1.Effect of pH value of reaction system on properties of pegylated bovine hemoglobin conjugate
Chen CHANG ; Guoxing YOU ; Wei WANG ; Weidan LI ; Ying WANG ; Kai ZHU ; Hong ZHOU ; Lian ZHAO ; Yuzhi CHEN
Military Medical Sciences 2024;48(10):753-759
Objective To explore the impact of pH value of the reaction system on the properties of bovine hemoglobin modified with aldehydeated polyethylene glycol(PEG-bHb).Methods PEG-bHb conjugates were synthesized under varying pH conditions(6.0,6.5,7.4 and 8.0)of the reaction system while consistent molar ratios,temperature,and reaction time were maintained.The structural and functional attributes of PEG-bHb were characterized.Results The proportion of methemoglobin decreased with an increase in pH.In a weakly acidic reaction environment,the PEG-bHb was found to be relatively highly modified.At pH 6.5,the average number of PEG chains attached to the bHb surface was 6.86±0.38.Selective PEG modification of the N-terminal α-NH2 groups was more pronounced under weakly acidic conditions.Specifically,at pH 6.5,the modification efficiency of the N-terminal α-NH2 groups of bHb by aldehyde-activated PEG reached 95.4%for the α-chains and 99.3%for the β-chains.The PEG modification influenced the heme region microenvi-ronment of bHb,with minimal structural impact observed at pH 6.5.After modification,the oxygen affinity of PEG-bHb was enhanced,the Hill coefficient was reduced,and there were significant increases in colloid osmotic pressure,viscosity,and particle size,all of which differed markedly from the unmodified bHb group(P<0.001).Conclusion The synthesis of PEG-bHb under weakly acidic conditions can result in a high degree of selective modification of the N-terminal α-NH2 groups and an overall high degree of modification.
2.Long-term therapeutic efficacy and prognosis analysis of complex high-risk coronary heart disease patients undergoing elective percutaneous coronary intervention with extracorporeal membrane oxygenation combined with intra-aortic balloon pump
Tian-Tong YU ; Shuai ZHAO ; Yan CHEN ; You-Hu CHEN ; Gen-Rui CHEN ; Huan WANG ; Bo-Hui ZHANG ; Xi ZHANG ; Bo-Da ZHU ; Peng HAN ; Hao-Kao GAO ; Kun LIAN ; Cheng-Xiang LI
Chinese Journal of Interventional Cardiology 2024;32(9):501-508
Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1%vs.0.7%,P=0.030),left main disease(43.9%vs.27.0%,P=0.018),triple vessel disease(90.9%vs.75.5%,P=0.009),and RCA chronic total occlusion disease(60.6%vs.35.5%,P<0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9%vs.16.7%,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7%vs.9.2%,P=0.031).The rates of 1-month MACE(4.5%vs.2.6%,P=0.435)and 1-year MACE(7.6%vs.7.9%,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95%CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95%CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.
3.Effects of standardized environmental enrichment on cognitive function and serum BDNF level in patients with post-stroke dementia
Tian-Tian ZHOU ; Wen-Jie SU ; You-Cong LIN ; Bi-Neng CHEN ; Song-Yong LIAN
Medical Journal of Chinese People's Liberation Army 2024;49(7):790-795
Objective To explore the effects of standardized environmental enrichment(EE)on cognitive function and serum brain-derived neurotrophic factor(BDNF)levels in patients with post-stroke dementia.Methods A prospective study was conducted,including 80 patients with post-stroke dementia admitted to Department of Traditional Chinese Medicine Rehabilitation,910th Hospital of the Joint Logistics Support Force of Chinese PLA from January 2021 to May 2023.Patients were randomly divided into control group,cognitive training(COG)group,aerobic exercise training(AE)group and environmental enrichment(EE)group,with 20 cases in each group.All patients received routine treatment,with COG group receiving additional cognitive function training(30 minutes each time),AE group receiving additional aerobic exercise training(30 minutes each time),and EE group receiving both aerobic exercise and cognitive function training(15 minutes of aerobic exercise training and 15 minutes of cognitive training each time).The training was conducted once a day,5 days a week,for a total of 8 weeks.The patients'mini-mental state scale(MMSE),modified Barthel index(MBI),Hamilton depression scale(HAMD),stroke-specific quality of life(SS-QOL)score and serum levels of BDNF were assessed before treatment,at 4 weeks and 8 weeks of treatment,respectively.Results Before treatment,there were no significant differences in general information,MMSE,MBI,HAMD,SS-QOL scores,and serum levels of BDNF among the four groups(P>0.05).After 4 and 8 weeks of treatment,the above indicators of the four groups were improved compared with those before treatment,with all differences being statistically significant(P<0.05).Inter-group comparison showed that after 4 and 8 weeks of treatment,MMSE,MBI,SS-QOL scores,and serum BDNF levels in COG,AE and EE groups were significantly higher than those in control group,and HAMD scores were significantly lower than those in control group(P<0.05).In addition,MMSE,MBI,SS-QOL scores and BDNF levels of group EE were better than those of other 3 groups,while HAMD scores were lower than those of other 3 groups,with all differences being statistically significant(P<0.05).There was no significant difference in above outcome indicators between COG group and AE group after 4 and 8 weeks of treatment(P>0.05).Conclusion Standardized enrichment environment can significantly enhance cognitive function,daily living abilities of post-stroke dementia patients,alleviate depression symptoms,and improve the quality of life,which may be related to the increase in serum BDNF levels.
4.Dawn of CAR-T cell therapy in autoimmune diseases
Yuxin LIU ; Minghao DONG ; Yunhui CHU ; Luoqi ZHOU ; Yunfan YOU ; Xiaowei PANG ; Sheng YANG ; Luyang ZHANG ; Lian CHEN ; Lifang ZHU ; Jun XIAO ; Wei WANG ; Chuan QIN ; Daishi TIAN
Chinese Medical Journal 2024;137(10):1140-1150
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.
5.Voluntary blood donation among undergraduates in Beijing: status and influencing factors of knowledge, attitude and practice
Kexiang SHI ; Mei YOU ; Linyi CHEN ; Mingzhu XIE ; Xinyao LIAN ; Wenjun SUN ; Juan DU ; Qingbin LU
Chinese Journal of Blood Transfusion 2022;35(4):415-419
【Objective】 To explore the status quo and influencing factors of knowledge, attitude and practice of voluntary blood donation among undergraduates in Beijing. 【Methods】 A questionnaire was designed on the basis of literature, using the method of convenience sampling to survey the undergraduates from 39 universities in Beijing. The t-test, analysis of variance and χ2 test were used to compare the differences in knowledge, attitude and practice of voluntary blood donation among different groups, and logistic regression model was performed to analyze the influencing factors. 【Results】 A total of 1 075 valid questionnaires were collected from undergraduates of 39 universities in Beijing. The results showed that the proportion of the participants who had good knowledge about voluntary blood donation was 69.21% (744/1 075). No statistically significant difference was noticed on the scores of voluntary blood donation knowledge between males and females (P>0.05). The scores of voluntary blood donation knowledge of medical students were higher than those of other subjects (P<0.05). The scores of voluntary blood donation knowledge of juniors and above were higher than those of lower grades (P<0.05). The rate of undergraduates participating voluntary blood donation in Beijing was 30.98% (333/1 075). A total of 67.26% (723/1 075) of students had donation intention, 9.49% (102/1 075) didn’t and 23.25% (250/1 075) were not sure. No statistically significant differences in blood donation intention were observed among undergraduates by genders and grades (P>0.05). The rate of medical students’ intention to donate blood was higher than that of other subjects (P<0.05). 【Conclusion】 The rate of voluntary blood donation among undergraduates in Beijing was above the middle level compared with other regions in China, but the practice of voluntary blood donation is far away from the intention. Therefore, it’s necessary to improve the level of knowledge, attitude and practice of undergraduates, especially non-medical college students, so as to improve the rate of voluntary blood donation among the undergraduates in Beijing.
6.Receiving Human Immunodeficiency Virus Serostatus Disclosure from Male Sexual Partners and Related Factors among Men Who Have Sex with Men Aged 50 and Above.
Jun LIAN ; Xiao-You SU ; Xin-Yue CHEN ; Wen-Jun WANG ; Fei YU ; Guo-Dong MI ; Yuan-Li LIU
Acta Academiae Medicinae Sinicae 2022;44(2):221-226
Objective To investigate the rate and correlates of receiving human immunodeficiency virus(HIV) serostatus disclosure from their most recent male sexual partners among men who have sex with men(MSM) aged 50 and above. Methods With a geosocial networking application,we recruited participants through online convenience sampling to collect the demographic variables,behavioral information,receiving HIV serostatus disclosure,etc.Univariate and multivariate analyses were performed to interpret the associated factors of receiving HIV serostatus disclosure. Results Overall,38.4%(398/1037) of participants received HIV serostatus disclosure from their most recent male sexual partners.The multivariable analysis demonstrated that the following populations were less likely to receive HIV serostatus disclosure from their most recent male sexual partners:participants with junior high school degree or below(OR=0.660,95%CI=0.473-0.922, P=0.015) compared to those with senior high school degree or above;participants unemployed(OR=0.537,95%CI=0.322-0.896, P=0.017) and employed(OR=0.663,95%CI=0.466-0.944, P=0.022) compared to those retired;participants without knowledge about HIV or acquired immune deficiency syndrome(AIDS) compared to those with knowledge about HIV/AIDS(OR=0.636,95%CI=0.466-0.868, P=0.004);participants having ≥2 male sexual partners in the last year(OR=0.433,95%CI=0.320-0.586, P<0.001) compared to those having none or one male sexual partner;participants never been tested for HIV(OR=0.544,95%CI=0.403-0.734, P<0.001) compared to those ever been tested for HIV;participants ever been diagnosed to have sexually transmitted infection(STI)(OR=0.472,95%CI=0.349-0.637, P<0.001) compared to those never diagnosed to have STI;and participants with higher level of HIV stigma(OR=0.742,95%CI=0.604-0.912, P=0.005). Conclusions Our findings indicated that the MSM aged 50 and above had low possibility of receiving HIV serostatus disclosure from the most recent male sexual partners.Education,employment status,number of sexual partners,HIV/AIDS-related knowledge,HIV testing behaviors,STI infection history,and HIV stigma contributed to this result.
Acquired Immunodeficiency Syndrome
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Disclosure
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Female
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HIV
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HIV Infections
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Homosexuality, Male
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Humans
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Male
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Sexual Behavior
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Sexual Partners
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Sexual and Gender Minorities
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Sexually Transmitted Diseases/diagnosis*
7.Mechanism of micro RNA-1182 overexpression in inhibiting malignant phenotype of glioma cells
Zhihao ZHAI ; Bin LUO ; Xiaowen LIAN ; Jianliang CHEN ; Yuanqiang ZHONG ; Hengxing YOU
Chinese Journal of Neuromedicine 2021;20(10):973-980
Objective:To investigate the micro RNA (miR)-1182 expression in glioma, and explore the regulation role and mechanism of miR-1182 overexpression in malignant phenotype of glioma cells.Methods:(1) The data of miR-1182 expressions of 198 glioma samples and survival of these glioma patients were downloaded from the official website of Chinese Glioma Genome Atlas(CGGA), and the differences of miR-1182 expression levels among glioma tissues of different pathologic types and different WHO grades were compared. Kaplan-Meier survival curve was used to analyze the relation between miR-1182 expression level and patient survival. (2) Human glioma cell lines A172, LN229, T98G, U87, and U251, and human normal astrocyte cell line NHA were routinely cultured in vitro, and the miR-1182 expression levels in each group were detected by real-time quantitative PCR (qPCR). (3) U87 and U251 cells were divided into miR-1182 transfection group and negative control group; the miR-1182 mimics and miR-1182 negative control sequence were transfected, respectively. After 48 h of transfection, 5-ethynyl-2'-deoxyuridine (EdU) staining was used to detect the cell proliferation ability, flow cytometry was used to detect the cell apoptosis, Transwell assay was used to detect the cell migration ability, and Western blotting was used to detect the expression levels of cyclin (C-myC, C-Jun, CCND1, and P21), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), and epithelial-mesenchymal transformation (EMT) pathway related proteins (N-cadherin, β-catenin, and vimentin). Results:(1) The miR-1182 expressions in glioma tissues of WHO grading III and IV were significantly lower as compared with those in glioma tissues of WHO grading II ( P<0.05). The median survival time in patients from the low miR-1182 expression group ([701.00±11.14] d) was significantly shorter than that in the high miR-1182 expression group ([1812.00±23.21] d, P<0.05). (2) As compared with that in NHA cell group, the miR-1182 expression levels in A172, LN229, T98G, U87 and U251 cell groups were significantly decreased ( P<0.05), and the decrease was most significant in U87 and U251 cell groups. (3) As compared with the negative control group, the U87 and U251 cells in miR-1182 transfection group had significantly weaker proliferation ability, significantly higher apoptosis rate, significantly decreased number of transmembrane cells, significantly decreased protein expression levels of C-MyC, C-Jun and CCND1, significantly increased P21 protein expression level, significantly decreased expression levels of PI3K, phosphorylated (p)-PI3K, Akt and p-Akt, and significantly decreased expression levels of N-cadherin, β-catenin and vimentin ( P<0.05). Conclusions:Glioma patients with low miR-1182 expression have poor prognosis. Low miR-1182 expression is noted in glioma cells. Overexpression of miR-1182 can inhibit the malignant phenotype of glioma cells, which may be related to cell cycle-related proteins, PI3K/Akt, and EMT pathway ralated proteins.
8.Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules () in Patients with Parkinson's Disease and Syndrome of Shen (Kidney) Essence Deficiency.
Shi-Ya CHEN ; Shao-Jian XIAO ; You-Ning LIN ; Xi-Yu LI ; Qian XU ; Sha-Sha YANG ; Lian-Hong HUANG ; Jing CAI
Chinese journal of integrative medicine 2020;26(6):412-419
OBJECTIVE:
To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach.
METHODS:
Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction.
RESULTS:
A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B.
CONCLUSIONS
CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).
9.Flavonoids from the aerial parts of Lespedeza cuneata
Jian ZHOU ; Chuang-jun LI ; Fang-you CHEN ; Lian-qiu WU ; Jie MA ; Jing-zhi YANG ; Dong-ming ZHANG
Acta Pharmaceutica Sinica 2019;54(11):2055-2058
The chemical constituents of the aerial parts of
10.27-Hydroxycholesterol modulates lung cancer cell proliferation by activation of LXR signaling pathway
You-Yun FU ; Ting CHEN ; Xiao-Jing LIN ; Jing GAO ; Xue-Mei LIAN
Chinese Journal of Pathophysiology 2019;35(2):267-272
AIM:To investigate the effect of cholesterol metabolite 27-hydroxycholesterol (27-OHC) on the proliferation of lung cancer cells.METHODS:Human lung cancer A549 cells were treated with 27-OHC at different concentrations (0, 0.3125, 0.625, 1.25, 2.5, 5 and 10μmol/L) for 24~48 h.The cell viability, cell cycle, cell proliferation, the intracellular cholesterol levels and cholesterol metabolism-related molecule expression were subsequently assessed by CCK-8 assay, flow cytometry, Ed U staining, tissue total cholesterol detection kit, real-time PCR and Western blot.RESULTS:27-OHC decreased the viability of the A549 cells in a dose-and time-dependent manner (P<0.01) and inhibited the cell proliferation (P<0.05).The expression of typical liver X receptor (LXR) downstream target proteins including ATP-binding cassette transporter A1 (ABCA1) , low-density lipoprotein receptor (LDLR) , and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CR) were modulated, which promoted the efflux of intracellular cholesterol, and reduced cholesterol influx and de novo synthesis, resulting in decreased intracellular cholesterol levels and cell viability.Furthermore, the inhibitory effect of 27-OHC on A549 cell viability was significantly attenuated after the LXR pathway was partially blocked by 5μmol/L GSK2033 treatment (P<0.05).CONCLUSION:27-OHC inhibits A549 cell proliferation via activation of LXR signaling pathway.

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