Objective:To investigate the role of phosphatase and tensin homolog (PTEN) neddylation in the dysregulation of regulatory T cell (Treg) immune function in rheumatoid arthritis (RA) and further explore the pathogenesis of RA.Methods:Peripheral blood samples were collected from 45 healthy volunteers and 45 RA patients in the Yuyao People′s Hospital from Sep. 2021 to Dec. 2022. ELISA was performed to detect the expression levels of the inflammatory factor IFN-γ and Treg-related cytokine IL-10 in serum, and flow cytometry was used to assess the proportion of CD4 +CD25 +FOXP3 + Treg cells. Western Blot analysis was conducted to measure the expression levels of Nedd8-PTEN, ubiquitinated FASN, PTEN, FASN, Neddylation E3 enzyme XIAP, and ubiquitination E3 enzyme TRIM21 in isolated Treg cells. Group comparisons were conducted using an independent samples t-test or the Mann-Whitney U test. Results:Compared with the healthy control group, the expression of IFN-γ was significantly increased [(599± 65) pg/ml vs. (1 066±85) pg/ml, t=-2.06, P<0.001], while IL-10 levels [(601±49) pg/ml vs. (245±41)pg/ml, t=2.05, P<0.001] and the proportion of CD4 +CD25 +FOXP3 + Treg cell [(14.3±0.4)% vs.(6.2±0.6)%, t=19.36, P<0.001] were significantly decreased in the RA patient group (respectively). FASN in Treg cells of RA patients was significantly ubiquitinated, while the PTEN Neddylation level decreased. Additionally, TRIM21 expression was significantly upregulated in RA patients (0.66 ± 0.03 vs. 1.27 ± 0.04, t=-20.85, P<0.001), whereas the expression levels of PTEN (0.858±0.036 vs. 0.377±0.022, t=19.36, P<0.001), XIAP (1.107± 0.065 vs. 0.530±0.015, t=15.03, P<0.001), and FASN protein (1.654±0.031 vs. 0.858±0.025, t=34.64, P<0.001) were significantly downregulated. Conclusion:Decreased levels of PTEN protein Neddylation modification may inhibit the entry of PTEN protein into the nucleus, thereby promoting the ubiquitination degradation of FASN, suppressing fatty acid synthesis in Treg cells, affecting the stability of Treg cell immunosuppressive function, and possibly promoting the progression of RA.

Objective By detecting the changes of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)in brain tissue,as well as serum S-100β and neuron specific enolases(NSE)in neonatal rats with hypoxic-ischemic encephalopathy(HIE)under differ-ent treatment regimens,the anti-inflammatory and neuroprotective effects of hydrogen gas were explored.Methods HIE animal model was made from 7-day-old newborn SD rats,and then divided into sham operation group,control group,test group 1(saturated hydro-gen saline group),test group 2(mild hypothermia group),and test group 3(combination group)according to completely random number table method.No special treatment was given in the sham operation group,while the control group only had modeling,test group 1 was in-traperitoneally injected with saturated hydrogen saline after modeling,test group 2 was treated with mild hypothermia after modeling,test group3 was treated with mild hypothermia combined with injection of saturated hydrogen saline after modeling.At 1,3 and 7days after modeling,10 rats from each group were decapitated and brain tissue was collected for enzyme-linked immunosorbent assay(ELISA)de-tection of IL-6 and TNF-α,and serum was collected to detect the expression levels of S-100β and NSE.Results The expression levels of IL-6,TNF-α in the brain tissue,S-100β,and NSE in serum of the control group were increased significantly 1day after modeling,began to decline at 3days,and returned to normal at 7days.Compared with the sham operation group,the expression levels of various indicators in the 1day and 3days were statistically significant(P＜0.05).However,the expression levels of various indicators in test group 1and 2decreased compared with the control group on 1day and 3days after modeling(P＜0.05),but were higher than those in test group 3 and sham operation group,with statistical significance(P＜0.05).There was no statistical significance in the comparison of various indicators between test group 1 and 2 at each stage(P＞0.05).Conclusion Hydrogen treatment can reduce the inflammatory response level of the nervous system to some extent,and also has a certain neuroprotective effect on HIE in neonatal rats.

Objective By detecting the changes of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)in brain tissue,as well as serum S-100β and neuron specific enolases(NSE)in neonatal rats with hypoxic-ischemic encephalopathy(HIE)under differ-ent treatment regimens,the anti-inflammatory and neuroprotective effects of hydrogen gas were explored.Methods HIE animal model was made from 7-day-old newborn SD rats,and then divided into sham operation group,control group,test group 1(saturated hydro-gen saline group),test group 2(mild hypothermia group),and test group 3(combination group)according to completely random number table method.No special treatment was given in the sham operation group,while the control group only had modeling,test group 1 was in-traperitoneally injected with saturated hydrogen saline after modeling,test group 2 was treated with mild hypothermia after modeling,test group3 was treated with mild hypothermia combined with injection of saturated hydrogen saline after modeling.At 1,3 and 7days after modeling,10 rats from each group were decapitated and brain tissue was collected for enzyme-linked immunosorbent assay(ELISA)de-tection of IL-6 and TNF-α,and serum was collected to detect the expression levels of S-100β and NSE.Results The expression levels of IL-6,TNF-α in the brain tissue,S-100β,and NSE in serum of the control group were increased significantly 1day after modeling,began to decline at 3days,and returned to normal at 7days.Compared with the sham operation group,the expression levels of various indicators in the 1day and 3days were statistically significant(P＜0.05).However,the expression levels of various indicators in test group 1and 2decreased compared with the control group on 1day and 3days after modeling(P＜0.05),but were higher than those in test group 3 and sham operation group,with statistical significance(P＜0.05).There was no statistical significance in the comparison of various indicators between test group 1 and 2 at each stage(P＞0.05).Conclusion Hydrogen treatment can reduce the inflammatory response level of the nervous system to some extent,and also has a certain neuroprotective effect on HIE in neonatal rats.

Objective:To investigate the role of phosphatase and tensin homolog (PTEN) neddylation in the dysregulation of regulatory T cell (Treg) immune function in rheumatoid arthritis (RA) and further explore the pathogenesis of RA.Methods:Peripheral blood samples were collected from 45 healthy volunteers and 45 RA patients in the Yuyao People′s Hospital from Sep. 2021 to Dec. 2022. ELISA was performed to detect the expression levels of the inflammatory factor IFN-γ and Treg-related cytokine IL-10 in serum, and flow cytometry was used to assess the proportion of CD4 +CD25 +FOXP3 + Treg cells. Western Blot analysis was conducted to measure the expression levels of Nedd8-PTEN, ubiquitinated FASN, PTEN, FASN, Neddylation E3 enzyme XIAP, and ubiquitination E3 enzyme TRIM21 in isolated Treg cells. Group comparisons were conducted using an independent samples t-test or the Mann-Whitney U test. Results:Compared with the healthy control group, the expression of IFN-γ was significantly increased [(599± 65) pg/ml vs. (1 066±85) pg/ml, t=-2.06, P<0.001], while IL-10 levels [(601±49) pg/ml vs. (245±41)pg/ml, t=2.05, P<0.001] and the proportion of CD4 +CD25 +FOXP3 + Treg cell [(14.3±0.4)% vs.(6.2±0.6)%, t=19.36, P<0.001] were significantly decreased in the RA patient group (respectively). FASN in Treg cells of RA patients was significantly ubiquitinated, while the PTEN Neddylation level decreased. Additionally, TRIM21 expression was significantly upregulated in RA patients (0.66 ± 0.03 vs. 1.27 ± 0.04, t=-20.85, P<0.001), whereas the expression levels of PTEN (0.858±0.036 vs. 0.377±0.022, t=19.36, P<0.001), XIAP (1.107± 0.065 vs. 0.530±0.015, t=15.03, P<0.001), and FASN protein (1.654±0.031 vs. 0.858±0.025, t=34.64, P<0.001) were significantly downregulated. Conclusion:Decreased levels of PTEN protein Neddylation modification may inhibit the entry of PTEN protein into the nucleus, thereby promoting the ubiquitination degradation of FASN, suppressing fatty acid synthesis in Treg cells, affecting the stability of Treg cell immunosuppressive function, and possibly promoting the progression of RA.

Objective To analyze the prevalence of chronic diseases and its influencing factors of dust-exposed male workers in a coal mine. Methods A total of 9 782 dust-exposed male workers from a coal mine in Shanxi Province were selected as the study subjects using the purposive sampling method. Their occupational health examination results were collected to analyze the prevalence of chronic diseases and its influencing factors. Results The prevalence of dyslipidemia, hyperuricemia, hypertension and diabetes were 40.3%, 30.7%, 23.5% and 5.6%, respectively. The prevalence of chronic diseases was 64.8%. Among them, the prevalence of having one, two, three or more chronic diseases were 36.5%, 21.6% and 6.7%, respectively. The prevalence of comorbid chronic diseases was 28.3%, with the highest prevalence of concurrent dyslipidemia and hyperuricemia of 11.0%. The results of binary logistic regression analysis showed that the risk of chronic disease was higher in workers <40 years old, smoking, overweight, obesity and total working years >20 years (all P<0.05). The results of multinomial logistic regression analysis showed that workers <40 years old, overweight, obesity and total working years >20 years were risk factors for having one chronic disease (all P<0.05). The workers <40 years old, smoking, overweight, obesity and total working years >20 years were risk factors for having two chronic diseases (all P<0.05). The workers <40 years old, smoking, alcohol consumption, overweight, obesity, other types of work, and working years >20 years were risk factors for having three or more chronic diseases (all P<0.05). Conclusion The prevalence of chronic diseases is high and the comorbidity of chronic diseases is common among dust-exposed male workers. The main influencing factors were age, smoking, alcohol consumption, overweight, obesity, type of work, and working year. Workers with more contributing factors have higher risk of chronic comorbidities.

Objective: To examine the association between neonatal birth weight and maternal type 2 diabetes (T2DM), so as to provide insights into the formulation of the early T2DM prevention and improvements of maternal and children health. Methods: Single-nucleotide polymorphisms (SNPs) were collected from two genome-wide association studies (GWAS) that examined the association between neonatal birth weight and maternal T2DM. Inverse variance weighted method was employed for forward Mendelian randomization with 26 birth weight-associated SNPs as instrumental variables and maternal T2DM as the study outcome and for reverse Mendelian randomization with 18 maternal T2DM-associated SNPs as instrumental variables and maternal effects of neonatal birth weight as the study outcome. The heterogeneity was examined using Cochran's Q test, and the pleiotropy was evaluated using MR-Egger regression, while the robustness of the results was evaluated using leave-one-out test. Results: Cochran's Q test detected heterogeneity across two studies (P=0.019, 0.038), and random effect models were employed. Mendelian randomization showed that an increase in neonatal birth weight by per standard error (approximately 488 g) resulted a 29.9% reduction in the risk of maternal T2DM (OR=0.701, 95%CI: 0.547-0.899), and maternal T2DM increased the neonatal birth weight by 0.074 standard errors (OR=1.074, 95%CI: 1.043-1.106). No horizontal pleiotropy was seen for instrumental variables (P=0.241, 0.188). With each SNP excluded in turn, the results of Mendelian randomization study were robust. Conclusion There are bidirectional associations between neonatal birth weight and risk of maternal T2DM.

Objective:To investigate the preventive effects of intravenous N-acetylcysteine(NAC)administration on contrast-induced nephropathy(CIN)following coronary intervention in elder patients with coronary heart disease(CHD)complicated with moderate to severe renal dysfunction.Methods:In this retrospective study, 242 elderly patients with CHD and moderate to severe renal insufficiency hospitalized in the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University and undergone coronary angiography from January 2018 to February 2022 were included and divided into two groups: the treatment group(100 cases)receiving NAC plus a continuous intravenous drip of 0.9% sodium chloride solution before and after surgery and the control group(142 cases)treated with only a continuous intravenous drip of 0.9% sodium chloride solution.To ensure the comparability of important baseline data between the two groups, a 1∶1 propensity score matching analysis was used, and 70 patients in each group were finally included.Pre-and post-operative serum creatinine(Scr)and blood urea nitrogen(BUN)values were recorded, the endogenous creatinine clearance(Ccr)and estimated glomerular filtration rate(eGFR)were calculated, and the incidences of CIN and changes in renal function indicators were compared between the two groups.Results:After coronary intervention, the incidence of CIN in the treatment group was significantly lower than that in the control group(1/70 or 1.4% vs.8/70 or 11.4%, P=0.033). In the treatment group, Scr[(186.01±36.62)μmol/L vs.(195.84±36.39)μmol/L, t=4.957, P<0.001]and BUN[(13.97±2.89)mmol/L vs.(14.84±2.85)mmol/L, t=5.206, P<0.001]decreased, while Ccr[(31.84±6.54)ml/min vs.(30.08±5.65)ml/min, t=-5.076, P<0.001]and eGFR[(31.60±6.93)ml·min -1·1.73m -2vs.(29.82±5.92)ml·min -1·1.73m -2, t=-5.200, P<0.001]increased, compared with pre-operative levels.In the control group, Scr[(186.65±27.28)μmol/L vs.(182.53±22.08)μmol/L, t=-1.783, P=0.079]and BUN[(17.57±3.33)mmol/L vs.(17.13±3.35)mmol/L, t=-2.234, P=0.029]increased, but Ccr[(30.57±6.37)ml/min vs.(31.06±6.01)ml/min, t=1.435, P=0.156]and eGFR[(30.76±6.46)ml·min -1·1.73m -2vs.(31.26±6.02)ml·min -1·1.73m -2, t=1.436, P=0.156]decreased, compared with pre-operative levels, and there was no significant difference except BUN(all P>0.05). Conclusions:For elderly patients with coronary heart disease complicated with moderate to severe renal insufficiency, the use of NAC before and after coronary intervention can reduce the risk of CIN and help improve renal function.

The placement of the flexible ureteroscopic sheath during lithotripsy may injure the ureter. We have developed a double-tube flexible ureteral access sheath. Thirteen patients with renal calculi were treated with double-tube and flexible sheath in one stage. CT examination of 13 cases showed that the ureter was normal. The double-tube flexible ureteral access sheath makes the operation of sheathing easy, safe and effective.

OBJECTIVE: To study the mechanism of tumor necrosis factor( TNF)-α and its receptor( TNFR) signal transduction pathways in regulating cell apoptosis of alveolar macrophage( AM) in coal workers' pneumoconiosis( CWP).METHODS: Twenty-four coal workers with pneumoconiosis at stage Ⅰ were selected as CWP group and four observation subjects exposed to coal were chosen as observation group by using simple random sampling method. The bronchoalveolar lavage fluids of whole-lung lavage of two groups were collected. AMs were separated and purified. Then they were divided into 6 groups: a control group,a superoxide dismutase( SOD) group,a TNF/TNFR group,an anti-TNF-α antibody group,a Caspase-8 suppression group and a nuclear factor-κB( NF-κB) suppression group. The AMs of 6 groups with corresponding treatment were cultivated. After 24 hours,the cells were harvested and proteins extracted. The relative expression of TNF-α,TNFR1,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 protein was detected by Western blotting. RESULTS: The protein relative expression of TNF-α,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 in CWP group was significantly higher than those in the observation group( P < 0. 05). The protein relative expression of TNF-α,TNFR1,Caspase-8,Caspase-3 and NF-κB P50 in the TNF/TNFR group and the anti-TNF-αantibody group was lower than that of the control group( P < 0. 05). The above indexes in the anti-TNF-α antibody group were lower than that of the NF-κB suppression group( P < 0. 05). The protein relative expression of TNFR1,Caspase-8and Caspase-3 in the TNF/TNFR group was higher than that of the SOD group and the Caspase-8 suppression group( P <0. 05). The protein relative expression of TNFR1,Caspase-8 and NF-κB P50 in the TNF/TNFR group was lower than that of the NF-κB suppression group( P < 0. 05). Among the CWP patients,the relative expression of TNFR2 and NF-κB P65 in the TNF/TNFR group was lower than that of the control group( P < 0. 05),and higher than that of the SOD group( P <0. 05). CONCLUSION: AM apoptosis mediated by TNF-α/TNFR/NF-κB signal transduction pathway plays an important role in the occurrence and development of CWP. The TNF-α/TNFR/NF-κB signal transduction pathways inhibited or blocked at different stages can affect the expression of proteins related to AM apoptosis.

Objective To explore the influence of 50 chewing method on postoperative rehabilitation of gastric cancer patients.Methods Totals of 235 patients, having undergone radical resections for gastric cancer during February to December 2015 in Department of stomach oncological surgery in a certain grade-III Level A tumor hospital, were divided according to random number table into observation group with 118 cases, and control group with 117 cases. Patients in the control group were cared by routine diet requirement, while patients in the observation group received extra guidance and training to use the“50 chewing method”. Recovery time of early intestinal exhaust and appetite, change in body mass and incidence of complications of patients in the two groups were compared.Results Recovery time of early intestinal exhaust of patients in the observation group was (69.1±5.3) h, with appetite recovery time (71.1±12.6) h and weight loss (3.2±1.4) kg, all lower than that in the control group (P<0.05). Postoperative complications happened to both groups. In the observation group, nausea/abdominal distension happened to 14 patients and intestinal obstruction to 1;while in the control group, nausea/vomit happened to 26 patients and intestinal obstruction to 7 ( P<0. 05 ) . Conclusions “50 chewing method” can accelerate recovery of gastrointestinal function of gastric cancer patients and reduce incidence of complications during postoperative recovery period.