BACKGROUND:Studies have shown that both Panax notoginseng saponins and concentrated growth factor can promote fracture healing,but there are few studies addressing their combined effects on fracture healing.Panax notoginseng saponins may accelerate fracture healing by promoting the release of concentrated growth factor-related factors over a certain period of time. OBJECTIVE:To study the effect of Panax notoginseng saponins on concentrated growth factor release and fracture healing in rats. METHODS:Eighteen 8-week-old Sprague-Dawley rats were numbered and randomly divided into three groups:Panax notoginseng saponins group,model control group and blank group.Panax notoginseng saponins group was fed with Panax notoginseng saponins for 2 weeks.Model control group was given 2 mL of normal saline for 2 weeks and blank group was fed normally.Concentrated growth factor was obtained by the centrifugation method both from the Panax notoginseng saponins group and model control group.After 1 week of normal feeding,all animals underwent modeling for femoral fracture.The Panax notoginseng saponins group and the model control group were implanted with autologous concentrated growth factor,and then the release concentration of growth factors at different time points(1 hour,1,3,5,7,9 and 11 days)were measured by ELISA.Fracture healing was assessed based on postoperative X-ray and hematoxylin-eosin staining of bone tissues. RESULTS AND CONCLUSION:Compared with the model control group,the Panax notoginseng saponins group had higher release concentrations of vascular endothelial growth factor A and transforming growth factor β at 7,9,and 11 days,Platelet-derived growth factor BB at 5,9,and 11 days,and basic fibroblast growth factor at 1-11 days(P<0.01).X-ray examinations indicated that fracture healing in the Panax notoginseng saponins group was better than that in the model control group,and fracture healing in these two groups was better than that in the blank group at 2 months after surgery.Hematoxylin-eosin staining results found that the constituent osteocyte density in the Panax notoginseng saponins group was greater than that in the model control group,and the constituent osteocyte density in these two groups was better than that in the blank group.These findings indicate that Panax notoginseng saponins can increase the concentration of concentrated growth factor-related factors.After intervention with Panax notoginseng saponins,concentrated growth factors are more advantageous in promoting fracture healing in rats.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

Objective: To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC). Methods: The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. Results: Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group. Conclusion VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

Objective·To investigate the effect of F-box only protein 38(FBXO38)on the ocular melanoma proliferation and the potential regulatory pathway.Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA(shRNA)and FBXO38 overexpression plasmids respectively.Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR(qRT-PCR)and Western blotting.The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay.By using The Cancer Genome Atlas(TCGA)database,differentially expressed genes were analyzed in the high and low expression groups of FBXO38.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed to reveal the signaling pathways associated with FBXO38.CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels.qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38.Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group,while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group(P＜0.05).Clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay showed that FBXO38 knockdown significantly enhanced the proliferation of A375 and OMM2.3 cells(P＜0.05),while overexpression of FBXO38 inhibited melanoma cell proliferation(P＜0.05).Enrichment analysis showed that in skin cutaneous melanoma and uveal melanoma,FBXO38 expression influenced the phosphoinositide 3-kinase/protein kinase B(PI3K-Akt)pathway activation.Compared with those in the control group,the inhibition rates of P13K inhibitor LY294002 and mTOR1 inhibitor Everolimus in the FBXO38 knockdown group significantly improved(P＜0.05),while their inhibition rates of the overexpression group significantly decreased compared with those of control cells(P＜0.05).Western blotting results showed that after knocking down FBXO38,expression levels of PTEN,P21 and P53 proteins decreased,while expression level of MDM2 protein increased.The qRT-PCR results showed a significant decrease in P53 transcription level(P＜0.05)and a significant increase in MDM2 transcription level in FBXO38 knockdown cells(P＜0.05).Conclusion·FBXO38 plays a role in regulating the proliferation of ocular melanoma,and this regulatory effect is related to the PI3K-Akt signaling pathway.

Objective:To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM).Methods:Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM.Results:As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio ( HR)=0.81, 95% CI: 0.70-0.94] and a 33% lower risk of all-cause mortality ( HR=0.67, 95% CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% ( HR=0.50, 95% CI: 0.45-0.56), 50% ( HR=0.50, 95% CI: 0.41-0.61), and 27% ( HR=0.73, 95% CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% ( HR=0.45, 95% CI: 0.38-0.53), 56% ( HR=0.44, 95% CI: 0.32-0.59), and 40% ( HR=0.60, 95% CI: 0.44-0.82), respectively. Conclusion:Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

Objective:To investigate the incidence of acute kidney injury (AKI) following pancreaticoduodenectomy and related risk factors in elderly patients.Methods:The clinical data of elderly patients who underwent pancreaticoduodenectomy in Henan Provincial People′s Hospital from January 2017 to June 2020 were collected retrospectively. According to the changes of serum creatinine within 48 h or 7 days after operation, the patients were divided into AKI group and non-AKI group. The basic clinical characteristics of the two groups were compared, and the incidence of AKI was calculated. Multivariate logistic regression model was used to analyze the risk factors of postoperative AKI.Results:A total of 322 elderly patients were enrolled, with age of (67.1±5.2) years old (60-85 years old) and 186 males (57.76%). Among 322 elderly patients, there were 41 patients (12.73%) suffering from AKI following pancreaticoduodenectomy. Compared with the non-AKI group, the level of bilirubin in AKI group was higher ( Z=-2.012, P=0.044), and the level of hemoglobin in AKI group was lower ( Z=-2.111, P=0.035). Multivariate logistic regression analysis showed that increased preoperative total bilirubin ( OR=1.003, 95% CI 1.000-1.006, P=0.027) and postoperative exploratory laparotomy ( OR=3.936, 95% CI 1.071-14.460, P=0.039) were the independent influencing factors for AKI after pancreaticoduodenectomy in elderly patients. Conclusions:The incidence of AKI after pancreaticoduodenectomy in elderly patients is 12.73%. Preoperative high bilirubin and postoperative exploratory laparotomy may be the independent risk factors for AKI after pancreaticoduodenectomy in elderly patients.

Objective:To analyze the influencing factors of death in patients with acute respiratory distress syndrome (ARDS) combined with acute kidney injury (AKI) in intensive care unit (ICU) after continuous renal replacement therapy (CRRT).Methods:The demographic and clinical data of ICU patients with ARDS combined with AKI after CRRT at Henan Provincial People's Hospital from January 1, 2018 to December 31, 2018 were collected. According to the final treatment results of this hospitalization, the patients were divided into death group and survival group. Survival was defined as the improved patient's condition and hospital discharge. Death was defined as the patient's death during the ICU hospitalization or confirmed death after abandoning treatment and automatically being discharged from the hospital in the follow-up. The basic clinical characteristics and CRRT status between the two groups were compared. Multivariate logistic regression method was used to analyze the influencing factors of death in patients.Results:A total of 132 patients were enrolled, of which 90 patients (68.2%) died, with 84 males (63.6%) and median age of 59(45, 73) years. Compared with the survival group, the death group had higher age, proportion of malignant tumors, sequential organ failure assessment (SOFA) score, number of organ dysfunction and proportion of positive balance of fluid accumulation at 72 hours, longer time from entering ICU to CRRT, and lower mean arterial pressure (minimum value) and oxygenation index (all P<0.05). Multivariate logistic regression analysis results showed that the age≥60 years old ( OR=4.382, 95% CI 1.543-12.440, P=0.006), large number of organ dysfunction ( OR=1.863, 95% CI 1.109-3.130, P=0.019), high SOFA score ( OR=1.231, 95% CI 1.067-1.420, P=0.004) and long time from ICU admission to CRRT ( OR=1.224, 95% CI 1.033~1.451, P=0.020) were independent influencing factors of death in patients with ARDS combined with AKI after CRRT, and high oxygenation index ( OR=0.992, 95% CI 0.986-0.998, P=0.010) was an independent protective factor for patients' prognosis. Conclusions:The mortality of patients with ARDS combined with AKI after CRRT is still high. The age≥60 years old, large number of organ dysfunction, high SOFA score and long time from ICU admission to CRRT are independent influencing factors for death, and high oxygenation index is an independent protective factor for prognosis in patients with ARDS combined with AKI after CRRT.

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 (

Objective: To investigate the relationship between duration of sleep and all-cause mortality in patients with type 2 diabetes. Methods: A total of 17 452 type 2 diabetic patients who were under the National Basic Public Health Service Project, in Changshu county, Qinghe district and Huai’an district in Huai’an city of Jiangsu province, were recruited as participants. Cox proportional hazards regression models were used to estimate the associations between different levels on the duration of sleep and all-cause mortality. Stratified analysis was performed according to factors as gender, age, and lifestyle. Results: Among the 67 912 person-years of observation, from the fo1low- up program, the median time of follow-up was 4 years, with 1 057 deaths occurred during the follow-up period. Taking patients with duration of sleep as 7 h/d for reference, the multivariate adjusted hazard ratios (95%CI) of all-cause mortality appeared as ≤6, 8, 9 and ≥10 h/d were 1.14 (0.94-1.37), 1.10 (0.91-1.32), 1.33 (1.05-1.70), and 1.52 (1.24-1.87), respectively which were associated with the duration of sleep. Data from the subgroup analysis showed that this was consistent with the whole population. Longer duration of sleep was associated with the all-cause mortality but no significant association was found between shorter duration of sleep and the all-cause mortality. Conclusion Longer duration of sleep seemed to have increased the risk of all-cause mortality in type 2 diabetic patients.

Objective: To evaluate the risk of 10-year risk of ischemic cardiovascular disease (ICVD) in patients with type 2 diabetes aged 35 years old and above in two cities of Jiangsu province. Methods: From December 2013 to January 2014, a total of 15 624 patients with type 2 diabetes aged 35 years old and above, who received national basic public health service in Changshu county of Suzhou city, Huai′an and Qinghe districts of Huai′an city, Jiangsu province, were recruited by cluster sampling method. Face-to-face questionnaire survey, anthropometric and laboratory measurements were conducted to collect exposures to ICVD risk factors. Improved Ten Year Risk Assessment Table of ICVD in Chinese was used to assess the risk score and the absolute risk of developing ICVD. Results: The participants were (62.2±9.7) years old, of which 6 137 were men (39.3%). Among the participants, the highest rate of exposure to ICVD risk factors was high systolic blood pressure (74.8%, n=11 685), followed by high total cholesterol (70.7%, n= 11 051).The score of 10-year risk for ICVD was (10.4±3.3) and the median (P₂₅-P₇₅) value of absolute risk was 15.6% (6.8%-32.7%). 16.7% (n=2 602) participants were under extremely high risk of 10-year risk for ICVD, 23.8% (n=3 714) under high-risk and 24.0% (n=3 746) under middle-risk. Among the total risk score of ICVD, age (49.1%), hypertension (17.7%) and diabetes (15.5%) accounted for relatively high proportion, however, smoking (11.0%) was the most important risk factor except for age (47.4%) and systolic blood pressure (20.5%) in male participants. Conclusion Patients with type 2 diabetes aged 35 years old and above in two cities of Jiangsu Province have a high risk of developing ICVD for 10 years, especially in elderly, female, hypertension patients and male smokers.