1.Correlation Between Cardiovascular Events and Traditional Chinese Medicine Syndrome in Patients with Rheumatoid Arthritis:A Cross-Sectional Study
Fuyuan ZHANG ; Quan JIANG ; Jun LI ; Yuchen YANG ; Xieli MA ; Tian CHANG ; Congmin XIA ; Jian WANG ; Xun GONG
Journal of Traditional Chinese Medicine 2025;66(15):1572-1578
ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis(RA) and traditional Chinese medicine(TCM) syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide, in which general information such as name, gender, age, height, body weight, and course of disease were collected by completing a questionnaire; patients were classified into eight types of syndrome according to the information of their four examinations,i.e. wind-dampness obstruction syndrome, cold-dampness obstruction syndrome, dampness-heat obstruction syndrome, phlegm-stasis obstruction syndrome, stasis-blood obstructing collateral syndrome, qi-blood deficiency syndrome, liver-kidney insufficiency syndrome, and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events, they were divided into the occurrence group and the non-occurrence group, and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events, and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included, including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height, gender, insomnia, appetite, white blood cell(WBC), hemoglobin(HGB), platelets(PLT), rheumatoid factor(RF), anti-cyclic peptide containing citrulline(CCP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), γ-glutamyl transpeptidase(GGT), urea creatinine(CREA), and glucose(GLU)(P>0.05). The TCM syndromes between groups showed significant statistic differences(P<0.05). Patients in occurrence group had longer disease duration, heavier body weight, and older age; more severe conditions such as disease activity(DAS-28), number of painful joints(TJC), number of swollen joints(SJC), health questionnaire scores(HAQ), visual analog scores(VAS), restlessness, and fatigue; higher blood sedimentation rate(ESR), low-density lipoprotein(LDL-C), triglyceride(TG), total cholesterol(TC), D-Dimer, and lower high-density lipoprotein(HDL-C)(P<0.05). The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome[OR=5.937, 95%CI (4.434, 7.949), P<0.001]. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes, and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.
2.Expression and function of CDYL-interacting protein MYH9 in mouse testis.
Huan-Tong GONG ; Yan-Mei QUAN ; Yun-Xia ZHANG ; Han-Fei ZHU ; Xiao-Yu XIA
National Journal of Andrology 2025;31(9):771-779
OBJECTIVE:
To identify the CDYL-interacting proteins in murine testis and investigate the mechanism of CDYL involved in spermatogenesis.
METHODS:
CDYL-interacting partners in testis were identified using co-immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression pattern of CDYL-interacting protein MYH9 was analyzed through immunohistochemistry (IHC), confocal immunofluorescence (IF) and Western blot (WB) in mouse testicular cells. The effect of the Cdyl conditional knockout (CdylcKO) in spermatogenic cell on Myh9 expression was quantified via RT-qPCR, WB and IF imaging in both spermatids and spermatozoa from cauda epididymides.
RESULTS:
Direct interaction between MYH9 and CDYL was confirmed in murine testis. During spermiogenesis, MYH9 exhibited co-localization with CDYL at the manchette structure, and binding to F-ACTIN, the component of manchette. In cauda epididymal spermatozoa, MYH9 signal concentrated on acrosomal region and continuously distributed along the tail length. Conditional deletion of Cdyl in spermatogenic cell resulted in the transcriptional downregulation of Myh9. In spermatids, CdylcKO led to reduced but retained MYH9 localization to the disorganized manchette structure. In spermatozoa from CdylcKO mice, abnormalities of MYH9 localization were observed, including attenuation of acrosomal signal and/or partial vanishment/enhancement of tail signal.
CONCLUSION
In murine spermatids, MYH9 protein is localized to the manchette structure, with its expression and subcellular distribution is affected by CDYL protein. CDYL-MYH9 interaction is essential for the spermiogenesis.
Animals
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Male
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Mice
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Testis/metabolism*
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Myosin Heavy Chains/metabolism*
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Spermatogenesis
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Mice, Knockout
3.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Arthritis, Rheumatoid/drug therapy*
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Glucocorticoids/therapeutic use*
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Medicine, Chinese Traditional
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Retrospective Studies
4.Pathogenesis and Therapeutic Approaches of Systemic Lupus Erythematosus Secondary Gynecological and Obstetric Diseases Based on the Theory of "Bi (痹) of both Body and Viscera"
Hui XU ; Quan JIANG ; Congmin XIA ; Rouman ZHANG ; Xun GONG ; Chuanhui YAO ; Zixia LIU ; Yuchen YANG ; Xieli MA
Journal of Traditional Chinese Medicine 2025;66(23):2438-2442
Systemic lupus erythematosus (SLE) may lead to secondary gynecological and obstetric disorders such as decreased ovarian reserve function, menstrual abnormalities, and adverse pregnancy outcomes. Based on "bi (痹) of both body and viscera" theory, this paper proposed that the core mechanism of SLE secondary gynecological and obstetric diseases lies in the mutual transformation between "body bi" and "viscera bi", which together affect the uterus. Physiologically, uterus forms an internal-external network with the body and viscera through the meridians and blood vessels. Pathologically, when the healthy qi is deficient, nourishment of the body and viscera is impaired; when toxins and stasis accumulate, pathogenic factors disturb the uterus through the chong (冲) and ren (任) meri-dians. The resulting obstruction in the uterus can, in turn, manifest externally and aggravate damage to the body and viscera. Therefore, the pathogenesis of SLE secondary gynecological and obstetric diseases follows a dynamic trajectory of "body bi first, body bi affecting viscera, and then bi of both body and viscera". In treatment, the principle of harmonizing and balancing the healthy qi is emphasized. The main approach is to regulate the viscera, stabilize the body, and nourish the uterus, with the coordination of nourishing the viscera through the body, thereby achieving simultaneous treatment of both body and viscera. This highlights the guiding significance of the "bi of both body and viscera" theory in preventing and treating SLE secondary gynecological and obstetric diseases.
5.Distritution Characteristics of TCM Syndromes and Evaluation of Traditional Chinese Medicine Efficacy in 2506 Rheumatoid Arthritis Patients with Different Course of Disease:A Real-World Retrospective Study
Zhengyao SHEN ; Jingtao LI ; Yuchen YANG ; Shujuan ZHANG ; Quan JIANG ; Xun GONG
Journal of Traditional Chinese Medicine 2025;66(23):2453-2459
ObjectiveTo investigate the syndrome evolution patterns, characteristics of the used herbal medicinals, and efficacy variations across different stages of rheumatoid arthritis (RA) progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN), 2,506 RA patients were retrospectively enrolled and categorized into <6 months group (166 cases), 6 months to <5 years group (1063 cases), 5 to <20 years group (1067 cases), and ≥20 years group (210 cases). Syndromes were differentiated before and after traditional Chinese medicine (TCM) treatment, including damp-heat obstruction, wind-damp obstruction, cold-damp obstruction, blood stasis obstructed in the collaterals, phlegm-stasis obstruction, liver-kidney insufficiency, qi and blood deficiency, and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) and 28-joint disease activity score based on C-reactive protein (DAS28-CRP) before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome (49/166, 29.5%), wind-dampness obstruction syndrome (46/166, 27.7%), and dampness-heat obstruction syndrome (43/166, 25.9%). For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years, the dominant syndrome was dampness-heat obstruction syndrome (324/1063, 30.5% and 318/1067, 29.8%, respectively). In patients with disease duration ≥20 years, liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated, each accounting for 25.24% (53/210). The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction (201/738, 27.2%), liver-kidney insufficiency (119/367, 32.4%), and phlegm-stasis obstruction syndromes (73/172, 42.4%). These were classified as high-frequency syndromes. After treatment, damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome, while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao (Radix et Rhizoma Glycyrrhizae) and Baishao (Radix Paeoniae Alba). In the <6 months group and the 6 months to <5 years group, high-frequency herbs also included Fangfeng (Radix Saposhnikoviae), Duhuo (Radix Angelicae Pubescentis), Chuanxiong (Rhizoma Chuanxiong), and Qianghuo (Radix et Rhizoma Notopterygii). In the 5 to <20 years group and the ≥20 years group, the usage of Huangqi (Radix Astragali), Fuling (Poria), Niuxi (Radix Achyranthis Bidentatae), and Danggui (Radix Angelicae Sinensis) increased, while the proportion of Fangfeng and Duhuo decreased. After treatment, the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased (P<0.05). There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups (P<0.01). Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group (OR=0.4), 5~20 years group (OR=0.5), and ≥20 years group (OR=0.4) compared to the <6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency, with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA, with superior efficacy in patients with disease duration shorter than 6 months.
6.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
7.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
8.3-Methyladenine alleviates early renal injury in diabetic mice by inhibiting AKT signaling
Benju LIU ; Yelei WANG ; Haiwen REN ; Liwen OU ; Xuan DENG ; Mengxin HUANG ; Xin WU ; Quan GONG
Journal of Southern Medical University 2024;44(7):1236-1242
Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.
9.3-Methyladenine alleviates early renal injury in diabetic mice by inhibiting AKT signaling
Benju LIU ; Yelei WANG ; Haiwen REN ; Liwen OU ; Xuan DENG ; Mengxin HUANG ; Xin WU ; Quan GONG
Journal of Southern Medical University 2024;44(7):1236-1242
Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.
10.Curative Effect of Tripterygium wilfordii Polyglycoside Tablets in Treatment of Rheumatoid Arthritis in Real World Based on Propensity Score Matching
Xieli MA ; Quan JIANG ; Xun GONG ; Congmin XIA ; Chuanhui YAO ; Tian CHANG ; Zixia LIU ; Yuchen YANG ; Jiameng LIU ; Zhengyao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):125-131
ObjectiveTo evaluate the clinical efficacy and safety of Tripterygium wilfordii polyglycoside tablets (TWP) in the treatment of rheumatoid arthritis (RA) in the real world. MethodDiagnosis and treatment data of patients with RA in Chinese medicine rheumatology registration research information platform information database (CERTAIN) from January 1,2019 to January, 2024 were collected. According to the inclusion and exclusion criteria, data were screened. The included data were divided into an exposure group and a control group according to the use of TWP or not. Propensity score matching (PSM) was used in both groups to keep the baseline balanced and comparable. The disease activity score (DAS28-ESR) of 28 joints based on the erythrocyte sedimentation rate (ESR)before and after treatment was compared between the two groups, as well as health assessment questionnaire (HAQ),visual analogue scale (VAS),tender joint count (TJC),swollen joint count (SJC), patient's global assessment (PGA),evaluator's global assessment (EGA),laboratory indexes, clinical curative effect, and adverse reactions. ResultA total of 3 978 patients were included,including 929 in the exposure group and 3 049 in the control group. Before PSM,there were significant differences in demographic information,DAS28-ESR score,PGA,EGA,HAQ,VAS scores,SJC, and TJC between the two groups (P<0.05). After successful PSM matching,922 patients in the exposure group and 922 patients in the control group were included. There was no significant difference in demographic information and DAS28-ESR between the two groups before treatment,and the differences in other indexes between the two groups decreased to varying degrees. After treatment,the DAS28-ESR,PGA,EGA,HAQ,SJC,TJC,VAS scores, ESR,and IgG immune index of the two groups were significantly lower (P<0.01). Compared with those in the control group after treatment,the DAS28-ESR,PGA,EGA,HAQ,VAS scores, and ESR in the exposure group after treatment decreased more significantly (P<0.05,P<0.01). There was no significant difference in TJC in the exposure group after treatment. However, TJC in the exposure group was significantly higher than that in the control group before treatment (P<0.05). In terms of TJC reduction,the exposure group performed better than the control group. There was no significant difference in SJC and IgG between the exposure group and the control group after treatment. After treatment,the clinical symptoms of poor appetite,insomnia and many dreams,upset,fatigue,and fear of wind and cold in the two groups were improved. Except that the proportion of women in the exposure group was higher than that in the control group (P<0.01),there was no significant difference in the incidence of other adverse reactions between the two groups after treatment. ConclusionTWP to treat RA can effectively reduce DAS28-ESR,PGA,EGA,HAQ,TJC,and VAS scores and improve the general symptoms. Except for the women at childbearing age with fertility requirements that TWP is not applicable,it shows good security.

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