1. Mechanism of Dahuangtang pellets in regulating podocyte autophagy of diabetic nephropathy mice through AMPK/mTOR/ULK1 signaling pathway
Beibei SU ; Yonglin LIANG ; Chunxia XUE ; Pu ZHANG ; Xiaoli PEI ; Lixia YANG ; Xiangdong ZHU ; Xia YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):260-269
		                        		
		                        			
		                        			 AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli. 
		                        		
		                        		
		                        		
		                        	
2.Mechanism of Dahuang Tangluo Pills in Improving Renal Inflammatory Injury in Diabetic Kidkdey Disease by Regulating AGEs/RAGE/IKK/NF-κB Pathway
Pu ZHANG ; Jianqing LIANG ; Xia YANG ; Min BAI ; Xiangdong ZHU ; Chunxia XUE ; Beibei SU ; Yunhui ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):77-85
		                        		
		                        			
		                        			ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease (DKD) in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose (FBG). Mice with FBG ≥ 16.7 mmol·L-1, increased urine output, and persistent albuminuria were considered successful in model establishment. After successful modeling, they were randomly divided into a model group, a dapagliflozin group (1.5 mg·kg-1·d-1), and high, medium, and low dose groups of Dahuang Tangluo pills (3.6, 1.8, 0.9 g·kg-1·d-1, respectively), with eight mice in each group. All medication groups were administered orally, while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks, the survival status of the mice was observed, and their body weight, FBG, and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining, Masson staining, and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products (AGEs) and receptors for advanced glycation end products (RAGE) proteins. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were utilized to detect the gene and protein expression levels of AGEs, RAGE, inhibitor of nuclear factor-κB (NF-κB) kinase (IKK), and NF-κB in the renal tissues of mice in each group. ResultCompared with control group, the model group showed a significant increase in body weight, FBG, serum creatinine (SCr), urinary microalbumin/urine creatinine ratio (ACR), total cholesterol (TC), and triglycerides (TG) (P<0.05). The levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in renal tissues were significantly elevated (P<0.05). Renal histopathological staining and electron microscopy revealed loose arrangement, gaps, structural disarray, mesangial proliferation, and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE, IKK, and NF-κB genes in renal tissues (P<0.05). Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues (P<0.05). Western blot results showed a significant increase in the expression of AGEs, RAGE, IKK, and NF-κB proteins in renal tissues (P<0.05). After drug intervention, compared with model group, the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight, FBG, SCr, and ACR (P<0.05), and a significant decrease in TC in mouse serum (P<0.05), while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum (P<0.05). All treatment groups showed a significant reduction in ICAM-1, IL-6, and TNF-α in renal tissues (P<0.05). Renal histopathological staining and electron microscopy showed improved kidney injury, decreased collagen fiber deposition, and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE, IKK, and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Western blot results showed a significant decrease in the expression of AGEs, RAGE, IKK, and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice, possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway. 
		                        		
		                        		
		                        		
		                        	
3.Application of pulsed electromagnetic fields in the treatment of orthopedic diseases
Hairui LIANG ; Zhencun CAI ; He ZHANG ; Siyu DUAN ; Beibei CHEN
Chinese Journal of Tissue Engineering Research 2024;28(12):1944-1949
		                        		
		                        			
		                        			BACKGROUND:Pulsed electromagnetic field is a non-invasive and non-radiative treatment method.Clinical use of pulsed electromagnetic fields in the treatment of orthopedic diseases has achieved certain results. OBJECTIVE:To review the current clinical application of the pulsed electromagnetic field in the treatment of orthopedic diseases,providing a scientific theoretical basis for the clinical treatment of orthopedic diseases. METHODS:The first author used a computer to search PubMed,CBM,Cochrane Library,CNKI,and WanFang Data for related studies on the pulsed electromagnetic field in the treatment of orthopedic diseases,using the keywords of"pulsed electromagnetic field,orthopedics,osteoarthritis,osteoporosis,bone healing,electromagnetic navigation"in English and Chinese.For the literature related to the same content,recent publications were selected.A total of 69 articles were selected from the search results for review. RESULTS AND CONCLUSION:Pulsed electromagnetic field has a definite curative effect on fracture healing.It can be used in the treatment of osteomyelitis by antibacterial,bactericidal,anti-inflammatory and promoting bone healing,and can inhibit osteoporosis and its progress.In addition,the treatment of early osteoarthritis,femoral head necrosis and postoperative rehabilitation of late joint replacement through various ways can become a treatment for orthopedic diseases.However,the therapeutic mechanism of the pulsed electromagnetic field for a variety of orthopedic diseases is still unclear,and most of the research is still in the primary stage.In the future,it is still necessary to obtain more reliable evidence from high-quality research and clinical trials to provide a more perfect basis for the clinical treatment of orthopedic diseases.
		                        		
		                        		
		                        		
		                        	
4.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
		                        		
		                        			
		                        			Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
		                        		
		                        		
		                        		
		                        	
5.A survey on maternal adverse symptoms and functionality in the third trimester and postpartum
Ya LIU ; Xu QIAN ; Chunyi GU ; Shuang LIANG ; Beibei SHEN ; Liping SUN
Shanghai Journal of Preventive Medicine 2024;36(8):771-778
		                        		
		                        			
		                        			ObjectiveTo use the maternal morbidity WOICE Tool(Chinese version)to investigate the maternal morbidity in Shanghai, and to examine the current situation and associated factors of adverse symptoms and impaired functioning in the third trimester and postpartum period. MethodsPregnant women who made their initial visit and established a medical record at a tertiary obstetrics and gynecology hospital in Shanghai from March to August 2021 were recruited and a baseline survey was completed. The prevalence of maternal morbidity was surveyed in the third trimester and first 6 weeks postpartum. ResultsSelf-reported adverse physical symptoms were observed in 89.8% of women in the third trimester and 86.1% in first 6 weeks postpartum. The prevalence rates of anxiety and depression were 4.1% and 6.2% in the third trimester, and 6.2% and 7.5% in first 6 weeks postpartum, respectively. The proportions of women reporting impaired functioning were 80.3% in the third trimester and 64.1% in first 6 weeks postpartum, respectively. Physical symptoms were associated with parity, education, the newborn’s health status, and risk of experiencing violence. Psychological symptoms were associated with age, household responsibilities, employment status, the newborn’s health status, pre-pregnancy body mass index (BMI), and risk of experiencing violence. Functionality was associated with the type of registered residence, education level, household responsibilities, and risk of experiencing violence. ConclusionThe physical health status of pregnant and postpartum women in Shanghai is better than that in the middle-income regions abroad, with anxiety and depression at average levels compared to national statistics in China. Physical, psychological, and functional status are affected by multiple factors including personal, health, family, and work conditions. Preventive measures should be taken from various perspectives to mitigate adverse symptoms and impaired functioning, and to improve the positive experience of pregnancy and childbirth. 
		                        		
		                        		
		                        		
		                        	
6.Modulation of synaptic damage by Bushen Tiansui Decoction via the PI3K signaling pathway in an Alzheimer’s disease model
HUI Shan ; ZHENG Qing ; LI Hongli ; ZHU Lemei ; WU Beibei ; LIANG Lihui ; YANG Jingjing
Digital Chinese Medicine 2024;7(3):284-293
		                        		
		                        			Methods:
		                        			 (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. 
		                        		
		                        			Results:
		                        			  (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). 
		                        		
		                        			Conclusion
		                        			BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway. 
		                        		
		                        		
		                        		
		                        	
7.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
		                        		
		                        			
		                        			Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
		                        		
		                        		
		                        		
		                        	
8.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
		                        		
		                        			
		                        			Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
		                        		
		                        		
		                        		
		                        	
9.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
		                        		
		                        			
		                        			Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
		                        		
		                        		
		                        		
		                        	
10.Analysis of Cognition Status and Influencing Factors of Medical Research Ethics Review Standards among Physicians in Tertiary Hospitals
Jinling GUO ; Beibei LIU ; Shanshan YIN ; Hua FENG ; Shuying LIANG
Chinese Hospital Management 2024;44(10):62-66
		                        		
		                        			
		                        			Objective To understand the cognition status of medical scientific research ethics review norms among physicians in tertiary hospitals and the factors influencing their awareness.Methods A survey was conducted using a questionnaire.A total of 2 067 questionnaires were distributed to physicians in tertiary hospitals in Henan Province,with an effective response rate of 81.95%.Results(1)Physicians'awareness rate of Regulations on Ethical Review of Biomedical Research Involving Human Subjects reached 69.01%,while that of Opinions on Strengthening Ethical Governance in Science and Technology was only 34.30%.A total of 310 respondents were aware of all six medical research ethics-related regulations.(2)1 153 respondents were familiar with all four basic principles of medical ethics.(3)78.98%of physicians had received training in medical research ethics knowledge.Learning through medical school and special lectures made it easier for physicians to understand medical research ethics knowledge(P<0.05).(4)The results of binary logistic regression analysis showed that educational level,membership in an ethics committee,and receipt of ethics training significantly influenced physicians'understanding of medical research ethics knowledge(P<0.05).Conclusion Physicians have low awareness of newly issued medical research ethics review norms,targeted training is needed to enhance physicians'research ethics literacy.
		                        		
		                        		
		                        		
		                        	
            
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