Objective To investigate the risk factors for cardiovascular disease(CVD)in patients with rheumatoid arthritis(RA).Methods Clinical data of 225 patients with RA admitted to the Second Affiliated Hospital of Zhengzhou University from January 2023 to September 2024 were collected,and the patients were divided into CVD group(n=50)and non-CVD group(n=175)according to whether they were complicated by CVD.Univariate and multivariate Logistic regression was used to analyze the risk factors of CVD in RA patients.Results Univariate Logistic regression analysis showed that age,hematocrit,red cell volume distribution width(RDW),erythrocyte sedimentation rate,neutrophil to high density lipoprotein ratio(NHR)and platelet to lymphocyte ratio(PLR)were all influencing factors for CVD in RA patients(P＜0.05).Multivariate Logistic regression analysis showed that age,RDW,NHR and PLR were all risk factors for CVD in RA patients(P＜0.05).The results of receiver operating characteristic curve analysis showed that the area under the curve(AUC)of age,RDW,NHR and PLR diagnosed CVD in RA patients were 0.844,0.797,0.572 and 0.713,respectively.The combined diagnosis AUC of four indexes was 0.898.Conclusion The risk of CVD in RA patients is influenced by many factors,and the combination of age,RDW,NHR,and PLR can improve early diagnosis of CVD in RA patients.

Objective:Exploring the toxic effects of aspartame (APM) exposure on mice intestine and its potential mechanisms.Methods:Animal experimental research was conducted from July 2023 to May 2024 on the exposure omics platform of the School of Public Health at Capital Medical University. Using a random number table method, 6-8-week-old male C57BL/6J mice were divided into three groups: 0 mg/kg (control group), 150 mg/kg aspartame exposure group, and 500 mg/kg aspartame exposure group, once a day. After 8 weeks of gavage, intestinal permeability tests were performed, and serum was collected from the mice for biochemistry tests. Hematoxylin-eosin staining was used to evaluate the pathological phenotype of the mice′s major organs and colorectal tissues. Transmission electron microscopy (TEM) was used to observe changes in the microscopic structure of the tight junctions in the colorectal epithelium. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence (IF) were used to analyze the mRNA levels of tight junction-related genes ( Claudin-1, Occludin, and Tjp-1) and the protein expression levels of tight junction-related proteins (Claudin-1, Occludin, and Tjp-1) in the colorectal tissues of the mice. Comparisons between data were performed using one-way analysis of variance (ANOVA). Results:There were no statistically significant differences in the serum blood biochemistry indicators of mice in the 150 mg/kg and 500 mg/kg aspartame exposure groups compared to the control group. H&E staining showed no significant pathological changes in the major organs and colorectal tissues of mice in the aspartame exposure groups. The results of the intestinal permeability assay showed statistically significant differences in serum FITC-dextran content between groups. The serum FITC-dextran content of mice in the control group and aspartame low and high dose exposure groups were (286.9±33.26), (354.9±78.88) and (350.9±37.87) ng/ml, respectively, with statistically significant differences ( F=4.486, P<0.05). Two-by-two comparisons revealed that the differences between the low or high dose groups and the control group were significant ( q=3.78,3.50, P<0.05), but there was no statistically significant difference between the low and high dose groups ( q=0.23, P>0.05).Transmission electron microscopy revealed disruption and blurred structure of tight junctions in the colorectal epithelium of mice in the low and high-dose aspartame exposure groups. The qRT-PCR results showed that the relative mRNA expression of Claudin-1 and Occludin in mice colon was significantly lower in 150 mg/kg and 500 mg/kg exposed mice, but there was no significantly difference in the expression of the mRNA between the low and high dose groups. The qRT-PCR results showed that the relative mRNA expression levels of Claudin-1 and Occludin in the colon of mice from the control group, 150 mg/kg, and 500 mg/kg aspartame exposure groups were (1.06±0.39, 0.44±0.16, 0.51±0.15) and (1.01±0.10, 0.32±0.17, 0.58±0.17), respectively. The differences were statistically significant ( F=10.26, 31.26, P<0.05). The Tukey test results indicated that the mRNA levels of Claudin-1 and Occludin in the colon of mice in the 150 mg/kg and 500 mg/kg aspartame exposure groups were significantly lower than those in the control group ( q=5.86, 5.18, 11.09, 6.78, P<0.05), but there was no statistically significant difference between the low-dose and high-dose exposure groups ( q=0.68, 4.31, P>0.05). There was no significantly difference in the mRNA expression of Tjp-1 gene in the colon of mice in all groups ( F=1.18, P>0.05). The protein levels of Claudin-1 and Occludin in the colorectal tissues of mice in the 150 mg/kg ( q=7.25, 5.62, P<0.05) and 500 mg/kg ( q=5.35, 5.66, P<0.05) aspartame exposure groups were significantly downregulated, however, there was no significantly difference in the 500 mg/kg compared to 150 mg/kg aspartame exposure group ( q=0.30, 1.64, P>0.05). And the protein level of ZO-1 showed no significant differences between groups ( F=0.43, P>0.05). Conclusion:Aspartame exposure may leads to decreased expression of colorectal tight junction genes Claudin-1 and Occludin and intestinal mechanical barrier damage in mice.

Objective:Exploring the toxic effects of aspartame (APM) exposure on mice intestine and its potential mechanisms.Methods:Animal experimental research was conducted from July 2023 to May 2024 on the exposure omics platform of the School of Public Health at Capital Medical University. Using a random number table method, 6-8-week-old male C57BL/6J mice were divided into three groups: 0 mg/kg (control group), 150 mg/kg aspartame exposure group, and 500 mg/kg aspartame exposure group, once a day. After 8 weeks of gavage, intestinal permeability tests were performed, and serum was collected from the mice for biochemistry tests. Hematoxylin-eosin staining was used to evaluate the pathological phenotype of the mice′s major organs and colorectal tissues. Transmission electron microscopy (TEM) was used to observe changes in the microscopic structure of the tight junctions in the colorectal epithelium. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence (IF) were used to analyze the mRNA levels of tight junction-related genes ( Claudin-1, Occludin, and Tjp-1) and the protein expression levels of tight junction-related proteins (Claudin-1, Occludin, and Tjp-1) in the colorectal tissues of the mice. Comparisons between data were performed using one-way analysis of variance (ANOVA). Results:There were no statistically significant differences in the serum blood biochemistry indicators of mice in the 150 mg/kg and 500 mg/kg aspartame exposure groups compared to the control group. H&E staining showed no significant pathological changes in the major organs and colorectal tissues of mice in the aspartame exposure groups. The results of the intestinal permeability assay showed statistically significant differences in serum FITC-dextran content between groups. The serum FITC-dextran content of mice in the control group and aspartame low and high dose exposure groups were (286.9±33.26), (354.9±78.88) and (350.9±37.87) ng/ml, respectively, with statistically significant differences ( F=4.486, P<0.05). Two-by-two comparisons revealed that the differences between the low or high dose groups and the control group were significant ( q=3.78,3.50, P<0.05), but there was no statistically significant difference between the low and high dose groups ( q=0.23, P>0.05).Transmission electron microscopy revealed disruption and blurred structure of tight junctions in the colorectal epithelium of mice in the low and high-dose aspartame exposure groups. The qRT-PCR results showed that the relative mRNA expression of Claudin-1 and Occludin in mice colon was significantly lower in 150 mg/kg and 500 mg/kg exposed mice, but there was no significantly difference in the expression of the mRNA between the low and high dose groups. The qRT-PCR results showed that the relative mRNA expression levels of Claudin-1 and Occludin in the colon of mice from the control group, 150 mg/kg, and 500 mg/kg aspartame exposure groups were (1.06±0.39, 0.44±0.16, 0.51±0.15) and (1.01±0.10, 0.32±0.17, 0.58±0.17), respectively. The differences were statistically significant ( F=10.26, 31.26, P<0.05). The Tukey test results indicated that the mRNA levels of Claudin-1 and Occludin in the colon of mice in the 150 mg/kg and 500 mg/kg aspartame exposure groups were significantly lower than those in the control group ( q=5.86, 5.18, 11.09, 6.78, P<0.05), but there was no statistically significant difference between the low-dose and high-dose exposure groups ( q=0.68, 4.31, P>0.05). There was no significantly difference in the mRNA expression of Tjp-1 gene in the colon of mice in all groups ( F=1.18, P>0.05). The protein levels of Claudin-1 and Occludin in the colorectal tissues of mice in the 150 mg/kg ( q=7.25, 5.62, P<0.05) and 500 mg/kg ( q=5.35, 5.66, P<0.05) aspartame exposure groups were significantly downregulated, however, there was no significantly difference in the 500 mg/kg compared to 150 mg/kg aspartame exposure group ( q=0.30, 1.64, P>0.05). And the protein level of ZO-1 showed no significant differences between groups ( F=0.43, P>0.05). Conclusion:Aspartame exposure may leads to decreased expression of colorectal tight junction genes Claudin-1 and Occludin and intestinal mechanical barrier damage in mice.

Objective To investigate the risk factors for cardiovascular disease(CVD)in patients with rheumatoid arthritis(RA).Methods Clinical data of 225 patients with RA admitted to the Second Affiliated Hospital of Zhengzhou University from January 2023 to September 2024 were collected,and the patients were divided into CVD group(n=50)and non-CVD group(n=175)according to whether they were complicated by CVD.Univariate and multivariate Logistic regression was used to analyze the risk factors of CVD in RA patients.Results Univariate Logistic regression analysis showed that age,hematocrit,red cell volume distribution width(RDW),erythrocyte sedimentation rate,neutrophil to high density lipoprotein ratio(NHR)and platelet to lymphocyte ratio(PLR)were all influencing factors for CVD in RA patients(P＜0.05).Multivariate Logistic regression analysis showed that age,RDW,NHR and PLR were all risk factors for CVD in RA patients(P＜0.05).The results of receiver operating characteristic curve analysis showed that the area under the curve(AUC)of age,RDW,NHR and PLR diagnosed CVD in RA patients were 0.844,0.797,0.572 and 0.713,respectively.The combined diagnosis AUC of four indexes was 0.898.Conclusion The risk of CVD in RA patients is influenced by many factors,and the combination of age,RDW,NHR,and PLR can improve early diagnosis of CVD in RA patients.

The health effects associated with environmental pollutants remain one of the major public health issues at present. The research method focusing on the population as the research subjects is limited by reliable cohorts, and the research method targeting individual molecules cannot fully reflect the biological health effects under environmental pollutant stress. Using high-throughput multi-omics, machine learning, and epigenetic detection to conduct targeted research and joint analysis on cells, organoids, organs, animals, and humans in different biological dimensions will help provide data support for the study of potential targets and biological effects of environmental pollutants, providing a theoretical basis for the risk assessment and safety evaluation of environmental pollutants.

Background The population with diabetes in China is increasing year by year. Current research has found that either air pollution or temperature has an impact on the occurrence and development of diabetes, but the interaction between the two is unclear yet. Objective To investigate the effects and the lag effects of air pollutants and temperature on the risk of hospital admission for type 2 diabetes in Hefei, Anhui Province from 2016 to 2019, as well as to verify potential interaction between air pollutants and temperature. Methods This study collected hospital admission data for patients with type 2 diabetes from a tertiary hospital in Hefei, Anhui Province, and the corresponding monitoring data on air pollutants and meteorological factors from 2016 to 2019. Firstly, a distributed lag non-linear model (DLNM) was used to explore the effects of air pollutants and temperature on the risk of hospital admission for type 2 diabetes. Subsequently, a bivariate response surface model was used to explore potential interaction between temperature and various pollutants on frequency of hospital admission due to diabetes. Temperature was further divided into lower, medium, and higher levels by percentiles during the study period, and the potential interaction between air pollutants and temperature strata were verified . Results After controlling long-term trend, seasonal trend, holiday effect, and day of the week effect, the results of single pollutant models showed that for every 10 μg·m⁻³ increase in fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), and nitrogen dioxide (NO₂), the relative risk (RR) values for hospital admission due to type 2 diabetes were 1.032 (95%CI: 1.021, 1.043), 1.018 (95%CI: 1.008, 1.026), and 1.037 (95%CI: 1.016, 1.058), respectively; for every 1 mg·m⁻³ increase in carbon monoxide (CO), the RR value for hospital admission due to type 2 diabetes was 1.319 (95%CI: 1.163, 1.495); the increases in sulfur dioxide (SO₂), ozone (O₃), and daily average temperature showed no statistically significant impact on hospital admission due to type 2 diabetes. The results of bivariate response surface models suggested that daily average temperature and various pollutant levels spontaneously affected the risk of hospital admission for type 2 diabetes, but the stratified analysis did not find significant differences in the effect of PM_2.5 on the risk of hospital admission due to type 2 diabetes across different temperature strata. Conclusion Increases in the concentrations of PM_2.5, PM₁₀, NO₂, and CO elevate the risk of hospital admission for type 2 diabetes. This study could not confirm the interactions between daily average temperature and various pollutants.

Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Objective To explore the expression of serum growth differentiation factor-8(GDF-8)and silent information regulator 4(Sir4)in elderly patients with chronic heart failure(CHF)and their relationship with left ventricular remodeling and cardiac function.Methods A total of 300 CHF patients admitted in our hospital from Jan 2021 to Dec 2023 were recruited and assigned into an observation group,and 100 healthy individuals who took physical examination during the same period served as control group.Based on New York Heart Association(NYHA)heart function classification,the patients in the observation group were divided into Grade Ⅰ(60 cases),Ⅱ(72 cases),Ⅲ(102 cases),and Ⅳ(66 cases)subgroups.Their clinical data were collected,serum GDF-8 and Sir4 levels were detected,left ventricular remodeling was evaluated with echocardiography,and cardiac dysfunction was assessed with NYHA cardiac function grading.Pearson and Spearman correlation analyses were used to analyze the correlation of GDF-8 and Sir4 levels with left ven-tricular remodeling and myocardial injury.Results The observation group had significantly larger left atrial diameter(LAD)and left ventricular end diastolic diameter(LVEDD),thicker left ven-tricular posterior wall thickness(LVPWT)and interventricular septum thickness(IVST),and higher left ventricular mass index(LVMI)and serum Sir4 and GDF-8 levels(42.46±4.75 mm vs 36.39±5.33 mm,54.63±7.96 mm vs 47.42±8.08 mm,9.44±1.21 mm vs 8.49±0.88 mm,9.27±1.58 mm vs 8.66±1.71 mm,141.49±5.32 g/m2 vs 106.52±7.33 g/m2,3.69±1.06 g/L vs 1.48±0.42 g/L,33.75±10.64 g/L vs 19.08±5.13 g/L,P＜0.01),but lower LVEF[(40.02±10.14)％vs(63.64±6.13)％,P＜0.01]and left ventricular remodeling index(LVRI,1.05±0.24 g/ml vs 1.32±0.33 g/ml,P＜0.01)when compared with the control group.The levels of Sir4 and GDF-8,as well as LVMI,were gradually increased,while the LVRI was decreased in Grades Ⅰ,Ⅱ,Ⅲ,and Ⅳ subgroups in turn,with statistical differences in the subgroups(P＜0.01).Pearson and Spearman correlation analyses showed that Sir4 and GDF-8 levels were positively correlated with LAD,LVEDD,LVPWT,IVST,LVMI,and NHYA cardiac function grade(P＜0.01),and nega-tively with LVEF and LVRI(P＜0.01).Conclusion Serum Sir4 and GDF-8 levels are abnormally elevated in elderly CHF patients,and their levels are positively correlated with the severity of left ventricular remodeling and the severity of cardiac dysfunction.

Objective:To investigate the value of modified early warning score (MEWS) combined with D-dimer test in the establishment of an acute pancreatitis severity evaluation model.Methods:The clinical data of 357 patients with acute pancreatitis who received treatment in the Second Affiliated Hospital of Anhui Medical University, China between January 2017 and December 2018 were collected for this study. The receiver operating characteristic curve was used to determine the optimal cut-off value of MEWS combined with D-dimer test for predicting non-mild acute pancreatitis. The relationship between MEWS and D-dimer level was analyzed using regression analysis. The area under the curve (AUC) was used to evaluate the ability of each factor to predict the severity of acute pancreatitis. The sensitivity and specificity of the new model to predict non-mild acute pancreatitis were calculated.Results:According to the receiver operating characteristic curve, the AUC of D-dimer, MEWS, and new model were 0.702, 0.628 and 0.734 respectively ( P < 0.05). The AUC of the new model in predicting non-mild acute pancreatitis was significantly higher than that of MEWS and D-dimer test (0.734 > 0.702 > 0.628, Z = 3.20, P < 0.01). Conclusion:The ability of the new model established based on MEWS and D-dimer to predict the severity of acute pancreatitis is stronger than that of each of MEWS and D-dimer. The new model is simple, convenient and more suitable for clinical use.

Objective:To determine a simpler and more practical scoring standard for predicting mucosal histological healing in ulcerative colitis (UC).Methods:From April 11, 2017 to February 8, 2021, 68 UC patients diagnosed with mucosal healing under endoscopy and hospitalized at Department of Gastroenterology, the Tenth People′s Hospital of Tongji University and during the same period 60 healthy individuals who underwent endoscopy for health checkup were retrospectively analyzed. Modified Mayo score and ulcerative colitis endoscopic index of severity (UCEIS), the modified Nancy index and Robarts histopathology index were determined based on the collected clinical data, endoscopic reports and histopathological evaluation. The proportions of neutrophils, eosinophils, and plasma cells in the colonic mucosal lamina propria were calculated. The proportions of activated neutrophils and T cells in the colonic mucosal lamina were calculated according to CD177 and CD40L, respectively. The new clinical and laboratory diagnostic formulas were determined by multivariate logistic regression analysis, the effectiveness of the equations was evaluated by receiver operating characteristic curve (ROC).Results:Among the 68 patients with UC, the modified Mayo score was 0.7 (0.4, 1.1), the UCEIS was 0.5 (0.3, 0.8), the Nancy index was 5.9±3.2, and the Robarts histopathology index was 2.6±1.7. According to multivariate logistic regression analysis, the formula for clinical diagnosis of histological healing was Y1=-21.09+ 355.9 X1+ 305.8 X2+ 44.91 X3 ( X1, X2 and X3 were the proportions of neutrophils, eosinophils, and plasma cells, respectively). The results of ROC analysis indicated that Y1<-0.747 was the cut-off value of diagnosis of histological healing, and the area under the curve (AUC) was 0.986 and 95% confidence interval ( CI) was 0.922 to 1.000 ( P<0.001), the sensitivity was 97.10% and the specificity was 91.20%. The formula of laboratory diagnosis of histological healing was Y2=-10.57+ 469.1 X1 + 132.7 X2 + 101.2 X3 + 18.56 X4 ( X1, X2, X3, and X4 were the proportions of CD177 + neutrophils, eosinophils, CD40L + T cells and plasma cells, respectively). The results of ROC analysis indicated that Y2<1.960 was the cut-off value of diagnosis of histological healing, and the AUC was 0.980, 95% CI was 0.913 to 0.999 ( P<0.001), the sensitivity was 84.78%, and the specificity was 100.00%. The new clinical and laboratory diagnostic criteria were positively correlated with the Nancy histological index ( r=0.411 and 0.308, P=0.001 and 0.011), and Robarts histopathology index ( r=0.311, 0.273, P=0.010 and 0.024). Conclusions:Compared with the Nancy index, the new clinical and laboratory diagnostic criteria are simpler and more practical. The new clinical diagnostic formula Y1<-0.747 and the new laboratory diagnosis formula Y2<1.960 are the independent factors for predicting histological healing in UC patients.