Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Objective lo investigate the protective effect of dihydromyricetin(DHM)against exercise-induced muscle damage(EIMD)in mice and its potential mechanism. Methods Adult male C57BL/6J mice were randomly divided into control group(CG),exercise group(EG),and exercise+100 mg/kg weightd DHM(DHM)group.The intervention lasted for four weeks,during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day.The day after the training,a 90-min treadmill exercise(slope:0 and speed:18 m/min)was conducted in both EG and DHM groups.Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise,followed by the measurement of serum creatine kinase(CK)and lactate dehydrogenase(LDH)activities,total superoxide dismutase(T-SOD)activity,malondialdehyde(MDA),and skeletal muscle mitochondrial enzyme complex Ⅰ and Ⅱ activities.Histological changes in the skeletal muscle were observed by transmission electron microscopy,and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG.The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention.Western blotting demonstrated that the expressions of sirtuin type 3(SIRT3),estrogen-related receptor alpha,and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. Conclusion DHM can relieve EIMD in mice,possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial A. senticosus samples based on atpI and atpB_rbcL according to the previous chloroplast genome sequencing results, and determinated the content of syringin by HPLC to evaluated the quality of commercial samples. A total of 80 A. senticosus samples were collected from 47 cities in 24 provinces. DNA was extracted to amplify the products of atpI and atpB_rbcL by PCR. The results showed that 7 haplotypes (H2, H5, H8, H10, H12, H14, H23) were formed by the combined analysis of the two gene fragments. H2 from Yichun in Heilongjiang, Shangzhi in Harbin, Suihua in Heilongjiang, Fushun in Liaoning, Benxi in Liaoning, Changbai in Jilin and Jingyu in Jilin were the dominant genotype, representing 58.75% of the total samples. H14 and H23 were the unique haplotypes of the producing area. It is speculated that the commercial A. senticosus samples with haplotypes of H14 and H23 are from Raohe, Shuangyashan, Heilongjiang and Mingshui, Suihua, Heilongjiang, respectively. HPLC analysis indicated that the content of syringin in 73.96% of the samples met the Pharmacopoeia standards. There was a significant difference in the content of syringin among the samples, ranging from 0.003 7% to 0.524 5%, with a difference of 0.520 8%, indicating that the quality of the samples in the market of A. senticosus was uneven. However, there were no significant differences in the contents of syringin in the commercial A. senticosus among different haplotypes. The content of syringin in the haplotype H23 in the market sample is relatively high, so it may be a germplasm with better quality. This study researched the germplasm resources and medicinal materials quality of commercial A. senticosus samples and will help guide the commercial circulation, reasonable medication of A. senticosus, and the screening of excellent germplasm.

Objective To develop a prediction tool for post-endoscopic retrograde cholangiopancreatography(ER-CP)early biliary tract infection(PEEBI)in patients with choledocholithiasis,and assist clinical decision-making be-fore ERCP and early personalized intervention after ERCP.Methods An observational bidirectional cohort study was adopted to select inpatients with choledocholithiasis who underwent ERCP in a hospital.Directed acyclic graph(DAGs)and the least absolute shrinkage and selection operator(LASSO)were used to predict PEEBI based on lo-gistic regression,and the models were compared and validated internally and externally.Results From January 1,2020 to September 30,2023,a total of 2 121 patients with choledocholithiasis underwent ERCP were enrolled,of whom 77(3.6％)developed PEEBI,mostly in the first 2 days after surgery(66.2％).The major influencing fac-tors for PEEBI were non-iatrogenic patient-related factors,namely diabetes mellitus(OR=2.43,95％CI:1.14-4.85),bile duct malignancy(OR=3.95,95％CI:1.74-8.31)and duodenal papillary diverticulum(OR=4.39,95％CI:1.86-9.52).Compared with the LASSO model,the DAGs model showed higher ability(3.0％)in com-prehensive discrimination(P=0.007),as well as good differentiation performance(D=0.133,P=0.894)and cal-ibration performance(x2=5.499,P=0.703)in external validation.Conclusion The DAGs model constructed in this study has good predictive performance.With the help of this tool,targeted early preventive measures in clinical practice can be taken to reduce the occurrence of PEEBI.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Purpose::Intramedullary nailing is the preferred internal fixation technique for the treatment of subtrochanteric fractures because of its biomechanical advantages. However, no definitive conclusion has been reached regarding whether combined cable cerclage is required during intramedullary nailing treatment. This study is performed to compare the clinical effects of intramedullary nailing with cerclage and non-cerclage wiring in the treatment of irreducible spiral subtrochanteric fractures.Methods::Patients with subtrochanteric fractures admitted to our center from January 2013 to December 2021 were retrospectively analyzed. The patients were enrolled in the case-control study according to the inclusion and exclusion criteria and divided into the non-cerclage group and the cerclage group. The patients' clinical data, including the operative time, intraoperative blood loss, hospital stay, reoperation rate, fracture union time, and Harris hip score, were compared between these 2 groups. Categorical variables were compared using Chi-square or Fisher's exact test. Continuous variables with normal distribution were presented as mean ± standard deviation and analyzed with Student's t-test. Nonnormally distributed variables were expressed as median (Q 1, Q 3) and assessed using the Mann-Whitney test. A p < 0.05 was considered significant. Results::In total, 69 patients were included in the study (35 patients in the non-cerclage group and 34 patients in the cerclage group). The baseline data of the 2 groups were comparable. There were no significant difference in the length of hospital stay (z = -0.391, p = 0.696), operative time (z = -1.289, p = 0.197), or intraoperative blood loss (z = -1.321, p = 0.186). However, compared with non-cerclage group, the fracture union time was shorter (z = -5.587, p < 0.001), the rate of nonunion was lower (χ 2= 6.030, p = 0.03), the anatomical reduction rate was higher (χ 2= 5.449, p = 0.03), and the Harris hip score was higher (z =-2.99, p = 0.003) in the cerclage group, all with statistically significant differences. Conclusions::Intramedullary nailing combined with cable cerclage wiring is a safe and reliable technique for the treatment of irreducible subtrochanteric fractures. This technique can improve the reduction effect, increase the stability of fracture fixation, shorten the fracture union time, reduce the occurrence of nonunion, and contribute to the recovery of hip joint function.

Objective:To explore the risk factors for complications related to internal fixation after Inter-Tan intramedullary nail fixation in the treatment of intertrochanteric fractures in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 314 elderly patients with intertrochanteric fractures admitted to the Seventh Medical Center of the Chinese PLA General Hospital from January 2016 to December 2020, including 100 males and 214 females, aged 60-98 years [(80.2±8.2)years]. All the patients underwent Inter-Tan intramedullary nail fixation. According to the 2018 AO/OTA classification, 103 patients were with stable fractures and 211 with unstable fractures. The patients were further divided into complication groups and non-complication groups according to the presence of the complications during the follow-up. Six patients (5.8%) with stable fractures had the complications including nonunion in 4 and cut-out in 2. Twenty-eight patients (13.3%) with unstable fractures developed the complications, including nonunion in 5, cut-out in 20, cut-through in 1, and broken nails in 2. With the internal fixation-related complications after surgery as dependent variables, and gender, age, complications [hypertension, coronary heart disease, arrhythmia, pulmonary infection, chronic obstructive pulmonary disease (COPD), renal insufficiency, diabetes], bone density, waiting time for surgery, anesthesia method, reduction method, reduction quality, tip-apex distance, head screw displacement and other influencing factors as independent variables, univariate and multivariate Logistic regression analyses were conducted on the patients with stable fractures and unstable fractures separately to screen the independent risk factors of internal fixation-related complications.Results:For the patients with stable fractures, the univariate analysis indicated significant differences in bone density and reduction quality between the complication group and non-complication group ( P<0.05 or 0.01); the multivariate Logistic regression analysis showed that bone density T value ≤-3.0 SD ( OR=33.17, 95% CI 2.40, 457.82, P<0.01) and poor reduction quality ( OR=71.38, 95% CI 3.58, 1 422.02, P<0.01) were significantly correlated with the incidence of the postoperative complications. For the patients with unstable fractures, the univariate analysis indicated significant differences in age, reduction quality, bone density, tip-apex distance, and screw displacement between the complication group and non-complication group ( P<0.05 or 0.01); the multivariate Logistic regression analysis showed that age >80 years ( OR=2.82, 95% CI 1.01, 7.93, P<0.05), bone density T value ≤-3.0 SD ( OR=6.10, 95% CI 2.06, 17.51, P<0.01), poor reduction quality ( OR=12.25, 95% CI 2.90, 51.79, P<0.01), tip-apex distance ≥25 mm ( OR=3.65, 95% CI 1.20, 11.08, P<0.05), and head screw displacement <4 mm ( OR=7.26, 95% CI 2.54, 20.81, P<0.01) were significantly correlated with the postoperative complications. Conclusion:For Inter-Tan intramedullary nail fixation of intertrochanteric fractures in elderly patients, low bone density and poor reduction quality are independent risk factors for the postoperative complications in patients with stable intertrochanteric fractures; old age, low bone density, poor reduction quality, tip-apex distance, and head screw displacement are independent risk factors for the postoperative complications in patients with unstable fractures.

Objective:To explore the risk factors for heart failure after hip fracture surgery in the elderly patients and the impact of heart failure on their prognosis.Methods:A retrospective study was conducted to analyze the data of 1,478 elderly patients with hip fracture who had been admitted to The 7th Medical Center, General Hospital of the Chinese People's Liberation Army from January 2012 to December 2019. There were 482 males and 996 females with an age of 81 (75, 90) years. The patients were divided into a failure group and a failure-free group based on whether they had experienced any heart failure during postoperative hospitalization. After the clinical data were compared between the 2 groups, the variables with P<0.05 were included in the following multivariate logistic regression analysis to determine the risk factors for postoperative heart failure in the elderly patients with hip fracture. The mortality rates at 30 days and 1 year after operation, hospital stay, and incidence of postoperative complications were compared between the 2 groups. Results:Postoperative heart failure occurred in 7.0% (104/1,478) of the patients. The multivariate logistic regression analysis showed that advanced age ( OR=1.035, 95% CI: 1.006 to 1.065, P=0.018), male ( OR=1.727, 95% CI: 1.125 to 2.651, P=0.012), arrhythmia ( OR=1.830, 95% CI: 1.104 to 3.031, P=0.019), a high volume of blood transfusion ( OR=1.100, 95% CI: 1.001 to 1.209, P=0.048), and preoperative use of anticoagulant or antiplatelet drugs ( OR=1.921, 95% CI: 1.053 to 3.505, P=0.033) were risk factors for postoperative heart failure in the elderly patients with hip fracture. In the failure group, the mortality rates at 30 days and 1 year after operation were 9.6% (10/104) and 22.1% (23/104), and the incidence of postoperative complications was 32.7% (34/104), all significantly higher than those in the failure-free group [3.6% (49/1,374), 13.8% (190/1,374), and 17.5% (241/1,374)] ( P<0.05). The hospitalization time for the failure group was 14 (11, 19) days, significantly longer than that for the failure-free group [11 (9, 15) days] ( P<0.05). Conclusions:Advanced age, male, arrhythmia, a high volume of blood transfusion, and preoperative use of anticoagulant or antiplatelet drugs are risk factors for heart failure in the elderly patients after hip fracture surgery. Patients with heart failure may face poor prognosis, a high mortality rate, multiple complications, and long hospital stay.

Objective:To compare the failure risks between restricted and unrestricted cephalomedullary nail sliding during InterTAN intramedullary nail fixation for intertrochanteric fractures in the elderly patients.Methods:A retrospective study was conducted to analyze the data of 192 elderly patients with intertrochanteric fracture who had been admitted to Department of Orthopaedics, The Seventh Medical Center, General Hospital of the People's Liberation Army from January 2021 to December 2022. The patients were divided into 2 groups based on whether the set screws were tightened or not during surgery. In the observation group of 78 cases, there were 31 males and 47 females with an age of (80.2±7.7) years, and 23 cases of type 31-A1 and 55 cases of type 31-A2 by the AO classification. Their set screws were not tightened during surgery to allow the cephalomedullary nail sliding. In the control group of 114 cases, there were 40 males and 74 females with an age of (81.6±7.8) years, and 42 cases of type 31-A1 and 72 cases of type 31-A2. Their set screws were tightened during surgery to restrict the cephalomedullary nail sliding. The incidence of postoperative fixation complications and sliding distances of the cephalomedullary nail within 1 year after surgery were compared between the 2 groups in the total fractures and in the stable and unstable fractures as well.Results:There was no statistically significant difference in the preoperative general data between the 2 groups of patients, indicating comparability ( P>0.05). The incidence of fixation complications within 1 year after surgery was 5.1% (4/78) for the observation group and 12.3% (14/114) for the control group, showing no statistically significant difference between the 2 groups ( P>0.05). The sliding distance of the cephalomedullary nail in the observation group [7.05 (6.00, 8.25) mm] was significantly larger than that in the control group [5.65 (3.55, 7.00) mm] ( P<0.05). For stable fractures, the incidence of fixation complications within 1 year after surgery was 7.1% (2/28) for the observation group and 7.0% (3/43) for the control group, showing no statistically significant difference ( P>0.05), and the sliding distance of the cephalomedullary nail in the observation group [6.00 (5.25, 7.00) mm] was significantly greater than that in the control group [3.05 (2.00, 5.00) mm] ( P<0.05). For unstable fractures, the incidence of fixation complications within 1 year after surgery for the observation group patients [4.0% (2/50)] was significantly lower than that for the control group patients [15.5% (11/71)], and the sliding distance of the cephalomedullary nail in the observation group [8.00 (6.70, 10.00) mm] was significantly greater than that in the control group [6.00 (4.87, 7.57) mm] ( P<0.05). Conclusions:In the InterTAN intramedullary nail fixation for intertrochanteric fractures in the elderly patients, tightening of set screws is crucial because it not only increases the stability but also limits compression at the fracture site. It is recommended not to tighten the set screws for unstable fractures, but further observation is needed before it can be determined whether the set screws should be tightened or not for stable fractures.