1.Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Regulation by Traditional Chinese Medicine: A Review
Qingzhi LIANG ; Zhengtao CHEN ; Ruoran ZHOU ; Jiying LI ; Yuan ZHANG ; Chunguang XIE ; Qiyue YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):226-235
		                        		
		                        			
		                        			Atherosclerosis (AS) is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries, and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress (ERS) is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment, while excessive ERS can cause unfolded protein reaction, activate inflammation, oxidative stress, apoptosis, autophagy, and other downstream pathways, and lead to cell damage, or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS, affects endothelial cells, smooth muscle cells, macrophages, endothelial progenitor cells, and other cell components closely related to its occurrence and development, influences the progress of AS by regulating cell function, and promotes the formation of AS plaque, the transformation of stable plaque to unstable plaque, and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS, and it is a research hotspot at present. Traditional Chinese medicine (TCM) believes that the origin of AS is the imbalance of Yin and Yang, the disharmony of Zangfu organs, and the abnormal operation of Qi, blood, and body fluid, which leads to the accumulation of phlegm, blood stasis, and other pathological products in the pulse channels, making the blood flow blocked or misfunction and causing the disease, which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex, and the symptoms are diverse, TCM has significant advantages in treating AS because of its multiple targets, multiple pathways, stable efficacy, strong individualization, and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer, Chinese herbal extract, Chinese herbal compound, and proprietary medicine, so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS. 
		                        		
		                        		
		                        		
		                        	
2.Elevated monocyte to lymphocyte ratio is associated with the in-hospital mortality risk in elderly patients with acute myocardial infarction
Qingzhi ZHOU ; Yan CHEN ; Qing XU ; Yuanyuan HAN ; Xin ZHAO
Chinese Journal of Arteriosclerosis 2024;32(4):325-331
		                        		
		                        			
		                        			Aim To investigate whether elevated monocyte to lymphocyte ratio(MLR)is associated with the in-hospital mortality risk in elderly patients with acute myocardial infarction(AMI).Methods The medical history of 1 550 elderly patients with AMI hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Dalian Medical University from December 2015 to December 2021 was retrospectively collected,including 132 patients who died during hospitalization.It mainly includes gender,age,height,body weight,blood routine,lipid related indicators,fast-ing blood glucose(FBG),myocardial enzyme,type of myocardial infarction,estimated glomerular filtration rate(eGFR),in-hospital outcomes,prevalence of heart failure,diabetes,hypertension,and use of statins and antiplatelets during hospi-talization.According to ROC curve analysis,patients with MLR>0.342 were defined as high MLR group(n=699),whereas patients with MLR≤0.342 were defined as low MLR group(n=851).Results The age,white blood cell count,monocyte count,MLR,cardiac troponin I(cTnI),FBG,eGFR<60 mL/(min·1.73 m2),male patients,heart failure,and proportion of all-cause deaths occurred during hospitalisation were higher in the high MLR group than those in the low MLR group(P<0.05),body mass index(BMI),lymphocyte count,low density lipoprotein cholesterol(LDLC),eGFR>60 mL/(min·1.73 m2),hypertension,and use of antiplatelet agents were lower in the high MLR group compared to the low MLR group(P<0.05).Multivariate Logistic regression results showed that high MLR was independently asso-ciated with the in-hospital mortality risk in elderly AMI patients(OR=1.812,95%CI:1.106~2.969,P=0.018).The results of ROC curve analysis showed that the predictive ability of MLR combined with cTnI or FBG would be significantly improved,and the area under ROC curve was 0.789 and 0.739,respectively.Restrictive cubic spline(RCS)analysis results indicated a linear dose-response relationship between MLR and in-hospital outcomes in elderly AMI patients.Conclusion Elevated MLR is independently associated with the in-hospital mortality risk in elderly AMI patients,and cli-nicians can consider using MLR indicators in daily diagnosis for risk stratification and related treatment of such patients to improve their short-term prognosis.
		                        		
		                        		
		                        		
		                        	
3.Highly sensitive H2O2-scavenging nano-bionic system for precise treatment of atherosclerosis.
Xiaoyu LIANG ; Huiyang LI ; Xuanling LI ; Xinxin TIAN ; Aiai ZHANG ; Qingzhi LUO ; Jianwei DUAN ; Youlu CHEN ; Liyun PANG ; Chen LI ; Xing-Jie LIANG ; Yong ZENG ; Jing YANG
Acta Pharmaceutica Sinica B 2023;13(1):372-389
		                        		
		                        			
		                        			In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.
		                        		
		                        		
		                        		
		                        	
4.Autophagy of Vascular Endothelial Cells Influences Diabetic Macroangiopathy: Based on Theory of Qi Deficiency and Stagnation
Qingzhi LIANG ; Zhengtao CHEN ; Yulin LENG ; Zehua ZHANG ; Qiyue YANG ; Hong GAO ; Chunguang XIE
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):178-185
		                        		
		                        			
		                        			The basic pathological change of diabetic macroangiopathy is atherosclerosis (AS), which is mainly associated with vascular endothelial cells (VECs) injury, oxidative stress, glucose and lipid metabolism disorders, hemorheological abnormalities, and endoplasmic reticulum stress. The injury and dysfunction of VECs are the initiating factors of diabetic macroangiopathy. Autophagy is a subcellular self-protection mechanism that regulates basic intracellular metabolism through lysosome-mediated degradation of proteins and damaged organelles to maintain homeostasis. Insufficient autophagy of VECs leads to enhanced inflammation, apoptosis, and oxidative stress of VECs, which promotes AS. According to the theory of traditional Chinese medicine (TCM), diabetic macroangiopathy corresponds to the syndrome of internal deficiency and pathogen invasion, with Qi deficiency and stagnation as the key pathogenesis. Qi deficiency is the root cause, and Qi stagnation is the manifestation. The disease occurs with the initial cause of nutrient-defense disharmony and instability of vessels, the main cause of the deficiency of kidney Qi and the lack of source for generation and transformation, the internal cause of Qi and blood loss in the viscera and the stagnation of Qi, blood, and fluid, and the superficial cause of the stagnation of pathological products and the damage of vessels. Autophagy is a microscopic manifestation of Qi, which has the function of dispelling pathogens and maintaining homeostasis. Insufficient autophagy of VECs leads to Qi deficiency and stagnation, and the gradual deficiency and heavy stagnation of Qi lead to insufficient autophagy, which form a vicious cycle. Modern research has demonstrated that regulating the autophagy of VECs is the main way to prevent and treat AS, and TCM can exert the therapeutic effect in a multi-target and multi-pathway manner. Therefore, based on the theory of Qi deficiency and stagnation, the method of tonifying deficiency of and removing stagnation can be adopted to select prescriptions for regulating the autophagy of VECs and treating AS, which can slow down the procession of diabetic macroangiopathy. 
		                        		
		                        		
		                        		
		                        	
5.Prevention and Treatment of Diabetic Nephropathy by Regulating Endoplasmic Reticulum Stress with Traditional Chinese Medicine: A Review
Zhengtao CHEN ; Qingzhi LIANG ; Yuan ZHANG ; Yan YANG ; Mengping WANG ; Chunguang XIE ; Hong GAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):227-239
		                        		
		                        			
		                        			Diabetic nephropathy (DN) is one of the serious and common microvascular complications of diabetes mellitus (DM) and the main cause of end-stage renal disease (ESRD). Endoplasmic reticulum stress (ERS) is a common stress defense mechanism in eukaryotic cells. In the ERS state, cells activate the unfolded protein response (UPR) to enhance the folding of unfolded proteins and the degradation of misfolded proteins, so as to restore the normal physiological function of the endoplasmic reticulum and avoid cell damage. However, excessive or chronic persistent ERS can induce apoptosis, inflammation, oxidative stress and other pathways to eventually cause cell damage. In recent years, a large number of studies have confirmed that ERS is closely associated with the occurrence and development of DN. In the case of DN, ERS is involved in the damage or protection of podocytes, glomerular mesangial cells, renal tubular epithelial cells, and glomerular endothelial cells. The regulation of ERS has become one of the hotspots in the prevention and treatment of DN and has received extensive attention in the field of traditional Chinese medicine. This paper systematically expounds the role of ERS in the occurrence and development of DN and summarizes the ERS-targeted regulation of DN by traditional Chinese medicine, with a view to providing certain research ideas for the prevention and control of DN with traditional Chinese medicine. 
		                        		
		                        		
		                        		
		                        	
6.Pathogenesis and Treatment of Diabetic Macroangiopathy Based on Theory of Hidden Pathogen Damaging Collaterals
Qingzhi LIANG ; Yulin LENG ; Zhengtao CHEN ; Mengyuan CAI ; Zehua ZHANG ; Hong GAO ; Hongyan XIE ; Chunguang XIE
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(14):194-199
		                        		
		                        			
		                        			The basic pathological change of diabetic macroangiopathy is atherosclerosis, and the metabolism legacy effect of hyperglycemia will cause continuous damage to the large vessels. Oxidative stress is a common mechanism for diabetes and its chronic complications and it is also the basis of the metabolism legacy effect which keeps damaging the large vessels. Anti-oxidant therapy can delay the course of diabetic macroangiopathy. According to the theory of traditional Chinese medicine (TCM), the pathogenicity of hidden pathogen is concealing, lingering, and refractory. On the basis of the syndrome and treatment of collateral diseases, vessel-collateral theory, and hidden pathogen theory of TCM, the pathological changes of diabetic macroangiopathy are summarized as pathogen concealment-accumulation of sugar and lipids leading to phlegm and blood stasis-accumulation of toxins-damage to vessels and collaterals-hardening vessels. The core pathogenesis is the hidden pathogen damaging the collaterals, and the basic pathological change is vessel hardening. The toxins of sugar, lipid, phlegm, and stasis are the pathological products and the key to be treated. According to this theory, the medicinal materials with the functions of activating blood to dredging collaterals, resolving phlegm to clearing collaterals, Promoting qi to unblocking collaterals and removing toxins to shunting collaterals can be selected for prescription. These medicinal materials can inhibit the generation of reactive oxygen species, affect the oxidase activity, and enhance the antioxidant capacity, thereby regulating the oxidative stress response, protecting the vascular endothelial function, reducing the damage of the large blood vessels, and slowing down the progression of the disease. Such therapy is of great significance in clinical practice and research, providing a new idea for the prevention and treatment of diabetic macroangiopathy. 
		                        		
		                        		
		                        		
		                        	
7.Analysis and prospect of free medication for severe mental disorders in Beijing
Yun CHEN ; Qingzhi HUANG ; Ying XYU ; Bin LI ; Rui XI ; Xiaohu HAN ; Yu ZHAO ; Keyue FU
Journal of Public Health and Preventive Medicine 2020;32(5):15-19
		                        		
		                        			
		                        			Objective   To analyze the situation and changing trend of free medication service in Beijing from 2013 to 2020, and to propose policies and service improvement measures.   Methods   A retrospective survey was conducted in Beijing to collect and analyze the service subjects, service process, drug catalog, fiscal investment and patient participation of free medication in each district in recent years.   Results   Among the 16 districts of Beijing, 81.25% of the districts included the patients listed in Item (2) of Paragraph 2 of Article 30 of the Mental Health Law into the scope of free medication, and 75% of the districts broke the restriction that the service targets were registered residents in Beijing. 56.25% of the districts provided a variety of free medication modes, and 81.25% of the districts provided a mode of nearby community service. The catalog of free medications in various areas was still based on the Beijing catalog, and only 18.75% of the districts supplemented the list. In 2020, the total investment of free medicines and subsidies was 88.3768 million RMB, and the per capita investment was 1 616.02 RMB. The total cost showed an increasing trend year by year. From 2013 to 2020, the difference of per capita annual financial investment in drugs and subsidies was statistically significant (F=9.248, P<0.001). The per capita cost basically showed an increasing trend year by year except for individual years. In 2020, 54,688 patients participated in the free medication service in Beijing, and the participation rate was 67.23%. From 2013 to 2020, the difference of annual participation rate of patients was statistically significant (χ2=37098.759, P<0.001), and the number and proportion of patients increased year by year. Conclusion The practice of the district level has proved feasible to expand the scope of free medication service and to optimize the service process, which should be paid more attention in the future. With the continuous advancement of policies and services, the level of patient participation in various areas will tend to be relatively balanced after rising year by year.
		                        		
		                        		
		                        		
		                        	
8.Impact of the neglected Cysticercus cellulose infection on mental health among school-aged children in Tibetan agricultural areas.
Ruixue YE ; Yuju WU ; Qingzhi WANG ; Min CAO ; Tiaoying LI ; Xingwang CHEN ; Huan ZHOU
Journal of Central South University(Medical Sciences) 2018;43(10):1137-1144
		                        		
		                        			
		                        			To determine the impact of Cysticercus cellulose (C. cellulose) infection on mental health among school-aged children in Tibetan agricultural areas of Sichuan Province.
 Methods: In October 2015, all primary schools located in Tibetan agricultural areas in Yajiang, Ruoergai, and Muli county of Sichuan Province were selected as the research sites. All school-aged children at five- and six-grade were enrolled for the study by a multistage stratified cluster sampling method. Antibodies against C. cellulose were detected. Mental Health Test and questionnaire survey were conducted for school-aged children to collect data. The impact of C. cellulose infection on mental health among school-aged children was analyzed with the multilevel linear regression.
 Results: A total of 2 453 school-aged children were investigated. The C. cellulose seropositive rate was 6.03% (148/2 453). There were 0.16% (4/2 453) patients with seropositive accompanied by seizure, 2.28% (56/2 453) with seropositive accompanied by headache, 2.08% (51/2 453) with seropositive accompanied by frequent weak, and 0.41% (10/2 453) were seropositive accompanied by frequent nausea. The rate of C. cellulose infection was 4.53% (111/2 453). The mean score of the mental health test was 6.59±2.61. There were significant difference in score of mental health test in children whose demographic characteristics were different. The mental health scores of school-aged children were clustered at the school level. After controlling the factors of demographic characteristics, the result of multilevel model demonstrated that the factor of school-aged children with C. cellulose seropositive accompanied by headache was statistically significant (β=1.14, P=0.017).
 Conclusion: The status of C. cellulose infection among school-aged children in Tibetan agricultural areas is not optimistic. C. cellulose infection has impacted on mental health of local school-aged children. It is necessary to strengthen the prevention and control of C. cellulose infection in epidemic area.
		                        		
		                        		
		                        		
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		                        			diagnosis
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		                        			epidemiology
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		                        			Cysticercus
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		                        			Humans
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		                        			Mental Health
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		                        			Neurodevelopmental Disorders
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		                        			epidemiology
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		                        			etiology
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		                        			Seroepidemiologic Studies
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		                        			Tibet
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		                        			epidemiology
		                        			
		                        		
		                        	
9.A biomechanical comparison of cable tension band fixation for tibial avulsion fractures of the anterior cruciate ligament
Jianchun LIN ; Zhongguo LIU ; Qingzhi CHEN ; Heguo CAI
Chinese Journal of Orthopaedic Trauma 2018;20(4):341-345
		                        		
		                        			
		                        			Objective To compare cable tension band fixation with other 3 fixations in terms of biomechanical stability for tibial avulsion fractures of the anterior cruciate ligament (ACL).Methods Eighty fresh porcine knees were randomized into 4 equal groups (n =20).For each knee,all the soft tissues were removed only to keep the femur-ACL-tibia complex.The knee complexes were used to create fracture models of standard Meyers-Mc Keever type Ⅲ at the ACL attachment region using a swing saw.The fracture fragments in the 4 groups were subjected to fixation respectively with intramedullary lag screws,high-strength suture,tension band wire and cable tension band.All the specimens were subsequently tested on a Material Testing Machine at a load rate of 60 mm/mm.The 4 groups were compared in terms of ultimate failure load,yield load,and fragmental displacement under single-cycle loading and multi-cyclic loadings.Results Cable tension band fixation displayed significantly higher ultimate failure,higher yield load and lower fragmental displacement than all the other 3 fixations (P < 0.05).Conclusion As cable tension band fixation,which is convenient and economical,provides better biomechanical stability than other 3 fixations for tibial avulsion fractures of the ACL,it may allow earlier functional and weight-bearing exercise after operation.
		                        		
		                        		
		                        		
		                        	
10.Pathologic markers for evaluation of reversibility in pulmonary hypertension related to congenital heart disease.
Li LI ; Li HUANG ; Guo CHEN ; Shian HUANG ; Chao LIU ; Hongyue WANG ; Xuejin DUAN ; Qingzhi WANG ; Ranxu ZHAO ; Jianguo HE
Chinese Journal of Pathology 2016;45(1):31-36
OBJECTIVETo assess the pathologic markers for evaluation of reversibility in pulmonary hypertension (PAH) related to congenital heart disease.
METHODSTwenty-eight patients with congenital heart disease complicated by PAH were subclassified into reversible pulmonary hypertension (RPAH) and irreversible pulmonary hypertension (IPAH), according to post-operative mean pulmonary artery pressure (MPAP). Pulmonary vascular lesion was analyzed according to Ruan's method. Mean medium thickness percent, mean medium area percent and pulmonary arteriolar density were measured by quantitative morphometry. Immunohistochemical study for transgelin and filamin A was carried out.
RESULTSAmongst the 28 cases studied, 24 were RPAH and 4 were IPAH. Of the 24 patients with RPAH, 13 (54.2%, 13/24) had pulmonary vascular lesion of grade 0, 9 (37.5%, 9/24) of grade 1 and 2 (8.3%, 2/24) of grade 2. Of the 4 patients with IPAH, 1 had lesion of grade 1, 1 of grade 2 and 2 of grade 3. Both preoperative and postoperative MPAP were higher in IPAH patients than that in RPAH patients[(53.3±23.4) mmHg versus (34.1±12.7) mmHg, P=0.020 and (35.0±8.8) mmHg versus (17.8±3.9) mmHg, P<0.01]. Compared to patients with pulmonary vascular lesion of grades 0 and 1, the preoperative MPAP in patients with grades 2 and 3 showed no significant difference, but the postoperative MPAP was higher (P<0.05 or 0.01). Compared to control group, mean medium thickness percent and mean medium area percent were significantly higher in RPAH and IPAH categories (12.0±3.5, 8.5±2.0 versus 5.7±1.0, P<0.01 and 55.8±11.1, 49.0±9.4 versus 34.0±5.5, P<0.01). Mean medium thickness percent was significantly higher in IPAP group than that in RPAH group (12.0±3.5 versus 8.5±2.0, P=0.001). Correlation analysis demonstrated that mean medium thickness percent and mean medium area percent had positive correlation with preoperative and postoperative MPAP. There was no correlation between grading of pulmonary vascular lesion and reversibility. Transgelin and filamin A had stronger staining in pulmonary vascular smooth muscle cells in IPAH than those in RPAH and controls(P<0.05).
CONCLUSIONSPathologic assessment of lung biopsy remains the gold standard for evaluation of the reversibility in PAH related to congenital heart disease. Mean medium thickness percent, mean medium area percent and immunoreactivity for transgelin and filamin A are useful parameters.
Biomarkers ; metabolism ; Biopsy ; Filamins ; metabolism ; Heart Diseases ; complications ; pathology ; Humans ; Hypertension, Pulmonary ; complications ; diagnosis ; pathology ; Lung ; pathology ; Microfilament Proteins ; metabolism ; Muscle Proteins ; metabolism
            

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