Objective:To investigate the key mechanism of transforming growth factor-β (TGF-β) inducing the expression of interleukin-17D (IL-17D) in lung cancer-associated fibroblast (CAF) and promoting the recruitment of myeloid-derived suppressor cells (MDSCs).Methods:C57BL/6 mice were established for B16 lung melanoma metastasis model (tumor model group), and control group was set up, 6 mice in each group. Flow cytometry (FACS) was used to detect the lung CAF and the changes of its ability to secrete IL-17D and the proportion of MDSCs in tumor mice. The changes of TGF-β level in lung tumor were examined by ELISA and quantitative real-time PCR (RT-qPCR). Lung fibroblasts were screened by FACS, and the effects of TGF-β on the secretion of IL-17D, C-C motif chemokine ligand (CCL)2 and CCL7 in fibroblasts were detected by RT-PCR. The migration of MDSCs under the condition of TGF-β stimulating fibroblasts was detected by Transwell.Results:The proportion of CAF (CD45 -CD326 -CD31 -) in the tumor model group was higher than that in the control group [(28.02±2.23)% vs. (7.35±2.14)%, t=9.956, P<0.001]. The ability of CAF to secrete IL-17D in the tumor model group was significantly higher than that in the control group [(38.27±2.93)% vs. (19.04±3.16)%, t=5.995, P=0.001]. The proportion of MDSCs in the tumor model group was significantly higher than that in the control group [(12.93±1.27)% vs. (8.21±1.40)%, t=4.804, P=0.009]. Compared with the control group, the protein and transcription levels of TGF-β in lung of the tumor model group were significantly increased [(1 685.07±135.61) ng/L vs. (1 047.98±68.50) ng/L, t=5.051, P=0.002; 2.17±0.03 vs. 1.00±0.05, t=51.237, P<0.001]. In vitro, lung fibroblasts were stimulated with different concentrations of TGF-β (0, 5 and 10 μg/L) for 24 hours, the relative expressions of IL-17D mRNA secreted by stimulated fibroblasts were 0.42±0.01, 0.67±0.01 and 0.84±0.04 respectively, the relative expressions of CCL2 mRNA in each group were 0.89±0.08, 1.08±0.04, 1.19±0.01 and CCL7 were 0.53±0.05, 0.65±0.04, 0.74±0.03 respectively. With the increase of TGF-β concentration, the expression levels of IL-17D, CCL2 and CCL7 in fibroblasts were significantly increased ( F=57.384, P<0.001; F=15.802, P=0.004; F=14.544, P=0.005). In addition, compared with the control group (0 μg/L TGF-β), fibroblasts treated with 10 μg/L TGF-β for 24 hours could promote the migration of MDSCs in spleen of tumor mice [(9.59±0.21)% vs. (2.14±0.24)%, t=6.585, P<0.001]. Conclusion:TGF-β can induce high expression of IL-17D in lung CAF, which is an important factor in promoting the expressions of CCL2 and CCL7 and the migration of MDSCs in tumor microenvironment.

OBJECTIVETo investigate the effect of body mass index (BMI) on new-onset non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).

METHODSSubjects with T2DM were recruited from the population of individuals attending the Affiliated General Hospital of North China University for routine health examination between 2006 and 2007 and offered participation in this community-based prospective cohort study. Enrollees were categorized into groups according to weight assessed by baseline BMI (underweight, normal, overweight, and obese groups). Cumulative incidence of NAFLD was compared between each group and the effect of baseline BMI on new-onset NAFLD was assessed by Cox regression analysis.

RESULTSThe cumulative incidence of NAFLD increased in conjunction with increases in weight (low weight: 69%, normal weight: 73%, overweight: 90%, obese: 97%; P<0.01). Subjects in the overweight and obese groups showed an increased risk of NAFLD (relative risk (RR)=2.00, 95% CI: 1.76-2.29 and =2.87, 95% CI: 2.42-3.40; P<0.01), compared to those in the normal weight group. Moreover, after adjustment for baseline factors (e.g.age, sex) risk of NAFLD remained higher for the overweight and obese subjects (RR=1.73, 95% CI: 1.49-2.00 and =2.12, 95% CI: 1.73-2.60; P<0.01).

CONCLUSIONRisk of NAFLD in T2DM patients increases in parallel to increase in weight assessed by BMI. BMI appeared to be an independent risk factor for NAFLD.

Body Mass Index ; China ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Humans ; Incidence ; Non-alcoholic Fatty Liver Disease ; Obesity ; Prospective Studies ; Risk Factors

Objective To evaluate the prognostic value of preoperative neutrophil-to lymphocyte ratio (NLR) in invasive breast carcinomas of no special type.Methods we retrospectively analyzed the clinical and pathological data of all breast cancer patients at Shanghai Huangpu District Cental Hospital from Jan.2012 to Dec.2012.The optimal cutoff value was obtained by ROC.The difference among variables was calculated by chi-square test.DFS and OS were estimated using Kaplan-Meier method.Cox analysis was performed to analyze clinical parameters for their prognostic relevance.Results A total of 493 were eligible.The optimal cutoff value of NLR was 2.057.The sensitivity was 0.767 and specifity was 0.327 at the optimal cutoff point.Univariate analysis showed that patients with NLR higher than 2.057 had significantly lower DFS (P=-0.001) than patients with NLR equal or lower than 2.057,while the overall survival rate was not statistically different (P=0.131).The Cox proportional multivariate hazard model revealed that higher NLR was independently related with poor DFS with hazard ratio 5.649(95％ confidence interval 3.128-10.201,P=0.002).Conclusions Preoperative NLR is an independent predictor of DFS in breast cancer patients.Further validation and a feasibility study are required before it can be considered for clinical use.

Objective To investigate the effects of fasting serum triglycerides (TG) levels at different baseline on the risk of new-onset acute pancreatitis (AP) in in-service and retired employees of Kailuan Group.Methods A total of 125 178 in-service and retired employees of Kailuan Group who received health check-ups from 2006 to 2009 and had no AP history but had complete TG data were prospectively enrolled.According to quantile level,the baseline serum fasting TG level of study subjects were divided into ＜1.01 mmol/L group (n=42 128),1.01 to 1.64 mmol/L group (n=41 711) and ＞ 1.64 mmol/L group (n=41 339).The incidence of new-onset AP of these three groups was analyzed.The survival curve was plotted by Kaplan-Meier method.The cumulative incidence rate was calculated and tested by log-rank method.And multivariate Cox proportional hazards regression model was performed to calculate hazard ratios (HR) of baseline fasting serum TG level for AP.Results After followed up for (7.36±1.23) years,a total of 193 cases of AP occurred.The incidences of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.43 events/10 000 person-years,2.37 events/10 000 person-years and 2.49 events/10 000 person-years,respectively.The cumulative incidence rates of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞1.64 mmol/L group were 0.10％ (44/42 128),0.18％ (73/41 711) and 0.18％ (76/41 339),respectively,and the difference was statistically significant (x2 =9.998,P=0.007).The results of multivariate Cox proportional hazards regression model analysis indicated that the risk of AP increased in 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group compared with that of ＜1.01 mmol/L group,HR and 95％ confidence interval (CI) were 1.56 (1.07 to 2.29) and 1.57 (1.06 to 2.32),respectively.After excluded onset AP within one year,with a control group of ＜1.01 mmol/L group,the results of multivariate Cox proportional hazards regression model analysis indicated that the HR and 95％CI for AP of 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.70 (1.11 to 2.58) and 1.69 (1.10 to 2.60),respectively.Conclusion Baseline fasting serum TG levels over 1.01 mmol/L may increase the risk of AP.

Objective:To explore the relationship between risk perception and health promoting lifestyle profile in population with cardiovascular disease (CVD), and construct a prediction model for clinical screening and targeted intervention.Methods:A cross-sectional survey method was used to select 272 people at moderate and high risk of CVD from the Second Affiliated Hospital of Zhejiang University School of Medicine from March to August 2022. The general information questionnaire, Chinese version of Attitude and Beliefs about Cardiovascular Disease Knowledge and Risk Questionnaire (ABCD-C), and Health Promoting Lifestyle Profile-II (HPLP Ⅱ) were used. Based on multiple regression analysis, a nomogram model for health promoting lifestyle in high-risk CVD population was constructed.Results:Among 272 participants, male 150 cases, female 122 cases, aged (60.58 ± 10.64) years old. The total ABCD-C score was (56.57 ± 5.69), and the total HPLP Ⅱ score was (111.92 ± 12.47). ABCD-C score was significantly positively correlated with HPLP Ⅱ score ( r=0.556, P<0.01). The median of HPLP Ⅱ total score (111 points) was used as the cut-off point for low level of health-promoting lifestyle (≤111 points) and high level of health-promoting lifestyle (>111 points), and used it as the dependent variable, smoking ( OR=0.215, 95% CI 0.104-0.446) was a barrier factor for participants to adopt healthy lifestyle; being married ( OR=14.237, 95% CI 1.963-103.238), having a family average monthly income higher than 5 000 yuan ( OR=4.101, 95% CI 1.369-12.288), higher score of CVD prevention knowledge ( OR=1.660, 95% CI 1.373-2.007), perceived benefits and intention to change physical activity ( OR=1.445, 95% CI 1.255-1.663), perceived benefits and intention to change healthy diet ( OR=1.322, 95% CI 1.058-1.654) were promoting factors. Conclusions:The health-promoting lifestyle of populations at risk for CVD is above-average, influenced by factors such as smoking, marital and economic status, risk attitudes, and beliefs. Utilizing the nomogram model for early screening and targeted risk communication among key populations may contribute to improving their health behavior.

Objective: The present study examined the effects of surgical and conservative treatment on the curative effect of patients with condylar fracture to determine the best treatment scheme and indication. Methods : A total of 339 clinical cases of condylar fracture were selected, and pain severity, degree of mouth opening, angle of condylar fracture (calculated as the difference in the angle of the condylar between the fractured side and uninjured side) and the height of the mandibular ramus (calculated as the difference in the height of the mandibular ramus between the fractured side and uninjured side) of patients at admission were measured and analyzed. The effects of surgical treatment (rigid internal fixation) and conservative treatment (functional therapy) were evaluated and compared 6 months after treatment. Results : Among the patients with a condylar fracture displacement angle ≥ 11.50°, Significantly more (χ2= 26.38, P < 0.05) patients exhibited good recovery 6 months after surgical treatment [69.4% (118/170)] than those after conservative treatment [35.4% (29/82)]. Among the patients with a condylar fracture displacement angle < 11.50°, there was not a significant difference (χ2= 0.55, P > 0.05) between the numbers of patients who exhibited good recovery 6 months after surgical treatment [52.4% (22/42)] and conservative treatment [44.4% (20/45)]. Among the patients with mandibular ramus height ≥ 4.19 mm, significantly more (χ2= 20.35, P < 0.05) patients exhibited good recovery 6 months after surgical treatment [64.7% (112/173)] compared with those after conservative treatment [35.6% (32/90)]. Among the patients with mandibular ramus height < 4.19 mm, there was not a significant difference (χ2= 0.21, P > 0.05) between the numbers of patients who exhibited good recovery 6 months after surgical treatment [46.7% (14/30)] and conservative treatment [41.3% (19/46)]. Conclusion Patients with a displacement angle of condyle fracture greater than 11.50° and a mandibular ramus height less than 4.19 mm exhibit the greatest pain and a better effect from surgical treatment than those from conservative treatment.

Objective: By implementing the best practice of bedtime and position after diagnostic adult lumbar puncture,we hope to establish a scientific and standardized nursing routine for lumbar puncture, shorten the bed-rest time after lumbar puncture, and improve the comfort of patients. Methods: By reviewing literatures related to positions after adult lumbar puncture and post-dural puncture headache, six best practice were concluded. By combining the best evidence and the clinical circumstances, the evidenced-based criteria were established and then applied in the Neurology Department. Results: After two rounds of reviews, the results showed that except the 93.3% compliance with the new evidence, all other four criteria had 100% complacence. Comparing before and after applying the evidence, there was no statistically significant difference for the occurrence of post-dural puncture headache or dizziness(P>0.05), there was a statistically significant reduction of back pain from 28.3%(30/106) to 15.1%(18/119)(χ² value was 5.799, P<0.05) when the evidence was applied. Conclusions The best practice shows that patients needn′t lie on bed for 4 to 6 hours after lumbar puncture, the occurrence of back pain is lowered and the comfort level of the patient is improved in those who rest with pillow or activities.

INTRODUCTION: Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis. METHODS: In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 -8 ). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR-Egger, and weighted median regression) were used to ensure that our results more reliable. RESULTS: All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30-1.58, P = 2.51 × 10 -13 ). The results of MR-Egger and weighted median regression exhibited similar trends (MR-Egger OR = 1.40 [95% CI, 1.08-1.81], P = 1.61 × 10 -2 ; weighted median OR = 1.39 [95% CI, 1.21-1.61], P = 1.62 × 10 -6 ). MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. CONCLUSIONS Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.
Humans ; Atrial Fibrillation/genetics* ; Genome-Wide Association Study ; Waist Circumference/genetics* ; Computational Biology ; Databases, Factual

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines