OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.

Objective:To construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

OBJECTIVE To investigate the effects of coptisine on endogenous metabolites in a dextran sulfate sodium(DSS)-in-duced ulcerative colitis(UC)mouse model,and to explore its potential mechanisms of action employing non-targeted metabolomics technology.METHODS SPF-grade male C57BL/6 mice were randomly divided into a control group,a model group,a sulfasalazine group(100 mg·kg-1),and low and high dose groups of coptisine groups(25,50 mg·kg-1).To induce ulcerative colitis(UC),all groups except the control group had free access to a 2.5%DSS solution for 7 days.At the same time,they also received daily intragastric ad-ministration of their corresponding treatments until the 10th day.Body weight changes,stool characteristics,and bloody stool occur-rence were recorded daily,and the disease activity index(DAI)was calculated.After the experiment,colon tissues were collected for pathological examination.Through UPLC-Q-TOF-MS/MS,non-targeted metabolomic analysis was performed to identify differential metabolites,and metabolic pathway enrichment analysis was conducted using the KEGG database.RESULTS Compared to the model group,coptisine significantly ameliorated weight loss,DAI scores,and pathological damage in colon tissues of UC mice(P<0.05,P<0.01).Metabolomic analysis identified 56 differential metabolites,mainly involved in purine metabolism,tryptophan metabo-lism,niacin and nicotinamide metabolism,glutathione metabolism,and the biosynthesis of phenylalanine,tyrosine,and tryptophan.Coptisine intervention significantly reversed the abnormal expression of these metabolites.CONCLUSION Coptisine can markedly improve metabolic disorders in DSS-induced UC mice by modulating multiple key metabolic pathways,thereby exerting a therapeutic effect.

Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.

OBJECTIVE: To explore the application value and clinical effect of 3D printing combined with customized bone plate in the treatment of acetabular fracture. METHODS: From June 2020 to June 2022, 11 patients with acetabular fractures underwent preoperative planning using 3D printing technology and were treated with customized bone plates including 8 males and 3 females, aged 25 to 66 years old. The fractures were classified according to Letournel-Judet:4 posterior wall fractures, 2 T-type fractures, 2 transverse posterior wall fractures, 2 double column fractures, and 1 anterior column with posterior semi-transverse fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, postoperative drainage volume, postoperative fracture healing time, and hip function score were recorded and analyzed. RESULTS: The operation time of 11 patients was 80 to 150 min, intraoperative blood volume was 150 to 700 ml, fluoroscopy frequency was 2 to 6, postoperative drainage flow was 60 to 195 ml, and the fracture healing time was 2.5 to 6.0 months. Fracture reduction was evaluated according to Matta score:anatomical reduction in 3 cases and satisfactory reduction in 8 cases. Eleven patients were followed up for 7 to 18 months. The hip Merle d'Aubigne function scores were excellent in 6 cases, good in 3 cases, fair in 1 case and poor in 1 case. Incision fat liquefaction occurred in 1 case and obturator nerve traction in 1 case. CONCLUSION The application of 3D printing technology combined with customized bone plates in the treatment of acetabular fracture is effective. In addition, the printed model can provide the operator with the results of the three-dimensional shape of the fracture, which is convenient for surgical reduction and effectively improves the efficiency of surgery.
Humans ; Female ; Male ; Middle Aged ; Acetabulum/surgery* ; Printing, Three-Dimensional ; Adult ; Aged ; Bone Plates ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods*