1.Effect of Stattic on the survival of mouse heart allograft by regulating memory CD4+T cell-mediated acute rejection
Shiliang LI ; Yi FENG ; Ming FANG ; Yan ZHOU
Organ Transplantation 2025;16(1):74-82
Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4+ T cells (CD4+Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4+Tm, and the EdU method was used to detect the effect of Stattic on CD4+Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4+Tm (CD4+CD44+CD62L+) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4+Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4+Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4+Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4+Tm- mediated acute rejection.
2.Pharmacodynamic study of Tianjiang xueshuantong pills in the treatment of coronary heart disease
Wenjie LI ; Yingying LI ; Jiang BIAN ; Ting LIU ; Yunxuan GUAN ; Xibiao ZHANG ; Shiliang ZHOU ; Li SUN ; Xi JIANG
China Pharmacy 2025;36(11):1358-1363
OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease, acute myocardial ischemia model, hyperlipidemia model, blood stasis model, and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high, medium, and low doses (0.6, 1.2 and 2.4 g/kg) on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase (LDH), creatine kinase-MB (CK- MB)], oxidative stress factors [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH)], inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1)], myocardial infarction percentage, serum lipid indexes [total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL)], platelet aggregation function 话:022-84845240。E-mail:jiangx@tjipr.com [maximum aggregation rate (MAR)], and thrombus formation indexes [thrombosis time, thrombus mass, thrombus protein content, plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (t-PA)] were evaluated in the rat models. RESULTS In myocardial ischemia tests, Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB, LDH, MDA, GSH, IL-6, TNF-α, IL- 1β, and MCP-1 in serum (P<0.05 or P<0.01). In hyperlipidemia tests, high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC, LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests, different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats (P<0.01). In artery thrombosis tests, high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation (P< 0.01), significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum (P<0.01). CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions, including anti-myocardial ischemia, lipid-lowering, and anti-thrombotic effects.
3.Structural design and mechanical analysis of a "drum-shaped" balloon-expandable valve stent in expanded configuration.
Youzhi ZHAO ; Qianwen HOU ; Jianye ZHOU ; Shiliang CHEN ; Hanbing ZHANG ; Aike QIAO
Journal of Biomedical Engineering 2025;42(5):945-953
Stent migration is one of the common complications following transcatheter valve implantation. This study aims to design a "drum-shaped" balloon-expandable aortic valve stent to address this issue and conduct a mechanical analysis. The implantation process of the stent was evaluated using a method that combines numerical simulation and in vitro experiments. Furthermore, the fatigue process of the stent under pulsatile cyclic loading was simulated, and its fatigue performance was assessed using a Goodman diagram. The process of the stent migrating toward the left ventricular side was simulated, and the force-displacement curve of the stent was extracted to evaluate its anti- migration performance. The results showed that all five stent models could be crimped into a 14F sheath and enabled uniform expansion of the native valve leaflets. The stress in each stent was below the ultimate stress, so no fatigue fracture occurred. As the cell height ratio decreased, the contact area fraction between the stent and the aortic root gradually decreased. However, the mean contact force and the maximum anti-migration force first decreased and then increased. Specifically, model S5 had the smallest contact area fraction but the largest mean contact force and maximum anti-migration force, reaching approximately 0.16 MPa and 10.73 N, respectively. The designed stent achieves a "drum-shaped" change after expansion and has good anti-migration performance.
Stents
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Prosthesis Design
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Heart Valve Prosthesis
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Humans
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Aortic Valve/surgery*
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Stress, Mechanical
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Transcatheter Aortic Valve Replacement/instrumentation*
4.Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages.
Xin LIU ; Yi FANG ; Mincong HUANG ; Shiliang TU ; Boan ZHENG ; Hang YUAN ; Peng YU ; Mengyao LAN ; Wu LUO ; Yongqiang ZHOU ; Guorong CHEN ; Zhe SHEN ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(2):1039-1055
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
5.Study on the correlation between glycolipids and prostate volume in patients with benign prostatic hyperplasia
Xiaobo XIANG ; Tong ZHOU ; Shiliang LI ; Xiu ZHU ; Longmei DING ; Dongmei MA
Chinese Journal of Preventive Medicine 2024;58(9):1384-1387
To study the clinical correlation between fasting plasma glucose, lipid metabolism, prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia, and to explore the combined effect as diagnostic indicators. A total of 108 patients with benign prostatic hyperplasia treated in Beijing University of Chinese Medicine Third Affiliated Hospital from June 2021 to March 2023 were retrospectively analyzed as the hyperplasia group, and 98 healthy physical examination personnel were selected as the control group during the same period. Compare the differences in levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small and dense low-density lipoprotein cholesterol (sdLDL-C), homocysteine, lipoprotein a (LPa), prostate specific antigen (PSA), and free prostate specific antigen (fPSA) between two groups of patients. Using Pearson analysis method to analyze the correlation between the above indicators and the size of prostate volume in patients with benign prostatic hyperplasia; using multiple linear regression to analyze the influencing factors of prostate volume enlargement; draw receiver operating characteristic (ROC) curves and analyze the application value of individual and combined detection of HDL, FPG, PSA, and fPSA. The results showed that there were significant differences in HDL, FPG, PSA, and fPSA levels between the control group and the proliferative group( P<0.05). The size of prostate volume is negatively correlated with HDL( r=-0.183, P<0.05) and positively correlated with FPG ( r=0.202, P<0.05), PSA( r=0.412, P<0.05), and fPSA( r=0.425, P<0.05). The results of multiple linear regression analysis showed that HDL( P=0.000), FPG( P=0.048), PSA( P=0.044), and fPSA ( P=0.012) were risk factors for increased volume of benign prostatic hyperplasia; ROC curve analysis shows that the AUC of HDL, FPG, PSA, and fPSA combined detection is 0.823, which is better than individual detection. In conclusion,HDL, FPG, PSA, fPSA has close correlation with hyperplasia of prostate, the joint detection may has better prediction for benign prostatic hyperplasia.
6.Study on the correlation between glycolipids and prostate volume in patients with benign prostatic hyperplasia
Xiaobo XIANG ; Tong ZHOU ; Shiliang LI ; Xiu ZHU ; Longmei DING ; Dongmei MA
Chinese Journal of Preventive Medicine 2024;58(9):1384-1387
To study the clinical correlation between fasting plasma glucose, lipid metabolism, prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia, and to explore the combined effect as diagnostic indicators. A total of 108 patients with benign prostatic hyperplasia treated in Beijing University of Chinese Medicine Third Affiliated Hospital from June 2021 to March 2023 were retrospectively analyzed as the hyperplasia group, and 98 healthy physical examination personnel were selected as the control group during the same period. Compare the differences in levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small and dense low-density lipoprotein cholesterol (sdLDL-C), homocysteine, lipoprotein a (LPa), prostate specific antigen (PSA), and free prostate specific antigen (fPSA) between two groups of patients. Using Pearson analysis method to analyze the correlation between the above indicators and the size of prostate volume in patients with benign prostatic hyperplasia; using multiple linear regression to analyze the influencing factors of prostate volume enlargement; draw receiver operating characteristic (ROC) curves and analyze the application value of individual and combined detection of HDL, FPG, PSA, and fPSA. The results showed that there were significant differences in HDL, FPG, PSA, and fPSA levels between the control group and the proliferative group( P<0.05). The size of prostate volume is negatively correlated with HDL( r=-0.183, P<0.05) and positively correlated with FPG ( r=0.202, P<0.05), PSA( r=0.412, P<0.05), and fPSA( r=0.425, P<0.05). The results of multiple linear regression analysis showed that HDL( P=0.000), FPG( P=0.048), PSA( P=0.044), and fPSA ( P=0.012) were risk factors for increased volume of benign prostatic hyperplasia; ROC curve analysis shows that the AUC of HDL, FPG, PSA, and fPSA combined detection is 0.823, which is better than individual detection. In conclusion,HDL, FPG, PSA, fPSA has close correlation with hyperplasia of prostate, the joint detection may has better prediction for benign prostatic hyperplasia.
7.Advances in endoscopic sleeve gastroplasty for the treatment of obesity and metabolic disease
Shiliang DONG ; Fuqing ZHOU ; Wenhui CHEN ; Cunchuan WANG ; Zhiyong DONG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):803-806
Obesity poses a serious threat to human health, and although bariatric surgery has been proven effective treatment for morbidly obese patients, its surgical risks and high medical costs limit its clinical application and popularity. Endoscopic sleeve gastroplasty (ESG), as a relatively new endoscopic surgery technique for weight loss, has satisfactory weight loss effects compared to laparoscopic sleeve gastrectomy and lifestyle interventions, while preserving the normal structure of the stomach. Its weight loss effects and safety have been validated in multicenter studies abroad. Although, ESG has not yet been widely performed in China, with the gradual maturity of this technique, its prospects are worth attention in the field of weight loss. In the future, large-scale, long-term, multi-center studies are urgently needed in China to clarify the long-term effects, remission of comorbidities, and occurrence of complications of ESG surgery in obese and metabolic disease patients.
8.Efficacy analysis of laparoscopic sleeve gastrectomy in morbidly obese patients aged 10-21 years
Shiliang DONG ; Wenhui CHEN ; Jie GUO ; Yalun LIANG ; Fuqing ZHOU ; Cunchuan WANG ; Zhiyong DONG
Chinese Journal of Gastrointestinal Surgery 2023;26(11):1064-1070
Objective:To investigate the efficacy of laparoscopic sleeve gastrectomy (LSG) in morbidly obese patients aged 10 to 21 years.Methods:We conducted a retrospective analysis of clinical data from 89 out of 200 patients who underwent LSG at the Gastrointestinal Surgery/Weight Loss Center of the First Affiliated Hospital of Jinan University between January 2015 and December 2020. The primary outcome measures were the completion rate of LSG, the incidence of perioperative complications, and weight-related indicators 3, 6, 12, and ≥24 months postoperatively. Additionally, we compared glucose metabolism, lipid metabolism, vitamin levels, liver function, and other relevant biochemical variables before and after surgery. Normally distributed continuous data are presented as x±s. Because the numbers of patients at each follow-up time point were not identical with the number of patients in the study cohort preoperatively, independent sample t-tests were used for intergroup comparisons. Non-normally distributed continuous data are presented as M( Q1, Q3), and Mann-Whitney U tests were used for intergroup comparisons. Results:Among the 89 patients, 35 were male (39.3%), the mean age was (18±2) years, and mean body mass index (BMI) 38.5±4.8 kg/m2; 37 of the patients having a BMI greater than 40 kg/m2. Additionally, 63 patients (70.8%) had fatty livers, 34 (38.2%) hyperuricemia, 31(34.8%) sleep apnea syndrome, 20 (22.4%) gastroesophageal reflux, eight (8.9%) type 2 diabetes, and two (2.2%) hypertension. All 89 patients underwent LSG surgery successfully, with no conversions to open surgery. During the perioperative period, there were no cases of major bleeding, gastric leakage, or infections. Notable postoperative symptoms included nausea, vomiting, and pain, most of which improved by the second postoperative day. BMI values 3, 6, and 12 months postoperatively had decreased to 31.5±5.8 kg/m2, 28.6±4.3 kg/m2, and 26.3±4.4 kg/m2, respectively. All of these BMI values differed significantly from preoperative values (all P<0.05). At 12 and ≥24 months postoperatively, the percentages of total weight loss were (31.3±9.3)% and (33.1±10.5)%, respectively, both differing significantly from 3 months postoperatively (20.5±5.1)% (all P<0.05). The percentages of excess weight loss at 12 and ≥24 months postoperatively were 91% (70%, 113%) and 95% (74%, 118%) , respectively, both differing significantly from the percentage of total weight loss 3 months postoperatively (56% [45%, 72%]) (both P<0.05). Alanine transaminase and aspartate transaminase serum concentrations decreased from preoperative values of 44.4 (25.5, 100.5) U/L and 29.0 (9.5, 48.0) U/L to 14.0 (10.8, 18.3) U/L and 13.0 (10.5, 17.3) U/L, respectively, ≥24 months postoperatively. Hemoglobin A1c decreased from 5.6 (5.3, 5.8)% preoperatively to ≥24 months postoperatively 5.3 (5.0, 5.4)%. High-density lipoprotein increased from 1.0 (0.9, 1.2) mmol/L preoperatively to 1.4 (1.1, 1.6) mmol/L ≥24 months postoperatively. Vitamin B12 decreased from 350.0 (256.8, 441.3) μg/L preoperative to 230.3(195.4, 263.9) μg/L ≥24 months postoperatively. All differed significantly from preoperative values (all P<0.05). Conclusion:LSG has favorable efficacy in morbidly obese patients aged 10 to 21 years. However, further confirmation is required through long-term, multicenter, randomized, controlled trials.
9.Advances in endoscopic sleeve gastroplasty for the treatment of obesity and metabolic disease
Shiliang DONG ; Fuqing ZHOU ; Wenhui CHEN ; Cunchuan WANG ; Zhiyong DONG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):803-806
Obesity poses a serious threat to human health, and although bariatric surgery has been proven effective treatment for morbidly obese patients, its surgical risks and high medical costs limit its clinical application and popularity. Endoscopic sleeve gastroplasty (ESG), as a relatively new endoscopic surgery technique for weight loss, has satisfactory weight loss effects compared to laparoscopic sleeve gastrectomy and lifestyle interventions, while preserving the normal structure of the stomach. Its weight loss effects and safety have been validated in multicenter studies abroad. Although, ESG has not yet been widely performed in China, with the gradual maturity of this technique, its prospects are worth attention in the field of weight loss. In the future, large-scale, long-term, multi-center studies are urgently needed in China to clarify the long-term effects, remission of comorbidities, and occurrence of complications of ESG surgery in obese and metabolic disease patients.
10.Efficacy analysis of laparoscopic sleeve gastrectomy in morbidly obese patients aged 10-21 years
Shiliang DONG ; Wenhui CHEN ; Jie GUO ; Yalun LIANG ; Fuqing ZHOU ; Cunchuan WANG ; Zhiyong DONG
Chinese Journal of Gastrointestinal Surgery 2023;26(11):1064-1070
Objective:To investigate the efficacy of laparoscopic sleeve gastrectomy (LSG) in morbidly obese patients aged 10 to 21 years.Methods:We conducted a retrospective analysis of clinical data from 89 out of 200 patients who underwent LSG at the Gastrointestinal Surgery/Weight Loss Center of the First Affiliated Hospital of Jinan University between January 2015 and December 2020. The primary outcome measures were the completion rate of LSG, the incidence of perioperative complications, and weight-related indicators 3, 6, 12, and ≥24 months postoperatively. Additionally, we compared glucose metabolism, lipid metabolism, vitamin levels, liver function, and other relevant biochemical variables before and after surgery. Normally distributed continuous data are presented as x±s. Because the numbers of patients at each follow-up time point were not identical with the number of patients in the study cohort preoperatively, independent sample t-tests were used for intergroup comparisons. Non-normally distributed continuous data are presented as M( Q1, Q3), and Mann-Whitney U tests were used for intergroup comparisons. Results:Among the 89 patients, 35 were male (39.3%), the mean age was (18±2) years, and mean body mass index (BMI) 38.5±4.8 kg/m2; 37 of the patients having a BMI greater than 40 kg/m2. Additionally, 63 patients (70.8%) had fatty livers, 34 (38.2%) hyperuricemia, 31(34.8%) sleep apnea syndrome, 20 (22.4%) gastroesophageal reflux, eight (8.9%) type 2 diabetes, and two (2.2%) hypertension. All 89 patients underwent LSG surgery successfully, with no conversions to open surgery. During the perioperative period, there were no cases of major bleeding, gastric leakage, or infections. Notable postoperative symptoms included nausea, vomiting, and pain, most of which improved by the second postoperative day. BMI values 3, 6, and 12 months postoperatively had decreased to 31.5±5.8 kg/m2, 28.6±4.3 kg/m2, and 26.3±4.4 kg/m2, respectively. All of these BMI values differed significantly from preoperative values (all P<0.05). At 12 and ≥24 months postoperatively, the percentages of total weight loss were (31.3±9.3)% and (33.1±10.5)%, respectively, both differing significantly from 3 months postoperatively (20.5±5.1)% (all P<0.05). The percentages of excess weight loss at 12 and ≥24 months postoperatively were 91% (70%, 113%) and 95% (74%, 118%) , respectively, both differing significantly from the percentage of total weight loss 3 months postoperatively (56% [45%, 72%]) (both P<0.05). Alanine transaminase and aspartate transaminase serum concentrations decreased from preoperative values of 44.4 (25.5, 100.5) U/L and 29.0 (9.5, 48.0) U/L to 14.0 (10.8, 18.3) U/L and 13.0 (10.5, 17.3) U/L, respectively, ≥24 months postoperatively. Hemoglobin A1c decreased from 5.6 (5.3, 5.8)% preoperatively to ≥24 months postoperatively 5.3 (5.0, 5.4)%. High-density lipoprotein increased from 1.0 (0.9, 1.2) mmol/L preoperatively to 1.4 (1.1, 1.6) mmol/L ≥24 months postoperatively. Vitamin B12 decreased from 350.0 (256.8, 441.3) μg/L preoperative to 230.3(195.4, 263.9) μg/L ≥24 months postoperatively. All differed significantly from preoperative values (all P<0.05). Conclusion:LSG has favorable efficacy in morbidly obese patients aged 10 to 21 years. However, further confirmation is required through long-term, multicenter, randomized, controlled trials.

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