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.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Objective To explore the effects of transverse cervical artery related skin flaps in repairing skin soft tissue defects in the neck and shoulder.Methods A total of 13 patients with soft tissue defects in neck and shoulder admitted to Linyi People's Hospital from January 2018 to January 2022 were selected.The wounds of patients were repaired with transverse cervical artery related skin flaps,and the donor area was repaired with direct suturing and/or full-thick skin graft from the inguinal area.The survival,appearance and texture of the flap after surgery were recorded.The wound healing in the donor area and the survival of the grafted skin were observed.The follow-up was conducted for 5 to 12 months,and the appearance of the grafted flap and the recovery of function in the surgical area were observed.Results The flaps had good survival in the first stage after surgery,the color and texture of the flap matched well with the surrounding tissue,and the wound healing in the donor area was good.During the follow-up,the function and appearance of neck and shoulder for patients recovered well.Conclusion The advantages of transverse cervical artery related skin flaps in repairing skin soft tissue defects in the neck and shoulder is that the color and texture of the flap matched well with the surrounding tissue,with reliable blood circulation,and the appearance and postoperative function recover well,which is worthy of promotion and application in clinic.

Tumor microenvironment(TME)is the foundation for tumor survival,which is composed of various types of cells,tumor blood vessels,secretory factors,and extracellular matrix(ECM)within the tumor.The unique regulatory mechanism triggered by the vigorous metabolic demand of tumor plays an important role in its tumorigenesis,metastasis,invasion,and treatment resistance.A deeper understanding of the metabolic transformation and tumor-immune cell interactions in the TME will enable the development of therapeutic technologies that precisely target TME metabolism,facilitate the development of combination treatment strategies,and improve the clinical response rate of existing immunotherapies.This paper reviews the composition,metabolism and regulatory mechanisms of TME,summarizes the research progress of immunotherapy strategies targeting the physiological characteristics of TME,and discusses the prospects for clinical application of precision immunotherapy strategies targeting TME,which are expected to enhance immunotherapy drugs response and infiltration degree.

OBJECTIVE To investigate the changes of air aerosols in the digestive endoscope cleaning and disinfec-tion room under real working conditions and observe the purification effects of aerosols under different ventilation and disinfection modes.METHODS Under the real working conditions(with both the air conditioner and recircu-lating air disinfection machine under the working mode),the air samples were collected every 1 hour from 8:00 to 16:00 from the digestive endoscope cleaning and disinfection room of Ren Ji Hospital,Shanghai Jiao Tong U-niversity School of Medicine from May 2023 to Oct.2023;the contents of particulate matters(PM)and microor-ganisms in the air were detected.At the busiest moment of the cleaning and disinfection room,the air was respec-tively sampled from the cleaning and disinfection room with the working condition modes of air condition systems,recirculating air disinfection machine or natural ventilation before the starting of systems and after the work for 0.5 hour,1 hour and 2 hours.The contents of PMs and microorganisms were detected.RESULTS The PM0.5 con-centrations during various time periods met the Grade 9 ISO clean room standard(≤35,200 particles/L)under the real working conditions,and the content of airborne viable particles also conformed to the Class Ⅲ environmental requirements(≤500 CFU/m3).All of the three ventilation and disinfection methods showed certain effects on purification of the con-tents of PM0.5 and microorganisms after the ventilation for 2 hours,the contents of PMs and microorganisms of the air disinfection machine group decreased most remarkably,followed by the air conditioner group,the natural ventilation group the least.There were no significant differences in the PM concentration and the content of microorganisms among the three groups at the time points;there were only significant differences in the PM concentration and the content of mi-croorganisms of the air disinfection machine group after the ventilation for 2 hours,0.5 hour and 1 hour(P＜0.05).CONCLUSIONS Both the air conditioning systems and recirculating air disinfection machine under the working con-dition mode have certain effect on purification of the contents of PM and microorganisms,and the specific effect need to be further studied.The implementation of multicenter dynamic surveillance with the help of intelli-gent techniques may provide reference for the optimization of ventilation and disinfection strategies.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To explore the effects of transverse cervical artery related skin flaps in repairing skin soft tissue defects in the neck and shoulder.Methods A total of 13 patients with soft tissue defects in neck and shoulder admitted to Linyi People's Hospital from January 2018 to January 2022 were selected.The wounds of patients were repaired with transverse cervical artery related skin flaps,and the donor area was repaired with direct suturing and/or full-thick skin graft from the inguinal area.The survival,appearance and texture of the flap after surgery were recorded.The wound healing in the donor area and the survival of the grafted skin were observed.The follow-up was conducted for 5 to 12 months,and the appearance of the grafted flap and the recovery of function in the surgical area were observed.Results The flaps had good survival in the first stage after surgery,the color and texture of the flap matched well with the surrounding tissue,and the wound healing in the donor area was good.During the follow-up,the function and appearance of neck and shoulder for patients recovered well.Conclusion The advantages of transverse cervical artery related skin flaps in repairing skin soft tissue defects in the neck and shoulder is that the color and texture of the flap matched well with the surrounding tissue,with reliable blood circulation,and the appearance and postoperative function recover well,which is worthy of promotion and application in clinic.

Tumor microenvironment(TME)is the foundation for tumor survival,which is composed of various types of cells,tumor blood vessels,secretory factors,and extracellular matrix(ECM)within the tumor.The unique regulatory mechanism triggered by the vigorous metabolic demand of tumor plays an important role in its tumorigenesis,metastasis,invasion,and treatment resistance.A deeper understanding of the metabolic transformation and tumor-immune cell interactions in the TME will enable the development of therapeutic technologies that precisely target TME metabolism,facilitate the development of combination treatment strategies,and improve the clinical response rate of existing immunotherapies.This paper reviews the composition,metabolism and regulatory mechanisms of TME,summarizes the research progress of immunotherapy strategies targeting the physiological characteristics of TME,and discusses the prospects for clinical application of precision immunotherapy strategies targeting TME,which are expected to enhance immunotherapy drugs response and infiltration degree.