Objective:To investigate whether celastrol can increase the cytotoxic activity of γδ T cells against osteosarcoma (OS) cells line HOS through TRAIL way. Methods:The death receptors 4/5 (DR4/5) protein levels in the OS cell lines HOS was in-vestigated by Western blot analysis. Zoledronate ( ZOL) was used to induceγδT cells from PBMCs of healthy volunteers.γδT cell cy-totoxicity against HOS cells was investigated by a standard lactate dehydrogenase release assay ( LDH ) . Results:Celastrol increased DR4/5 protein expression in HOS ( P<0. 05 ) .γδ T cells from PBMCs of healthy volunteers showed cytotoxicity against HOS ( P<0. 05). Following co-culture with HOS pre-treated with celastrol (1 μmol/L) for 24 h,γδ T cells showed significantly higher cytotoxicity against HOS (P<0. 05). The induction of DR4/5 molecules increased lysis of HOS by γδ T cells which was abolished by addition of a blocking TRAIL antibody. Conclusion:Celastrol can enhance γδ T cells'cytotoxic activity against OS cells line HOS through TRAIL way.

To analyze the risk factors for peri-operative mortality in patients with total anomalous pulmonary venous connection (TAPVC). Methods: A total of 563 TAPVD patients including atrial septal defect, ventricular septal defect and patent ductus arteriosus treated in our hospital from 1996-10 to 2012-12 were retrospectively investigated. There were 219 (38.9%) male, the mean age of patients was (4.6±9.0) years and the mean body weight was (13.2±14.6) kg. The patients were divided into 2 groups: Death group, n=34 and Survival group, n=529. Risk factors for peri-operative mortality were studied by single and multi Logistic regression analysis. Results: The overall peri-operative mortality was 6.0% (34/563). Compared with Survival group, Death group had more patients≤1 year of age (P=0.008), the higher ratio of elective surgery (P=0.002), the longer cardiopulmonary bypass time (P=0.000) and longer aorta clamping time (P=0.001). Multi Logistic regression analysis presented that the age≤1 year was the independent risk factor for TAPVC peri-operative death (OR=3.802, P=0.013) and elective surgery was the protective factor for TAPVC peri-operative death (OR=0.234, P=0.027). Conclusion: The patient's age≤1 year was the independent risk factor for TAPVC peri-operative death, while elective surgery was the protective factor for TAPVC peri-operative death.

Objective To investigate the effects of esophagogastric intramural anastomosis on preventing reflux esophagitis by restoring the cardiac function after esophagectomy.Methods The clinical data of 66 esophagem or cardiac cancer patients(test group)who received esophagogastrie intramural anastomosis at Second Affiliated Hospital of Xi'an Jiaotong University from January 2002 to October 2008 were retrospectively analyzed.Sixty-five patients who received stapled anastomosis during the same period were in control group.Postoperative conditions of patients in the 2 groups were compared by chi-square test and t test.Results (1)Reflux condition:there were 3 patients with degree I and 63 without reflux in test group,and 23 with degree Ⅰ,19 with degree Ⅱ,7 with degree Ⅲ and 16 without reflux in control group.There was a significant difference between the 2 groups(X~2=137.3,P<0.05);(2)results of barium meal fluoroscopy:12 patients in test group and 41 patients in control group had barium reflux,with significant difference between the 2 groups(X~2=27.4,P<0.05);(3)results of gastroscopy:9 patients in test group and 46 patients in control group had morphological changes of mucosa,with significant difference between the 2 groups(X~2=43.5,P<0.05);(4)esophageal sphincter pressure:the pressure of lower esophageal sphincter was(3.4±0.8)kPa in test group and(2.5±0.6)kPa in control group,and the pressure of upper esophageal sphincter wag(7.4±1.7)kPa in test group and(4.2±0.8)kPa in control group.There was a significant difference in esophageal sphincter pressure between the 2 groups(t=4.98,11.59,P<0.05).Conclusion Esophagogastric intramural anastomosis can partly restore the cardiac function and prevent reflux esophagitis effectively.

Objective To investigate the long-term anticoagulation starus and relation of INR and complica-tion,best anticoagulation range and clinical significance in patients after mechanical heart valve replacement. Meth-ods The data of blood clotting test series(containing PT,PT% ,PTR,INR,Fbg,APTT) for patients after 6 months of mechanical heart valve replacement were collected, then the cases were divided into 4 groups according to their INR levels( group Ⅰ : INR < 1.5; group Ⅱ : INR 1.5 ～ 2.0 ; group Ⅲ : INR 2.1 ～ 2.5 ; group Ⅳ : INR > 2.5 ). Results Group Ⅰ contained 28 person-times, with their dosage of warfarin for (3.61 ± 1.44 ) mg, INR 1.38 ± 0. 12, core-bral embolism occurred for 4 person-times,with a inception rate of 14%. Group Ⅱ contained 92 person-times,with their dosage of warfarin for (3.5±1.37)mg,INR 1.65±0. 14,hemorrhinia occurred for 2 person-times,with a in-ception rate of 2%. Group Ⅲ contained 80 person-times, with their dosage of warfarin for (3.18±1.63 )mg, INR 2.23±0.19 ,bematuria occurred for 2 person-times, bemorrhinia occurred for 2 person-times, with a total inception rate of 5% ; Group Ⅳ contained 16 person-times, with their dosage of warfarin for ( 2.32 ± 1. 23 ) mg, INR 2.80± 0.19, hemorrhinia occurred for 2 person-times and hemoptysis occurred for 1 person-times, with a total inception rate of 18.7%. The person-times in group Ⅱ and Ⅲ accounted for 79.6% and the complication rate was the lowest when INR was between 1.5-2.5. Conclusions INR levels between 1.5-2.5 is the most secure, which is the best antico-agu]ation range in our region. Since the anticoagulation strength dynamically changes, the long-term anticoagulation status in patients after mechanical heart valve replacement should be deeply concerned.

BACKGROUND:Titanium artificial cervical disc has good biocompatibility, but titanium al oy is shown to have poor biological activity, low bonding strength, easy release of metal ions under physiological conditions.
OBJECTIVE:To observe the effects of different coating for the titanium plate of domestic cervical artificial disc on adhesion and differentiation ability of rat bone marrow mesenchymal stem cel s.
METHODS:Passage 3 bone marrow mesenchymal stem cel s from Wistar rats were seeded into 24-wel titanium plates with hydroxyapatite coating, titanium powder+hydroxyapatite coating and bare titanium plate. Cel culture was terminated after 24 and 48 hours, and the cel growth was observed under scanning electron microscope. After 24 hours of inoculation, osteogenic inducer was added;then, cel supernatant was col ected at 3, 5, 7 days after cel lysis and centrifugation to detect the activity of alkaline phosphatase.
RESULTS AND CONCLUSION:After composite culture with titanium plates with hydroxyapatite coating or
titanium powder+hydroxyapatite coating, cultured cel s were in polygonal shape, and pseudopodia were extended into the micropores that were adhered closely to the material surface. Cel s cultured with bare titanium plates had poor differentiation and adhesion rate. With time, the expression of alkaline phosphatase was increased in each group, especial y in the groups of titanium plates with hydroxyapatite coating and titanium powder+hydroxyapatite coating (P<0.05). These findings indicate that titanium plates with hydroxyapatite coating or titanium powder+hydroxyapatite coating can promote adhesion and differentiation of rat bone marrow mesenchymal stem cel s.

Objective:To investigate the diagnostic performance of continuous-time random-walk (CTRW) diffusion model combined with vesical imaging-reporting and data system (VI-RADS) in the diagnosis of muscle invasion of bladder cancer.Methods:In this case-control study, 64 patients with pathologically confirmed bladder urothelial carcinoma in Peking University First Hospital were retrospectively enrolled from August 2022 to March 2023. The patients were divided into the muscle invasive bladder cancer (MIBC) group and the nonmuscle invasive bladder cancer (NMIBC) group (29 cases and 35 cases, respectively) according to the pathological results. All patients underwent bladder MRI within 4 weeks before surgery, including T 2WI, conventional diffusion weighted imaging (DWI), and multi-b-value DWI. The CTRW model was used to obtain three quantitative diffusion parameters, including D m (an anomalous diffusion coefficient), α (related to temporal diffusion heterogeneity), and β (related to spatial diffusion heterogeneity). The apparent diffusion coefficient (ADC) was calculated using a mono-exponential model. The VI-RADS scores were evaluated based on T 2WI and conventional DWI. The Mann-Whitney U test was used to compare the diffusion parameters between the MIBC group and the NMIBC group. The combination of the parameters was investigated with logistic regression analysis. The diagnostic performance for muscle invasion of bladder cancer was evaluated by receiver operating characteristic analysis and the area under the curve (AUC). The difference between AUC was compared using the DeLong test. Results:There were statistically significant differences in ADC, D m, and α between the MIBC group and the NMIBC group ( Z=-2.31, -2.91, -3.97, P=0.021, 0.004,<0.001). No significant difference was found in β between the two groups ( Z=1.69, P=0.091). The AUC (95% CI) of D m and α for diagnosing MIBC were 0.712 (0.587-0.838) and 0.790 (0.676-0.904) respectively, both of which were higher than that of ADC (AUC 0.669, 95% CI 0.537-0.801) with statistically significant differences ( Z=2.86, 2.27, P=0.004, 0.023). The AUC (95% CI) of CTRW (D m+α) was 0.782 (0.661-0.876), which was significantly higher than that of ADC ( Z=2.35, P=0.019). The AUC (95% CI) of VI-RADS score and VI-RADS combined with CTRW parameter (VI-RADS+D m+α) were 0.823 (0.716-0.930) and 0.900 (0.799-0.961) respectively, with a statistically significant difference between them ( Z=2.16, P=0.031). Conclusion:The D m and α parameters in the CTRW diffusion model show better performance than the ADC in the mono-exponential model for muscle-invasive evaluation of bladder cancer, and the CTRW diffusion model can enhance the diagnostic performance of VI-RADS.

Posterior reversible encephalopathy syndrome is a clinical and radiological entity,caused by a variety of reasons.We report a case of rhabdomyolysis complicated by posterior reversible encephalopathy and suggest that giving fluids early,use of diuretics and alkalization of urine may be reasonable for patients with rhabdomyolysis.Monitoring blood pressure is noteworthy to prevent target organ damage,and if patient condition steadily deteriorates,hemodialysis should be initiated.

BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. METHODS: Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. RESULTS: lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. CONCLUSION Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
Humans ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; MAP Kinase Signaling System ; MicroRNAs/metabolism* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; RNA, Long Noncoding/metabolism* ; Triple Negative Breast Neoplasms/pathology*

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Objective:To study the morphologic features of the fusion site of proximal tibial epiphysis in normal adults and analyze its potential clinical value based on Mimics three-dimensional (3D) reconstruction.Methods:CT images of knee joint of 68 patients without obvious abnormalities of lower limbs were retrospectively analyzed in electronic database of our hospital from June 2020 to June 2021, including 41 males and 27 females. The mean age of the patients was 38.7±8.4 years (range, 25-55 years), and the mean body mass index (BMI) was 25.3±4.0 kg/m 2 (range, 18.75-41.8 kg/m 2). Mimics 3D reconstruction technique was used to reconstruct the 3D model of the proximal tibia and epiphyseal fusion site. The relationship between the surface area of epiphyseal fusion site and age and BMI was studied, and the changes of cortical thickness and density at epiphyseal fusion site were also explored. Results:The fusion site of adult epiphyseal reconstructed by Mimics 3D reconstruction is a complex wavy surface structure in 3D space. The surface area of the epiphyseal fusion site was 2,994.7±645.3 mm 2 (range, 1,704.0-4,650.0 mm 2) obtained by 3-Matic Research 12.0. The fusing area of male epiphysis was 3 269.3±533.9 mm 2 than that of female 2,577.6±578.7 mm 2, the difference was statistically significant ( t=5.06, P<0.001). However, there was no significant correlation between the epiphyseal fusion site surface area and age ( R2=0.02, P=0.268) and BMI ( R2=0.04, P=0.125). Mimics software was used to obtain the CT values of bone cortex at the epiphysis line and the distal end of the epiphysis line at 10 mm and 20 mm levels as 451.059±74.953 Hu, 1,018.412±125.732 Hu and 1,414.162±107.848 Hu, respectively. The thickness of bone cortex was 1.814±0.090 mm, 2.511±0.089 mm and 3.189±0.185 mm at 10 mm and 20 mm layers of epiphysis line and distal epiphysis line, respectively. Conclusion:In this study, Mimics 3D reconstruction technique was used to visualize the fusion site of the proximal tibial epiphysis in normal adults. The epiphyseal fusion site of adult is a undulating plate-like structure, and the cortical bone density of epiphyseal fusion site is low and thin, theoretically, it is easy to fracture under indirect violence.