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.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

Objective : To characterize MMP12 as a pan-cancer marker and assess its screening value as a tumor serum marker. Methods : Bioinformatics tools such as GEPIA2,GSCA,cBioPortal,and GeneMANIA were used to analyze the pan-cancer features of MMP12 in TCGA datasets,including encompassing differential gene expression analysis,prognostic analysis,DNA methylation analysis,gene structural variation analysis and immune microenvironment analysis.Furthermore,serum samples we collected from patients with lung adenocarcinoma,breast invasive carcinoma,esophageal squamous cell carcinoma,stomach adenocarcinoma,liver hepatocellular carcinoma,and healthy individuals.ELISA was used to detect MMP12 expression in serum,and the screening performance was evaluated using the area under the ROC curve.Additionally,we followed up 28 ESCC patients and compared serum MMP12 levels between 19 patients with disease progression and 9 patients with stable disease. Results: The pancancer feature analysis revealed a significant negative correlation between MMP12 mRNA expression and its promoter DNA methylation(P<0.05),as well as a positive correlation with gene copy number variations(P<0.05).MMP12 mRNA expression was up-regulated in 14 cancer tissues compared to normal tissues next to cancer(P<0.05) and was associated with poor prognosis of cancer patients(P<0.05).Immunocorrelation analysis showed that MMP12 was significantly associated with immunity,infiltration of stromal cells,tumor mutational burden(TMB) and microsatellite instability(MSI)(P<0.05).ROC curve analysis indicated that MMP12 could serve as a potential biomarker for screening lung adenocarcinoma,breast invasive carcinoma,esophageal squamous cell carcinoma,stomach adenocarcinoma,and liver hepatocellular carcinoma.In a 30-month follow-up study of esophageal squamous cell carcinoma patients,the expression of MMP12 was higher in the disease progression group than that in the stable group. Conclusion MMP12 serves as a potential prognostic and screening marker of pan-cancer.

Objective To identify factors associated with gastrointestinal heat retention in preschool children,and to provide a foundational understanding for future clinical investigations. Methods A case-control study was performed,which involved children from kindergartens in the Longgang District of Shenzhen City,Guangdong Province,from May to July 2021. Using the Children's Gastrointestinal Heat Retention Diagnostic Self-assessment Scale,subjects were allocated into a case group (children diagnosed with gastrointestinal heat retention) and a control group (children without this condition). An online survey was used to collect data on dietary behaviors,caregivers' feeding behaviors,early antibiotic use,daily routines,and birth conditions. SPSS 27.0 software was used to facilitate precise sociodemographic matching and paired logistic regression analysis to explore the association between gastrointestinal heat retention and the above factors. Results From the analysis of 51,252 matched cases,the study found that several factors contributed to an increased risk of gastrointestinal heat retention. These factors included reduced food intake compared to peers,reports of picky eating by caregivers,distractions during meals,pronounced dietary preferences,disinterest in food,meal durations ≥ 25 min,reluctance to sample new foods,consistent refusal of specific food types for over one month,irregular meal locations,coercive feeding practices,use of micronutrient supplements,allowing children too much freedom in food choice,persuading children to eat,infrequent encouragement to experiment with new foods,early antibiotic introduction,inadequate sleep,and premature birth (P<0.05). In contrast,exclusive breastfeeding in the first six months,engagement in moderate to massive physical activity,and regular napping patterns were associated with a reduced risk of gastrointestinal heat retention (P<0.05). Conclusion The suboptimal dietary habits,improper feeding practices,insufficient physical activity,inadequate sleep,and premature antibiotic exposure may be significant risk factors for gastrointestinal heat retention. Future research dedicated to unraveling the cause of gastrointestinal heat retention should prioritize these elements.

Objective To investigate the effect of mesenchymal stem cells(MSCs)combined with immunosuppressants(IS)on immune rejection in a rat model of liver transplantation.Methods F344 rats were divided into Normal group(without any intervention),PS group(injected with an equal volume of normal saline),MSC group(injected with MSC),IS group(injected with IS),and MSC+IS group(injected with MSC and IS),with 8 rats in each group.For all rats except those in the Normal group,the Kamada's double-cuff method was used to establish a model of orthotopic liver transplantation,without reconstruction of the hepatic artery.HE staining and Masson staining were performed for rat liver tissue,and the degree of liver fibrosis was analyzed;immunohistochemical experiments were used to measure the infiltration of T cells and NK cells,and immunofluorescence assay was used to analyze macrophage M2 polarization.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for survival analysis.Results Compared with the PS group,the MSC+IS group had a significantly prolonged survival time(P＜0.01),and the MSC group,the IS group,and the MSC+IS group had a significant improvement in the histological structure of the liver and a significant reduction in the degree of liver fibrosis(all P＜0.000 1),as well as a significant reduction in the infiltration of NK and T cells(all P＜0.000 1)and a significant increase in the degree of macrophage M2 polarization(all P＜0.000 1).The MSC+IS group had a significantly better effect than the MSC group and the IS group.Conclusion MSCs combined with IS can improve liver histopathology,reduce inflammatory cell infiltration,promote macrophage M2 polarization,and exert an immunosuppressive effect in rats after liver transplantation.

Objective To systematically review the evidence from systematic reviews of the application models and health benefits of virtual reality(VR)technology in physical activities and health domains in children and adolescents with cere-bral palsy(CP). Methods PubMed,Embase,CINAHL,SPORTDiscus,Google Scholar,PsycINFO and CNKI were searched to collect and screen systematic reviews published from January,2020 to March,2024 on the application of VR technology in physical activities and health for children with CP.The relevant evidence was reported following PRISMA guidelines. Results A total of eight English researches from China,Saudi Arabia,Indonesia and Brazil were included,involving 5 692 children and adolescents with CP,came primarily from interdisciplinary journals in clinical medicine,thera-py and clinical risk management,games and gamification,and physical movement therapy.The subjects aged four to 18 years,with spastic hemiplegia and spastic diplegia.The VR technologies featured five typical applica-tion models:immersive environment simulation;interactive motion gamification;virtual training and coaching;AI-based activity data tracking and analysis,and motion capture and feedback,biofeedback integration and wear-able technology applications;and augmented reality integration.Interventions lasted 15 to 90 minutes a time,one to 15 times a week,with intensities ranging from moderate to vigorous and durations from one to 24 weeks.The application of VR technology might increase the interest in participating in physical activities,enhance the interactive experience,through integration with wearable and biofeedback technologies,enable timely monitor-ing,tracking,analysis and feedback on children's activity statuses,improving their physical and functional abili-ties. Conclusion VR technology including immersive environment simulation and interactive motion gamification may im-prove interest in physical activities,physical quality and functional abilities,promoting behavioral health,and en-hancing overall health levels and quality of life of children and adolecents with CP.

Objective To investigate the application effect of fiberoptic bronchoscopy and alveolar lavage therapy in the diagnosis and treatment of recurrent wheezing diseases in children. Methods A total of 151 children with recurrent wheezing diseases were enrolled, and divided into control group (n=84) and study group (n=67) based on different diagnostic and therapeutic methods. The control group received conventional diagnosis and treatment, while the study group underwent fiberoptic bronchoscopy combined with alveolar lavage therapy. The time to resolution of symptoms and length of hospital stay were compared between the two groups. Additionally, lung function [forced expiratory volume in 1 second (FEV₁), FEV₁/forced vital capacity (FEV₁/FVC) and peak expiratory flow (PEF)], exhaled nitric oxide (FeNO), serum inflammatory mediator levels [C-reactive protein (CRP), procalcitonin (PCT) and white blood cell (WBC) count] and clinical efficacy were compared. Results The absence time of wheezing and pulmonary rales and hospital stay in the study group were significantly shorter than those in the control group (P < 0.05). After treatment, FEV₁, FEV₁/FVC and PEF in two groups were significantly higher than before treatment, and the study group was significantly higher than the control group (P < 0.05). After treatment, FeNO, CRP, PCT and WBC in two groups were significantly lower than before treatment, and the study group was significantly lower than the control group (P < 0.05). The total effective rate of the study group was 94.03%, which was significantly higher than 77.38% of the control group (P < 0.05). Conclusion Fiberoptic bronchoscopy and alveolar lavage are effective in the diagnosis and treatment of recurrent asthmatic diseases in children, which can effectively relieve symptoms, shorten hospital stay, and improve lung function, FeNO and serum inflammatory mediators.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

ObjectiveTo investigate the possible mechanism of electroacupuncture at "Neiguan" （PC6） and "Zhongwan" （RN12） in the treatment of functional dyspepsia （FD）. MethodsSPF male SD rats were randomly divided into model group， Neiguan （PC6） group， Zhongwan （RN12） group， and Neiguan-Zhongwan （PC6-RN12） group， with 8 rats in each group. Except for the normal group， the other groups of rats were cogavaged with 0.1% sucrose iodoacetamide solution combined with small platform standing training to establish FD rat models. After successful modeling， the rats in the normal group and model group were tied up for 30 min/d for 7 days； the Neiguan group， Zhongwan group， and Neiguan-Zhongwan group were treated with electroacupuncture intervention at "Neiguan" （PC6）， "Zhongwan" （RN12）， and "Neiguan" - "Zhongwan" （PC6-RN12） acupoints， respectively， using continuous wave， frequency of 2 Hz， current intensity of 1 mA， 30 min/d， and continuous intervention for 7 days. The general condition of rats in each group was observed. After treatment， the body weight and food intake of rats were measured， and the gastric emptying rate was calculated； HE staining was performed on the gastric antrum tissue of rats to observe the histopathologic changes； the expressions of calcitonin gene-related peptide （CGRP） and Ghrelin protein in gastric antrum were detected by Western Blot； the metabolites in gastric antrum tissues were detected by liquid chromatography-mass spectrometry （LC-MS）， and differential metabolites were screened by correlation analysis， then Metabo Analyst 5.0 and KEGG databases were used for metabolic pathway analysis. ResultsUnder light microscope， the gastric antrum structure was complete and the glands were abundant. No obvious inflammation and edema were found in gastric mucosa. Compared with the normal group， the body weight， food intake， and gastric emptie rate of rats in model group decreased， the expression of Ghrelin protein decreased and the expression of CGRP protein increased in gastric antrum tissue （P＜0.01）. Compared with model group， the body weight， food intake， and gastric emptance rate of rats in Neiguan group， Zhongwan group and Neiguan-Zhongwan group all increased， CGRP protein expression decreased in Neiguan group， and Ghrelin protein expression increased and CGRP protein expression decreased in Zhongwan group and Neiguan-Zhongwan group （P＜0.01 or P＜0.05）. Compared with Neiguan-Zhongwan group， Ghrelin protein expression decreased and CGRP protein expression increased in Neiguan group and Zhongwan group （P＜0.05 or P＜0.01）. Metabolomics results showed that compared with normal group， the content of metabolites adenosine diphosphate ribose， adenosine monophosphate and adenosine diphosphate in gastric antrum tissue of model group decreased； compared with model group， the contents of adenosine diphosphate， adenosine diphosphate and citicoline in Neiguan group increased， the contents of nicotine adenine dinucleotide， cytidine diphosphate ethanolamine and citicoline in Zhongwan group increased， and the contents of adenosine diphosphate， cytidine diphosphate and citicoline in Neiguan-Zhongwan group increased （P＜0.05 or P＜0.01）. Compared with model group， the main metabolic pathways of different metabolites in PC6-RN12 group were glycerophospholipid metabolism， taurine and hypotaurine metabolism， purine metabolism， starch and sucrose metabolism. ConclusionElectroacupuncture at “Neiguan” and “Zhongwan” acupoints can effectively regulate gastrointestinal motility and improve FD symptoms in FD rats， and the effect is better than that of "Neiguan" or "Zhongwan" acupoints alone. The mechanism may be related to the influence of related metabolites on energy metabolism， glucose metabolism and nucleotide metabolism， thereby regulating gastrointestinal motility hormones.