Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.

According the Good Clinical Practice(GCP)and programmatic requirements,we analyze the management characteristics and the costs of drugs for clinical trials in different specialties from the drug management;The characteristics of the management of drugs for different specialties was summarize and the differential factors that may affect the management cost was explored,so as to provide theoretical support for the research institutions to utilize the resources in a rational and efficient way.This article provides a guarantee for the drug management with the aim of enhancing the quality and efficiency of clinical trials.

Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.

Objective This study aims to discuss and summarize the management system for drugs used in clinical trials,with the objective of elevating the management standards.Methods Considering the situation of diverse departmental needs and the multi-campus structure,the study analyzed and explored the management of drugs for clinical trials to build a corresponding management system,including pharmacy construction,equipment,personnel qualifications,data management,drug reception,storage,distribution,and recycling protocols.The effecttivness of the system was evaluated through comparative analysis of data from 2022 to 2023 at our hospital.Result Improvements in the management of drugs for clinical trials were observed in 2023 across varous aspects.Conclusion Refining the management system of drugs for clinical trials can enhance Good Clinical Practice(GCP)supervision and service,providing an important reference for the management system.

According the Good Clinical Practice(GCP)and programmatic requirements,we analyze the management characteristics and the costs of drugs for clinical trials in different specialties from the drug management;The characteristics of the management of drugs for different specialties was summarize and the differential factors that may affect the management cost was explored,so as to provide theoretical support for the research institutions to utilize the resources in a rational and efficient way.This article provides a guarantee for the drug management with the aim of enhancing the quality and efficiency of clinical trials.

Objective This study aims to discuss and summarize the management system for drugs used in clinical trials,with the objective of elevating the management standards.Methods Considering the situation of diverse departmental needs and the multi-campus structure,the study analyzed and explored the management of drugs for clinical trials to build a corresponding management system,including pharmacy construction,equipment,personnel qualifications,data management,drug reception,storage,distribution,and recycling protocols.The effecttivness of the system was evaluated through comparative analysis of data from 2022 to 2023 at our hospital.Result Improvements in the management of drugs for clinical trials were observed in 2023 across varous aspects.Conclusion Refining the management system of drugs for clinical trials can enhance Good Clinical Practice(GCP)supervision and service,providing an important reference for the management system.

Objective:To analyze the dynamic development of physical, psychological, and cognitive degenerative multimorbidity among middle-aged and older Chinese adults (≥45 years old) while estimating the longitudinal association between socioeconomic status (SES) and the progression of multimorbidity.Methods:Based on data from the China Health and Retirement Longitudinal Study (2011-2020), the Sankey diagram was used to show the dynamic development of physical, psychological, and cognitive degenerative multimorbidity from 2011 to 2020. SES was constructed based on the level of education and total household wealth. Logistic regression was used to estimate OR and 95% CI to evaluate the association between SES and the progression of multimorbidity. Results:Of the 5 393 participants included, 4 484 (83.14%) of them developed new diseases, and the prevalence of physical, psychological, and cognitive degenerative multimorbidity increased from 38.04% to 74.23%. Compared to those with no reported disorders at baseline, participants with psychological disorder (for newly developed physical-cognitive multimorbidity: OR=4.59,95% CI: 2.89-7.29), cognitive disorder (for newly developed physical-psychological multimorbidity: OR=2.24,95% CI: 1.40-3.60), or their multimorbidity at baseline were more likely to progress to physical, psychological, and cognitive degenerative multimorbidity. After adjusting covariates, individuals with low SES were more likely to develop physical diseases ( OR=1.45, 95% CI: 1.11-1.89), cognitive disorder ( OR=1.84, 95% CI: 1.16-2.91), physical-psychological multimorbidity ( OR=1.87, 95% CI: 1.37-2.56), physical-cognitive multimorbidity ( OR=3.58, 95% CI: 2.54-5.06), psychological-cognitive multimorbidity ( OR=5.66, 95% CI: 3.04-10.55), and physical-psychological-cognitive multimorbidity ( OR=3.21, 95% CI: 2.06-5.01) in comparison to those with high SES. There is a dose-response relationship between SES and the multimorbidity progression (all trend P<0.001). Conclusions:The prevalence of physical, psychological, and cognitive degenerative multimorbidity increased significantly among middle-aged and older Chinese adults. Lower SES was associated with multiple patterns of physical, psychological, and cognitive disorders progression.

Objective:To analyze the changes of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasomes in peripheral blood of patients with diabetic nephropathy (DN) and its clinical significance.Methods:208 patients with type 2 diabetes (T2DM) admitted to our hospital from Feb. 2018 to Dec. 2020 were selected and were divided them into 3 groups according to the urine albumin (UA) /urinary creatinine (UC) ratio (UACR) : simple T2DM group (UACR<30 mg/g) 83 cases, microalbuminuria group (UACR 30-300 mg/g) 70 cases, and massive proteinuria group (UACR>300 mg/g) 55 cases; Fifty healthy volunteers were selected as the control group. General data of each group were collected. Western blot was used to detect the level of NLRP3 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) kit was used to detect the level of serum interleukin (IL) -1β and IL-18. Logistic regression was employed to analyze the occurrence of DN in T2DM patients. Receiver operating characteristic curve (ROC) curve was used to analyze the value of NLRP3, IL-1β, IL-18 in the diagnosis of DN in peripheral blood.Results:Compared with the control group, the course of disease, FBG, LDL-C, TG, TC, SCr, BUN, HbA1c, NLRP3 protein, IL-1β and IL-18 significant increased in the other 3 groups, and HDL-C, ALB, and eGFR were significant decreased, and the difference was statistically significant ( P<0.05) . The order of their level changes was: massive proteinuria group>microalbuminuria group>pure T2DM group; Pearson test found that peripheral blood NLRP3, IL-1β, IL-18 levels were significantly positively correlated with UACR, LDL-C, TG, and TC ( P<0.001) , while they were significantly negatively correlated with HDL-C ( P<0.001) .The results of unconditional Logistic regression analysis showed that the course of disease, FBG, HDL-C, LDL-C, TG, TC, SCr, BUN, ALB, HbA1c, eGFR, NLRP3 protein, IL-1β and IL-18 may all be related to DN-related in patients with T2DM ( P<0.05) . Multivariate analysis found that high levels of BUN, ALB, HbA1c, EGFR, NLRP3 protein and IL-1 were found β and IL-18 are high risk factors for DN in patients with T2DM ( P<0.05) . The ROC curve showed that the combination of peripheral blood NLRP3, IL-1β, and IL-18 predicted the highest AUC, sensitivity, and specificity of DN in patients with T2DM as 0.918, 93.40%, and 90.13%, respectively. Conclusions:Different stages of DN are often accompanied by increased levels of NLRP3, IL-1β, and IL-18 in peripheral blood. Strengthening the monitoring of NLRP3 inflammasome levels can help assess the renal function of patients and provides a theoretical basis for early diagnosis of DN.

Objective:To evaluate the effect of clinical pathway implementation on medical efficiency and medical expenses of patients with two common rheumatic immune diseases " rheumatoid arthritis" and " ankylosing spondylitis" diseases by using diagnosis related group (DRG) related indicators.Methods:The data of patients with two common rheumatic immune diseases " rheumatoid arthritis" and " ankylosing spondylitis" included in the clinical pathway management from January 2017 to December 2019 in the Department of Rheumatology and Immunology of Jinhua Hospital, Zhejiang University School of Medicine were carried out. The impact of clinical pathway implementation on the average hospital stay, average cost and average drug cost of patients with the two diseases were analyzed and compared , so as to evaluate the effect of the implementation of the clinical pathway.Results:From the implementation of clinical pathway in 2017 to 2019, the number of patients admitted and total medical specialty services in the two groups of " rheumatoid arthritis" and " ankylosing spondylitis" increased year by year ( P<0.01). The average length of stay, average cost and average drug cost of patients in the " rheumatoid arthritis" disease group decreased year by year, with statistically significant differences between groups (all P<0.01). The average length of stay in the ankylosing spondylitis group was shortened year by year, and the difference was statistically significant ( P<0.01). Compared with 2017, the average cost in 2018 decreased significantly, and the difference was statistically significant ( P<0.01). There was no significant difference in average cost between 2018 and 2019 ( P>0.05). The average cost in 2018 was significantly higher than that in 2017 ( P<0.05). After analyzing the causes and optimizing the clinical pathway, the average cost in 2019 was significantly lower than that in 2018 ( P<0.01). Conclusions:Through the implementation of clinical pathways and continuous optimization of pathway connotation during use, the diagnosis and treatment efficiency of patients with " rheumatoid arthritis" and " ankylosing spondylitis" can be significantly improved, and medical costs can be reduced, which is in line with the current medical reform needs.

Objective:To observe any effects of electroacupuncture (EA) on urodynamics and bladder c-Kit expression in rats with urination disorders after spinal cord injury (SCI).Methods:Complete spinal cord injury models were created in female Sprague-Dawley rats by transecting the spine at the thoracic or sacral level. On day 22 after the injury, the rats with successful modeling were randomized into a thoracic spinal cord injury (TSCI) group, a TSCI+ EA group, a sacral spinal cord injury (SSCI) group and an SSCI+ EA group, each of 10. Both EA groups were given 15 minutes of EA at the Guanyuan (CV4) and Sanyinjiao (SP6) points daily for 14 days. After the intervention, urination function was evaluated using bladder volume, compliance and residual urine volume. Hematoxylin and eosin staining was used to observe any morphological changes in bladder tissues. The gene and protein expression of c-Kit in bladder tissues were detected using real-time quantitative polymerase chain reactions and western blotting.Results:Compared with the sham group, the bladder volume and compliance of the TSCI group decreased significantly, while the average residual urine volume increased significantly. In the SSCI group the average residual urine volume, bladder volume and compliance all increased significantly. The modeling altered the morphology of the bladder in all of the SCI rats. The average expression of c-Kit mRNA and protein increased significantly in TSCI group, but both decreased significantly in the SSCI group. EA improved the histological structure of the SCI rats′ bladders.Conclusions:EA can bi-directionally regulate bladder c-Kit expression, and that is a possible mechanism for improving urinary incontinence and urine retention after an SCI.