1.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
2.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
3.Meta analysis of the correlation between chronic periodontitis and postmenopausal osteoporosis
Xuehui HU ; Hao YIN ; Zhiguo LUO ; Guoliang TANG ; Xuejun HE
Journal of Chinese Physician 2024;26(7):1010-1016
Objective:To systematically evaluate the correlation between chronic periodontitis and postmenopausal osteoporosis (PMOP).Methods:Electronic searches were conducted on Cochrane Library, Pubmed, Embase, Ovid, CNKI, CBM, VIP, and WF databases to collect research literature on the correlation between chronic periodontitis and PMOP. The Newcastle Ottawa Scale (NOS) criteria were used to evaluate the quality of the included literature, and RevMan 5.3 software was used for meta-analysis. The outcome measures were clinical attachment loss (CAL), probing depth (PD), plaque index (PI), calculus index (CI), bleeding on probing (BOP), and simplified oral hygiene index (OHI-S).Results:A total of 16 articles were included, with a total of 1587 patients. Compared with the postmenopausal non osteoporosis group, the osteoporosis group showed significant abnormalities in CAL [standardized mean difference (SMD)=1.09, 95% CI: 0.62-1.57, P<0.001], PD(SMD=0.71, 95% CI: 0.28-1.14, P<0.001), PI(SMD=0.43, 95% CI: 0.29-0.56, P<0.001), and OHI-S(SMD=0.28, 95% CI: 0.22-0.35, P<0.001) indicators, as well as in BOP(SMD=0.01, 95% CI: -0.48-0.49, P=0.97) and GI(SMD=0.01, 95% CI: -0.48-0.49, P=0.97). At the level of 0.24 and 95% CI: -0.34 to 0.81, P=0.42, there was no statistically significant difference. Conclusions:Women with PMOP exhibit more significant changes in indicators such as CAL, PD, PI, and OHI-S, suggesting that postmenopausal women with osteoporosis are more likely to suffer from periodontitis.
4.Difference of optic nerve subarachnoid space area between normal tension glaucoma and primary open-angle glaucoma and its correlation with related factors
Zhizheng TANG ; Xuehui WU ; Xueping CHEN ; Yaofang LIANG
Chinese Journal of Postgraduates of Medicine 2020;43(9):775-779
Objective:To investigate the optic nerve subarachnoid space area (ONSSA) in patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) and its correlation with related factors.Methods:Fifty-three patients with NTG (Group A) and 46 patients with POAG (Group B) were selected from January 2016 to May 2019 in Gaozhou Traditional Chinese Medicine Hospital of Guangdong Province. None of them received any treatment. Another 40 patients with health examination (Group C) were selected. Body mass index, blood pressure, 24-hour intraocular pressure, visual field damage, visual axis length and central corneal thickness were measured in each group. Two-dimensional ultrasound was performed to analyze the difference of ONSSA in the retrobulbar 3 to 7 mm range in each group, and the correlation between ONSSA and clinical related factors was analyzed.Results:The ONSSA in group A was significantly smaller than that in group B and group C: (5.07 ± 0.83) mm 2 vs. (6.19 ± 0.90) and (6.57 ± 1.43) mm 2, the differences were statistically significant ( t = 5.219 and 6.107, P < 0.05). ONSSA in group A was positively correlated with the mean intraocular pressure and maximum intraocular pressure of 24 hours ( r = 0.658 and 0.479, P < 0.05), while ONSSA in group B and C was not correlated with the mean intraocular pressure and maximum intraocular pressure of 24 hours ( P > 0.05). ONSSA was not correlated with age, body mass index, mean arterial pressure, central corneal thickness, visual field damage and visual axis length ( P > 0.05). Conclusions:ONSSA of NTG patients is lower than that of POAG patients and healthy people, and the ONSSA of NTG patients is correlated with the mean intraocular pressure and maximum intraocular of 24 hours.
5.Changes of inflammatory factor level in 2-diabetes patients before and after improving glycemic control
Lixin ZHAO ; Fumei TANG ; Yajie LIU ; Xuehui YANG ; Bin HOU ; Jun SHI ; Zhizhong LIU
Clinical Medicine of China 2015;31(6):503-506
Objective To investigate the inflammation levels of 2-diabetes patients before and after 3 months of improving glycemic control.Methods A longitudinal study was performed in a subgroup of 48 subjects with T2D and poor glycemic control.Forty-four healthy individuals were taken as control group.The serum concentration of C-reactionprotein (CRP),interleukin-6 (IL-6),interleukin-6 (IL-8),transforming growth factor-β1 (TGF-β1) and transforming growth factor-β1 (MCP1) in all participants were measured simultaneously by multiplexed Luminex assay.Results The serum levels of CRP,MCP-1 of 2-diabetes patients were 3.96 (3.45,5.58) mg/L and (195.0± 129.8) ng/L,significant higher than those in control group (2.25 (1.24,3.22) mg/L,(148.5±85.7) ng/L),and the differences were significant(t=-2.580,P=0.010;t=-2.118,P =0.047).No significant difference was found in the serum levels of IL-6,IL-8,TGF-β lbetween the two groups (P>0.05).TGF-β1 level in patients with good glycemic control decreased to 26.85 (23.17-31.12) ng/l,significant lower than that before glycemic control (43.5(26.5-62.25) g/L;Z=-2.191,P=0.028),and there were no significant differences among the other 4 kinds of inflammatory factors before and after blood glucose control(CRP:Z =-0.937P =0.372;IL-6:Z =-0.875,P =0.396;IL-8:Z =-1.215,P =0.286;MCP-1:t =-1.846,P=0.065).Conclusion Low grade systemic inflammation status in T2D patients.Improvement of glycemic control reduces TGF-β1 levels and plays a key role in delaying the development of diabetic nephropathy.
6.Clinical outcomes of proximal humeral internal locking system self-locking plates in treatment of proximal humeral fractures
Kanglai TANG ; Xiaokang TAN ; Xuehui WU ; Ge XU ; Jicheng GONG ; Huaqing WANG ; Zhao XIE ; Shuzhi MA ; Xuquan WANG ; Jianzhong XU
Chinese Journal of Trauma 2008;24(10):790-793
Objective To evaluate the clinical results of proximal humeral internal locking sys-tem(PHILOS)self-locking plates in treatment of proximal humeral fractures. Methods There were 35 patients including 19 males and 16 females(at mean age of 53.5 years,ranging from 29 to 92 years)with proximal humeral fractures treated with PHILOS plate.According to the Neer's classification sys-tem,there were two-part fractures in 19 patients,three-part fractures in 15 and four-part fractures in 1.Surgery was performed with PHILOS serf-locking plate via dehopectoral approach.All patients were fol-lowed up for mean 18.9 months(6-46 months)and evaluated by using Constant score and X-rays. Re-suits X-rays proved that all fractures got good reduction and complete healing during 8-12 weeks.The latest Constant scores was mean 89.5 points(82-94 points).There were no complications including plate loosing.humenral head necrosis or gleno-humeral ioint osteoarthritis. Conclusion PHILOS plate is a good choice for treatment of proximal humeral fractures because of its advantages including easy operation,stable fixation,good clinical results and few complications.
7.Analysis on wound infection of patients at different periods after Chinese Wenchuan earthquake
Xuehui WU ; Xuquan WANG ; Qiang ZHOU ; Kanglai TANG ; Zheng GAO ; Dong SUN ; Tingting ZHENG ; Jianzhong XU
Chinese Journal of Trauma 2008;24(9):756-759
Objective To discuss how to reduce the incidence of postoperative infection and am-putation of patients after earthquake.Methods The wound infection and corresponding therapeutic outcome were analyzed in 592 patients in front line hospitals and station hospitals.Results The inci-dence of infection was 30. 7% in patients treated in front hospital within 8 hours post-trauma but 79. 9% after 8 hours post-trauma. There included 1 patient(0. 2%) with amputation due to clostridial myonecro-sis and 5(1. 2%)with amputation due to serious infection. Incidelice of postoperative wound infection was 7. 1% after selective operation for close injury. The incidence of infection in patients in station hospi-tals was 50. 8%, with no amputation, because they received debridement and antibiotics in site or front line hospitals. No postoperative infection was found in patients with close injury treated with selective op-eration in station hospitals. The major bacteria of wound infection in either front line hospitals or station hospitals were enterococcus faecalis and Eschrichia Coli. Incidence of combined infection was higher than that of single infection. And Gram-Negative bacillus infection exceeded Gram-Positive bacillus infection. The major wound infection obrained effective control through treatment with sensitive antibiotics.Con-clusions After earthqiale, the incidence of infection in patients with open injury is high, with high am-putation rate due to serious infection. Therefore, we propose performing as soon as possible debridement and external fixation with antibiotic treatment but reducing internal fixation. The postoperative infection late of patients with close injury in front line hospitals is much higher than that in station hospitals;their-fore, patients with stable vital signs should be transported to station hospitals as early as possible in order to reduce incidenee of infection.
8.Mini-open reconstruction of lateral collateral ligaments of ankle with partial tendon of its peroneus brevis
Qianbo CHEN ; Kanglai TANG ; Xuehui WU ; Ge XU ; Xiaokang TAN ; Binghua ZHOU ; Yunping ZHOU ; Jianzhong XU
Chinese Journal of Trauma 2008;24(5):340-343
Objective To describe a new technique with mini-open reconstruction of lateral ligaments of ankle with partial tendon of its peroneus brevis and evaluate its effect in treatment of chronic lateral ankle instability. Methods A total of 11 cases of chronic lateral ankle instability;at mean age of 27.6 years(16-42 years),were treated with mini-open reconstruction of the lateral ligaments of the ankle with partial tendon of its peroneus brevis.The mean delay between the initial episode of ankle sprain and the surgery was 10.3 months(4-32 months).Postoperatively,all cases were examined with MRI,stress X-rays and comparative stability of bilateral ankle inspection at clinical follow-up.The function of the ankle were evaluated bv American Orthopaedic Foot & Ankle Society (AOFAS)score and ankle-hind foot scale. Results The average duration of follow-up was 17.5 months(12-37 months).The mean AOFAS ankle-hindfoot score was 88.3 points(72-96 points)at the time of the latest follow-up,including excellent result in 6 cases(55%),good in 4(36%)and fair in 1(9%).MRI results showed that the ruptured lateral collateral ligaments of the ankle were repaired and remodeled very well in all patients.There was no recurrence of the ankle instability or other complications. Conclusion Mini-open reconstruction of the lateral ligaments of ankle with partial tendon of its peroneus brevis is safe and effective for treatment of chronic lateral ankle instability.
9.Principle of multi-echelon medical care for the injured in Chinese Wenchuan earthquake
Fei LUO ; Xuquan WANG ; Qiang ZHOU ; Kanglai TANG ; Xuehui WU ; Fei DAI ; Qingyi HE ; Tingting ZHENG ; Jianzhong XU
Chinese Journal of Trauma 2008;24(8):583-586
Objective To discuss the application value and improvement of principle of multi-echelon medical care in emergent rescue of the injured in Chinese Wenchuau earthquake. Methods The author analyzed and evaluated the medical rescue that was done at disaster site, in the front line hospital and higher level hospitals during earthquake. Results A total of 4 689 patients were treated at disaster site, including 413 patients with severe injury, of whom 3 died. Different kinds of operations including debridement were performed at disaster site, with infection incidence of open wound was nearly 80%. In the front hne hospital, 1 400 patients were treated, with 200 operations done. Of all, 110 patients with severe trauma were treated emergenfly, with an amputation rate of 3.0% and postoperative infection incidence of 66.8%. In the station hospitals, 125 patients received definite surgeries, with 1-5 surgeries per injury site. There was no postoperative cross infection, amputation or death. Conclusions The multi-echelon medical care is the basic mode for medical rescue of large number of patients in natural disaster rescue. First aid at disaster site should be performed as early as possible. Transportation is crucial for successful rescue and an improved patient grading system can help increase the efficiency of rescue. The front line hospitals should mainly provide life support, debridement and fixation of simple fracture, while the specific treatment and definite surgery should be carried out in the station hospitals.
10.Clinical outcomes of modified Bristow operation with mini-open incision in treatment of recurrent anteroinferior shoulder dislocation
Ge XU ; Kanglai TANG ; Xuehui WU ; Zhao XIE ; Xiaokang TAN ; Jicheng GONG ; Huaqing WANG ; Huifeng YANG ; Jianzhong XU
Chinese Journal of Trauma 2008;24(10):814-816
Objective To introduce a new modified Bristow operation with mini-open incision and evaluate jts clinical outcomes in treatment of recurrent anteroinferior shoulder dislocation. Methods A total of 11 patients with recurrent anteroinferior shoulder dislocation were treated with modified Bristow op-eration with mini-open incision.The anterior skin incision with 3-5 mm was made to explore the coracoid process with"moving window"technique.Then.the coracoid process and its short head of biceps were os-teotornjed.transferred and fixed on the anteroinferior potion of scapular neck through the rotator cuff inter-space.All patients were followed up for an average period of 15.8 months(6-48 months)by using modified Rowe score. Results The average operation time was 45 minutes(40-65 minutes).The modified Rowe 8core ranged from 80 to 95 points.excellent in all patients, with SUCCESS rate of 100% and without any re-currence or complication. Conclusions Compared with traditional operation.the modified Bristow oper-ation has smaller incision,less trauma.shorter operation duration and better clinical results.


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