1.Treating Type 2 Diabetic Nephropathy by Down-regulating NOX4 to Inhibit the Oxidative Stress Pathway in Mesenchymal Stem Cells
Shu-Qi FENG ; Guo-Rong JIN ; Qun-Hang XUE ; Min HE ; Ze-Hang WANG ; Jia-Xin YAO ; Long CHEN ; Yu-Jiao WANG ; An-Xiu ZHANG ; Sheng HE ; Bing-Rui ZHOU ; Jun XIE
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):730-740
Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P<0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P<0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P<0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P<0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P<0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.
2.Treating Type 2 Diabetic Nephropathy by Down-regulating NOX4 to Inhibit the Oxidative Stress Pathway in Mesenchymal Stem Cells
Shu-Qi FENG ; Guo-Rong JIN ; Qun-Hang XUE ; Min HE ; Ze-Hang WANG ; Jia-Xin YAO ; Long CHEN ; Yu-Jiao WANG ; An-Xiu ZHANG ; Sheng HE ; Bing-Rui ZHOU ; Jun XIE
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):730-740
Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P<0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P<0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P<0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P<0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P<0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.
3.Suggestions for revision of the epilepsy items in the military disability appraisal norms
Shu-Yi QU ; Ze CHEN ; Yuan-Hang PAN ; Ze-Zhi WANG ; Xin-Bo ZHANG ; Yong-Hong LIU
Medical Journal of Chinese People's Liberation Army 2024;49(1):6-9
Epilepsy is a common neurological disease,has the characteristics of recurrent attacks and long-term treatment,thus bringing great pressure to patients and their families.Therefore,it is particularly important to do a good job of disability assessment.In recent years,with the development of the discipline,academic organizations such as the International League Against Epilepsy(ILAE)and China Association Against Epilepsy(CAAE)have successively updated the definition and diagnostic criteria of epilepsy and seizures.However,some items of epilepsy in the current Criteria for Disability Rating of Military Personnel(Trial)issued by People's Liberation Army(PLA)in 2011 can no longer meet the latest guidelines at home and abroad.Therefore,we suggest that the items related to epilepsy in the Criteria for Disability Rating of Military Personnel(Trial)should be revised to ensure that the disability evaluation being completed fairly and successfully.
4.Discussion of the methodology and implementation steps for assessing the causality of adverse event
Hong FANG ; Shuo-Peng JIA ; Hai-Xue WANG ; Xiao-Jing PEI ; Min LIU ; An-Qi YU ; Ling-Yun ZHOU ; Fang-Fang SHI ; Shu-Jie LU ; Shu-Hang WANG ; Yue YU ; Dan-Dan CUI ; Yu TANG ; Ning LI ; Ze-Huai WEN
The Chinese Journal of Clinical Pharmacology 2024;40(2):299-304
The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.
5.Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke.
Te BA ; Kai-Hang SUN ; Jing WANG ; Ze-Ran WANG ; Bo-Mo SANG ; Hong-Kuan LI ; Hao-Ran GUO ; Xue YANG ; Yu-Jie ZHENG ; Xiao-Feng ZHAO
Chinese Acupuncture & Moxibustion 2023;43(6):691-696
The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.
Humans
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Ischemic Stroke
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Chemokine CXCL12
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Acupuncture Therapy
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Mesenchymal Stem Cells
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Inflammation
6.Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023)
Yuan XIONG ; Bobin MI ; Chenchen YAN ; Hui LI ; Wu ZHOU ; Yun SUN ; Tian XIA ; Faqi CAO ; Zhiyong HOU ; Tengbo YU ; Aixi YU ; Meng ZHAO ; Zhao XIE ; Jinmin ZHAO ; Xinbao WU ; Xieyuan JIANG ; Bin YU ; Dianying ZHANG ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Qikai HUA ; Mengfei LIU ; Yiqiang HU ; Peng CHENG ; Hang XUE ; Li LU ; Xiangyu CHU ; Liangcong HU ; Lang CHEN ; Kangkang ZHA ; Chuanlu LIN ; Chengyan YU ; Ranyang TAO ; Ze LIN ; Xudong XIE ; Yanjiu HAN ; Xiaodong GUO ; Zhewei YE ; Qisheng ZHOU ; Yong LIU ; Junwen WANG ; Ping XIA ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Dongliang WANG ; Fengfei LIN ; Jiangdong NI ; Aiguo WANG ; Dehao FU ; Shiwu DONG ; Lin CHEN ; Xinzhong XU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Yingze ZHANG ; Xiaobing FU ; Guohui LIU
Chinese Journal of Trauma 2023;39(6):481-493
Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.
7. Dental non-metric traits of Han and Zhuang people
Chen YANG ; Lu-Fei WANG ; Hui QIAO ; Hai-Ge ZHU ; Shao-Qing WEN ; Jing-Ze TAN ; Hang ZHANG
Acta Anatomica Sinica 2023;54(3):357-367
[Abstract] Objective To investigate the relationship between the Han, Zhuang and the World populations by comparing the frequency of dental non-metric traits. Methods From 2015 to 2019, ten dental non-metric traits were sampled from He’nan, Jiangsu and Guangxi Zhuang Autonmous Region, with sample size of 1785(674 He’ nan, 547 Jiangsu, 388 Guangxi Han, 176 Guangxi Zhuang). Principal component analysis, multidimensional scaling and neighbor network were carried out. Results East Asian populations could be clearly divided into two major groups, Northeast Asian and Southeast Asian. Han and Zhuang populations were close to the Northeast Asian populations, but were far from the Southeast Asian populations. There were also some north-south differences within Han populations. Conclusion Both Sundadonty and Sinodonty are existed in East Asian populations. Han and Zhuang populations dental non-metric traits are closer to the Sinodonty.
8.Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells.
Tao ZHANG ; Hang-Ze RUAN ; Yong-Chen WANG ; Yu-Qi SHAO ; Wei ZHOU ; Shi-Jun WENG ; Yong-Mei ZHONG
Neuroscience Bulletin 2022;38(6):622-636
Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.
9.Expert consensus on diagnosis, prevention and treatment of perioperative lower extremity vein thrombosis in orthopedic trauma patients (2022 edition)
Wu ZHOU ; Faqi CAO ; Ruiyin ZENG ; Baoguo JIANG ; Peifu TANG ; Xinbao WU ; Bin YU ; Zhiyong HOU ; Jian LI ; Jiacan SU ; Guodong LIU ; Baoqing YU ; Zhi YUAN ; Jiangdong NI ; Yanxi CHEN ; Dehao FU ; Peijian TONG ; Dongliang WANG ; Dianying ZHANG ; Peng ZHANG ; Yunfei ZHANG ; Feng NIU ; Lei YANG ; Qiang YANG ; Zhongmin SHI ; Qiang ZHOU ; Junwen WANG ; Yong WANG ; Chengjian HE ; Biao CHE ; Meng ZHAO ; Ping XIA ; Liming XIONG ; Liehu CAO ; Xiao CHEN ; Hui LI ; Yun SUN ; Liangcong HU ; Yan HU ; Mengfei LIU ; Bobin MI ; Yuan XIONG ; Hang XUE ; Ze LIN ; Yingze ZHANG ; Yu HU ; Guohui LIU
Chinese Journal of Trauma 2022;38(1):23-31
Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.
10.Bilateral superior cervical ganglionectomy attenuates cardiac remodeling and improves cardiac function in pressure-overloaded heart failure mice.
Ge Rui LI ; Hang LI ; Zhan LYU ; Ze CHEN ; Yang Gan WANG
Chinese Journal of Cardiology 2021;49(4):345-352
Objective: To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Methods: Pressure-overloaded HF mouse model was produced by severe thoracic aorta banding (sTAB). Bilateral superior cervical ganglionectomy (SCGx) was performed 2 weeks after sTAB. Twenty four 6-week-old male C57BL/6 mice were randomized divided into 4 groups (n=6 each): control group: sham sTAB+sham SCGx; denervated group: sham sTAB+SCGx; HF group: sTAB+sham SCGx; denervated HF group: sTAB+SCGx. Cardiac function was measured by echocardiography at week 0, 1, 2, and 4 after sTAB, respectively. All mice were sacrificed at the end of week 4 and heart tissues were harvested. HE and Masson staining were performed. Immunohistochemical staining (IHC) for tyrosine hydroxylase (TH), adrenergic receptor β1 (AR-β1) and CD68 was performed. Western blot was used to determine the protein expression level of TH, B type natriuretic peptide (BNP), and AR-β1. Results: Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (P>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (P<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (P<0.05), which was similar between denervated HF group and control group (P>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (P<0.05). IHC showed that TH+nerves and CD68+ macrophages were significantly increased in HF mice as compared to control mice (P<0.05), whereas this change was abolished in denervated HF group. AR-β1 was significantly down-regulated in HF group compared with control group (P<0.05), which was not affected by denervation (P>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (P<0.05), whereas this difference was diminished in denervated HF group (P>0.05). Conclusion: Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.
Animals
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Cross-Sectional Studies
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Ganglionectomy
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Heart Failure
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Male
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Mice
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Mice, Inbred C57BL
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Stroke Volume
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Ventricular Function, Left
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Ventricular Remodeling

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