1.Shexiang-Tongxin dropping pills alleviate myocardial injury in rats with coronary microembolization via cGAS-STING signaling pathway
Yangchun LIU ; Huafeng YANG ; Wanzhong HUANG ; Qiang SU ; Yuan HUANG
Chinese Journal of Pathophysiology 2025;41(11):2150-2156
AIM:To investigate the protective effect of Shexiang-Tongxin dropping pills(STDP)against myo-cardial injury induced by coronary microembolization(CME)in rats,with a focus on the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.METHODS:Thirty-two Sprague-Dawley rats were randomly allocated into four groups using a random number table:sham group,CME group,STDP group,and RU.521 group,with 8 rats per group.A rat model of CME was established via the injection of embolic microspheres into the left ventricle.The rats in sham group received an equal volume of normal saline via left ventricular injection instead,those in STDP group were given STDP(40 mg/kg)by oral gavage once daily for 14 consecutive days before CME modeling,and those in RU.521 group were intraperitoneally injected with RU.521(5 mg/kg)once daily for 7 consecutive days before CME modeling.Echocardiography was performed to evaluate cardiac function 24 h after modeling.HE staining was used to observe pathological changes in myocardial tissue,and TTC staining was applied to detect myocardial infarction areas.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of interleukin(IL)-1β and tumor necrosis factor(TNF)-α.A commercial assay kit was employed to detect myocardial injury marker cardiac troponin I(cTnI).Western blot was performed to analyze the expression of cGAS-STING pathway-related proteins in cardiac tissues.RESULTS:Compared with sham group,the rats in CME group exhibited significantly impaired cardiac function and a marked increase in serum cTnI levels(P<0.05).In contrast,compared with CME group,the rats in both STDP group and RU.521 group demonstrated significant improvements in cardiac function and reductions in cTnI levels((P<0.05).Furthermore,HE staining and TTC staining revealed that the rats in CME group had loosely arranged myocardial fibers,swollen cardiomyo-cytes,and an increased myocardial infarction erea compared with sham group(P<0.05).Meanwhile,the expression lev-els of inflammatory factors IL-1β and TNF-α,as well as the relative expression of cGAS,STING and NF-κB p-p65 pro-teins were significantly increased(P<0.05).In comparison,the rats in STDP group and RU.521 group showed a signifi-cant reduction in myocardial infarction area,down-regulated expression of cGAS,STING,and NF-κB p-p65 proteins,and markedly decreased levels of IL-1β and TNF-α compared with CME group(P<0.05).CONCLUSION:STDP pre-treatment ameliorated myocardial injury,cardiac dysfunction and myocardial infarct size induced by CME.The underlying mechenism may involve the suppression of the cGAS-STING signaling pathway,thereby attenuating myocardial inflamma-tion after CME.
2.Shexiang-Tongxin dropping pills alleviate myocardial injury in rats with coronary microembolization via cGAS-STING signaling pathway
Yangchun LIU ; Huafeng YANG ; Wanzhong HUANG ; Qiang SU ; Yuan HUANG
Chinese Journal of Pathophysiology 2025;41(11):2150-2156
AIM:To investigate the protective effect of Shexiang-Tongxin dropping pills(STDP)against myo-cardial injury induced by coronary microembolization(CME)in rats,with a focus on the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.METHODS:Thirty-two Sprague-Dawley rats were randomly allocated into four groups using a random number table:sham group,CME group,STDP group,and RU.521 group,with 8 rats per group.A rat model of CME was established via the injection of embolic microspheres into the left ventricle.The rats in sham group received an equal volume of normal saline via left ventricular injection instead,those in STDP group were given STDP(40 mg/kg)by oral gavage once daily for 14 consecutive days before CME modeling,and those in RU.521 group were intraperitoneally injected with RU.521(5 mg/kg)once daily for 7 consecutive days before CME modeling.Echocardiography was performed to evaluate cardiac function 24 h after modeling.HE staining was used to observe pathological changes in myocardial tissue,and TTC staining was applied to detect myocardial infarction areas.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of interleukin(IL)-1β and tumor necrosis factor(TNF)-α.A commercial assay kit was employed to detect myocardial injury marker cardiac troponin I(cTnI).Western blot was performed to analyze the expression of cGAS-STING pathway-related proteins in cardiac tissues.RESULTS:Compared with sham group,the rats in CME group exhibited significantly impaired cardiac function and a marked increase in serum cTnI levels(P<0.05).In contrast,compared with CME group,the rats in both STDP group and RU.521 group demonstrated significant improvements in cardiac function and reductions in cTnI levels((P<0.05).Furthermore,HE staining and TTC staining revealed that the rats in CME group had loosely arranged myocardial fibers,swollen cardiomyo-cytes,and an increased myocardial infarction erea compared with sham group(P<0.05).Meanwhile,the expression lev-els of inflammatory factors IL-1β and TNF-α,as well as the relative expression of cGAS,STING and NF-κB p-p65 pro-teins were significantly increased(P<0.05).In comparison,the rats in STDP group and RU.521 group showed a signifi-cant reduction in myocardial infarction area,down-regulated expression of cGAS,STING,and NF-κB p-p65 proteins,and markedly decreased levels of IL-1β and TNF-α compared with CME group(P<0.05).CONCLUSION:STDP pre-treatment ameliorated myocardial injury,cardiac dysfunction and myocardial infarct size induced by CME.The underlying mechenism may involve the suppression of the cGAS-STING signaling pathway,thereby attenuating myocardial inflamma-tion after CME.
3.Analysis on the preventive effect of amifostine on peripheral neurotoxicity in patients with gastrointestinal cancer undergoing chemotherapy
Feng ZHOU ; Wanzhong HUANG ; Yu XIA ; Qiongchun PENG ; Jianchun FU
Clinical Medicine of China 2019;35(3):246-249
Objective To study the protective effect of aminophosphate on peripheral neurotoxicity in patients with gastrointestinal cancer undergoing chemotherapy.Methods Eighty patients receiving mFOLFOX6 regimen chemotherapy in the Eighth Affiliated Hospital of Sun Yat-sen University from June 2015 to February 2018 were selected as the study subjects.They were divided into study group and control group according to random number table method.The control group was given mFOLFOX6 regimen for chemotherapy,while the study group was given intravenous infusion of amphostatin before using mFOLFOX6 regimen for chemotherapy.The occurrence of peripheral neurotoxicity,motor nerve conduction velocity (MSV),sensory nerve conduction velocity (SCV) levels of median nerve and peroneal nerve before and after chemotherapy,short-term efficacy and blood toxicity were compared between the two groups.Results The total incidence of peripheral neurotoxicity was 17.50% (7/40) in the study group and 82.50% (33/40) in the control group,and the difference was statistically significant (x2 =33.800;P =0.000).The SCV levels of median nerve and peroneal nerve in the study group after chemotherapy was (53.68±3.02) m/s,(54.96 ±3.01) m/s,and those in the control group were(45.17±3.07) m/s、(44.97±3.03) m/s,and the difference was statistically significant (t =12.498,14.794;P =0.000,0.000).There was no significant difference in the total effective rate (87.50%,35/40) between the study group and the control group(90.00%,36/40) (x2 =0.125;P =0.723).The total incidence of hematotoxicity was 42.50% (17/40) in the study group and 77.50% (31/40) in the control group,and the difference was statistically significant(x2 =10.208;P=0.000).Conclusion Amfostine has a better preventive effect on peripheral neurotoxicity incancer patients undergoing chemotherapy,which is conducive to reducing the risk of hematotoxicity.which is worthy of clinical application.
4.Effect of oridonin on the gene expression of human esophageal carcinoma cell SHEEC and the target gene screening
Shaobin WANG ; Wanzhong HUANG ; Yu ZHONG ; Xiaojie LI ; Junhui CHEN
Cancer Research and Clinic 2013;(2):73-76
Objective To detect the effect of oridonin(ORI)on the gene expression of human esophageal carcinoma cell SHEEC and to screen the tumor cell apoptosis target genes.Methods The gene expression of human esophageal carcinoma cell SHEEC without and with ORI induction for 1 hours and 8 hours were detected with microarray technique,respectively.The differentially expressed genes were identified and verified with fluorecent quantitative PCR.Results A total of 1011 genes showed up or down regulation more than twice after ORI induction(including 280 genes after 1 hour and 731 genes after 8 hours induction respectively).In these genes,17 genes with the top extent of up or down regulation were identified,which were involved in the cell signal transduction,transcription regulation,and cell apoptosis.These 17 differentially expressed genes were verified with real-time PCR,and 12 genes were statistically significant.Conclusion In the 12 differentially expressed genes with statistically significance,there may have tumor cell apoptosis target genes induced by ORI through mitochondrion route.
5.Clinicopathological and genetic feathers of 14 Fabry nephropathy patients
Zhiyong CAI ; Suxia WANG ; Youkang ZHANG ; Qiuyuan FANG ; Yu HUANG ; Xin ZHENG ; Wanzhong ZOU
Chinese Journal of Nephrology 2012;(12):909-915
Objective To elucidate the clinicopathological and hereditary characteristics in Fabry nephropathy.Methods The clinical and pathological features of 14 patients with Fabry nephropathy were collected.The activities of α-Gal A were measured in 4 probands.Screenings of GLA mutations were done in 12 patients.Results The ratio of Fabry nephropathy in the patients with renal biopsy was 0.074 % (14/19 005),the average diagnostic age was (30.57±9.32) years,male to female ratio was 2.5∶ 1.All the patients had proteinuria,and the median of urine total protein (UTP)was 1.71 g/24 h (0.32-4.71 g/24 h).Two of them got nephrotic proteinuria,5 of them got microscopic hematuria,4 of them got renal function insufficiency.Angiokeratomas was the most common manifestation (10/14),followed by cardiac involvement (6/14).Hypohidrosis and diseases of central neural system could also be seen in these patients.There were 9 classic phenotype,the remaining 5 were variants/renal variants.The family information was collected in 10 pedigrees,6 of them had family histories of kidney disease.Renal pathology showed vacuolization of glomerular visceral epithelial cells was the prominent feature,global and segmental glomerulosclerosis were seen in some patients by light microscopy.The myelin bodies or zebra bodies were identified in podocytes by electron microscopy,but only were found in some podocytes of 2 females.The activity of α-Gal A was decreased compared with the normal range in 4 probands.The mutations of GLA were demonstrated in 11 patients.Three novel mutations of GLA gene were identified,which were all deletion/insertion mutations with classic phenotypes.Most variants carried the mutations located in the buried/partial buried areas of α-Gal A (3/11).The classical phenotype carried GLA mutations as W162X,F169S,S201F,N272K,L310R,while variant phenotype carried GLA mutations as I91T,R112H,Q312H.Conclusions The ratio of Fabry nephropathy in patients with renal biopsy is 0.074%.Angiokeratomas and cardiac involvement are often accompanied with Fabry nephropathy.The genotypes of GLA may have close relationships with the phenotypes of Fabry nephopathy.
6.A female patient of Fabry disease complicated with thin basement membrane nephropathy and investigation of the kindred
Zhiyong CAI ; Youkang ZHANG ; Suxia WANG ; Qiuyuan FANG ; Linchang LIU ; Yu HUANG ; Hong ZHANG ; Xin ZHENG ; Yuqing CHEN ; Wanzhong ZOU
Chinese Journal of Nephrology 2011;27(1):1-6
Objective To elucidate the features of clinicopathology and mutation in Fabry disease complicated with thin basement membrane nephropathy (TBMN), and to investigate the kindred. Methods Data of clinicopathology and gene mutation of a female patient of Fabry disease complicated with TBMN admitted to the Department of Nephro]ogy in our hospital were analyzed. Members of her kindred were investigated simultaneously. Results Proband was a 41-year-old Chinese woman who presented syndrome of Fabry disease and TBMN including angiokeratomas, chronic pain, tinnitus, vertigo, left ventricular hypertrophy and nephropathy as proteinuria, microscopic hematuria and hypertension. A percutaneous renal biopsy was performed on the proband, which was consistent with FSGS and vaculization of podocytes by light microscopy.Electron microscopy showed concentric lamellated inclusions in some podocytes. Diffuse thinning of glomerular basement membrane (GBM) with a mean thickness of (216±31) nm was found. The diagnosis of TBMN with suspected Fabry disease was identified. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. One of her sisters only had microscopic hematuria. The activity of α-galacsidase A (α-Gal A )enzyme in the proband and her daughter was 33 units and 75 units respectively (the normal range is 100 to 500 units). They all carried the novel GLA mutation 1208 ins 21 bp and COL4A3 SNP c: 3627G>A(p:M1209I). While her sister who only had microscopic hematuria just carried the variant of COL4A3 gene-c:3627G >A (p:M1209I), and had the normal activity of α-Gal A with no mutation of GLA.Conclusion TBMN should be considered in the patients of Fabry disease with the condition of benign familial hematuria.
7.Effect of health management on quality of life of hypertensive patients living in underdeveloped rural regions
Xingming LI ; Yuzhen ZHANG ; Jianshi HUANG ; Wanzhong HAN ; Haibin SHI
Chinese Journal of Health Management 2010;04(5):264-267
Objective To evaluate the effectiveness of health management on quality of life of hypertensive patients living in underdeveloped rural regions. Methods Minqin County of Gansu Province was taken as research field, and health education covered all the population. Individual follow-up was adopted by quasi-experiment,and SF-8 scale was used to evaluate the change of scores of quality of life at baseline and the end of the study. Results The score of various dimension of quality life of interventive group showed a significant decrease at the end of follow-up ( P < 0. 05) , and the net score of general health status was 10. 92,the net score of impact to social role exerted by physical function was 9. 59,and the net score of social function was 4.61. Moreover, there was statistical difference between the intervention group and the control group for their quality of life(P <0. 05) , which showed in detail that each dimension of quality of life of the intervention group had higher score than that of the control group, after adjusting baseline difference by analysis of covariance. Conclusions All these results suggest that the active screening, following up and health education, conducted by the primary health care staff of township hospitals, under the idea of health management, can improve the quality of life of hypertension patients effectively in the rural area of underdeveloped region.

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