1.Study on the Effect of Liuwei Dihuang Pills on Regulating the Antigen Cross-Presenting Ability of Dendritic Cells by Interfering with Gap Junctional Communication Function
Yue SONG ; Man-Si XU ; Xue-Ying ZHONG ; Wen-Jing ZHANG ; Xiao-Yi CHEN ; Biao-Yan DU ; Jian-Yong XIAO ; Kun WANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):169-177
Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.
2.Mechanism of peimine improving chronic obstructive pulmonary disease induced by lipopolysaccharide combined with cigarette smoke in mice
Pei CHEN ; Xiao-Ju CHEN ; Zhu-Man DU ; Cao-Hui WANG
Acta Anatomica Sinica 2024;55(2):215-221
Objective To investigate the effects and mechanisms of peimine(PME)on chronic obstructive pulmonary disease(COPD)in mice.Methods The mice were randomly divided into 4 groups(20 mice in each group),control group,PME group,chronic obstructive pulmonary disease group and treatment group.Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke.The effects of PME on COPD model mice was analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on COPD model mice were analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on inflammatory factor tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting.The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium(DHE)staining and Western blotting.The effects of PME on nuclear factor kappa-B(NF-κB)pathway and nuclear factor erythroid 2-related factor 2(Nrf2)pathway were analyzed by protein immunoblotting.Results Compared with the COPD group,PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice,and the wet/dry weight ratio of lung tissue was significantly reduced.Compared with the control group,the levels of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced.In addition,compared with the control group,the protein expression of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced.Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2)protein in COPD group was significantly lower than that in control group,while PME treatment could improve the level of superoxide dismutase protein.The analysis of MDA content in lung tissue showed that compared with the COPD group,the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment.Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα)and the transfer of NF-κB p65 to the cell nucleus,and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1)in the lung tissue of mice treated with PME significantly increased.Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.
3.Clinical trial of compound sabal berry tablet in the treatment of patients with bladder discomfort after electrocision of benign prostatic hyperplasia
Yu-Feng DU ; Huang-Hui CHEN ; Qun-Jie TAN ; Xiao-Yong GUO
The Chinese Journal of Clinical Pharmacology 2024;40(18):2670-2674
Objective To observe the effects of compound sabal berry tablet on bladder discomfort(BD)after electrocision of benign prostatic hyperplasia(BPH).Methods Patients with BPH undergoing transurethral resection of the prostate were divided into treatment group and control group.The control group was treated with tamsulosin hydrochloride sustained-release capsules(0.2 mg,qd)on the day after surgery,while treatment group was treated with compound sabal berry tablets(0.5 g,tid)on basis of control group.All patients were treated for 4 weeks.The clinical curative effect,prostate symptoms,overactive bladder symptoms,changes of urodynamics[maximum detrusor pressure(MDP),maximum urine flow rate(Qmax),maximum cystometric capacity(MCC)],occurrence of BD,inflammatory response indexes[interleukin-6(IL-6),IL-17,tumor necrosis factor-α(TNF-α)]and safety were compared between the two groups.Results There were 45 cases in control group and 49 cases in treatment group.After treatment,total response rate of treatment group was higher than that of control group[95.92%(47 cases/49 cases)vs 82.22%(37 cases/45 cases)],the differences were statistically significant(P<0.05).After treatment,international prostate symptom scores(IPSS)in treatment group and control group were(7.62±1.38)and(10.49±2.05)points;overactive bladder symptom scores(OABSS)were(2.78±0.64)and(3.92±0.72)points;MDP were(32.09±5.12)and(28.32±4.69)cmH2O;Qmax were(18.42±2.53)and(15.37±2.18)mL·s-1;MCC were(289.46±36.81)and(261.42±33.54)mL;incidence of BD were 18.37%(9 cases/49 cases)and 37.78%(17 cases/45 cases);levels of serum IL-6 were(11.34±2.09)and(15.03±2.56)pg·mL-1;levels of serum IL-17 were(30.12±4.73)and(37.57±5.01)pg·mL-1;levels of serum TNF-α were(82.06±12.95)and(98.63±15.70)pg·mL-1.The differences were statistically significant in the above indexes between the treatment group and control group(all P<0.05).The adverse drug reactions in treatment group were mainly on dizziness,rash,nausea and diarrhea,while adverse drug reactions in control group were mainly on dizziness,rash and diarrhea.There was no significant difference in the incidence of adverse reactions between the two groups[10.20%(5 cases/49 cases)vs 8.89%(4 cases/45 cases),P>0.05].Conclusion Compound sabal berry tablet can relieve prostate symptoms and overactive bladder symptoms,improve urodynamics,reduce BD and alleviate inflammatory response in BPH patients after transurethral resection of the prostate.
4.Bioequivalence study of rasagiline mesylate tablets in Chinese healthy subjects
Gang CHEN ; Xiao-Lin WANG ; Si-Qi ZANG ; Ze-Juan WANG ; Xiao-Na LIU ; Ai-Hua DU ; Min LI ; Ya-Nan ZHANG ; Dan ZHANG ; Li-Na ZHANG ; Jin WANG
The Chinese Journal of Clinical Pharmacology 2024;40(19):2885-2890
Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90%confidence interval(CI)of the geometric mean ratio(GMR)were 94.11%-118.06%,99.22%-107.74%and 99.16%-107.44%for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00%-125.00%.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90%CI of GMR were 96.99%-101.19%and 97.17%-101.41%for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00%-125.00%.The 95%upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00%-125.00%.The incidence of adverse events in fasting and fed studies was 22.86%and 22.92%,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.
5.Interpretation of specification for service of cancer screening for workers
Hongda CHEN ; Bin LU ; Ying ZHENG ; Peng DU ; Xiao QI ; Kai ZHANG ; Yuying LIU ; Junli WEI ; Donghua WEI ; Jiyong GONG ; Yunchao HUANG ; Zhenya SONG ; Xi CHU ; Dong DONG ; Wenjing ZHENG ; Min DAI
Chinese Journal of Epidemiology 2024;45(4):486-489
As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.
6.Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China
Yalei KE ; Lang PAN ; Jun LYU ; Dianjianyi SUN ; Pei PEI ; Yiping CHEN ; Ling YANG ; Huaidong DU ; Robert CLARKE ; Junshi CHEN ; Zhengming CHEN ; Xiao ZHANG ; Ting CHEN ; Runqin LI ; Litong QI ; Liming LI ; Canqing YU
Chinese Journal of Epidemiology 2024;45(6):779-786
Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.
7.Physical performance evaluated by the timed up and go test and its correlation with sleep in the elderly in China
Yu DU ; Xinxin MA ; Jingjing DUAN ; Jianhong XIAO ; Jian LIN ; Xiong'ang HUANG ; Chao LIU ; Binbin WANG ; Ting DENG ; Tao CHEN ; Wen SU
Chinese Journal of Geriatrics 2024;43(1):29-33
Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.
8.Correlation Analysis Between Ultrasound Ossification Ratio and Exercise Intensity in Adolescents
Li ZHANG ; Hanze DU ; Yixuan ZHANG ; Yamei YANG ; Zeqing ZHAO ; Xiaoyuan GUO ; Shi CHEN ; Hui PAN ; Xiao YANG ; Jianchu LI
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1198-1203
To evaluate the correlation between ultrasound ossification ratio(OR) and exercise intensity among adolescents. This cross-sectional study used stratified sampling to select adolescents aged 11-15 years from a sports school and some ordinary middle schools in Shandong Province in June 2023. The participants were divided into two groups: competitive sports group (high exercise intensity), and general sports group (moderate exercise intensity), based on their exercise intensity. Ultrasound images of long bones from nine body regions (including 3 upper limb bones and 6 lower limb bones) were collected for both groups. Two sonographers interpreted the images and calculated the ultrasound OR values (the ratio of ossification center length to epiphyseal length on the standard ultrasound section). The intraclass correlation coefficient (ICC) was used to assess the consistency of image interpretation between the observers. Differences in ultrasound OR values between the two groups were compared, and multivariate Logistic regression analysis was performed to assess the correlation between ultrasound OR values and exercise intensity. A total of 252 adolescents who met the inclusion and exclusion criteria were included, with 154 in the competitive sports group (97 males and 57 females) and 98 in the general sports group (52 males and 46 females). The median height and average daily exercise duration were significantly higher in the competitive sports group than in the general sports group (all The medial femoral ultrasound OR value was correlated with exercise intensity among adolescents. This indicator may serve as an objective imaging parameter for assessing whether adolescent exercise meets recommended standards.
9.Study on influencing factors of neurobehavioral development in young children suspected of developmental delays
Xiaoman LI ; Lijuan HUANG ; Xiao WANG ; Zumin LIU ; Runmin GUO ; Xueyan NONG ; Xiujuan HUANG ; Jinyuan ZHU ; Yanting CHEN ; Jinlin DU
Acta Universitatis Medicinalis Anhui 2024;59(7):1244-1250
Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven-tion of neurobehavioral development delays in young children.Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pe-diatric Heart Scale)with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays,and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale,the basic information of the young children and their mothers at the time of birth were investigated,as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected.Results A total of 271 young children were included,196 males and 75 females.Young children had the lowest developmental quotient(DQ)in the language domain among the five domains(P<0.001).Multiple lin-ear regression models showed:compared with girls,the language domain DQ of boys decreased by 5.321 points(P=0.049,95%CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95%CI:-8.316--0.631).Compared with young children via natural vaginal delivery(NVD),the gross motor domain DQ of young children via caesarean section(CS)decreased by 4.890 points(P=0.008,95%CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95%CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95%CI:-12.826--2.416),per-sonal-social domain DQ decreased by 6.232 points(P=0.001,95%CI:-10.006--2.457).The results of bi-nary logistic regression models showed,compared with young children via NVD,the risk of gross motor domain retar-dation in young children increased(OR=1.763,95%CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95%CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95%CI:1.080-10.124).Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains,boys had lower DQ in language domain and personal-social domain than girls,and the development of young children via CS was slower than that via NVD.Fo-cus should be on the language development of young children especially on the language and personal-social devel-opment of boys.Carefully chose delivery way.Focus should be placed on assessment of young children's comprehen-sive neurobehavioral development in early time.
10.Anti-glioblastoma study of YHP-836, a novel PARP1/2 inhibitor, in combination with temozolomide
Jia-ling DENG ; Ting-ting DU ; Jie ZHOU ; Bai-ling XU ; Xiao-guang CHEN ; Ming JI
Acta Pharmaceutica Sinica 2024;59(6):1656-1663
The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (


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