4.Shikonin Inhibits Inflammation of Psoriasis Cell Model by Regulating cGAS/STING Signaling Pathway
Chong LYU ; Xianhua QIAO ; Juanjuan GAO ; Fei TIAN ; Kuilong ZHOU ; Chengcheng WANG ; Jiepeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):114-120
ObjectiveTo investigate the effect of shikosin (SHI) on psoriasis (PSO) and explore the underlying mechanism via the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodHaCaT cells were classified into normal culture(Control), a mixture of five proinflammatory cytokines(M5), low-, medium-, and high-dose SHI (L-SHI, M-SHI, and H-SHI, respectively), and SHI+ADU-S100 groups. The cells in the M5 group were stimulated with 10 μg·L-1 interleukin (IL)-1α, IL-17, IL-22, tumor necrosis factor (TNF)-α, and oncostatin M (OSM) for 48 h. The cells in the L-SHI, M-SHI, and H-SHI groups were treated with 0.1, 1, 10 μmol·L-1 SHI, respectively, on the basis of the treatment in the M5 group. The cells in the SHI+ADU-S100 group were treated with 10 μmol·L-1 STING activator ADU-S100 on the basis of the treatment in the H-SHI group. The methyl thiazolyl tetrazolium (MTT) assay and colony formation assay were employed to examine the effect of SHI on the proliferation of HaCaT cells. The wound healing assay was employed to examine the effect of SHI on the migration of HaCaT cells. Flow cytometry was employed to detect the effect of SHI on the apoptosis of HaCaT cells. Enzyme-linked immunosorbent assay was employed to measure the levels of IL-1β, IL-6, IL-15, IL-23, and interferon-γ (IFN-γ) in HaCaT cells. Western blot was employed to determine the protein levels of cGAS and STING in HaCaT cells. ResultCompared with Control group, the M5 group showed decreased survival rate, colony formation, and would healing rate of HaCaT cells, increased apoptosis rate, elevated levels of IL-1β, IL-6, IL-15, IL-23, and IFN-γ, and up-regulated protein levels of cGAS and STING (P<0.01). Compared with the M5 group, the L-SHI, M-SHI, and H-SHI groups showed increased survival rate, cell colony formation, and wound healing rate, decreased apoptosis rate, lowered levels of IL-1β, IL-6, IL-15, IL-23, and IFN-γ, and down-regulated protein levels of cGAS and STING (P<0.01). Compared with the H-SHI group, the SHI+ADU-S100 group showed decreased survival rate, cell colony formation, and wound healing rate, increased apoptosis rate, risen levels of IL-1β, IL-6, IL-15, IL-23, and IFN-γ, and up-regulated protein levels of cGAS and STING (P<0.01). ConclusionSHI can inhibit the inflammation in the cell model of PSO by inhibiting the cGAS/STING signaling pathway.
5.Construction and practice of an informatization management system for institutional ethical review
Luyuan ZHANG ; Chong LI ; Zhiyong DENG ; Hongying LI ; Xiaoxu ZHU ; Min CHEN ; Weiling LYU ; Mo ZHOU
Chinese Medical Ethics 2024;37(2):219-223
With the progress of society,the global development of scientific and technical research activities,and the increasing number of medical Institutional Review Board(IRB)review projects,the construction and management of electronic informatization have become extremely important.In the process of electronic information construction in institutional ethics review,it is necessary to take into account the new policy of ethical governance of science and technology,consider the system and standard operating procedures of IRB,and develop reasonable processes based on practical work,simplify manual operation,improve the accuracy of project management,achieve refined management,and facilitate communication among researchers,ethics committee secretaries,and members.
6.Association between serum ferritin levels and body fat distribution in patients with type 2 diabetes mellitus
Chong-Yang CHEN ; Xiao-Yu LYU ; Yang-Ting ZHAO ; Lu-Xia LIU ; Ya-Wen WANG ; Kai LI ; Jing-Fang LIU
Medical Journal of Chinese People's Liberation Army 2024;49(4):380-386
Objective To explore the relationship between serum ferritin levels and body fat distribution in patients with type 2 diabetes mellitus(T2DM).Methods A retrospective analysis was conducted on 151 patients with T2DM who were hospitalized in the Department of Endocrinology of the First Hospital of Lanzhou University from June to November 2020,and all the patients were divided into high serum ferritin(n=50)and normal serum ferritin(n=101)groups according to their serum ferritin levels.The visceral fat area(VFA),subcutaneous fat area(SFA),liver fat,height,weight and waist circumference(WC)were measured,as well as blood glucose,lipid indexes,body mass index(BMI)and visceral adiposity index(VAI)were also calculated.t-test or nonparametric test was used to compare the differences between the two groups,and the relationship between serum ferritin levels and body fat distribution was analyzed by Pearson or Spearman correlation analysis,multiple linear regression and logistic regression.Results The VAI and WC were significantly higher in high serum ferritin group[3.13(2.16,4.58)and(96.66±7.78)cm]than in normal serum ferritin group[2.66(1.66,3.81)and(91.96±9.75)cm,P<0.05].The prevalence of central obesity and dyslipidemia was higher in high serum ferritin group(88.0%and 90.0%)than in normal serum ferritin group(68.3%and 75.2%);and the composition ratios of poor glycemic control and insulin resistance(96.0%and 62.0%)were also higher than in normal serum ferritin group(78.2%and 40.6%)(P<0.05),there were no statistically significant differences in BMI,VFA,and SFA levels,as well as antidiabetic drug use and chronic complications of diabetes mellitus between the two groups(P>0.05).Serum ferritin levels in T2DM patients were positively correlated with VAI,WC,triglyceride(TG),fasting blood glucose(FPG),HbA1c,dyslipidemia and serum creatinine(r=0.171,0.207,0.187,0.243,0.270,0.162,0.162;P<0.05),and negatively correlated with age,sex and diabetes course(r=-0.191,-0.434,-0.352;P<0.05).Multivariate linear regression analysis showed that in male T2DM patients,duration of diabetes and FPG were risk factors for increased levels of serum ferritin.However,WC and VAI did not significantly affect serum ferritin levels.In female patients with T2DM,the course of diabetes,TG and VAI were the factors influencing serum ferritin(P<0.05).Conclusion Dyslipidemia and visceral fat accumulation are risk factors for elevated serum ferritin levels in female T 2DM patients.
7.Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages
Xiaomin LIU ; Hongyuan DUAN ; Dongqi ZHANG ; Chong CHEN ; Yuting JI ; Yunmeng ZHANG ; Zhuowei FENG ; Ya LIU ; Jingjing LI ; Yu ZHANG ; Chenyang LI ; Yacong ZHANG ; Lei YANG ; Zhangyan LYU ; Fangfang SONG ; Fengju SONG ; Yubei HUANG
Chinese Journal of Oncology 2024;46(4):354-364
Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (<60, 60-<70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.
8.Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages
Xiaomin LIU ; Hongyuan DUAN ; Dongqi ZHANG ; Chong CHEN ; Yuting JI ; Yunmeng ZHANG ; Zhuowei FENG ; Ya LIU ; Jingjing LI ; Yu ZHANG ; Chenyang LI ; Yacong ZHANG ; Lei YANG ; Zhangyan LYU ; Fangfang SONG ; Fengju SONG ; Yubei HUANG
Chinese Journal of Oncology 2024;46(4):354-364
Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (<60, 60-<70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.
9.Impact of ERCC1 C8092A gene polymorphism on the efficacy of platinum-based chemotherapy for lung cancer
LI Yixuan ; WANG Yiwei ; FU Yihui ; MENG Chong ; KUANG Shicheng ; LYU Pengfei ; ZHOU jing ; XU Qiongjun ; HUANG Hairong ; XIAO Sha
China Tropical Medicine 2024;24(1):65-
Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.
10.Diagnostic and intervention value of implantable cardiac monitor in patients over 60 years of age with unexplained syncope
Rui WANG ; Yanfei ZHANG ; Hongchao ZHANG ; Jia WANG ; Shuhui SHEN ; Jiabin TONG ; Junpeng LIU ; You LYU ; Jia CHONG ; Zhilei WANG ; Xin JIN ; Lin SUN ; Xu GAO ; Yan DAI ; Jing LIANG ; Haitao LI ; Tong ZOU ; Jiefu YANG
Chinese Journal of Cardiology 2024;52(7):784-790
Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

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