worse vision, hearing, and olfactory functions (48.2% vs 34.1%, 36.9% vs 23.0%, 9.5% vs 3.0%; χ 2=13.37, 16.11, 40.58, all P<0.001). They were also more likely to suffer from hypertension (70.8% vs 56.7%; χ 2=12.52, P<0.001), diabetes (42.3% vs 29.4%; χ 2=12.06, P<0.001), osteoarthritis (46.4% vs 30.3%; χ 2=18.39, P<0.001) and stroke (19.0% vs 13.3%; χ 2=4.28, P=0.039). Logistic regression analysis showed that frailty was independently associated with nutritional status ( OR=0.8, 95% CI: 0.7-0.9, P<0.001), depressive symptoms ( OR=1.1, 95% CI: 1.1-1.2, P<0.001), olfactory function ( OR=2.1, 95% CI: 1.4-3.0, P<0.001; OR=2.9, 95% CI: 1.4-5.9, P=0.003), and physical function ( OR=0.6, 95% CI: 0.6-0.7, P<0.001) after adjusting for covariates. Conclusions:The prevalence of frailty among elderly people in community is relatively high. Frailty in community elders is associated with physical function, psychological function, nutritional status, and olfactory function decline.

Objective:To analyze mobility limitation condition and its relationship with cognitive function in community-dwelling elderly.Methods:In this cross-sectional study, a total of 1 935 older adults aged≥60 years were recruited from May to September 2023 in Beijing Baizhifang Community Health Service Center and its five subordinate health service stations (Baizhifang Hutong health service station, Nancaiyuan community health service station, Youanmen community health service station, Younei West Street health service station and Shuanghuaili community health service station). The Short Physical Performance Battery (SPPB) was used to assess the mobility capacity of the elderly, and the elderly were divided into two groups with SPPB, the elderly with a SPPB≤9 points were grouped into mobility limitation group (645 cases), and the ones with a SPPB≥10 points were considered with normal mobility capacity (1 290 cases). The cognitive function of the older adults was assessed with the mini-mental state examination; and the gender, age, calf circumference, history of chronic disease, frailty status, cognitive function, nutritional status, depression status, hearing and vision condition of the two groups were compared with χ2 test or Mann-Whitney U non-parametric test. Multiple logistic regression analysis was used to analyze the mobility limitation and its relationship with cognitive function in the older adults. Results:Mobility limitation was found in 33.33% (645/1 935) of community-dwelling older adults. The proportions of advanced age, female, hypertension, diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, frailty, depression, cognitive impairment, hearing decline, and vision decline in the mobility limitation group were all significantly higher than those in the normal mobility capacity group (31.32% vs 13.41%, 69.92% vs 59.61%, 65.27% vs 54.03%, 33.80% vs 28.60%, 27.91% vs 19.53%, 17.83% vs 11.47%, 10.54% vs 7.36%, 13.18% vs 2.02%, 18.45% vs 6.59%, 14.73% vs 7.75%, 30.54% vs 20.31%, 45.58% vs 30.39%) (all P<0.05). Advanced age ( OR=2.542, 95% CI: 1.977-3.269), female ( OR=1.736, 95% CI: 1.390-2.167), stroke ( OR=1.426, 95% CI: 1.065-1.911), depression ( OR=2.292, 95% CI: 1.656-3.174), cognitive impairment ( OR=1.601, 95% CI: 1.154-2.220), frailty ( OR=5.199, 95% CI: 3.219-8.397) and vision decline ( OR=1.405, 95% CI: 1.124-1.756) were all positively correlated with the mobility limitation in the community-dwelling older adults (all P<0.05). Conclusion:The older adults in the community have a higher risk of mobility limitation, mobility limitation is a positive correlation factor of cognitive impairment.

Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

Objective:To analyze the association between sleep status and ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.Methods:It was a cross sentional study. Hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring from May 2021 to April 2023 in Shanghai Xinzhuang Town were enrolled. The demographic information and sleep status of patients were obtained from the questionnaire. A TM-2430 blood pressure monitor was used to measure 24-hour ambulatory blood pressure, and the relevant indicators, including blood pressure level and blood pressure coefficient of variation were documented. The association between sleep status and blood pressure indicators was analyzed with multivariate linear regression model.Results:A total 1 135 patients aged (65.07±12.61) years were enrolled, and 473 (41.67%) of whom were males. The sleep time was<7 hours in 76 cases, 7- 8 hours in 219 cases and >8 hours in 840 cases; the bedtime was earlier than 22∶00 in 415 cases, between 22∶00 and 23∶00 in 474 cases and later than 23∶00 in 246 cases; the wake-up time was before 6∶00 in 230 cases, between 6∶00 and 7∶00 in 521 cases and after 7∶00 in 384 cases. Multivariate linear regression analysis showed that after controlling for gender and age, the sleep time was negatively associated with diurnal, noctumal and 24-hour diastolic blood pressure levels (all P<0.05), and positively associated with diurnal and noctumal systolic blood pressure coefficient of variation, noctumal diastolic blood pressure coefficient of variation, and 24-hour systolic blood pressure coefficient of variation (all P<0.05).The bedtime was positively associated with diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), diastolic blood pressure (all P<0.05); and negatively associated with diurnal systolic blood pressure coefficient of variation, diurnal diastolic blood pressure coefficient of variation, noctumal systolic blood pressure coefficient of variation, 24-hour systolic blood pressure coefficient of variation, and 24-hour diastolic blood pressure coefficient of variation (all P<0.05). The wake-up time was positively associated with diurnal systolic blood pressure, diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), and positively associated with diurmal systolic blood pressure and diastolic blood pressure (both P<0.05). Conclusion:Sleep status is closely associated with ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.