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.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

To analyze the relationship between serum vitamin A and E levels and asthma risk in children aged 1-14 years. Based on a multi-center case-control study design, general information and vitamin A and E test data were collected from asthmatic children in the respiratory outpatient departments of four medical institutions in Hunan Province and control children undergoing health check-ups in the child healthcare departments during the same period from July 2017 to October 2019.After 1∶1 matching age and gender using propensity scores, a total of 2 454 research subjects were included. 1 730 boys and 724 girls, with an age range of 1-14 years, a median age of 3 years and a mean age of (3.58±2.83) years. The levels of vitamin A and E in the asthma group and the control group were compared. Binary Logistic regression was used to analyze the association between vitamin levels and asthma, and stratified analysis by age and gender was conducted. The results showed that a total of 3 447 research subjects were initially included in this study, and 2 454 research subjects were included after propensity scores matching (PSM). After matching, there was no statistically significant difference in age and gender between the two groups ( χ2=0.00 ,P>0.05), and the standardized mean difference (SMD) values were all less than 10%.The levels of vitamin A and E in the asthma group were significantly lower than those in the control group [(0.32±0.09)mg/L vs.(0.34±0.08)mg/L, t=4.94 ,P<0.001;(8.90±2.47)mg/L vs.(9.19±2.58) mg/L, t=2.79 ,P=0.005]. Compared to the normal vitamin A group, the high-risk subclinical deficiency group ( OR=1.53, 95% CI: 1.28-1.83) and the subclinical/clinical deficiency group ( OR=2.68, 95% CI: 1.81-3.97) were significantly positively associated with asthma risk. Compared to the normal vitamin E group, the vitamin E insufficient group was significantly associated with increased asthma risk ( OR=1.28, 95% CI: 1.03-1.57). Subgroup analysis revealed that subclinical/clinical vitamin A deficiency was significantly associated with increased asthma risk across all age groups and both genders (all P<0.05), whereas vitamin E insufficiency was only associated with higher asthma risk in the 1-3 age group and among girls ( P<0.05).In conclusion, subclinical or clinical deficiency of vitamin A may significantly increase the risk of asthma. Vitamin E deficiency is mainly associated with an increased risk of asthma in younger age groups (1-<3 age group) and girls.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires