1.Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways.
Yuan WANG ; Qiang WANG ; Di LUO ; Pu ZHAO ; Sha-Sha ZHONG ; Biao DAI ; Jia-Jyu WANG ; Yi-Tong WAN ; Zhi-Bin LIU ; Huan YANG
Chinese journal of integrative medicine 2023;29(5):448-458
OBJECTIVE:
To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.
METHODS:
Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.
RESULTS:
Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).
CONCLUSION
EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.
Mice
;
Humans
;
Animals
;
NADP/metabolism*
;
Toll-Like Receptor 4
;
HMGB1 Protein/metabolism*
;
Receptor for Advanced Glycation End Products/metabolism*
;
Blood-Brain Barrier/metabolism*
;
Neuroinflammatory Diseases
;
Electroacupuncture
;
Alzheimer Disease/therapy*
;
Hippocampus/metabolism*
;
Amyloid beta-Peptides/metabolism*
2.Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia.
Yi XIAO ; Jing-Ying ZHOU ; Hong-Zhi YIN ; Qian LIU ; Rong LUO ; Wei-Ai LIU ; Ge-Shu DU ; Huan ZHONG ; Mi LIU
Chinese Acupuncture & Moxibustion 2023;43(12):1435-1440
OBJECTIVES:
To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD.
METHODS:
A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats.
RESULTS:
In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group.
CONCLUSIONS
Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.
Rats
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Male
;
Animals
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Electroacupuncture
;
Dyspepsia/therapy*
;
Rats, Sprague-Dawley
;
Ghrelin
;
Gastrointestinal Hormones
;
Serotonin
;
Vasoactive Intestinal Peptide
;
Acupuncture Points
3.Clinical efficacy of atezolizumab plus bevacizumab in the first-line treatment of advanced huge hepatocellular carcinoma
Yan ZHANG ; Shan ZHONG ; Huan DENG ; Renjun WAN ; Wenqiang LUO ; Zhi ZHOU
Chinese Journal of Digestive Surgery 2022;21(S1):35-40
The incidence and mortality of hepatocellular carcinoma (HCC) is very high in China, which seriously threatens human life and health. There were limited treatment options for advanced HCC in the past, and the overall survival of HCC patients was poor. In recent years, immuno-therapy and targeted therapy have been recommended as effective means for the treatment of advan-ced HCC. The authors report a case of advanced huge HCC which has achieved a maintained partial response for 6 months after the treatment of atezolizumab combined with bevacizumab. The tumor shrunk by 32.4% and 47.5% after 3 and 6 months of treatment. Besides, the alpha-fetoprotein and abnormal tumor protein value of the patient continued to decrease without any adverse reactions. The treatment is evaluated as partial response and patients has a good short-term effect.
4.Safety and efficacy of left atrial appendage closure combined with patent foramen ovale closure for atrial fibrillation patients with patent foramen ovale.
Zhi Hong ZHAO ; Xiang SONG ; Sai Hua WANG ; Jun LUO ; Ying Biao WU ; Qian ZHU ; Ming FANG ; Qiang HUAN ; Xiao Gang ZHANG ; Bei TIAN ; Wei GU ; Luo Ning ZHU ; Shu Wen HAO ; Zhong Ping NING
Chinese Journal of Cardiology 2022;50(3):257-262
Objective: To analyze the safety and efficacy of combined left atrial appendage (LAA) and patent foramen ovale (PFO) closure in adult atrial fibrillation (AF) patients complicating with PFO. Methods: This study is a retrospective and cross-sectional study. Seven patients with AF complicated with PFO diagnosed by transesophageal echocardiography (TEE) in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to October 2020 were selected. Basic data such as age, gender and medical history were collected. The atrial septal defect or PFO occluder and LAA occluder were selected according to the size of PFO, the ostia width and depth of LAA. Four patients underwent left atrial appendage closure(LAAC) and PFO closure at the same time. PFO closure was performed during a one-stop procedure of cryoablation combined with LAAC in 2 patients. One patient underwent PFO closure at 10 weeks after one-stop procedure because of recurrent transient ischemic attack (TIA). All patients continued to take oral anticoagulants. TEE was repeated 8-12 weeks after intervention. In case of device related thrombus(DRT), TEE shall be rechecked 6 months after adjusting anticoagulant and antiplatelet drug treatment. Patients were follow-up at 1, 3, 6, 12, 24 months by telephone call, and the occurrence of cardio-cerebrovascular events was recorded. Results: Among the 7 patients with AF, 2 were male, aged (68.0±9.4) years, and 3 had a history of recurrent cerebral infarction and TIA. Average PFO diameter was (3.5±0.8)mm. Three patients were implanted with Watchman LAA occluder (30, 30, 33 mm) and atrial septal defect occluder (8, 9, 16 mm). 2 patients were implanted with LAmbre LAA occluder (34/38, 18/32 mm) and PFO occluder (PF1825, PF2525). 2 patients were implanted with LACbes LAA occluder (24, 28 mm) and PFO occluder (PF2525, PF1825) respectively. The patients were followed up for 12 (11, 24) months after operation. TEE reexamination showed that the position of LAA occluder and atrial septal defect occluder or PFO occluder was normal in all patients. DRT was detected in 1 patient, and anticoagulant therapy was adjusted in this patient. 6 months later, TEE showed that DRT disappeared. No cardiovascular and cerebrovascular events occurred in all patients with AF during follow-up. Conclusions: In AF patients complicated with PFO, LAAC combined with PFO closure may have good safety and effectiveness.
Adult
;
Aged
;
Atrial Appendage/surgery*
;
Atrial Fibrillation/surgery*
;
Cardiac Catheterization/methods*
;
China
;
Cross-Sectional Studies
;
Foramen Ovale, Patent/surgery*
;
Humans
;
Male
;
Middle Aged
;
Retrospective Studies
5.A National Cross-Sectional Survey Dataset on Common Disease and Influencing Factors of Chinese Internal Migrants in 2017.
Sheng-Fa ZHANG ; Wei LUO ; Yu-Huan MA ; Zhi-Li WANG ; Jing CHEN ; Fang ZHOU ; Xiao-Yu ZHANG ; Wei ZHOU
Chinese Medical Sciences Journal 2022;37(3):234-239
This data article describes the dataset from a national cross-sectional questionnaire survey on Chinese internal migrants in 2017. The survey was part of the Chinese Migrants Dynamic Survey, which is an annually conducted large-scale national questionnaire survey on internal migrants. The respondents in the described dataset were migrants and registered local residents aged over 15 years old. A multistage stratified probability-proportional-to-size (PPS) sampling method based on the 2016 annual report data of China Migrant Population was adopted. The questionnaire was designed to collect demographic information of respondents and their family members, intention of migration or settlement, health status, health services accessibility, social integration, and epidemic influencing factors of common diseases, including hypertension, type 2 diabetes, diarrhea, fever, rash, icterus, conjunctival redness, cold, and other illnesses or injuries. The sample population in this survey include 13,998 internal migrants and 14,000 registered local residents from eight domestic cities / prefecture / districts across China. It is the most widely covering and highly representative dataset on common diseases and influencing factors of internal migrants in China. The dataset can be used to study common diseases and influencing factors among floating Chinese population. It provides data support for government to improve healthcare accessibility and the equity of public health services for internal migrants in China.
Humans
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Aged
;
Adolescent
;
Transients and Migrants
;
Cross-Sectional Studies
;
Diabetes Mellitus, Type 2
;
China/epidemiology*
;
Health Status
6. Expression of elastin and collagen in rats with heart failure
Ke-Ke WANG ; Xiang-Guang MENG ; Qian WANG ; Zhi-Kun GUO ; Huan-Huan LUO ; Zhi-Kun GUO
Acta Anatomica Sinica 2022;53(5):637-643
Objective To investigate the expression of elastin and collagen in heart of rats with chronic heart failure and their related proteases. Methods Sprague-Dawley rat model of chronic heart failure was made by intraperitoneal injection of doxorubicin hydrochloride. Examination of cardiac function by echocardiography. ELISA and immunohistochemistry were used to detect brain natriuretic peptide ( BNP) , and Masson staining was used to detect myocardial fibrosis. The mRNA levels of elastin, I /IH collagen were detected by Real-time PCR and the expression levels of elastin, I/IH collagen, Matrix metalloproteinase (MMP)-2 and MMP-9 were detected by Western blotting. Results Compared with the control group, the heart function of rats in the model group decreased, the BNP content in serum increased, the expression of BNP in myocardial tissue was strongly positive, and the mRNA and protein expression of elastin decreased. Nevertheless, the mRNA and protein expression of I / IH collagen increased. At the same time, both MMP-2 and MMP-9 protein expression levels increased in model rat heart. Conclusion Heart failure leads to decreased expression of elastin, I /IH collagen expression increased, and the MMP-2 and MMP-9 may be involved in the regulation of this process.
7.Factors associated with death and attrition in HIV-infected children under initial antiretroviral therapy in Guangxi Zhuang Autonomous Region, 2004 - 2019.
Ye Sheng ZHOU ; Liu Hong LUO ; Mei LIN ; Hong Li CHEN ; Jing Hua HUANG ; Qiu Ying ZHU ; Huan Huan CHEN ; Zhi Yong SHEN ; Jian Jun LI ; Yi FENG ; Dan LI ; Ling Jie LIAO ; Hui XING ; Yi Ming SHAO ; Yu Hua RUAN ; Guanghua LAN
Chinese Journal of Epidemiology 2022;43(9):1430-1435
Objective: To investigate death and attrition in HIV-infected children under initial antiretroviral therapy (ART) and associated factors in Guangxi Zhuang autonomous region. Methods: This retrospective cohort study was conducted in HIV-infected children under initial ART in Guangxi from 2004 to 2019, data from ART information system of National comprehensive AIDS prevention and treatment information system. Cox proportional hazards models were used to assess factors associated with the death and attrition. Results: In 943 HIV-infected children, the overall mortality and attrition rates were 1.00/100 person-years and 0.77/100 person-years, respectively. The mortality and attrition rates within the first year of ART were 3.90/100 person-years and 1.67/100 person-years, respectively. The cumulative survival rate during the first, second, fifth and tenth year after ART was 96.14%, 95.80%, 93.68% and 91.54%, respectively. Multivariate Cox proportional hazards models results showed that being female (aHR=2.00, 95%CI: 1.17-3.40), CD4+T lymphocytes (CD4) counts before ART <200 cells/μl (aHR=2.79, 95%CI: 1.54-5.06), weight-for-age Z score before ART <-2 (aHR=2.38, 95%CI: 1.32-4.26), hemoglobin before ART <80 g/L (aHR=2.47, 95%CI: 1.24-4.92), initial ART with LPV/r (aHR=5.05, 95%CI: 1.15-22.12) were significantly associated with death; being female (aHR=2.23, 95%CI: 1.22-4.07) and initial ART with LPV/r (aHR=2.02, 95%CI: 1.07-3.79) were significantly associated with attrition. Conclusions: The effect of ART in HIV-infected children in Guangxi was better, but the mortality and attrition rates were high within the first year of treatment. It is necessary to strengthen the training in medical staff and health education in HIV-infected children and their parents in order to improve the treatment effect.
Anti-HIV Agents/therapeutic use*
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Child
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China/epidemiology*
;
Female
;
HIV Infections/drug therapy*
;
Humans
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Male
;
Proportional Hazards Models
;
Retrospective Studies
8.Effects of p16/pRb and JNK signaling pathways in hydroquinone-induced malignant transformation of TK6 cells.
Lin CHEN ; Wei Feng QIU ; Zhi Ming CUI ; Hui YANG ; Huan Wen TANG ; Hao LUO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(10):721-726
Objective: To investigate the cell cycle and apoptosis in hydroquinone (HQ) -induced malignant transformation of TK6 cells and its related regulatory mechanisms. Methods: TK6 cells were exposed to 20 μmol/L HQ, 24 h/time, once a week, for 19 weeks as experimental group and TK6 cells treated with phosphate buffer (PBS) for 19 weeks was used as control group from March 2014. In regulatory mechanism research, the cells were divided into four groups: control group, experimental group, control inhibitor group and experimental inhibitor group (inhibitor groups were added 10 μmol/L P600125) . Cell cycle and apoptosis were detected by flow cytometry. The protein expression of cell cycle-related proteins and JNK signaling pathway proteins were detected by Western blot. Results: Flow cytometry showed that compared with control group, the ratio of cells in the G0/G1 phase of the experimental group was significantly decreased (P=0.001) , and the ratio of cells in the S phase was significantly increased (P=0.002) . Western blotting demonstrated that the protein expressions of p-Rb (Ser780) , E2F1, Cyclin D1, p-p16 (Ser152) , JNK1, p-JNK1 (Thr183/Tyr185) , c-jun, p-c-jun (Ser63) (P=0.015, 0.021, 0.001, 0.001, 0.005, 0.001, 0.039, 0.003) were up-regulated, while the protein expressions of Rb (P=0.048) and p16 (P=0.002) were significantly down-regulated. After exposed to SP600125, compared with experimental group, there were no significant changes in cell cycle distribution (P=0.946) and apoptosis rate (P=0.923) in experimental inhibitor group. The expression of c-jun (P=0.040) protein was down-regulated, while the expression of Rb (P=0.027) protein was up-regulated in experimental inhibitor group. Conclusion: In HQ-induced TK6 cells malignant transformation, the cell cycle is arrested in the S phase, and the p16/pRb signaling pathway is inhibited, while the JNK signaling pathway is activated. However, the activated JNK signaling pathway may not be involved in the regulation of cell cycle.
Humans
;
Hydroquinones/toxicity*
;
MAP Kinase Signaling System
;
Cell Cycle
;
Cell Transformation, Neoplastic
;
Apoptosis
9.Research Progress of Animal Model of Tic Disorder and Its Application in Traditional Chinese Medicine
Peng FENG ; Zheng-gang SHI ; Huan YANG ; Zhi-qian SUN ; Wen-zhen LUO
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(15):207-213
Tic disorder (TD) is a neurodevelopmental disorder, with one or more motor and/or vocal disorders as the main symptoms. It brings many inconveniences to children's learning and life, and has a profound impact on children's character building. The pathogenesis of TD is mainly correlated with neurotransmitter release disorder, neuroimmune, genetic, trace element imbalance, diet and other factors, but has not been completely clear up to now. Western Medicine has obvious effects on TD, but with serious side effects. Compared with western medicine, traditional Chinese medicine (TCM) has the advantages of low adverse reactions and definite and lasting effect, and thus has been widely recognized by children and their families. In order to explore the pathogenesis of TD and the specific mechanism of TCM in the treatment of TD, many scholars have carried out a large number of in-depth animal experiments and made some achievements, but also exposed some defects, such as the single modeling method, failed to take into account other pathogenesis of TD, failure to combine the specific syndromes of TCM for targeted modeling, and failure to reflect the dialectic of TCM on the characteristics of governance. This paper reviews the modeling methods of common animal models, the comparison of advantages and disadvantages, and the changes of behavioral and biochemical indicators before and after the intervention with TCM compounds on TD animal models, so as to provide reference for the selection of animal models in future animal experimental research.
10. Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats
Yan LI ; Mei-qun CAO ; Wen-cong TAO ; Wei-min LI ; Huan-min LUO ; Zheng-zhi WU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(21):6-11
Objective: To explore the effect of Huangqisan on endoplasmic reticulum stress signaling pathway in liver tissues of high-fat diet-induced obese rats and its mechanisms. Method: Male SD rats were selected and fed with high-fat diet for 7 weeks continuously to establish an obese rat model. Then, the rats were randomly divided into model group, low and high-dose Huangqisan group (1.2, 2.4 g·kg-1), and Lipitor group (2 mg·kg-1), and orally administered with drugs for 15 consecutive weeks. The control group and the model group were perfused with the same volume of normal saline. The body weight, epididymal fat coefficient and liver coefficient of each group were determined separately. Fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were determined by biochemical reagent method. The epididymal visceral adipose tissue and liver pathological changes were observed by hematoxylin and eosin (HE) staining. And the protein expression levels of sterol regulation element-binding transcription factor 1 (SREBP-1c), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1α), p-inositol requiring enzyme 1 (p-IRE1α) in liver tissues were detected by Western blot methods. Result: Compared with the control group, the body weight, epididymal fat coefficient and liver coefficient of the model group were significantly increased(P<0.01), and the levels of FPG, TC, TG and LDL-C were also higher than those of the control group(P<0.05,P<0.01). The cell volume of epididymal fat and liver in the model group were enlarged, and numerous fat vesicles were observed in the cells. Meanwhile, the protein expression levels of the endoplasmic reticulum stress-related factors SREBP-1c, PERK, IRE1α/p-IRE1α were increased(P<0.05,P<0.01). Compared with the model group, high-dose and low-dose Huangqisan groups could significantly reduce the body weight, epididymal fat coefficient, liver coefficient and levels of glucose and lipid(P<0.05,P<0.01), and pathological examination showed that the lesion degrees of epididymal fat and liver tissues were alleviated obviously. In addition, Huangqisan could mostly reduce SREBP-1c, PERK, IRE1α/p-IRE1α protein expression levels to different degrees(P<0.05,P<0.01). Conclusion: Huangqisan could regulate the glucose and lipid metabolism, alleviate liver pathology and reduce body weight, and its mechanism was probably related to reduction of SREBP-1c, PERK, IRE1α/p-IRE1α proteins expression levels.

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