1.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
2.Research progress on the immune effects of photodynamic therapy
Wen-Xin CHOU ; Tian-Zhen SUN ; Ying GU ; Hong-You ZHAO
Medical Journal of Chinese People's Liberation Army 2024;49(6):718-725
As a novel tumor treatment,photodynamic therapy(PDT)has been widely used in clinical treatment of a variety of tumors due to its advantages,such as fewer adverse reactions,precise targeting and repeatability of treatment.Unlike conventional treatments,such as surgery,chemotherapy and radiotherapy,PDT not only eliminates the primary tumor but also effectively inhibits metastatic tumors by activating the body's immune response.However,the PDT-activated immune response is influenced by multiple factors,including the localization and dose of photosensitizer in the cells,light parameters,oxygen concentration in the tumor,and the integrity of immune function.This review summarizes the mechanisms behind the PDT-activated anti-tumor immune response,systematically examines the key influencing factors on the immune effect of PDT,and discusses the future development direction of PDT in cancer treatment.
3.Effects of citicoline on Keap1/Nrf2/ARE signaling pathway in mice with cerebral hemorrhage
Wei LU ; Hong YOU ; Min ZHANG ; Bao-Feng HE ; Rui MA ; Ya-Ya GAO ; Xin-Yu MA
The Chinese Journal of Clinical Pharmacology 2024;40(8):1175-1179
Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P<0.05,P<0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P<0.05,P<0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P<0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.
4.Mechanism of andrographolide alleviates lipopolysaccharide-induced fer-roptosis in renal tubular epithelial cells
Yi-Xin ZHANG ; Ming HUANG ; Guo-Dong CAO ; You-Cheng ZENG ; Liang LIN ; Xiao-Yue WANG ; Qing-Hong CHENG
Chinese Journal of Infection Control 2024;23(5):568-573
Objective To investigate the effect and mechanism of andrographolide(AG)on lipopolysaccharide(LPS)-induced ferroptosis in renal tubular epithelial cells(HK-2 cells).Methods HK-2 cells were treated with LPS to simulate the in vitro HK-2 injury model of sepsis.The cells were further treated with AG of 5,10,20,40 μmol/L and randomly divided into control group,LPS group,LPS+dimethyl sulfoxide group(DMSO group),and AG group.Cell viability was detected by the CCK-8 method,and the optimal concentrations of LPS and AG were screened.Cell morphological change,the levels of kidney injury markers,including neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS),as well as the expression levels of ferroptosis regulatory proteins such as solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and ferritin in each group were compared,and the pro-tective effect of AG treatment on the cells was evaluated.Results Compared with the control group,the cell viabi-lity and GSH content decreased significantly in HK-2 cells treated with 10 μg/mL LPS;cell shrinkage and adhesion ability were poor;the contents of oxidative products MDA and ROS,as well as the levels of kidney injury markers NGAL and KIM-1 increased significantly,while expression levels of SLC7A11 and GPX4 protein decreased;ferritin expression level increased;differences were all statistically significant(all P<0.05).Compared with LPS group,the cell viability,GSH content,as well as protein expression levels of SLC7A11 and GPX4 increased significantly after AG intervention,while ferritin expression level decreased,differences were all significant(all P<0.05).MDA content,ROS fluorescence intensity,and the levels of kidney injury markers NGAL and KIM-1 decreased sig-nificantly,difference were all significant(all P<0.05).Conclusion AG has a protective effect on LPS-induced HK-2 cell injury,possibly by activating SLC7A11/GPX4 pathway,reducing oxidative stress,up-regulating antioxi-dant enzyme activity,and alleviating ferroptosis.
5.Tick-borne pathogens infection of rodents at the border of China and the Democratic People's Republic of Korea
Zhuo WANG ; Qiong WU ; Xiao-Yang HUANG ; Guan-Peng HUANG ; You-Xin MA ; En-Rong MAO ; Guo-Shuang LENG ; Hong-Min ZHAO ; Bing LI ; Yi-Min WU
Chinese Journal of Zoonoses 2024;40(4):323-327
To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85%,12.88%,5.30%,3.79%,51.52%,and 6.06%,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9%(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.
6.Establishment of mice gait analysis system based on DeepLabCut algorithm to evaluate motor function of aging mice
Zhi-Hong LI ; Yi-Hua SHENG ; You LI ; Zhi-Xiang PENG ; Xing-Yao ZENG ; Xin-Li GU ; Jia-Yi TIAN ; Si-Di LI
Chinese Pharmacological Bulletin 2024;40(9):1792-1799
Aim To establish a gait analysis system based on DeepLabCut(DLC)algorithm for evaluating motor function in aged mice.Methods Based on DLC algorithm in deep learning technology,treadmill device and fully closed design were used in the system,including software and hardware.This system was applied to evaluate gait characteristics of mice due to aging un-der different movement modes.Correlation analysis was used to explore the effects of body weight and body length on gait indica-tors.Results This system realized the synchronous analysis of three-dimensional gait(lateral and ventral plane)of mice at specific gait speed,and automatically quantified 47 gait indica-tors.Using this system,it was found that during walking(15 cm·s-1),the standard deviation of body turning angle decreased,forelimb sway duration,standard deviation of knee angle,mean outward angles of left and right hind paw increased in 8 and 15 month-old mice,compared with 2-month-old mice.However,15-month-old mice showed decreased walking frequency,and in-creased stride width,total duration of double support,and knee extension and contraction distance.In addition,at trot(20 cm·s-1),15-month-old mice were unable to walk steadily,and 8-month-old mice had increased total duration of double support and mean outward angles of left hind paw,compared with 2-month-old mice.Correlation analysis revealed that indicators like walking frequency,stride width,forelimb sway duration,total duration of double support,standard deviation of knee an-gle,knee extension and contraction distance,were not affected by changes in body weight and body length.Conclusions The gait analysis system based on DLC algorithm can achieve a more sensitive,accurate and comprehensive evaluation of the gait of aged mice,distinguishing the gait characteristics of aged mice to maintain gait stability,and selecting behavioral indicators that better reflect the gait changes of aged mice.It provides a meth-odological basis for more effective assessment of efficacy and side effects of drugs for anti-aging and anti-decline of motor coordina-tion in the future.
7.Analysis of mental health status of Hainan residents
HONG Jian-he ; GAO Li ; WANG Xiao-dan ; DU Zhen-you ; LI Zhi-yun ; ZUO Qiu-hui ; WENG Xin-mei
China Tropical Medicine 2023;23(3):267-
Abstract: Objective To understand the mental health literacy level of residents in Hainan Province, and to provide evidence for promoting mental health promotion and improving the mental health literacy level of residents. Methods Multi-stage random sampling method was used to investigate The National Mental Health Literacy Questionnaire among 6 895 residents in 12 districts including Changjiang, Chengmai, Dongfang, Ledong, Lingshui, Haikou Longhua District, Haikou Meilan District, Qionghai, Sanya, Tunchang, Wenchang and Wuzhishan. Results In the survey 6 895 residents in 12 counties, cities, districts of Hainan Province, 365 of them reached the standard of mental health with the standard rate of 5.3%. The mental health knowledge score was (54.00±17.02) with the standard rate of 7.7%; the self-assessment score was (26.11±3.99) with the standard rate of 75.9%; the score of mental health skill was (26.22±7.25) with the standard rate of 44.8%. The mental health literacy level of medical workers was the highest, with the standard rate of 13.5% (112/830), and the mental health literacy level of farmers was the lowest, with the standard rate of 0.8% (13/1 647). The results of unconditional Logistic regression showed that the factors entering the regression model included educational background (OR=2.268), personal monthly income (OR=1.129), gender (OR=1.302), household registration (OR=0.776), and whether they had participated in mental health related courses OR training (OR=0.511). The higher the educational background and personal monthly income, the higher the psychological quality. The mental health of women was higher than that of men, and that of urban was higher than that of rural, and those who had participated in mental health related courses were higher than those who had not. Conclusions The mental health literacy level of Hainan residents is at a low level, and the influencing factors are multifaceted. It is suggested to strengthen the mental health monitoring comprehensively and carry out rich health education service mode for different groups.
8.Short-term outcomes and long-term quality of life after undergoing radical proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis for Siewert type II and III adenocarcinoma of the esophagogastric junction: A propensity score matching analysis.
Zhi Wen XU ; Kang ZHAO ; Qing Qi HONG ; Yi Fu CHEN ; Hai Bin WANG ; He Xin LIN ; Ting Hao WANG ; Liang Bin XIAO ; Jing Tao ZHU ; Su YAN ; Jun YOU
Chinese Journal of Gastrointestinal Surgery 2023;26(2):181-190
Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=3.663,P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ2=8.711, P=0.003 and χ2=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ2=3.386,P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ2=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.
Humans
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Anastomosis, Roux-en-Y
;
Retrospective Studies
;
Cohort Studies
;
Esophagitis, Peptic
;
Quality of Life
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Propensity Score
;
Gastrectomy/methods*
;
Esophagogastric Junction/surgery*
;
Anastomosis, Surgical/methods*
;
Adenocarcinoma/pathology*
;
Stomach Neoplasms/pathology*
;
Postoperative Complications
;
Treatment Outcome
9.Efficacy of thunder-fire moxibustion plus glucosamine sulfate potassium capsule in treating knee osteoarthritis: a clinical trial
Shuxiang SONG ; Wei TIAN ; Wei YOU ; Xin WANG ; Hong HE ; Xiaolu PEI
International Journal of Traditional Chinese Medicine 2023;45(12):1508-1511
Objective:To evaluate the clinical efficacy of thunder-fire moxibustion plus glucosamine sulfate potassium capsule in treating knee osteoarthritis (KOA).Methods:This study was a randomized controlled trial. A total of 90 participants with KOA in the Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from February 2020 to December 2021 were randomized and assigned into 3 groups, with 30 cases in each group according to the random number table method. The thunder-fire moxibustion group was only treated with thunder-fire moxibustion on Neixiyan and Dubi acupoints, while the medication group was only treated with oral glucosamine sulfate potassium capsule, and the thunder-fire moxibustion plus medication group was treated with thunder-fire moxibustion on Neixiyan and Dubi acupoints combined with oral glucosamine sulfate potassium capsule. All the three groups were treated for 4 weeks. The degree of joint pain and stiffness was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC); the amount of knee joint cavity effusion was detected by ultrasound; the knee circumference was measured to assess the degree of knee swelling.Results:After treatment, the amount of knee joint cavity effusion [(3.21±2.44) mm, (3.73±2.53) mm vs. (4.80±3.07) mm, F=6.82], the WOMAC score [(65.88±30.25), (77.74±28.27) vs. (86.58±31.50), F=7.92], knee circumference [(36.74±2.74) cm, (37.59±2.63) cm vs. (38.51±3.09) cm, F=8.94] in the thunder-fire moxibustion plus medication group and the thunder-fire moxibustion group were lower than those in the medication group ( P<0.01). Conclusion:Thunder-fire moxibustion plus oral glucosamine sulfate potassium capsule can reduce the amount of knee joint cavity effusion, WOMAC score and the degree of knee swelling, and the efficacy is better than thunder -fire moxibustion and oral glucosamine sulfate potassium capsule.
10.Co-load of silybin and doxorubicin by MoS2 nanosheets for synergetic chemotherapy and photothermal therapy of lung cancer
Hong CHEN ; Min GUO ; Zhi-huai CHEN ; Xin-qi WEI ; You-rui YANG ; Jian LIU ; Wei XU
Acta Pharmaceutica Sinica 2023;58(3):560-570
The active ingredient of traditional Chinese medicine, silybin (SBN), can inhibit the proliferation of cancer cells and enhance the anticancer effect of doxorubicin (DOX). However, due to non-targeting and short half-life of SBN and DOX, as well as different administration routes and pharmacokinetic processes, this combination drug cannot act on the tumor in the set order, seriously eliminating the synergistic effect between them and limiting the effect

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