1.Clinical significance of changes in serum complement C1q/ tumor necrosis factor-associated protein 3 levels in patients with rheumatoid arthritis
Ting ZENG ; Caiwen WEI ; Weixiang CHEN ; Lihua GU ; Yue QIAN ; Xinfeng ZHAO ; Yan SHEN
Chinese Journal of Rheumatology 2025;29(3):197-203
Objective:To investigate the changes of serum complement C1q/tumor necrosis factor-associated protein 3 (CTRP3) in patients with rheumatoid arthritis (RA) and its clinical significance.Methods:A total of 60 RA patients admitted to Chongming Hospital affiliated to Shanghai University of Medicine & Health Sciences (Chongming Branch of Xinhua Hospital) from January 2023 to February 2024 were collected.They were divided into a plaque group (38 cases) and a plaque free group (22 cases) according to the results of carotid intima-media thickness (cIMT) by carotid artery ultrasonography. ESR, CRP, blood lipid, HOMA-IR, RF, CCP antibody and CTRP3 levels were detected, and the relationship between CTRP3 levels and disease activity and atherosclerosis in RA patients was analyzed. The statistical analysis was carried out with independent t-test, analysis of variance, Pearson correlation analysis and logistic regression. Results:Serum CTRP3 level in RA patients was lower than that in healthy control group [(116±44)ng/ml and (184±63)ng/ml, t=-6.54, P=0.004]. The CTRP3 level in RA group with plaque was lower than that in RA group without plaque [(98±28) ng/ml and (123±38)ng/ml, t=-5.57, P=0.008]. Serum CTRP3 levels in RA patients were correlated with LDL-C ( r=-0.68, P=0.011), HOMA-IR ( r=-0.74, P=0.001), RF ( r=-0.46, P=0.042), anti-CCP antibody( r=-0.54, P=0.037), DAS28 ( r=-0.66, P=0.024) were negatively correlated with cIMT ( r=-0.76, P=0.001), and positively correlated with DMARDs duration ( r=0.51, P=0.040) and flow-mediated di latatiton ( r=0.70, P=0.004). The CTRP3 level [( OR(95% CI)=0.683(0.355, 0.807), P=0.023] was an independent correlation factor affecting cIMT. Conclusion:CTRP3 level in RA patients is significantly lower than that in healthy control group, and is negatively correlated with insulin resistance, autoantibody level and disease activity, and has a protective effect on early atherosclerosis in RA patients.
2.Characteristics of injury cases in Longhua District
CHEN Shaoyun ; CAO Sijing ; HUO Yongqi ; GU Chaonan ; YAN Xinfeng ; YU Chuanning
Journal of Preventive Medicine 2025;37(9):950-954,958
Objective:
To understand the characteristics of injury cases in Longhua District, Shenzhen City, Guangdong Province from 2021 to 2024, so as to provide the evidence for the development of injury prevention and control measures.
Methods:
The data of injury cases in the first visit due to injury in the sentinel hospitals of Longhua District from 2021 to 2024 were collected from the Shenzhen Injury Surveillance System. The time, cause, place, activity, intention, nature, position, severity, and outcome of injury were described.
Results:
From 2021 to 2024, a total of 167 524 injury cases were reported in Longhua District, with a male-to-female ratio of 1.89∶1. The incidence of injuries was higher in cases aged 30-<45 years (49 957 cases, 29.82%). Injuries mainly occurred from July to August (31 272 cases, 18.67%). The main cause of injury was falls (52 048 cases, 31.07%). Injuries mainly occurred at home (64 110 cases, 38.27%). Leisure activities were the main activities when injuries occurred (79 008 cases, 47.16%). Most of the injuries were unintentional (159 173 cases, 95.02%). The main type of injury was contusion/abrasion (71 900 cases, 42.92%). The main injury site was upper limb (64 247 cases, 38.35%). Most injuries were mild (131 369 cases, 78.42%). The main injury outcome was discharge after treatment, 160 882 cases (96.04%). The second cause of male injury was blunt force injury (30 140 cases, 27.49%), and the second cause of female injury was animal injury (14 648 cases, 25.31%). Fall was the leading cause of injury in people aged 0-<15 years and ≥65 years, and blunt force injury was the leading cause of injury in people aged 15-<65 years. The second place for male injuries was industrial and construction places (23 722 cases, 21.64%), and for female injuries was school/public places (9 644 cases, 16.66%). The first place for injuries in people aged 45-<65 years was in industrial and construction places. The proportions of fractures, moderate injuries, and hospitalizations increased with age (all P<0.05).
Conclusions
The main injury cases in Longhua District were males and people aged 30-<45 years. July and August were a period of high risk for injuries. People aged 0-<15 years and ≥65 years were the high-risk groups of falls. More attention should be paid to the fracture risk in the elderly.
3.The Role of APOE in Drug Resistance of Colon Cancer Based on Bioinformatics and Cell Experiments
Ruo SHU ; Huayou LUO ; Lijun SONG ; Yu GAO ; Yan HOU ; Xinfeng ZHANG ; Ying LI
Journal of Kunming Medical University 2025;46(9):15-22
Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.
4.Correlation analysis between serum adiponectin level and early vascular aging
Rui HU ; Yan WANG ; Jinyan REN ; Xinfeng WANG ; Yihan WANG ; Weifen CHEN ; Jinpeng CONG
Chinese Journal of Postgraduates of Medicine 2025;48(3):243-249
Objective:To study the relationship between serum adiponectin level and early vascular aging (EVA).Methods:The cross-sectional study method was used. Six hundred and seventy-two subjects who completed health checkup from June to December 2023 in the Affiliated Hospital of Qingdao University were selected. The subjects were divided into the EVA group (237 cases) and the control group (435 cases) based on brachial-ankle pulse wave velocity (baPWV). According to the adiponectin tertiles method, the subjects were divided into low adiponectin subgroup (2.4 to 6.6 mg/L, 225 cases), medium adiponectin subgroup (6.7 to 9.1 mg/L, 227 cases) and high adiponectin subgroup (9.2 to 19.8 mg/L, 220 cases). The basic demographic information, past history and serological indexes were recorded. Univariate and multivariate binary Logistic regression analyses were used to analyze the risk factors for EVA, and multivariate Logistic regression was used to analyze the effect of adiponectin on EVA.Results:The male proportion, age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, triglycerides (TG), fasting blood glucose (FBG), uric acid, glycated hemoglobin (HbA 1c), homocysteine, baPWV and alcohol history proportion in EVA group were significantly higher than those in control group: 64.98% (154/237) vs. 53.33% (232/435), 53 (47, 57) years old vs. 46 (39, 52) years old, (26.34 ± 3.37) kg/m 2 vs. (25.16 ± 3.91) kg/m 2, (132.27 ± 15.48) mmHg (1 mmHg = 0.133 kPa) vs. (117.30 ± 13.04) mmHg, (81.79 ± 11.04) mmHg vs. (71.93 ± 10.10) mmHg, 1.45 (1.03, 2.03) mmol/L vs. 1.08 (0.76, 1.65) mmol/L, 5.52 (5.03, 6.21) mmol/L vs. 5.14 (4.77, 5.56) mmol/L, (380.04 ± 96.43) μmol/L vs. (362.18 ± 94.94) μmol/L, 5.80 (5.50, 5.90)% vs. 5.70 (5.40, 5.82)%, 10.70 (9.01, 12.90) μmol/L vs. 9.96 (8.30, 12.20) μmol/L, 1 586 (1 511, 1 719) cm/s vs. 1 299 (1 215, 1 367) cm/s and 19.41% (46/237) vs. 13.56% (59/435), the adiponectin was significantly lower than that in control group: 7.00 (5.70, 8.75) mg/L vs. 8.40 (6.40, 10.60) mg/L, and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine and smoking history proportion between two groups ( P>0.05). The male proportion, BMI, systolic blood pressure, diastolic blood pressure, TG, FBG, uric acid, creatinine, HbA 1c, homocysteine, EVA incidence, baPWV, smoking history proportion and alcohol history proportion in low adiponectin subgroup and medium adiponectin subgroup were significantly higher than those in high adiponectin subgroup, furthermore, the indexes except HbA 1c in low adiponectin subgroup were significantly higher than those in medium adiponectin subgroup, and there were statistical differences ( P<0.05); the HDL-C in low adiponectin subgroup and medium adiponectin subgroup was significantly lower than that in high adiponectin subgroup, furthermore, that in low adiponectin subgroup was significantly lower than that in medium adiponectin subgroup, and there were statistical differences ( P<0.05); there were no statistical differences in age, TC and LDL-C among the three subgroups ( P>0.05). Univariate binary Logistic regression analysis result showed that age, male, BMI, alcohol history, systolic blood pressure, diastolic blood pressure, TG, FBG, uric acid and HbA 1c were the risk factors for EVA ( P<0.01 or <0.05), while the adiponectin was a protective factor for EVA ( P<0.01). Multivariate binary Logistic regression analysis result showed that age, systolic blood pressure, TG and FBG were risk factors for EVA ( OR = 1.098, 1.066, 1.209 and 1.268; 95% CI 1.069 to 1.127, 1.050 to 1.082, 1.007 to 1.451 and 1.069 to 1.502; P<0.01 or <0.05), while adiponectin was a protective factor ( OR = 0.892, 95% CI 0.828 to 0.962, P<0.01). Multivariable Logistic regression analysis result showed that adiponectin consistently remained a protective factor for EVA across unadjusted, preliminary adjusted and fully adjusted covariate models ( OR = 0.553, 0.580 and 0.576; 95% CI 0.451 to 0.678, 0.440 to 0.764 and 0.435 to 0.763; P<0.01). Conclusions:The serum APN level is negatively correlated with the risk of EVA, which may be an independent protective factor for the EVA.
5.Correlation analysis between serum adiponectin level and early vascular aging
Rui HU ; Yan WANG ; Jinyan REN ; Xinfeng WANG ; Yihan WANG ; Weifen CHEN ; Jinpeng CONG
Chinese Journal of Postgraduates of Medicine 2025;48(3):243-249
Objective:To study the relationship between serum adiponectin level and early vascular aging (EVA).Methods:The cross-sectional study method was used. Six hundred and seventy-two subjects who completed health checkup from June to December 2023 in the Affiliated Hospital of Qingdao University were selected. The subjects were divided into the EVA group (237 cases) and the control group (435 cases) based on brachial-ankle pulse wave velocity (baPWV). According to the adiponectin tertiles method, the subjects were divided into low adiponectin subgroup (2.4 to 6.6 mg/L, 225 cases), medium adiponectin subgroup (6.7 to 9.1 mg/L, 227 cases) and high adiponectin subgroup (9.2 to 19.8 mg/L, 220 cases). The basic demographic information, past history and serological indexes were recorded. Univariate and multivariate binary Logistic regression analyses were used to analyze the risk factors for EVA, and multivariate Logistic regression was used to analyze the effect of adiponectin on EVA.Results:The male proportion, age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, triglycerides (TG), fasting blood glucose (FBG), uric acid, glycated hemoglobin (HbA 1c), homocysteine, baPWV and alcohol history proportion in EVA group were significantly higher than those in control group: 64.98% (154/237) vs. 53.33% (232/435), 53 (47, 57) years old vs. 46 (39, 52) years old, (26.34 ± 3.37) kg/m 2 vs. (25.16 ± 3.91) kg/m 2, (132.27 ± 15.48) mmHg (1 mmHg = 0.133 kPa) vs. (117.30 ± 13.04) mmHg, (81.79 ± 11.04) mmHg vs. (71.93 ± 10.10) mmHg, 1.45 (1.03, 2.03) mmol/L vs. 1.08 (0.76, 1.65) mmol/L, 5.52 (5.03, 6.21) mmol/L vs. 5.14 (4.77, 5.56) mmol/L, (380.04 ± 96.43) μmol/L vs. (362.18 ± 94.94) μmol/L, 5.80 (5.50, 5.90)% vs. 5.70 (5.40, 5.82)%, 10.70 (9.01, 12.90) μmol/L vs. 9.96 (8.30, 12.20) μmol/L, 1 586 (1 511, 1 719) cm/s vs. 1 299 (1 215, 1 367) cm/s and 19.41% (46/237) vs. 13.56% (59/435), the adiponectin was significantly lower than that in control group: 7.00 (5.70, 8.75) mg/L vs. 8.40 (6.40, 10.60) mg/L, and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine and smoking history proportion between two groups ( P>0.05). The male proportion, BMI, systolic blood pressure, diastolic blood pressure, TG, FBG, uric acid, creatinine, HbA 1c, homocysteine, EVA incidence, baPWV, smoking history proportion and alcohol history proportion in low adiponectin subgroup and medium adiponectin subgroup were significantly higher than those in high adiponectin subgroup, furthermore, the indexes except HbA 1c in low adiponectin subgroup were significantly higher than those in medium adiponectin subgroup, and there were statistical differences ( P<0.05); the HDL-C in low adiponectin subgroup and medium adiponectin subgroup was significantly lower than that in high adiponectin subgroup, furthermore, that in low adiponectin subgroup was significantly lower than that in medium adiponectin subgroup, and there were statistical differences ( P<0.05); there were no statistical differences in age, TC and LDL-C among the three subgroups ( P>0.05). Univariate binary Logistic regression analysis result showed that age, male, BMI, alcohol history, systolic blood pressure, diastolic blood pressure, TG, FBG, uric acid and HbA 1c were the risk factors for EVA ( P<0.01 or <0.05), while the adiponectin was a protective factor for EVA ( P<0.01). Multivariate binary Logistic regression analysis result showed that age, systolic blood pressure, TG and FBG were risk factors for EVA ( OR = 1.098, 1.066, 1.209 and 1.268; 95% CI 1.069 to 1.127, 1.050 to 1.082, 1.007 to 1.451 and 1.069 to 1.502; P<0.01 or <0.05), while adiponectin was a protective factor ( OR = 0.892, 95% CI 0.828 to 0.962, P<0.01). Multivariable Logistic regression analysis result showed that adiponectin consistently remained a protective factor for EVA across unadjusted, preliminary adjusted and fully adjusted covariate models ( OR = 0.553, 0.580 and 0.576; 95% CI 0.451 to 0.678, 0.440 to 0.764 and 0.435 to 0.763; P<0.01). Conclusions:The serum APN level is negatively correlated with the risk of EVA, which may be an independent protective factor for the EVA.
6.Clinical significance of changes in serum complement C1q/ tumor necrosis factor-associated protein 3 levels in patients with rheumatoid arthritis
Ting ZENG ; Caiwen WEI ; Weixiang CHEN ; Lihua GU ; Yue QIAN ; Xinfeng ZHAO ; Yan SHEN
Chinese Journal of Rheumatology 2025;29(3):197-203
Objective:To investigate the changes of serum complement C1q/tumor necrosis factor-associated protein 3 (CTRP3) in patients with rheumatoid arthritis (RA) and its clinical significance.Methods:A total of 60 RA patients admitted to Chongming Hospital affiliated to Shanghai University of Medicine & Health Sciences (Chongming Branch of Xinhua Hospital) from January 2023 to February 2024 were collected.They were divided into a plaque group (38 cases) and a plaque free group (22 cases) according to the results of carotid intima-media thickness (cIMT) by carotid artery ultrasonography. ESR, CRP, blood lipid, HOMA-IR, RF, CCP antibody and CTRP3 levels were detected, and the relationship between CTRP3 levels and disease activity and atherosclerosis in RA patients was analyzed. The statistical analysis was carried out with independent t-test, analysis of variance, Pearson correlation analysis and logistic regression. Results:Serum CTRP3 level in RA patients was lower than that in healthy control group [(116±44)ng/ml and (184±63)ng/ml, t=-6.54, P=0.004]. The CTRP3 level in RA group with plaque was lower than that in RA group without plaque [(98±28) ng/ml and (123±38)ng/ml, t=-5.57, P=0.008]. Serum CTRP3 levels in RA patients were correlated with LDL-C ( r=-0.68, P=0.011), HOMA-IR ( r=-0.74, P=0.001), RF ( r=-0.46, P=0.042), anti-CCP antibody( r=-0.54, P=0.037), DAS28 ( r=-0.66, P=0.024) were negatively correlated with cIMT ( r=-0.76, P=0.001), and positively correlated with DMARDs duration ( r=0.51, P=0.040) and flow-mediated di latatiton ( r=0.70, P=0.004). The CTRP3 level [( OR(95% CI)=0.683(0.355, 0.807), P=0.023] was an independent correlation factor affecting cIMT. Conclusion:CTRP3 level in RA patients is significantly lower than that in healthy control group, and is negatively correlated with insulin resistance, autoantibody level and disease activity, and has a protective effect on early atherosclerosis in RA patients.
7.Modern Thinking on the Indications of Daoyin (导引) based on the Theory of "Wei (痿) Diseases should be Treated by Daoyin"
Yan YU ; Xueyin CHEN ; Lihong YANG ; Shaonan LIU ; Yu CHEN ; Lixiang LIU ; Ping YUE ; Jinpeng WU ; Xinfeng GUO
Journal of Traditional Chinese Medicine 2024;65(11):1170-1173
It has been proposed by Basic Questions On Proper Therapies for Different Diseases Geographically (《素问·异法方宜论篇》) that "wei (痿) diseases should be treated by Daoyin (导引)". Furthermore, it is clarified that the indications of Daoyin are those conditions related to spleen and dampness caused by dampness pathogen, excessive food intake and less exercise, and mainly manifested as heavy limbs, fatigue and flaccidity, which is similar to the metabolic imbalance in the early stage of glucose or lipid metabolism disorder in modern medicine. Based on modern clinical and basic research evidence, Daoyin can inhibit the response of inflammation, alleviate oxidative stress, regulate intestinal microbiota, and modulate gene expression to improve metabolic abnormalities, and this will provide ideas for researches on the indications of Daoyin.
8.Experimental study on metformin enhancing the sensitivity of colon cancer cells to 5-FU through CXCR4/Akt signaling pathway
Hongxia YAN ; Linxiu HE ; Xinfeng CAI ; Yixun ZHANG
Cancer Research and Clinic 2024;36(12):919-927
Objective:To investigate the effect of metformin on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and its possible mechanism.Methods:Colon cancer cell lines HCT-116 and HT-29 were cultured in vitro, and the CCK-8 method was used to determine cell viability after intervention with different concentrations (1.25, 2.5, 5, 10, 20, 40, 80 mmol/L) of metformin hydrochloride (MET-HCl) or different concentrations (1.25, 2.5, 5, 10, 20, 40 μmol/L) of 5-FU. The survival rate and 48-hour half maximal inhibitory concentration ( IC50) of the two drugs were calculated. The combined index (CI) of MET-HCl and 5-FU was calculated using the Chou-Talalay model, and the concentrations of MET-HCl and 5-FU in subsequent experiments were determined based on the concentration of the two drugs when the inhibition rate (Fa) was 0.5. The CCK-8 method and Annexin V-FITC/PI flow cytometry were used to detect the survival rate and apoptosis rate of HCT-116 cells or HT-29 cells treated with the two drugs alone and in combination at experimental concentrations, respectively. Cells treated with drug free culture flnid were used as the control group. CXCR4 specific small interfering RNA (siRNA) was transfected into HCT-116 cells and HT-29 cells, and the decreased ( P < 0.05) expression of CXCR4 protein detected by Western blotting indicated successful knockdown of CXCR4. CCK-8 method was used to detect the survival rate of cells with CXCR4 knockdown by two drugs alone and in combination, and the untransfected cells added drug free culture fluid were served as the si-control group. Western blotting was used to detect the expression of proteins related to the CXCR4/Akt signaling pathway in HCT-116 cells or HT-29 cells treated with two drugs alone or in combination. Results:CCK-8 assay showed that MET-HCl and 5-FU decreased the viability of HCT-116 and HT-29 cells in a concentration-time-dependent manner; at 48 h, IC50 of MET-HCl and 5-FU in HCT-116 cells were (13.0±5.8) mmol/L and (16.9±7.2) μmol/L, respectively, and IC50 in HT-29 cells were (8.6±2.8) mmol/L and (9.7±3.1) μmol/L, respectively. When the cell inhibition rates of HCT-116 cells or HT-29 cells detected by CCK-8 method were 50%, 75% and 90% after 48 h of treatment, the corresponding CI values of HCT-116 cells were 0.48, 0.37 and 0.25, and HT-29 cells were 0.57, 0.51 and 0.49, suggesting that the combination of the two drugs had a synergistic effect. Based on Fa = 0.5, the experimental concentrations of MET-HCl and 5-FU were determined to be 10 mmol/L and 5 μmol/L. CCK-8 method showed that after HCT-116 cells or HT-29 cells were treated with 10 mmol/L MET-HCl, 5 μmol/L 5-FU alone or in combination for 48 h, the cell viability of each drug group was lower than that of the control group (all P < 0.05), there was no statistically significant difference in cell viability between MET-HCl alone and 5-FU alone (both P > 0.05), and the cell viability of the combination of the two drugs was lower than that of the two drugs alone (both P < 0.01). After CXCR4 was knocked down, the cell viability of each drug group was lower than that of the si-control group (all P < 0.05), but there was no significant difference in cell viability between the two drugs alone and the combination of the two drugs (all P > 0.05). Flow cytometry showed that after 24 h of treatment, the apoptosis rate of HCT-116 cells or HT-29 cells treated with MET-HCl alone or the combination of the two drugs was higher than that of the control group (all P < 0.05), but there was no statistically significant difference in the apoptosis rate of cells treated with 5-FU alone compared to the control group (all P > 0.05); the apoptosis rate of HCT-116 cells treated with the combination of the two drugs was higher than that of the two drugs alone (both P < 0.05); the apoptosis rate of HT-29 cells treated with the combination of the two drugs was higher than that of 5-FU alone ( P < 0.05), but there was no significant difference with MET-HCl alone ( P > 0.05). Western blotting showed that the relative expression levels of CXCR4, p-Akt and XRCC1 proteins in HCT-116 or HT-29 cells treated with MET-HCl alone and in combination of two drugs were lower than those in the control group (all P < 0.05), but there was no statistically significant difference in the relative expression levels of the 3 proteins in the two cell lines treated with 5-FU alone compared to the control group (all P > 0.05); the relative expression levels of the 3 proteins in the two cell lines treated with MET-HCl alone and in combination of two drugs were lower than those treated with 5-FU alone (all P < 0.05), the relative expression levels of CXCR4 and p-Akt proteins in the two cell lines treated with the combination of two drugs were lower than those treated with MET-HCl alone (all P < 0.05), and the relative expression level of XRCC1 protein in HCT-116 cells treated with the combination of two drugs was lower than that in HCT-116 cells treated with MET-HCl alone ( P < 0.05), but there was no significant difference in the relative expression level of XRCC1 protein in HT-29 cells treated with the combination of two drugs and MET-HCl alone ( P > 0.05). Conclusions:MET-HCl may reduce the expression of XRCC1 through the CXCR4/Akt signaling pathway, thereby enhancing the sensitivity of colon cancer cells to 5-FU.
9.Correlation between longitudinal change trajectory of white blood cell and new-onset type 2 diabetes mellitus: a cohort study
Xinfeng WANG ; Fei GAO ; Ying SUN ; Shaoyou JIA ; Rui HU ; Weifen CHEN ; Jinyan REN ; Yan WANG
Chinese Journal of Health Management 2024;18(11):855-860
Objective:To explore the relationship between the longitudinal change trajectory of white blood cell (WBC) and new-onset type 2 diabetes mellitus(T2DM).Methods:It was a prospective cohort study. A total of 2 792 people who underwent health examinations at the Health Management Center of the Affiliated Hospital of Qingdao University from January 2019 to December 2023 for five consecutive years and met the research standards were selected as the study subjects. Group-based trajectory modeling (GBTM) was established. The target population was divided into three groups based on the longitudinal change trajectory of WBC: low-stable group, medium-stable group and high-stable group. The cumulative incidence of T2DM in the three groups were analyzed. Multivariate Cox proportional risk regression models were used to analyze the correlation between different WBC trajectory groups and the risk of T2DM in total population, males and females. A restricted cubic spline regression (RCS) model was used to analyze the dose-response relationship between baseline WBC and risk of T2DM.Results:The cumulative incidence rate of T2DM in low-stable group, medium-stable group and high-stable group increased gradually, which was 2.5%, 5.3% and 6.9%, respectively ( χ2=19.024, P<0.001). After adjusting for multiple confounding factors in the Cox proportional hazards regression model, no significant difference in the incidence risk of T2DM among the three WBC trajectory groups in males; While the hazard ratios in the high-stable and medium-stable group in women was 2.852(95% CI: 1.067-7.628) and 2.588 (95% CI: 1.133-5.912), respectively, when compared with that in the low-stable group (both P<0.05). RCS curve analysis showed a linear relationship between WBC and the risk of T2DM in female ( Pnon-linear=0.956), when the WBC count was>5.53×10 9/L, the risk of T2DM increased with the rise of WBC. Conclusion:Higher WBC trajectory is positively correlated with the risk of new-onset T2DM in female health examination population.
10.Experimental study on metformin enhancing the sensitivity of colon cancer cells to 5-FU through CXCR4/Akt signaling pathway
Hongxia YAN ; Linxiu HE ; Xinfeng CAI ; Yixun ZHANG
Cancer Research and Clinic 2024;36(12):919-927
Objective:To investigate the effect of metformin on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and its possible mechanism.Methods:Colon cancer cell lines HCT-116 and HT-29 were cultured in vitro, and the CCK-8 method was used to determine cell viability after intervention with different concentrations (1.25, 2.5, 5, 10, 20, 40, 80 mmol/L) of metformin hydrochloride (MET-HCl) or different concentrations (1.25, 2.5, 5, 10, 20, 40 μmol/L) of 5-FU. The survival rate and 48-hour half maximal inhibitory concentration ( IC50) of the two drugs were calculated. The combined index (CI) of MET-HCl and 5-FU was calculated using the Chou-Talalay model, and the concentrations of MET-HCl and 5-FU in subsequent experiments were determined based on the concentration of the two drugs when the inhibition rate (Fa) was 0.5. The CCK-8 method and Annexin V-FITC/PI flow cytometry were used to detect the survival rate and apoptosis rate of HCT-116 cells or HT-29 cells treated with the two drugs alone and in combination at experimental concentrations, respectively. Cells treated with drug free culture flnid were used as the control group. CXCR4 specific small interfering RNA (siRNA) was transfected into HCT-116 cells and HT-29 cells, and the decreased ( P < 0.05) expression of CXCR4 protein detected by Western blotting indicated successful knockdown of CXCR4. CCK-8 method was used to detect the survival rate of cells with CXCR4 knockdown by two drugs alone and in combination, and the untransfected cells added drug free culture fluid were served as the si-control group. Western blotting was used to detect the expression of proteins related to the CXCR4/Akt signaling pathway in HCT-116 cells or HT-29 cells treated with two drugs alone or in combination. Results:CCK-8 assay showed that MET-HCl and 5-FU decreased the viability of HCT-116 and HT-29 cells in a concentration-time-dependent manner; at 48 h, IC50 of MET-HCl and 5-FU in HCT-116 cells were (13.0±5.8) mmol/L and (16.9±7.2) μmol/L, respectively, and IC50 in HT-29 cells were (8.6±2.8) mmol/L and (9.7±3.1) μmol/L, respectively. When the cell inhibition rates of HCT-116 cells or HT-29 cells detected by CCK-8 method were 50%, 75% and 90% after 48 h of treatment, the corresponding CI values of HCT-116 cells were 0.48, 0.37 and 0.25, and HT-29 cells were 0.57, 0.51 and 0.49, suggesting that the combination of the two drugs had a synergistic effect. Based on Fa = 0.5, the experimental concentrations of MET-HCl and 5-FU were determined to be 10 mmol/L and 5 μmol/L. CCK-8 method showed that after HCT-116 cells or HT-29 cells were treated with 10 mmol/L MET-HCl, 5 μmol/L 5-FU alone or in combination for 48 h, the cell viability of each drug group was lower than that of the control group (all P < 0.05), there was no statistically significant difference in cell viability between MET-HCl alone and 5-FU alone (both P > 0.05), and the cell viability of the combination of the two drugs was lower than that of the two drugs alone (both P < 0.01). After CXCR4 was knocked down, the cell viability of each drug group was lower than that of the si-control group (all P < 0.05), but there was no significant difference in cell viability between the two drugs alone and the combination of the two drugs (all P > 0.05). Flow cytometry showed that after 24 h of treatment, the apoptosis rate of HCT-116 cells or HT-29 cells treated with MET-HCl alone or the combination of the two drugs was higher than that of the control group (all P < 0.05), but there was no statistically significant difference in the apoptosis rate of cells treated with 5-FU alone compared to the control group (all P > 0.05); the apoptosis rate of HCT-116 cells treated with the combination of the two drugs was higher than that of the two drugs alone (both P < 0.05); the apoptosis rate of HT-29 cells treated with the combination of the two drugs was higher than that of 5-FU alone ( P < 0.05), but there was no significant difference with MET-HCl alone ( P > 0.05). Western blotting showed that the relative expression levels of CXCR4, p-Akt and XRCC1 proteins in HCT-116 or HT-29 cells treated with MET-HCl alone and in combination of two drugs were lower than those in the control group (all P < 0.05), but there was no statistically significant difference in the relative expression levels of the 3 proteins in the two cell lines treated with 5-FU alone compared to the control group (all P > 0.05); the relative expression levels of the 3 proteins in the two cell lines treated with MET-HCl alone and in combination of two drugs were lower than those treated with 5-FU alone (all P < 0.05), the relative expression levels of CXCR4 and p-Akt proteins in the two cell lines treated with the combination of two drugs were lower than those treated with MET-HCl alone (all P < 0.05), and the relative expression level of XRCC1 protein in HCT-116 cells treated with the combination of two drugs was lower than that in HCT-116 cells treated with MET-HCl alone ( P < 0.05), but there was no significant difference in the relative expression level of XRCC1 protein in HT-29 cells treated with the combination of two drugs and MET-HCl alone ( P > 0.05). Conclusions:MET-HCl may reduce the expression of XRCC1 through the CXCR4/Akt signaling pathway, thereby enhancing the sensitivity of colon cancer cells to 5-FU.


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