1.Effect of NF-κB-regulated Drp-1 and PGC-1α in lung tissue of neonatal rats with meconium aspiration syndrome and its mechanism
Medical Journal of Chinese People's Liberation Army 2024;49(3):265-271
Objective To investigate the role of dynamin-related protein 1(Drp-1)and peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)in the lung tissues of neonatal rats with meconium aspiration syndrome(MAS)and its mechanism.Methods Fifty 2-3-week-old SD neonatal rats were randomly divided into five groups(n=10):control group,model group and SN50 low,medium and high concentration groups.In control group,2 ml/kg of saline was injected into the trachea after tracheal exposure,and 2 ml/kg of meconium suspension was injected into the trachea of the rest of groups;after 24 h,control and model groups were left untreated,and 100 μl of each of SN50 concentrations of 10,30,and 60 μg/ml was injected into SN50 low,medium,and high concentration groups intraperitoneally;the rats of each group were killed after 6 h,and the chest X-rays,the gross views of the lungs,the lung wet/dry weight ratios(W/D),and the lungs of the rats in control group and model group were examined.After 6 h,the rats in each group were executed,and the pathological changes of lung tissue were observed by chest radiographs,lung gross view,lung wet/dry weight ratio(W/D)and HE staining;Western blotting was used to detect the changes of nuclear factor κB(NF-κB)(p65),p-NF-κB p65(p-p65),Drp-1,and PGC-1α proteins expression in neonatal rat lung tissues,and immuno-histochemistry was used to observe the expression of p65,Drp-1,and PGC-1α related proteins expression in neonatal rat lung tissues.Results Compared with control group,model group showed inflammatory infiltration in the chest radiograph and gross view,and the W/D and lung injury pathology scores were significantly higher(P<0.05);compared with model group,the chest radiograph and gross view of inflammation were slightly reduced in SN50 low,medium and high concentration groups,and the W/D and lung injury pathology scores were significantly lower(P<0.05).Western blotting showed that,compared with control group,the protein expression levels of p-p65 and Drp-1 in the lung tissues of neonatal rats were significantly higher in model group(P<0.05),and the protein expression level of PGC-1α was significantly lower(P<0.05);compared with model group,the protein expression levels of p-p65 and Drp-1 were significantly lower in SN50 low,medium,and high concentration groups(P<0.05),and the difference in the protein expression level of PGC-1α in SN50 low concentration group was not statistically significant(P>0.05),whereas the PGC-1α expression levels in SN50 medium and high concentration groups were significantly higher(P<0.05);the difference in the total p65 protein expression levels in each group was not statistically significant(P>0.05).Immunohistochemical assay results showed that,compared with control group,p65 and Drp-1 protein expression levels were significantly higher in model group(P<0.05),and PGC-1α protein expression level was significantly lower(P<0.05);compared with model group,p65 protein expression level was significantly lower in SN50 low concentration group(P<0.05),and the difference in Drp-1 and PGC-1α protein expression levels were not statistically significant(P>0.05),Drp-1 protein expression level was significantly lower(P<0.05),and PGC-1α protein expression level was significantly higher(P<0.05)in SN50 middle and high concentration groups.Conclusion Fecal inhalation can induce lung tissue inflammation in neonatal rats,and the mechanism may be related to enhanced oxidative stress,promotion of mitochondrial dysfunction,activation of the Drp-1/NF-κB signaling pathway,and inhibition of PGC-1α protein expression.
2.The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1
Wan LIU ; Fei LIANG ; Tie-quan CAI ; Ying LI ; Le LI ; Shu-cai YANG ; Ying LIU ; Yan ZHAO
Acta Pharmaceutica Sinica 2024;59(1):135-142
Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (
3.A multicenter retrospective cohort study on the attributable risk of patients with Acinetobacter baumannii sterile body fluid infection
Lei HE ; Dao-Bin JIANG ; Ding LIU ; Xiao-Fang ZHENG ; He-Yu QIU ; Shu-Mei WU ; Xiao-Ying WU ; Jin-Lan CUI ; Shou-Jia XIE ; Qin XIA ; Li HE ; Xi-Zhao LIU ; Chang-Hui SHU ; Rong-Qin LI ; Hong-Ying TAO ; Ze-Fen CHEN
Chinese Journal of Infection Control 2024;23(1):42-48
Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
4.Motor function and quality of life in Parkinson's disease patients with freezing of gait
Ying GE ; Wowa ZHAO ; Lu ZHANG ; Xuan SHU ; Jiawei LI ; Ying LIU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(3):339-344
Objective To observe the differences in motor function and quality of life among mild-to-moderate Parkinson's disease(PD)patients with or without freezing of gait(FOG),and the correlation of FOG to motor function and quality of life. Methods From April,2021 to December,2022,132 mild-to-moderate PD patients aged 60 to 80 years were selected from Peking Union Medical College Hospital,and were divided into FOG group(n = 43)and non-FOG group(n = 89)according to the clinical features.They were assessed with Freezing of Gait Questionnaire(FOGQ),Berg Balance Scale(BBS),Timed"Up&Go"Test(TUGT),Five Times Sit to Stand Test(FTSST),isokinetic muscle strength,Unified Parkinson's Disease Rating Scale(UPDRS)and 39-item Parkinson's Disease Question-aire-39(PDQ-39). Results The BBS score was lower(Z =-2.354,P<0.05),and the TUGT,FTSST,UPDRS part 2 and part 3 scores,and the Parkinson's disease summary index(PDSI)were higher in FOG group than in non-FOG group(Z>3.074,t = 2.748,P<0.01).FOGQ score correlated with BBS score,UPDRS Part 2 and Part 3 scores,and PDSI(|r|>0.392,P<0.001). Conclusion FOG would impair motor function,activities of daily living and quality of life in mild-to-moderate PD pa-tients,and increase the risk of falls.
5.Mechanism of Mitochondrial Quality Control in Ovarian Aging and Intervention of Traditional Chinese Medicine: A Review
Fei YAN ; Yanfeng LIU ; Qi ZHAO ; Xingtong LIU ; Ying LI ; Chang SHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):291-298
Ovarian aging is a reproductive endocrine disease caused by a variety of factors leading to a gradual decline in ovarian function until ovarian failure, which seriously affects women's physical and reproductive health and is a major factor leading to female infertility. Mitochondria, the energy metabolism centers of cells, are critical for ovarian functions. Their structural and functional abnormalities are key pathological factors leading to the declined ovarian function. Mitochondrial quality control is an important endogenous regulatory mechanism for the maintenance of mitochondrial homeostasis and the improvement of mitochondrial functions. Abundant studies have shown that the dysregulation of mitochondrial quality control, characterized by mitochondrial oxidative damage, abnormal mitochondrial biogenesis, abnormal mitochondrial dynamics, abnormal mitochondrial autophagy, and dysregulated calcium homeostasis, is closely associated with the occurrence of ovarian hypofunction. Traditional Chinese medicine (TCM) is a treasure of China's medicine, demonstrating remarkable efficacy in the clinical treatment of ovarian aging-related diseases. In recent years, research progress has been achieved in the TCM treatment of ovarian aging by regulating mitochondrial quality control disorders in a multi-target and multi-pathway manner. However, systematic research remains to be carried out regarding the research progress in this field. Therefore, this article reviews the research progress in the TCM treatment of ovarian aging based on mitochondrial quality control, with a view to providing a theoretical basis for studying the clinical efficacy of TCM in the treatment of ovarian aging and a new strategy for the in-depth research on the prevention and treatment of ovarian aging by TCM.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
8.Time-Dependent Sequential Changes of IL-10 and TGF-β1 in Mice with Deep Vein Thrombosis
Juan-Juan WU ; Jun-Jie HUANG ; Yu ZHANG ; Jia-Ying ZHUO ; Gang CHEN ; Shu-Han YANG ; Yun-Qi ZHAO ; Yan-Yan FAN
Journal of Forensic Medicine 2024;40(2):179-185
Objective To detect the expression changes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)during the development of deep vein thrombosis in mice,and to explore the application value of them in thrombus age estimation.Methods The mice in the experimental group were subjected to ligation of inferior vena cava.The mice were sacrificed by excessive anesthesia at 1 d,3 d,5 d,7 d,10 d,14 d and 21 d after ligation,respectively.The inferior vena cava segment with thrombosis was extracted below the ligation point.The mice in the control group were not ligated,and the inferior vena cava segment at the same position as the experimental group was extracted.The ex-pression changes of IL-10 and TGF-β1 were detected by immunohistochemistry(IHC),Western blot-ting and real-time qPCR.Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis.Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group.The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation,respectively.The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group,and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group.The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation,respectively.The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group,and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes,and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.
9.Clinicopathologic characteristics and survival analysis of primary large B-cell lymphoma of the central nervous system
Qifan XU ; Rong SHEN ; Yige SHEN ; Yiwen CAO ; Ying QIAN ; Pengpeng XU ; Shu CHENG ; Li WANG ; Weili ZHAO
Chinese Journal of Hematology 2024;45(5):481-487
Objective:To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) .Methods:Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model.Results:Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy ( P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months ( P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL ( HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions:In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.
10.Mechanism of Chaijin JieYu Anshen formula regulating synaptic plasticity of hippocampal neurons in insomnia-concomitant depression rats based on HDAC5/MEF2C pathway
Ting-Ting REN ; Yu-Hong WANG ; Ying-Juan TANG ; Song YANG ; Hai-Peng GUO ; Ting-Ting WANG ; Ying HE ; Ping LI ; Hong-Qing ZHAO ; Zi-Yang ZHOU ; Man-Shu ZOU
Chinese Pharmacological Bulletin 2024;40(7):1248-1257
Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P<0.05,P<0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P<0.01,P<0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P<0.05,P<0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P<0.05,P<0.01 or P<0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

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