ObjectiveTo sort out the pre-ethical review status of drug clinical trials in a tertiary A hospital， summarize practical experience， and provide references for pre-ethical review. MethodA retrospective analysis was conducted on the ethical review of pre-ethical projects in a tertiary A hospital from 2018 to 2023. ResultsFrom 2018 to 2023， a total of 285 pre-ethical projects were reviewed in this tertiary hospital， including 79 projects where it served as the leading unit. Among these， 279 clinical trials ultimately received approval of the ethical review committee， while 6 projects were not approved due to sponsors’ refusal to modify study protocols. In terms of trial phases， phase III clinical trials constituted the largest proportion， and the oncology center was the department with the highest number of projects. In 2023， the average time for pre-ethical review projects from submission to approval was 43 calendar days， 3 days longer than for other project types. In 2023， this hospital reviewed 75 pre-ethical review projects， including 58 where it served as a participating unit. Among these， 42 projects received approval later than the leading unit， while 9 projects were approved earlier than the leading unit’s ethical approval date. Among the pre-ethical review projects applied in 2023， 70 projects obtained drug clinical trial notifications from the National Medical Products Administration， while 5 projects had unknown notification status due to the lack of ethical approval or discontinuation. Of the projects receiving approval notifications， 16 were annotated with matters requiring enhanced attention during clinical trials， and 7 necessitated protocol improvements. ConclusionThis tertiary A hospital has implemented multiple measures to optimize the management of pre-ethical review. This ethical review model does not compromise the quality of ethical review and contributes to accelerating the initiation of clinical trials. Notably， it is crucial to construct a patient-centered drug development system. Clinical trials guided by this concept align with ethical values， laying the foundation for the smooth conduct of clinical trials， assisting in the drug development process， and safeguarding patients’ medication needs.

Objective To evaluate the effect of parasternal intercostal plane block(PIB)on postopera-tive fatigue in elderly patients undergoing off-pump coronary artery bypass grafting(CABG).Methods A to-tal of 111 elderly patients undergoing elective off-pump CABG in Xuzhou Municipal Central Hospital from May 2021 to January 2023 were selected as the study subjects.The patients were divided into the control group(group C,n=55)and PIB group(group P,n=56)by adopting the random number table method.After induction of anesthesia,the patients in the group P received the ultrasound-guided bilateral PIB,and the group C received the equal volume of normal saline at the same site.The incidence rate of postoperative fatigue syn-drome(POFS)on postoperative 1,3,5,7 d and postoperative 8 weeks,NRS scores immediately after extuba-tion and at postoperative 12,24,48 h,postoperative opioid drugs consumption,ICU stay duration,hospitaliza-tion duration and adverse events occurrence were compared between the two groups.Results Compared with the group C,the incidence rates of POFS on postoperative 1,3,5,7 d and postoperative 8 weeks in the group P were significantly decreased,the NRS scores immediately after extubation and at postoperative 12,24 h in the group P were lower,the postoperative opioid drugs consumption were smaller,the ICU stay duration was shorter,and the differences were statistically significant(P＜0.05).The NRS score at postoperative 48 h and hospitalization duration had no statistical differences between the two groups(P＞0.05).No nerve block re-lated adverse events in the patients appeared during the study period.Conclusion The ultrasound guided PIB could effectively reduce the incidence rate of POFS in elderly patients undergoing off-pump CABG,promote the patients'prognosis and improve the recovery quality of the patients.

Due to the physiological peculiarities of pregnant women, general clinical studies exclude pregnant women. Therefore, there is a lack of evidence of precise medication for pregnant women with diseases worldwide, which poses a significant risk for them to use medication during pregnancy. Whether to include pregnant women as subjects in clinical research has always been a focus of ethical discussion. By providing a broad overview of pregnant women’s participation in clinical research from an ethical perspective, this paper explored the risks and challenges faced by pregnant women’s participation in clinical research, and provided theoretical basis and thinking paths for how to fairly and effectively include pregnant women as subjects and promoting clinical research on pregnant women.

OBJECTIVETo observe the effects of Qufengtongluo Recipe (QFTLR) on the expressions of cell cycle regulatory proteins in rat mesangial cells (MCs) in vitro and investigate the mechanism by which QFTLR inhibits MC proliferation.

METHODSUsing the methods of serum pharmacology, we studied the expressions of cell cycle regulatory proteins in rat MCs treated with QFTLR by laser scanning confocal microscope and immunohistochemistry.

RESULTSCompared with the normal control cells, the cells challenged with lipopolysaccharide (LPS) showed significantly enhanced expressions of cyclin D1, CDK2, and P21 (P<0.01) and obviously lowered protein expression of P27 (P<0.01). Treatment of the LPS-challenged cells with QFTLR and benazepril both resulted in significantly attenuated expressions of cyclin D1, CDK2, and P21 and obvious increase of P27 expression (P<0.05 or P<0.01), but QFTLR produced stronger effects than benazepril in regulating of cyclinD1, P21 and P27 protein expressions (P<0.05 or P<0.01).

CONCLUSIONQFTLR inhibits rat MC proliferation in vitro possibly by down-regulating the cellular expressions of cyclin D1, CDK2, and P21 and up-regulating the expression of P27 protein.

Animals ; Cell Line ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Mesangial Cells ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.
Cell Line ; Cell Proliferation ; Fermentation ; Furans ; Lipids ; Maleic Anhydrides ; MCF-7 Cells ; Structure-Activity Relationship

Objective To find time pint of the irreversible kidney injuru by observing renal pathological appearance and podocytes phenotype after complete ureteral obstruction.Methods The animal model of complete unilateral uretersal obstruction was consructed in 2-weekold and 2-month-old rats respectively.HE staining was employed to evaluate the degree of pathological changes,and immunofluorescence double staining to observe the transitional progression of podocyte.Results Grossly,there appeared pyelectasis at 2 h after obstruction and thinner renal cortex after 3 days of obstruction.Histologically,proximal tube display dilated and hydropic degeneration of tubular epithelial cells was observed after 12-day obstruction.The tubular epithelium showed distorted swelling after 3-day obstruction.Immunofluorescence double staining showed that podocytes decreased and the double-labeled macrophages was increased during 1 d to 2 d after unilateral ureteral obstruction operation.Conclusion Compared with control groups,the unilateral ureteral obstruction groups shows podocyte-to-macrophage transition at 1 d after the operation, while the pelvis shows obviously dilated.From the 1st day to the 7th day after unilateral ureteral obstruction,it shows increasing tendency of the podocytes transition.

Objective To understand the clinical characters and imaging features of Mirizzi syndrome.Methods All 15 patients were confirmed by operation , including 10 females and 5 males , aged 41～82 (mean age 65.1 years old). The course ranged from 4 days to 15 years. Among them, ERCP were performed in 8 patients, PTC in 2 patients, MRCP in 4 patients and CT in 3 patients.Results Cholangiography of Mirizzi syndrome revealed a broad, curvilinear impression on the common hepatic duct in the area where the cystic duct or gallbladder was in direct apposition, hepatic bile duct dilation above the level of the cystic duct. 6 cases were diagnosed to be Mirizzi syndrome preoperatively (3 cases in ERCP , 2 cases in PTC , 1 case in MRCP), 7 cases bile duct stone, 1 case bile duct dilation, 1 case normal. Conclusion Mirizzi syndrome is a rare disease . No pathognomonic features appear in either the history or the physical examination .Diagnosis requires a combination of ultrasonography , cholangiography (ERCP,PTC), CT and MRI .