1.Effectes of perfluorooctanoic acid exposure on mouse embryonic osteoblast precursor cells and its molecular mechanisms
Liming XUE ; Jiale XU ; Yuanjie LIN ; Yu'e JIN ; Dasheng LU ; Guoquan WANG
Shanghai Journal of Preventive Medicine 2025;37(7):629-635
ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.
2.Synthesis and in vitro antiviral effects against hepatitis C virus of oleanolic acid and ursolic acid derivatives
Shuwen XIAO ; Heyang ZHOU ; Yongsheng JIN ; Liming QIAO ; Wei ZHENG
Journal of Pharmaceutical Practice and Service 2025;43(10):503-508
Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus (HCV) activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.
3.Efficacy of different concentrations of ZKY001 eyedrops in the treatment of corneal epithelial defect after primary pterygium excision
Hua GAO ; Lei ZHU ; Jianjiang XU ; Liming TAO ; Yanling DONG ; Luxia CHEN ; Xiuming JIN ; Guigang LI ; Huping WU ; Ping ZHAO ; Wei CHEN ; Xiaoyi LI ; Weiyun SHI
International Eye Science 2024;24(12):1888-1894
AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.
4.Iodine nutritional status and influencing factors of pregnant women in Hangzhou City
Tingting ZHAO ; Liangliang HUO ; Xuhui ZHANG ; Bing ZHU ; Liming HUANG ; Xingyi JIN ; Sujuan ZHU ; Qilin SHENG
Chinese Journal of Endemiology 2024;43(1):49-55
Objective:To investigate the iodine nutritional status of pregnant women in Hangzhou City and analyze its influencing factors, in order to provide a basis for guiding pregnant women in Hangzhou City to supplement iodine scientifically.Methods:A stratified random sampling method was used to conduct a questionnaire survey on 1 400 pregnant women in Hangzhou City from March to October 2018. Random urine samples and household salt samples from pregnant women were collected, and the levels of urine iodine and salt iodine were measured using arsenic cerium catalytic spectrophotometry and direct titration, respectively. The iodine nutritional status of pregnant women with different basic characteristics and dietary levels were analyzed and compared (Kruskal-Wallis test), and the main influencing factors affecting the urinary iodine concentration level of pregnant women were identified (the ordinal multiple classification logistic regression analysis).Results:The median urinary iodine of pregnant women was 135.00 μg/L, and the qualified iodized salt consumption rate of pregnant women was 83.36% (1 167/1 400). In terms of basic characteristics, there were statistically significant differences in the distribution level of urine iodine among pregnant women with different pregnancy frequency, delivery frequency, and natural abortion frequency ( P < 0.05). In terms of diet, the frequency of consuming milk, yogurt, meat, and whether pregnant women consumed cabbage and cauliflower showed statistically significant differences in urinary iodine distribution levels ( P < 0.05). Ordinal multiple classification logistic regression analysis showed that the urine iodine levels of pregnant women who were pregnant twice were higher than those who were pregnant ≥3 times ( OR = 1.64, P = 0.003). Pregnant women who never or occasionally consumed yogurt had lower urine iodine levels than or equal to those who consumed 2 bottles of yogurt per day ( OR = 0.53, P = 0.044). Pregnant women who never or occasionally consumed meat and those who consumed meat once a week had higher urinary iodine levels than that who consumed meat ≥2 times per week ( OR = 1.40, 1.47, P < 0.05). Conclusions:The overall iodine nutrition of pregnant women in Hangzhou City is at an deficiency level. Pregnancy experience and dietary level are influencing factors on iodine nutrition of pregnant women. It is necessary to carry out in-depth health education for pregnant women, improve the dietary structure during pregnancy, and improve the abnormal iodine nutrition of pregnant women.
5.Construction and Application of Comprehensive Evaluation System of Operation Benefit of Clinical Departments in Cancer Hospitals
Jin WU ; Yan WU ; Binru FANG ; Shunjie JIANG ; Yongting YANG ; Hao ZHANG ; Xianhong HUANG ; Xiaohe WANG ; Liming ZHU
Chinese Hospital Management 2024;44(8):33-36
Objective To build a comprehensive evaluation system for the operating benefit of clinical departments in cancer hospitals,so as to provide data support for the fine operation management of hospitals.Methods Literature review and semi-structured interview were used to form the index pool.Two rounds of Delphi expert consultation were used to determine the index of the evaluation system,and the analytic hierarchy process was used to determine the index weight.Finally,the weighted TOPSIS was used for empirical case analysis.Results The positive coefficient in the two rounds of Delphi expert consultation were 82.6%and 100%,the authority coefficient was 0.808,and the coordination coefficient was between 0 and 1.All indexes at all levels passed the consistency test.Finally,a comprehensive evaluation system consisting of 4 dimensions,19 indexes in surgery,16 indicators in radiotherapy and 16 indicators in internal medicine was constructed.Indicators at all levels were tested for consistency,resulting in the construction of a comprehensive evaluation system consisting of 4 dimensions,19 indicators for surgery and 16 indicators each for radiotherapy and internal medicine departments.Conclusion The comprehensive evaluation system of operating benefit of clinical departments in cancer hospitals can help hospitals and departments to find out the shortcomings of operation,build the path of operating benefit improvement,and realize the connotation improvement and high-quality development of hospitals.
6.Research on the Improvement Path of Medical Staff's Report Intention on Adverse Events Based on Technology Acceptance Model
Jin WU ; Xinlu TONG ; Binru FANG ; Yu QIAN ; Yuwei FAN ; Xianhong HUANG ; Yongting YANG ; Liming ZHU
Chinese Hospital Management 2024;44(11):51-54,78
Objective Based on the technology acceptance model,to explore the influence mechanism of technical support,perceived interactivity,perceived usefulness,perceived ease of use and perceived risk on medical staff's report intention on adverse events,and to provide path suggestions for improving medical staff's report intention adverse events.Methods The multi-stage sampling method was used to select 637 medical staffs of tertiary public hospitals in Hangzhou who used the information-based platform to report adverse events as the research respondents,and the self-developed scale of report intention on adverse events was used as the research tool,monofactor analysis were conducted by Wilcoxon rank-sum test,and the structural equation model was used to analyze the influence path of their report intention on adverse events.Results Perceived ease of use and perceived usefulness have positive effects on medical staff's report intention on adverse events(β=0.264,0.658;P<0.001);Perceived risk negatively affected the medical staff's report intention on adverse events(β=-0.143,P<0.001).The indirect effects of perceived usefulness and perceived ease of use on medical staff's report intention on adverse events are 0.538 and 0.205,respectively.Conclusion Perceived usefulness and perceived ease of use plays a mediating role in perceived interactivity and medical staff's report intention on adverse events.
7.Construction and Application of Comprehensive Evaluation System of Operation Benefit of Clinical Departments in Cancer Hospitals
Jin WU ; Yan WU ; Binru FANG ; Shunjie JIANG ; Yongting YANG ; Hao ZHANG ; Xianhong HUANG ; Xiaohe WANG ; Liming ZHU
Chinese Hospital Management 2024;44(8):33-36
Objective To build a comprehensive evaluation system for the operating benefit of clinical departments in cancer hospitals,so as to provide data support for the fine operation management of hospitals.Methods Literature review and semi-structured interview were used to form the index pool.Two rounds of Delphi expert consultation were used to determine the index of the evaluation system,and the analytic hierarchy process was used to determine the index weight.Finally,the weighted TOPSIS was used for empirical case analysis.Results The positive coefficient in the two rounds of Delphi expert consultation were 82.6%and 100%,the authority coefficient was 0.808,and the coordination coefficient was between 0 and 1.All indexes at all levels passed the consistency test.Finally,a comprehensive evaluation system consisting of 4 dimensions,19 indexes in surgery,16 indicators in radiotherapy and 16 indicators in internal medicine was constructed.Indicators at all levels were tested for consistency,resulting in the construction of a comprehensive evaluation system consisting of 4 dimensions,19 indicators for surgery and 16 indicators each for radiotherapy and internal medicine departments.Conclusion The comprehensive evaluation system of operating benefit of clinical departments in cancer hospitals can help hospitals and departments to find out the shortcomings of operation,build the path of operating benefit improvement,and realize the connotation improvement and high-quality development of hospitals.
8.Research on the Improvement Path of Medical Staff's Report Intention on Adverse Events Based on Technology Acceptance Model
Jin WU ; Xinlu TONG ; Binru FANG ; Yu QIAN ; Yuwei FAN ; Xianhong HUANG ; Yongting YANG ; Liming ZHU
Chinese Hospital Management 2024;44(11):51-54,78
Objective Based on the technology acceptance model,to explore the influence mechanism of technical support,perceived interactivity,perceived usefulness,perceived ease of use and perceived risk on medical staff's report intention on adverse events,and to provide path suggestions for improving medical staff's report intention adverse events.Methods The multi-stage sampling method was used to select 637 medical staffs of tertiary public hospitals in Hangzhou who used the information-based platform to report adverse events as the research respondents,and the self-developed scale of report intention on adverse events was used as the research tool,monofactor analysis were conducted by Wilcoxon rank-sum test,and the structural equation model was used to analyze the influence path of their report intention on adverse events.Results Perceived ease of use and perceived usefulness have positive effects on medical staff's report intention on adverse events(β=0.264,0.658;P<0.001);Perceived risk negatively affected the medical staff's report intention on adverse events(β=-0.143,P<0.001).The indirect effects of perceived usefulness and perceived ease of use on medical staff's report intention on adverse events are 0.538 and 0.205,respectively.Conclusion Perceived usefulness and perceived ease of use plays a mediating role in perceived interactivity and medical staff's report intention on adverse events.
9.Construction and Application of Comprehensive Evaluation System of Operation Benefit of Clinical Departments in Cancer Hospitals
Jin WU ; Yan WU ; Binru FANG ; Shunjie JIANG ; Yongting YANG ; Hao ZHANG ; Xianhong HUANG ; Xiaohe WANG ; Liming ZHU
Chinese Hospital Management 2024;44(8):33-36
Objective To build a comprehensive evaluation system for the operating benefit of clinical departments in cancer hospitals,so as to provide data support for the fine operation management of hospitals.Methods Literature review and semi-structured interview were used to form the index pool.Two rounds of Delphi expert consultation were used to determine the index of the evaluation system,and the analytic hierarchy process was used to determine the index weight.Finally,the weighted TOPSIS was used for empirical case analysis.Results The positive coefficient in the two rounds of Delphi expert consultation were 82.6%and 100%,the authority coefficient was 0.808,and the coordination coefficient was between 0 and 1.All indexes at all levels passed the consistency test.Finally,a comprehensive evaluation system consisting of 4 dimensions,19 indexes in surgery,16 indicators in radiotherapy and 16 indicators in internal medicine was constructed.Indicators at all levels were tested for consistency,resulting in the construction of a comprehensive evaluation system consisting of 4 dimensions,19 indicators for surgery and 16 indicators each for radiotherapy and internal medicine departments.Conclusion The comprehensive evaluation system of operating benefit of clinical departments in cancer hospitals can help hospitals and departments to find out the shortcomings of operation,build the path of operating benefit improvement,and realize the connotation improvement and high-quality development of hospitals.
10.Research on the Improvement Path of Medical Staff's Report Intention on Adverse Events Based on Technology Acceptance Model
Jin WU ; Xinlu TONG ; Binru FANG ; Yu QIAN ; Yuwei FAN ; Xianhong HUANG ; Yongting YANG ; Liming ZHU
Chinese Hospital Management 2024;44(11):51-54,78
Objective Based on the technology acceptance model,to explore the influence mechanism of technical support,perceived interactivity,perceived usefulness,perceived ease of use and perceived risk on medical staff's report intention on adverse events,and to provide path suggestions for improving medical staff's report intention adverse events.Methods The multi-stage sampling method was used to select 637 medical staffs of tertiary public hospitals in Hangzhou who used the information-based platform to report adverse events as the research respondents,and the self-developed scale of report intention on adverse events was used as the research tool,monofactor analysis were conducted by Wilcoxon rank-sum test,and the structural equation model was used to analyze the influence path of their report intention on adverse events.Results Perceived ease of use and perceived usefulness have positive effects on medical staff's report intention on adverse events(β=0.264,0.658;P<0.001);Perceived risk negatively affected the medical staff's report intention on adverse events(β=-0.143,P<0.001).The indirect effects of perceived usefulness and perceived ease of use on medical staff's report intention on adverse events are 0.538 and 0.205,respectively.Conclusion Perceived usefulness and perceived ease of use plays a mediating role in perceived interactivity and medical staff's report intention on adverse events.

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