1.Targeting mitochondria:a vital therapeutic strategy for ischemic stroke
Li-Yuan MA ; Si-Yin CHEN ; Shao-Ping YIN ; Kai-Pei LUO ; Xian-Li MENG ; Lu YANG
Chinese Pharmacological Bulletin 2024;40(11):2025-2030
Ischemic stroke(IS)is a devastating neurological disease commonly around the world.Although modern medicine has recognized the confined mechanisms in the pathological process of cerebral ischemia,it has never been enough for the treatment of IS.Recent studies have confirmed the vital role of mitochondrial dysfunction in neuronal injury after cerebral ische-mia,thereby exerting a potential target for prevention and treat-ment of IS.Herein,we review the main molecular mechanisms of neuronal injury and death by mitochondrial dyshomeostasis under the condition of ischemia/hypoxia,especially mitochon-drial permeability transition pore opening,oxidative stress and apoptotic signaling.Given remodeling of mitochondrial function as a new idea for the management of IS,some emerging strate-gies containing mitochondrial antioxidant,mitophagy regulation and mitochondrial transfer also raise concern in this paper.
2.Mechanism of circ_0103552 regulating lung cancer A549 cell proliferation,migration and invasion by targeting miR-1200
Fang ZHOU ; Meng WANG ; Shi-Zhao CHENG ; Zheng WANG ; Si-Pei ZHANG ; Xi-Ke LU
Chinese Pharmacological Bulletin 2024;40(11):2099-2104
Aim To explore the effect of circ_0103552 on the proliferation,migration and invasion of lung cancer A549 cells and its possible mechanism.Meth-ods qRT-PCR was used to detect circ_0103552 and miR-1200 expression in lung cancer tissues and adja-cent tissues.A549 cells were grouped into si-NC,si-circ_0103552,miR-NC,miR-1200,si-circ_0103552+anti-miR-NC,si-circ_0103552+anti-miR-1200 groups.Cell proliferation,clone formation,migration and invasion were detected.The targeting relationship between circ_0103552 and miR-1200 was assessed u-sing the dual luciferase reporter experiment.The ex-pression of E-cadherin and N-cadherin protein was de-tected by Western blot.Results Compared with adja-cent tissues,circ_0103552 expression in lung cancer tissue increased(P<0.05),while miR-1200 expres-sion decreased(P<0.05).Circ_0103552 knockdown or miR-1200 overexpression reduced cell viability,N-cadherin,cloning,invasion,and promoted E-cadherin protein(P<0.05).Circ_0103552 could target miR-1200.Down-regulating miR-1200 could reverse the in-hibitory effect of circ_0103552 knockdown on prolifera-tion,migration and invasion,as well as the promotion effect on cell apoptosis(P<0.05).Conclusion Circ_0103552 could promote lung cancer cell progres-sion by targeting miR-1200.
3.Study on inhibitory effect of alisol B on non-small cell lung cancer based on network pharmacology and its mechanism
Liu-Yan XIANG ; Wen-Xuan WANG ; Si-Meng GU ; Xiao-Qian ZHANG ; Lu-Yao LI ; Yu-Qian LI ; Yuan-Ru WANG ; Qi-Qi LEI ; Xue YANG ; Ya-Jun CAO ; Xue-Jun LI
Chinese Pharmacological Bulletin 2024;40(12):2375-2384
Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.
4.Research on the construction of evaluation index system of internal control of medical equipment in public hospitals based on Delphi method and analytic hierarchy process
Qibo MA ; Mingzhuo DENG ; Shan LU ; Ni KANG ; Xiaochen SI ; Yu BAI ; Ming LI ; Xiangyu MENG ; Jianjun CHEN
China Medical Equipment 2024;21(5):133-137
Objective:To construct an evaluation index system of internal control medical equipment based on the internal control theory of The Committee of Sponsoring Organizations of the Treadway Commission(COSO)and combined with the current situation of medical equipment internal management in public hospitals,so as to provide reference and suggestions for the evaluation of internal control of medical equipment in public hospitals.Methods:Through literature research and expert consultation,the evaluation index system of internal control of medical equipment was preliminarily determined.Using the Delphi method,15 experts from 1 medical college and 3 tertiary hospitals in Beijing who were engaged in the use and management of medical equipment were selected to conduct two rounds of consultation on the evaluation index system of internal control of medical equipment,and the evaluation indicators were scored and screened.The analytic hierarchy process(AHP)was used to determine the index weights,and the internal control evaluation index system of medical equipment in public hospitals based on COSO was constructed.Results:The coefficient of the two rounds of expert consultation was 100%.The authority degree of consulting experts was 0.867.Finally,the evaluation index system of internal control of medical equipment in tertiary public hospitals was formed,which included 5 first-level indicators,17 second-level indicators and 50 third-level indicators.Conclusion:The evaluation index of internal control of medical equipment in public hospitals based on COSO has high expert enthusiasm,authority and coordination.The evaluation index system includes the unit level and the business level of internal control,with a wide coverage,which makes up for the limitations of traditional internal evaluation of medical equipment,which can make up for the limitations of the internal evaluation of traditional medical equipment,improve the internal control system of medical equipment in public hospitals,and optimize the medical equipment management system.
5.Association between Serum Uric Acid and the Early Marker of Kidney Function Decline among Chinese Middle-Aged and Older Population: Evidence from the China Health and Retirement Longitudinal Study.
Xu TANG ; Lu XU ; Ruo Gu MENG ; Yi Qing DU ; Shi Jun LIU ; Si Yan ZHAN ; Tao XU
Biomedical and Environmental Sciences 2023;36(3):231-240
OBJECTIVE:
To evaluate the association between serum uric acid (SUA) and kidney function decline.
METHODS:
Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m 2. Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines.
RESULTS:
A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline ( OR 1.14, 95% CI 1.03-1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women ( OR 1.22, 95% CI 1.03-1.45), those aged < 60 years ( OR 1.22, 95% CI 1.05-1.42), and those without hypertension and without diabetes ( OR 1.22, 95% CI 1.06-1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline ( OR 1.83, 95% CI 1.05-3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline.
CONCLUSION
The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.
Aged
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Female
;
Humans
;
Male
;
Middle Aged
;
China/epidemiology*
;
East Asian People
;
Glomerular Filtration Rate
;
Kidney/physiopathology*
;
Longitudinal Studies
;
Risk Factors
;
Uric Acid/blood*
6.Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults.
Xiao-Mei WANG ; Wen-Tao ZHU ; Long-Chen XU ; Ping-da ZHOU ; Jia-Meng ZHOU ; Wei WANG ; Si-Qi LU ; Jia-Yin WEI
China Journal of Chinese Materia Medica 2023;48(2):555-561
This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.
Adult
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Humans
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Databases, Factual
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Drugs, Chinese Herbal/therapeutic use*
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Dyspepsia/drug therapy*
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Medicine, Chinese Traditional
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Multicenter Studies as Topic
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Randomized Controlled Trials as Topic
7.Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels.
Ke-Ke LUO ; Hai-Yu ZHAO ; Nan SI ; Bao-Lin BIAN ; Wen XIA ; Yun-Qin CHEN ; Meng-Xiao WANG ; Xiao-Lu WEI ; Xing LI ; Guang-Yuan QIN ; Jian YANG ; Yan-Yan ZHOU ; Hong-Jie WANG
China Journal of Chinese Materia Medica 2023;48(4):1124-1131
A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans
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Adrenocorticotropic Hormone
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Hot Temperature
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Medicine, Chinese Traditional
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Adenosine Triphosphate
8.Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling.
Lu WANG ; Ying CHEN ; Ming-Min XU ; Wei CAO ; Qian-Hua ZHENG ; Si-Yuan ZHOU ; Jun-Peng YAO ; Meng-Han XI ; Hai-Yan QIN ; Ying LI ; Wei ZHANG
Chinese journal of integrative medicine 2023;29(5):459-469
OBJECTIVE:
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
METHODS:
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
RESULTS:
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.
CONCLUSION
EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.
Mice
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Animals
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Proto-Oncogene Proteins c-akt/metabolism*
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Phosphatidylinositol 3-Kinases/metabolism*
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Electroacupuncture
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Beclin-1
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Signal Transduction
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Constipation/therapy*
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TOR Serine-Threonine Kinases/metabolism*
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Autophagy
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Neuroglia/metabolism*
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Mammals/metabolism*
9.Effects of early enteral nutrition on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer
Lu-Gen ZUO ; Zhen ZHANG ; Lian WANG ; Meng ZHAO ; Qiu-Sheng WANG ; Yi-Qun YANG ; Ping-Sheng ZHU ; De-Li CHEN ; Mu-Lin LIU ; Si-Tang GE
Parenteral & Enteral Nutrition 2023;30(5):287-291
Objective:To investigate the effect of early postoperative enteral nutrition(EN)on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer,in order to provide reference for postoperative rehabilitation of such patients.Methods:Patients who received laparoscopic assisted radical gastrectomy in Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2020 to December 2022 were included in the analysis.According to the different ways of postoperative nutritional treatment,patients were divided into the observation group(early postoperative EN group)and the control group(parenteral nutrition group),and indexes such as postoperative rehabilitation,abdominal drainage flow and the level of inflammatory mediators in drainage fluid were compared between the two groups.Results:A total of 81 patients were included,including 41 in the observation group and 40 in the control group.Interval of the first postoperative exhaust(t=3.806;P<0.001)and resuming diet day(t=5.510;P<0.001),and length of postoperative hospital stay(t=2.401;P=0.019)in the observation group were shorter than those in the control group.Levels of peripheral blood albumin(t=14.040;P<0.001)and prealbumin(t=9.832;P<0.001)of the observation group at postoperative day(POD)5 were significantly higher than those of the control group,but there was no significant difference in hemoglobin level(t=1.477;P=0.144).The level of CRP in peripheral blood of the observation group at POD 5(t=7.758;P<0.001)and the incidence of postoperative SIRS[(12.2%,5/41)vs(32.5%,13/40),x2=4.830;P=0.028)]were significantly lower than those in the control group.The average drainage volume(t=6.858;P<0.001),drainage removal time(t=5.016;P<0.001),and TNF-α level(t=4.993;P<0.001)and IL-6 level(t=20.640;P<0.001)in postoperative drainage at POD 5 were significantly lower in the observation group than those in the control group.Conclusion:Early postoperative EN could accelerate the rehabilitation process after laparoscopic radical gastrectomy,improve postoperative nutritional status,and reduce abdominal inflammation.
10.Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice.
Meng-Han XI ; Lu WANG ; Wei ZHANG ; Qian-Hua ZHENG ; Hai-Yan QIN ; Xiang-Yun YAN ; Si-Jue CHEN ; Ying LI
Chinese Acupuncture & Moxibustion 2023;43(11):1279-1286
OBJECTIVES:
To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy.
METHODS:
A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry.
RESULTS:
Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group.
CONCLUSIONS
Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.
Mice
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Animals
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Electroacupuncture
;
Beclin-1
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Acupuncture Points
;
Constipation/therapy*
;
Intestine, Small
;
Autophagy
;
Water

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