1.Mechanism of Action of Coptidis Rhizoma and Ophiopogonis Radix in Delaying Diabetic Nephropathy Based on EGFR/PI3K/Akt Signaling Pathway
Shaoyu LI ; Man GONG ; Qiufang LI ; Liping DAI ; Guiqun WANG ; Qiuchen YANG ; Qiongqiong ZHANG ; Erping XU ; Yalin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):22-29
ObjectiveTo observe the effect of Coptidis Rhizoma and Ophiopogonis Radix on renal tissue injury and epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in rats with diabetic nephropathy (DN) and explore its possible mechanism of delaying DN. MethodThirty-six male Wistar rats were randomly divided into a normal group (6 rats) and a model group (30 rats). The model group was fed with a high-fat and high-sugar diet combined with streptozotocin (STZ) to establish a rat model of type 2 diabetes. After the successful preparation of the model, the rats were randomly divided into the model group, low, medium, and high dose groups of Coptidis Rhizoma and Ophiopogonis Radix (100, 200, 400 mg·kg-1), and metformin group (200 mg·kg-1). After administration, the levels of fasting blood glucose (FBG), 24 h urine protein (24 h-UTP), creatinine (SCr), urea nitrogen (BUN), and uric acid (UA) were detected. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes of renal tissue in rats. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the related protein expression of EGFR, PI3K, and Akt and their mRNA expression levels in the renal tissue of rats in each group. ResultsCompared with the normal group, the levels of FBG, SCr, BUN, UA, 24 h-UTP, and kidney index in the model group were significantly increased (P<0.01), most renal tubular epithelial cells were necrotic, and the content of collagen in glomeruli was significantly increased (P<0.01). Compared with the model group, the above indexes of rats in each administration group were improved to varying degrees. The FBG, SCr, BUN, UA, 24 h-UTP, and kidney index of rats in each dose group and metformin group were significantly decreased (P<0.01, P<0.05). The necrosis degree of renal tubular epithelial cells was reduced, and the fibrosis area was decreased (P<0.01). There related protein and mRNA expressions of EGFR, PI3K, and Akt were significantly increased (P<0.05, P<0.01). ConclusionCoptidis Rhizoma and Ophiopogonis Radix can alleviate renal tissue injury in rats with DN, and their mechanism may be related to the regulation of the EGFR/PI3K/Akt signaling pathway.
2.Promoting learning gains and practical ability of nursing students: the construction and empirical research of inquiry learning community
Bing YANG ; Fuying LI ; Shiqi XIE ; Yunmei ZHANG ; Siyuan YANG ; Shaoyu MOU ; Weichu LIU
Chinese Journal of Medical Education Research 2023;22(2):315-320
Objective:To develop an inquiry learning community centered on learning experience in the course of Nursing Clinical Comprehensive Experiment to verify the influence of this teaching mode on the learning gains and practical ability of nursing students. Methods:A total of 132 undergraduate nursing students form grade 3 in Chongqing Medical University were enrolled. The participants were randomly assigned to a learning community group ( n = 69) and a control group ( n = 63) using Minitab 14.0 software. The students in the learning community group adopted the inquiry learning community mode in accordance with the curriculum map for online self-learning, group discussion and skills practice, while the control group received the teacher-led teaching mode for offline theory teaching, operation teaching and skills practice. After the teaching intervention, both groups of students received the assessment questionnaire of learning gains and the comprehensive experimental ability evaluation. Chi-square test or paired t-test was performed using SPSS 23.0. Results:Compared with the control group, students in the learning community group reported that their sense of learning gain was enhanced ( P<0.001, Cohen d=0.97); sub-items showed that the effect size for the understanding of learning content ( P<0.001, Cohen d=1.22), the overall course situation ( P<0.001, Cohen d=0.90), the course activities ( P=0.000, Cohen d=0.83), and the information obtained ( P<0.001, Cohen d=1.16) was significantly different. The total score of practical ability of comprehensive experiment was significantly improved ( P = 0.005, Cohen d=0.51), in which the experimental situation displays ( P=0.002, Cohen d=0.55) and experimental effect ( P=0.006, Cohen d=0.49) were better than the control group. There was no significant difference in the performance of experimental preparation and case analysis between the two groups. Conclusion:Developing an inquiry learning community in nursing clinical comprehensive experiment can effectively enhance student' sense of learning gains and promote the improvement of clinical practical ability.
3.The deubiquitinating enzyme 13 retards non-alcoholic steatohepatitis via blocking inactive rhomboid protein 2-dependent pathway.
Minxuan XU ; Jun TAN ; Liancai ZHU ; Chenxu GE ; Wei DONG ; Xianling DAI ; Qin KUANG ; Shaoyu ZHONG ; Lili LAI ; Chao YI ; Qiang LI ; Deshuai LOU ; Linfeng HU ; Xi LIU ; Gang KUANG ; Jing LUO ; Jing FENG ; Bochu WANG
Acta Pharmaceutica Sinica B 2023;13(3):1071-1092
Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.
4.Comparison of clinical utility of 18F-FAPI-42 and 18F-FDG PET/CT imaging in the diagnosis of newly diagnosed lung cancer
Youcai LI ; Xiaoyao ZHANG ; Yan ZHANG ; Shaoyu LIU ; Penghao CHEN ; Fang WU ; Yanxiang ZHOU ; Peng HOU ; Wenhua LIANG ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(12):709-716
Objective:To compare the clinical utility of 18F-fibroblast activating protein inhibitor (FAPI)-42 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in newly diagnosed lung cancer patients. Methods:From May 2020 to September 2021, the images of 43 lung cancer patients (32 males, 11 females, age: 37-80 years) who pathologically confirmed and received 18F-FDG and 18F-FAPI-42 PET/CT within 2 weeks in the First Affiliated Hospital of Guangzhou Medical University were prospectively analyzed. The maximum standardized uptake value (SUV max) of 18F-FDG and 18F-FAPI-42 and the number of lesions detected by 2 imaging methods were compared by using paired t test and Wilcoxon rank sum test. Results:The 43 newly diagnosed lung cancer patients included 35 adenocarcinoma, 2 squamous cell carcinoma, 4 small cell lung cancer, and 2 high-grade neuroendocrine tumors. 18F-FAPI-42 had a very high tumor uptake (SUV max: 12.24±3.97) and lesion detection rate (positive rate: 100%(37/37)) in primary lung adenocarcinoma and squamous cell carcinoma. The uptake of 18F-FAPI-42 in lymph node (10.13±5.43), pleura (6.75(4.96, 8.58)) and bone lesion (7.18(4.33, 9.66)) were significantly higher than those of 18F-FDG (6.35±3.30, 2.69(1.81, 5.00), 4.38(2.96, 6.36); t=12.19, z values: 5.47, 5.79, all P<0.001). In lung adenocarcinoma and squamous cell carcinoma, although the uptake of 18F-FAPI-42 in brain metastases was significantly lower than that of 18F-FDG (0.72(0.15, 1.82) vs 6.53(4.65, 9.34); z=6.42, P<0.001), the tumor/background (T/B) ratio was significantly higher than that of 18F-FDG (3.54(1.15, 14.88) vs 0.96(0.77, 1.04); z=6.05, P<0.001). In lung adenocarcinoma and squamous cell carcinoma, the number of lesions detected by 18F-FAPI-42 PET/CT was significantly more than that of 18F-FDG (lymph node: 6.0(2.3, 11.5) vs 4.5(2.0, 10.8); brain: 2.0(1.0, 3.0) vs 0.0(0.0, 0.0); pleura: 6.0(2.8, 10.0) vs 4.0(0.8, 5.5); z values: 2.16, 3.10, 2.04, all P<0.05). However, in high-grade neuroendocrine tumors and small cell lung cancer, the SUV max of 18F-FAPI-42 in primary lesions (8.05±2.60), lymph node lesions (5.98±2.21) and brain lesions (0.44(0.13, 0.82)) were lower than those of 18F-FDG (16.28±5.17, 12.30±5.47, 4.94(4.84, 6.25); t values: 3.58, 7.52, z=3.06, all P<0.05). Conclusions:In lung adenocarcinoma and squamous cell carcinoma, 18F-FAPI-42 has a very high tumor uptake and lesion detection rate in primary tumor. In addition, compared with 18F-FDG PET/CT, 18F-FAPI-42 PET/CT shows clearer tumor contours and more lesions. Therefore, 18F-FAPI-42 is more suitable for preliminary staging of lung adenocarcinoma and squamous cell carcinoma than 18F-FDG, while the opposite is true in small cell lung cancer and high-grade neuroendocrine tumors.
5.Intensity of Intraoperative Spinal Cord Hyperechogenicity as a Novel Potential Predictive Indicator of Neurological Recovery for Degenerative Cervical Myelopathy
Guoliang CHEN ; Fuxin WEI ; Jiachun LI ; Liangyu SHI ; Wei ZHANG ; Xianxiang WANG ; Zuofeng XU ; Xizhe LIU ; Xuenong ZOU ; Shaoyu LIU
Korean Journal of Radiology 2021;22(7):1163-1171
Objective:
To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy.
Materials and Methods:
Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis.
Results:
The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028).
Conclusion
For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.
6.Intensity of Intraoperative Spinal Cord Hyperechogenicity as a Novel Potential Predictive Indicator of Neurological Recovery for Degenerative Cervical Myelopathy
Guoliang CHEN ; Fuxin WEI ; Jiachun LI ; Liangyu SHI ; Wei ZHANG ; Xianxiang WANG ; Zuofeng XU ; Xizhe LIU ; Xuenong ZOU ; Shaoyu LIU
Korean Journal of Radiology 2021;22(7):1163-1171
Objective:
To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy.
Materials and Methods:
Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis.
Results:
The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028).
Conclusion
For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.
7.Self-management in patients after mechanical heart valve replacement and the influential factors
Wanling WANG ; Shaoyu MOU ; Shaolan MOU ; Wenfeng TANG ; Xiaoqin LI ; Heke LI
Chinese Journal of Practical Nursing 2018;34(18):1365-1369
Objective To investigate the current status of self-management in patients after mechanical heart valve replacement(MHVR) and the influential factors. Methods The convenience sampling method was used to obtain the sample in Chongqing Province, and 400 participants after MHVR at a month in 3 top three hospitals were recruited (Department of Cardiothoracic Surgery, the First Hospital of Chongqing Medical University. The Second Clinical Medical College of Third Military Medical University. The Third Clinical Medical College of Third Military Medical University). Self-Management Scale for patients after Mechanical Heart Valve Replacement edited by ourselves were used to collect the data. Results The score of patients were 79-119 (96.81 ± 7.86) points. The influential factors were sex, age, education level and the resident manner. Conclusions The self-management level of patients after MHVR is not so bad, the male, advanced age, live with distant relatives or housemaid, low education level's patients' self-management ability are low, the medical workers should strenghen health education in these patients.
8.Bibliometric analysis of studies on medical teaching case library construction in China
Liqun CHEN ; Shaoyu MU ; Li WANG ; Fu DING ; Wenlong ZHAO ; Shan HE
Chinese Journal of Practical Nursing 2018;34(4):246-250
Objective To analyze current situation and development tendency of medical teaching case library construction and to provide information for medical teaching reform. Methods Bibliometrics was used to retrieve and analyze literatures on the subject of medical teaching case library construction from China National Knowledge Infrastructure, CBMdisc, VIP and Wanfang Data from construction to June 20th,2017. Results Totally 116 articles published in 71 journals were included.A gradual growth was found in the number of publication and funded articles. The average citation count was 2.05. A majority of articles were produced in Beijing, Guangdong and Shanghai. Medical teaching case library covered 9 majors and 42 courses and applied in class teaching (50.00%, 58/116), clinical practice (37.07%, 43/116), refresher training (2.59%, 3/116), assessment and evaluation (0.86%, 1/116). Satisfaction investigate,examination score analysis and expert review were commonly used to evaluate the quality of case library. Conclusions Researches in China on medical teaching case library construction were increasing in recent years.Case library were applied in various aspects of medical teaching,however, there still remained some problems.Articles on the subject of case library were not highly-cited.There was no core author group yet. The subject on medical case library still needed deep and further exploration. There′s suggestion that we should attach importance to medical case library construction and related study to push medical education reform.
9.Regulatory roles of rno-miR-30b-5p in expressions of IL-10 and TLR4 in rats with experimental autoimmune uveitis
Yuanyuan SUN ; Dadong GUO ; Meiqing CHEN ; Shaoyu LI ; Bin LIU ; Kai TANG ; Hongsheng BI
Recent Advances in Ophthalmology 2017;37(4):330-334
Objective To investigate the regulatory role of rno-miR-30b-5p in the expressions of interleukin-10 (IL-10) and toll-like receptor 4 (TLR4) in uveitis.Methods Both IL-10 and TLR4 gene 3'UTR lucfferase vectors and relevant binding site mutant vectors were constructed.Further,both rno-miR-30b-5p mimics and reporter gene vector were co-transferred into 293 T cells to validate the fluorescent alterations of the reporter gene expression to detect the interactions between rno-miR-30b-5p and the related target genes.Moreover,an experimental autoimmune uveitis (EAU) model was induced with IRBP peptide emulsion in rats,and both lymph node and spleen were isolated on day 12 after EAU induction.In order to measure rno-miR-30b-5p levels and IL-1 0,TLR4 expressions in spleen and lymph node,quantitative PCR and ELISA techniques were applied.Results The results of double lucfferase reporter gene expression analysis showed rno-miR-30b-5p mimic apparently down-regulated the fluorescence intensity of both IL-10 and TLR4 in wild type cells.After the mutation of the target site,the fluorescence intensity of the mutant vector was significantly reduced,accompanied by a significantly statistical difference (all P < 0.01).Moreover,animal results revealed the expressions of rno-miR-30b-5p were apparently decreased,whereas IL-10 and TLR4 were markedly increased in both lymph node and spleen (all P < 0.05).Conclusion Target identification shows that rno-miR-30b-5p can obviously regulate the expressions of 3'UTR gene with either IL-10 or TLR4 gene fragment,though its regulation might not be through the predicted site.The down-regulated expression of rno-miR-30b-5p in both spleen and lymph node in EAU rats result in the up-regulated expressions of both IL-10 and TLR4,further influence the development of uveitis.This study paves a way for the modulation of microRNA on the occurrence and development of uveitis,and will provide a new insight on treating uveitis.
10.Tumor necrosis factor-alpha antagonist combined with tyrosine kinase C gene- modified neural stem cell transplantation for spinal cord injury
Le WANG ; Ningning CHEN ; Tingting LI ; Xiaoyang ZHAO ; Fuxin WEI ; Shangbin CUI ; Yong WAN ; Shaoyu LIU
Chinese Journal of Tissue Engineering Research 2017;21(21):3338-3345
BACKGROUND:Whether controling of post-injury inflammatory response combined with neural stem cel (NSC) transplantation can improve the curative efficacy for spinal cord injury stil remains unclear. OBJECTIVE:To investigate the repair of spinal cord tissue, myelin regeneration, axon regeneration, motor function recovery and the possible mechanism after early application of tumor necrosis factor α antagonist (Etanercept) combined with tyrosine kinase C (TrkC) gene-modified NSC transplantation. METHODS:TrkC-overexpressed NSCs (TrkC-NSCs) were constructed by lentiviral transfection technique. The rat models of spinal cord transection injury were prepared, and then subjected to Etanercept combined with TrkC-NSCs transplantation. The number of neurons and neuroregeneration after injury were measured by Nissl's staining, immunofluorescence and western blot. The rat motor function was detected by Basso Beattie Bresnahan score and evoked potential. The myelin regeneration was detected by electron microscopy and toluidine blue staining. RESULTS AND CONCLUSION:Compared with the other groups, the Etanercept combined with TrkC-NSCs transplantation group had more survived anterior horn motor neurons at 28 days after injury, more myelin-encapsulated axons, higher Basso Beattie Bresnahan score, greater amplitude of the evoked potentials, and relatively shorter latency (alP < 0.05). These findings indicate that early application of tumor necrosis factor-α antagonist combined with TrkC-NSCs transplantation after spinal cord injury in rats can effectively promote myelin regeneration, axon regeneration, and further promote motor function recovery.

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