1.Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome
Na LIN ; Yanqiong ZHANG ; Changhong XIAO ; Shenghao TU ; Jianning SUN ; Shijun XU ; Representation Preparation GROUP
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):47-54
Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine, and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation, and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines, Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome (hereinafter referred to as the Guidelines) were compiled by our research group, in cooperation with the renowned experts in research fields including traditional Chinese medicine, clinical medicine, zoology and evidence-based medicine, which provide a meaningful reference for scientific research, teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place, consensus plays an auxiliary role, and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology, behavioral phenotypic consistency, and drug treatment predictability compared between animal models and human diseases, by the nominal group method, "recommendations" were formed for recommendations supported by evidence, and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types, arthritis modeling methods, external stimulation conditions, and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis, investigation of therapeutic mechanisms, and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.
2.Editorial Explanation of Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome
Na LIN ; Yanqiong ZHANG ; Changhong XIAO ; Shenghao TU ; Jianning SUN ; Shijun XU ; Xia MAO ; Representation Preparation GROUP
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):55-59
The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome (hereinafter referred to as the Guidelines) (No. T/CACM1567-2024) was published by Chinese Association of Chinese Medicine on January 11, 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately, and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models, this paper made a declaration of the workflow, technological links, development references, promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".
3.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.
4.Cuscutae Semen-Lycii Fructus Improves Spermatogenesis in Rat Model of Oligoasthenozoospermia by Inhibiting Oxidative Stress-induced Blood-testis Barrier Damage via Regulating SIRT1/Nrf2 Signaling Pathway
Wen DUAN ; Xiaojing ZHANG ; Wenjie DING ; Jianning JIN ; Guoqing CHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):29-38
ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia (OAS) and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsThirty-five male SD rats were randomized into a blank group (n=7) and a modeling group (n=28). The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups: model, Cuscutae Semen-Lycii Fructus granules (3.2 g·kg-1), Cuscutae Semen-Lycii Fructus total flavonoids (0.34 g·kg-1), and L-carnitine (0.38 g·kg-1), and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase (SOD), malondialdehyde (MAD), and glutathione peroxidase (GSH-Px) in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of SIRT1, Nrf2, Occludin, zonula occludens-1 (ZO-1), connexin 43 (CX43), and β-catenin. ResultsCompared with the blank group, the model group showed decreased total sperm count and motility (P<0.05, P<0.01), obvious damage in the testicular tissue and blood-testis barrier structure, reduced score of spermatogenic function (P<0.01), declined levels of GSH-Px and SOD in the testicular tissue (P<0.05), elevated level of MDA, and down-regulated protein levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin (P<0.05, P<0.01) and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, and β-catenin in the testicular tissue (P<0.05, P<0.01). After treatment, the testicular tissue, blood-testis barrier structure, and score of spermatogenic function (P<0.01) were improved in the Cuscutae Semen-Lycii Fructus granules group, Cuscutae Semen-Lycii Fructus total flavonoids group, and L-carnitine group. Compared with the model group, the treatment groups presented lowered levels of GSH-Px and SOD (P<0.05, P<0.01), and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group (P<0.05, P<0.01). ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage, thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.
5.Cuscutae Semen-Lycii Fructus Improves Spermatogenesis in Rat Model of Oligoasthenozoospermia by Inhibiting Oxidative Stress-induced Blood-testis Barrier Damage via Regulating SIRT1/Nrf2 Signaling Pathway
Wen DUAN ; Xiaojing ZHANG ; Wenjie DING ; Jianning JIN ; Guoqing CHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):29-38
ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia (OAS) and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsThirty-five male SD rats were randomized into a blank group (n=7) and a modeling group (n=28). The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups: model, Cuscutae Semen-Lycii Fructus granules (3.2 g·kg-1), Cuscutae Semen-Lycii Fructus total flavonoids (0.34 g·kg-1), and L-carnitine (0.38 g·kg-1), and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase (SOD), malondialdehyde (MAD), and glutathione peroxidase (GSH-Px) in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of SIRT1, Nrf2, Occludin, zonula occludens-1 (ZO-1), connexin 43 (CX43), and β-catenin. ResultsCompared with the blank group, the model group showed decreased total sperm count and motility (P<0.05, P<0.01), obvious damage in the testicular tissue and blood-testis barrier structure, reduced score of spermatogenic function (P<0.01), declined levels of GSH-Px and SOD in the testicular tissue (P<0.05), elevated level of MDA, and down-regulated protein levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin (P<0.05, P<0.01) and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, and β-catenin in the testicular tissue (P<0.05, P<0.01). After treatment, the testicular tissue, blood-testis barrier structure, and score of spermatogenic function (P<0.01) were improved in the Cuscutae Semen-Lycii Fructus granules group, Cuscutae Semen-Lycii Fructus total flavonoids group, and L-carnitine group. Compared with the model group, the treatment groups presented lowered levels of GSH-Px and SOD (P<0.05, P<0.01), and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group (P<0.05, P<0.01). ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage, thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.
6.Construction and application of a mixed-reality distance teaching model in neurosurgery
Rui HUI ; Hulin ZHAO ; Gang CHENG ; Wei LIU ; Zhi WANG ; Jianning ZHANG
Chinese Journal of Medical Education Research 2024;23(3):428-432
Objective:To explore the application effects of a neurosurgical mixed-reality distance teaching (NMDT) model in standardized residency training in neurosurgery.Methods:We built an NMDT system using mixed-reality technology and remote interaction technology, and designed the implementation procedure according to the teaching objectives. After the teaching activities were completed, a teaching satisfaction questionnaire survey was conducted among 20 neurosurgery resident trainees, in which they provided satisfaction scores for the same teaching content with different teaching models (i.e., the NMDT model and traditional teaching model). SPSS 22.0 software was used to perform the t test for data analysis. Results:There were significant differences between the NMDT model and the traditional teaching model in key indicators including the score for "completion of teaching objectives" (9.20±0.68 vs. 8.25±0.70, P<0.001) and the score for "satisfaction with learning gains" score (8.95±0.67 vs. 8.05±0.92, P=0.001). The NMDT model also outperformed the traditional teaching model in the other individual scores and the total score. Conclusions:The NMDT model can improve teaching quality, increase training efficiency, and enrich teaching content, which is worthy of promotion.
7.Analysis of risk factors for periprosthetic joint infection after primary total knee arthroplasty and construction of a nomogram prediction model
Shaoqiang YANG ; Peng FANG ; Dongsheng WANG ; Yu ZHANG ; Tao YUAN ; Jianning ZHAO ; Nirong BAO
Chinese Journal of Orthopaedic Trauma 2024;26(3):234-240
Objective:To investigate the risk factors for periprosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) and construct a nomogram model for prediction of such risks.Methods:In this retrospective study, we enrolled 69 patients with PJI after primary TKA (the infection group, n=69) who had been admitted to Department of Orthopedics, Nanjing Jinling Hospital, The First School of Clinical Medicine, Southern Medical University from January 2010 to December 2019. The non-infection group included the patients of the same kind but without postoperative infection during the same period who were matched according to time of admission, age, and gender in a ratio of 1∶3 ( n=207). The data on body mass index, anesthesia method, operation time, preoperative C-reactive protein, preoperative albumin, and comorbid medical conditions were collected from both groups to screen the risk factors for postoperative development of PJI using univariate and multivariate conditional logistic regression analyses. After a nomogram of the risk factors was plotted using R software, the consistency index (C-index) was calculated. The receiver operating characteristic curve, calibration curve, and clinical decision curve were drawn. Results:Multivariate conditional logistic regression analysis showed that preoperative albumin <35 g/L ( OR=7.166, 95% CI: 3.427 to 14.983, P<0.001), operation time >90 min ( OR=3.163, 95% CI: 1.476 to 6.779, P=0.003), diabetes mellitus ( OR=3.966, 95% CI: 1.833 to 8.578, P<0.001), rheumatic diseases ( OR=3.531, 95% CI: 1.362 to 9.156, P=0.009), and chronic lung diseases ( OR=4.734, 95% CI: 1.790 to 12.521, P=0.002) were risk factors for development of PJI after primary TKA. The nomogram constructed with R software visualized the model. The C-index of the nomogram was 0.809 (95% CI: 0.751 to 0.867), indicating a good predictive capability of the model. The calibration curves of the model showed that the nomogram was in good agreement with the actual observations. The decision curves showed that the threshold probabilities of the model ranged from 0.08 to 0.75, providing a good net clinical benefit. Conclusions:Preoperative low albumin, prolonged operation time, diabetes, rheumatic diseases, and chronic lung diseases may be the risk factors for PJI after primary TKA. The nomogram prediction model based on these factors can provide a reference for clinicians to prevent PJI.
8.Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma
Xiangyu LI ; Jianning YAO ; Xuyang DONG ; Liangxing CHENG ; Xuexiu ZHANG ; Mengge SU ; Haining ZHOU ; Jinlin XIE ; Zhaoxiang SONG ; Fei HAN
Chinese Journal of Oncology 2024;46(8):782-793
Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.
9.Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma
Xiangyu LI ; Jianning YAO ; Xuyang DONG ; Liangxing CHENG ; Xuexiu ZHANG ; Mengge SU ; Haining ZHOU ; Jinlin XIE ; Zhaoxiang SONG ; Fei HAN
Chinese Journal of Oncology 2024;46(8):782-793
Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.
10.Metrology analysis and thoughts of literatures on tinnitus associated with sudden deafness based on CiteSpace
Si CHEN ; Jianning ZHANG ; Yan HUO ; Wenchen LING ; Jiaqian WU ; Xinyu ZHAO ; Ming LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(7):719-726
Objective:To explore the incidence of sudden deafness accompanied with tinnitus, the selection of examination protocols and treatment, and to provide reference for the establishment of new guidelines for sudden deafness.Methods:CiteSpace software was used for analysis and data mining to analyze and summarize the computer-retrieved articles on diagnostic examination and treatment of sudden deafness accompanied with tinnitus collected from CNIC, Wanfang and Web of Science databases from 2011 to 2021.Results:A total of 207 randomized controlled studies were retrieved in this study, including 121 in Chinese and 86 in English. Finally, 74 Chinese literatures and 16 English literatures were included. Among the 74 valid Chinese literatures, 64 (86.5%) were accompanied with tinnitus, 58 (78.4%) with dizziness/vertigo, 25 (33.8%) with aural fullness, 10 (13.5%) with headache, 4 (5.4%) with insomnia, 4 (5.4%) with a mixture of dizziness and tinnitus, and 2 (2.7%) with vomiting. Among the 16 English literatures, 15 (93.8%) were accompanied with tinnitus, 12 (75.0%) with vertigo, 1 (6.3%) with aural fullness, and 1 (6.3%) with a mixture of various symptoms. Among the 64 Chinese articles mentioning tinnitus, only 9 mentioned tinnitus matching tests, and 1 mentioned that the treatment for tinnitus accompanying symptoms was sound therapy and psychological counseling. The incidence rates of tinnitus accompanying four different types of sudden deafness, from low to high, are as follows: low-to-mid frequency, 82.4%; mid-to-high frequency, 90.7%; complete deafness, 92.4%; and flat type, 92.8%.Conclusion:Tinnitus is the most common accompanying symptom of sudden deafness, and tinnitus matching test is an effective evaluation method. When establishing a scientific, comprehensive, and systematic diagnosis and treatment system or guidelines for sudden deafness, attention should be paid to the diagnosis and treatment of tinnitus symptoms and their adverse psychological reactions, in order to reduce the incidence of tinnitus patients in the later stage of recovery from sudden deafness.

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