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 investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To investigate the clinical efficacy of over-the-top reconstruction combined with the modified Lemaire technique in the treatment of anterior cruciate ligament (ACL) injuries with pivot-shift positive.Methods:From March 2020 to October 2021, a total of 46 patients with ACL injury and pivot-shift test grade II or above were admitted to Xinhua Hospital Affiliated to Dalian University. There were 28 males and 18 females, aged 28.0±10.5 years (range, 15-45 years). All cases were unilateral, including 17 cases of left knee and 29 cases of right knee. The pivot-shift test showed that 30 cases were grade II and 16 cases were grade III, and the cause of injury was sports injury. The semitendinosus muscle and gracilis muscle were harvested, and the ACL was reconstructed with the over-the-top combined modified Lemaire technique. The International Knee Documentation Committee (IKDC) score, Lysholm score and KT-2000 side-to-side difference before and after operation were compared.Results:All patients successfully completed the operation and were followed up for 26.6±2.3 months (range, 24-28 months). The Lysholm scores of the patients at 3 months and 24 months after operation were 73.6±4.3 and 91.6±2.8, which were higher than those before operation (58.5±4.6), and the difference was statistically significant ( F=18.351, P<0.001). The IKDC scores of patients at 3 months and 24 months after operation were 59.0±2.0 and 91.8±3.2, respectively, which were higher than those before operation 50.3±2.8, and the difference was statistically significant ( F=17.290, P<0.001). The side-to-side difference of KT-2000 was 1.7±0.8 mm and 1.5±0.4 mm at 3 and 24 months after operation, respectively, which was lower than that before operation (5.9±1.1 mm), and the difference was statistically significant ( F=14.192, P<0.001). At 24 months after operation, 3 patients had pivot shift test grade I and 4 patients had Lachman test grade I, but they complained of good knee stability and did not receive further treatment. At the last follow-up, there were no complications such as incision and intra-articular infection, deep vein thrombosis, knee stiffness, quadriceps musculus ossificans myositis, and reconstruction ligament rupture. All patients returned to sports with an average time of 15.7±2.6 months (range, 12-24 months). Conclusion:Over-the-top reconstruction combined with the modified Lemaire technique for the treatment of ACL injury with positive pivot shift test effectively improves knee function and promotes the patient's return to sports, with a low incidence of surgical complications.

Objective:To investigate the tau deposition pattern in Alzheimer′s disease (AD) and its correlation with cognition by 18F-MK6240 PET imaging. Methods:From August 2021 to February 2022, 46 elderly people over 55 years old (16 males, 30 females; age (68.9±7.7) years) were included from outpatient and community in Shanghai. Structural brain MRI, β-amyloid (Aβ) PET imaging, tau-PET imaging and comprehensive neuropsychological tests batteries were conducted. The subjects were divided into AD group ( n=16) and normal cognition (NC) group ( n=30) according to the 2018 National Institute on aging and Alzheimer′s Association (NIA-AA) diagnostic criteria. Quantitative analysis was conducted to investigate the tau deposition pattern in AD after preprocessing 18F-MK6240 PET images with MRI images. SUV ratio (SUVR) of brain regions such as entorhinal cortex, hippocampus, parahippocampal gyrus, amygdala, insular lobe, frontal lobe, precuneus, occipital lobe, thalamus and putamen were analyzed, with cerebellum as reference region. The differences of tau deposition in brain regions between AD and NC groups were analyzed by independent-sample t test. The associations between SUVR and Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment-Basic (MoCA-B) score were analyzed by Pearson correlation analysis. Results:AD displayed a significant tau deposition in frontal lobes, temporal lobes and parietal lobes compared with NC. SUVR of brain regions in AD group were higher than those in NC group ( t values: 3.37-9.61, all P<0.05). SUVR in brain regions were negatively correlated with MMSE score ( r values: from -0.735 to -0.350, all P<0.05) and MoCA-B score ( r values: from -0.723 to -0.367, all P<0.05). Conclusion:18F-MK6240 PET can demonstrate the tau deposition in the brain of AD patients, and the tau deposition is related to cognitive function.

Objective To explore the factors that contribute to the anxiety and depression in obstructive sleep apnea hypopnea syndrome (OSAHS) patients in terms of excessive daytime sleepiness (EDS) and sleep quality.Methods A total of 196 OSAHS patients,including 103 severe patients and 93 mild-moderate patients,were enrolled.Polysomnography was carried on at the sleep center of the First Hospital of China Medical University between May 2013 and November 2015.According to the Epworth sleepiness scale (ESS) and the subject daytime sleepiness symptom,all patients were divided into EDS group and non-EDS group.The patients' general information and subjective symptoms were recorded.Emotional states were assessed with self-rating anxiety scale (SAS) and self-rating depression scale (SDS).Sleep quality was evaluated with Pittsburgh sleep quality index (PSQI).The anxiety and depression related factors were studied by regression analysis.Results (1) In severe OSAHS group,the patients with EDS showed higher PSQI(6.22± 2.57 vs.4.05± 3.72,P＜0.01) and oxygen desaturation index(ODI)[(57.70±17.53) events/h vs.(48.23 ± 22.01)events/h,P＜0.05] when compared with those without EDS.(2) In both severe and mild-moderate OSAHS groups,the patients with EDS presented higher SAS scores (severe:33.86±7.60 vs.28.95 ± 4.71,mild-moderate:37.46± 10.68 vs.33.40± 11.07,P＜0.05)and SDS scores(severe:32.81 ± 8.36 vs.28.90±4.53,mild-moderate:36.98± 12.77 vs.31.70±10.94,P＜0.05)when compared with those without EDS.(3) The multiple regression analysis showed that the SAS scores were related to ESS,PSQI,insomnia and nasal obstruction (R2=0.356,P＜0.05),and the SDS scores were related to ESS,PSQI and insomnia(R2=0.344,P＜0.05).Conclusions The anxiety and depression of OSAHS patients are closely related to the severity of EDS and sleep quality.Both severe and mild-moderate OSAHS patients with EDS have worse anxiety and depression scores.

Background and purpose:Numerous researches indicated that the expression of pituitary tumor transforming gene1 (PTTG1) was correlated with the severity of glioma tumors. However the specific mechanism of PTTG1 is not clear in glioma. In this study, we explored the role and significance of PTTG1 in the invasion of glioma cells. Methods:Western blot was used to detect the expression of PTTG1 protein in various glioma cell lines. siRNA plasmid was used to transfect U87 cells. Western blot was used to analyze the expression of PTTG1 protein in transfected U87 cells. Matrigel invasion assay was used to detect the invasive ability in the cells being transfected in vitro. Western blot was used to analyze epithelial growth factor (EGF) induced protein phosphorylation of ARK5 and Akt in the cells being transfected PTTG1 plasmid (siPTTG1/U87) and scrambled siRNA (Scr/U87). Results:The expression of PTTG1 protein was higher in all glioma cell lines. After transfection, the invasion of siPTTG1/U87 was obviously decreased after 5 min with EGF stimulation than the Scr/U87, the phosphorylation of ARK5 and Akt was significantly enhanced. However, whether or not the existence of EGF, the phosphorylation of ARK5 and Akt had no differences in siPTTG1/U87. Conclusion:In glioma cells, PTTG1 protein is high expressed and maybe have an important function in glioma cells invasion through Akt-ARK5 signaling pathway.

Objective To investigate the risk factors of type 2 diabetes mellitus(T2DM) in patients with nonalcoholic fatty liver disease (NAFLD) and correlations with carotid atherosclerosis.Methods The clinical data of 51 cases of N AFLD with T2DM (NAFLD with T2DM group),43 cases of NAFLD(NAFLD group) and 45 healthy objects (control group) were collected.The clinical biochemical features,carotid intima-media thickness (IMT) were observed.Results The BMI and smoking rate in NAFLD with T2DM group and NAFLD group were significandy higher than those in control group [(27.25 ±3.16),(26.31 ± 2.63) kg/m2 vs.(23.12 ±3.44) kg/m2,43.1％(22/51),37.2％(16/43) vs.13.3％(6/45)](P＜0.05).The ratio of family history of T2DM in NAFLD with T2DM group was significantly higher than that in NAFLD group and control group[66.7％(34/51)vs.32.6％(14/43),8.9％(4/45)](P ＜ 0.05).Compared with control group,the level of total cholesterol (TC),trigalloyl glycerol (TG),low density lipoprotein cholesterol (LDL-C),alanine transaminase(ALT),aspartic transaminase(AST),IMT in NAFLD with T2DM group and NAFLD group were significantly higher [(5.39 ± 0.85),(5.12 ± 0.77) mmol/L vs.(4.11 ± 0.64) mmol/L,(2.77 ± 1.11),(2.32 + 1.04) mmol/L vs.(1.21 ± 0.52) mmol/L,(2.98 ±0.93),(2.76 +0.78) mmol/L vs.(2.15 ±0.57) mtmol/L,(48.4 ± 18.9),(43.3 ± 16.5) U/L vs.(21.4 ± 13.6) U/L,(46.2 ± 16.7),(42.1 ± 17.5) U/L vs.(20.5 ± 12.6) U/L,(1.95 ±0.93),(1.26±0.51) mmvs.(0.71 ±0.22) mm](P＜ 0.05),while the level of high density lipoprotein cholesterol (HDL-C) was significantly lower [(1.01 ± 0.35),(1.13 + 0.22) mmol/L vs.(1.31 ± 0.26) mmol/L] (P ＜ 0.05).The level of above mentioned index,there were no significant difference between NAFLD with T2DM group and NAFLD group (P ＞ 0.05).The level of fasting blood glucose (FBG),2-hour postprandial blood glucose (2 h PBG),glycosylated hemoglobin (HbA1c),fasting insulin (FINS),2-hour postprandial insulin (2 h PINS) and insulin resistance index of HOMA (HOMA-IR) in NAFLD with T2DM group were significantly higher than those in NAFLD group and control group [(8.15 ± 1.48) mmol/L vs.(5.10 ± 1.32),(5.62 ± 0.88) mmol/L,(13.67 ± 1.59) mmol/L vs.(7.31 ± 1.25),(8.64± 1.35) mmol/L,(7.03 ±0.84)％ vs.(5.16 ±0.72)％,(5.53 ±0.61)％,(13.32 ±4.55) mU/L vs.(6.06 ±3.11),(9.13 ±4.37) mU/L,(106.37 ±21.45) mU/L vs.(33.21 ± 18.87),(46.34 ± 16.39) mU/L,3.88 + 2.14 vs.1.13 ± 0.36,2.23 ± 1.15] (P ＜ 0.05).Carotid IMT,the incidence of carotid plaque and Crouse scores of plaque in NAFLD with T2DM group were significandy higher than those in NAFLD group [(1.95 ±0.93) mm vs.(1.26 ±0.51) mm,64.7％(33/51) vs.30.2％(13/43),(3.11 ±0.57) nn vs.(1.35 ± 0.49) mm] (P ＜ 0.05).The regression analysis showed that family history of T2DM,FBG,2 h PBG,FINS,2 h PINS were independently associated with T2DM.Conclusions Family history of T2DM,FBG,2 h PBG,FINS,2 h PINS are the main risk factors for the onset of T2DM in NAFLD.The risk of carotid atherosclerosis is increased in patients of NAFLD with T2DM.

Objective To characterize the biomechanical behavior and properties of the chondrons enzymatically isolated from rabbit knee articular cartilage in virto. Methods Eight months old New Zealand white rabbits were randomly divided into chondroctye and chondron groups (4 rabbits in each group). In chondrocyte groups, the full articular cartilages from both knees were enzymatically isolated to chondrocytes by 0.4% pronase and 0.025% collagenase type-Ⅱ in turn. In chondron groups, chondrons were obtained from articular cartilage using the mixture of 0.3% dispase (a neutral protease) and 0.2% collagenase type-Ⅱin at 37C for 3 h. The micropipette aspiration was used to quantify changes in biomechanical properties of chondrons and chondrocytes and the viscoelastic parameters, including K1, K2, E∞ (equilibrium modulus), E0(instantaneous modulus), and μ (apparent viscosity), were calculated coupled with standard linear half-space viscoelastic solid model. Results In response to a constant negative pressure of 0.2-0.4 kPa, the chondrocytes exhibited standard linear viscoelastic solid properties. Namely, the cells showed an initial elastic response followed by a viscoelastic creep response. then cells continued to enter into the micropipette with a monotonically decreasing rate of deformation, until reaching equilibrium within about (110±18) s. Comparing with chondrocytes, the chondrons exhibited significant viscoelasticity under a greater negative pressure of 1.0-1.2 kPa. But the instantaneous length deformed into the micropipette significantly reduced, and the equilibrium time reduced to (36.5±4.5) s. The equilibrium modulus (E∞), the instantaneous modulus (E0) and the apparent viscosity (μ) of chondrons were significantly higher than the those of chondrocytes. Conclusion Comparing with chondrocytes, the chondrons exhibited significant viscoelastic properties, and viscoelastic properties of chondrons have increased in vitro.