Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective To investigate the effects of menaquinone-4(MK4)on the activation and function of CD8+T cells.Methods An in vitro culture system for primary mouse CD8+T cells was established by isolating these cells from the spleen using CD8a T cell isolation kit.The isolated CD8+T cells were then incubated and activated in a 96-well plate coated with anti-CD3/CD28 antibodies.The impact of MK4 on the activation and cytokine secretion of CD8+T cells was explored by quantifying the expression levels of CD8+T cell activation receptors and cytokines using flow cytometry.Additionally,the concentrations of these cytokines in the culture supernatant were measured by enzyme-linked immunosorbent assay(ELISA).The influence of MK4 on the anti-tumor function of CD8+T cells was evaluated by co-culturing colorectal cancer MC38 cells of mice with CD8+T cells at different ratios,and the effect of MK4 was assessed by detecting tumor cell apoptosis.Results High-purity primary CD8+T cells of mice(97.5％)were isolated using the magnetic bead,which could be activated by pre-coated CD3/CD28 antibodies and showed proliferation.Compared with the control group,the MK4-treated group exhibited increased expressions of CD25,CD69 and CD44 on CD8+T cells,as well as higher production and secretion levels of interleukin-2(IL-2),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)and granzyme B.In addition,CD8+T cells in the MK4-treated group induced a higher percentage of tumor cell apoptosis(36.7％)compared with the control group(29.1％).Conclusion MK4 can enhance the activation of CD8+T cells and promote anti-tumor functions.

Objective:To investigate the application value of peri-gastric devasculariza-tion without dissociation of esophagus for portal hypertension.Methods:The retrospective and descriptive study was conducted. The clinical data of 94 patients with portal hypertension who were admitted to three medical centers, including 75 cases in the People′s Hospital of Ningxia Hui Autonomous Region, 12 cases in the People′s Hospital of Wuhai and 7 cases in the People′s Hospital of Wuzhong, from July 2018 to December 2022 were collected. There were 68 males and 26 females, aged 46(range, 21-70)years. All 94 patients underwent peri-gastric devascularization without dissociation of esophagus. Observation indicators: (1) intraoperative condition; (2) postoperative complications; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Intraoperative condition. All 94 patients underwent surgery success-fully without operation death, including 82 cases receiving open surgery and 12 cases receiving laparoscopic surgery. The operation time and volume of intraoperative blood loss were (183±85)minutes and 289(range, 158-560)mL, respectively, for the 94 patients. (2) Postoperative complications. Of 94 patients, early portal vein thrombosis occurred in 24 cases, intra-abdominal infection occurred in 2 cases, hepatic encephalopathy occurred in 1 case, pulmonary embolism occurred in 1 case, intra-abdominal hemorrhage requiring operation to stop bleeding occurred in 1 case and pleural effusion requiring drainage occurred in 1 case. All patients with postoperative complications were cured after treatment. None of the 94 patient had postoperative esophageal complications such as odynophagia or dysphagia. (3) Follow-up. All 94 patients were followed up for 38(range, 6-60)months. Of the 45 patients with paraesophageal vein, there were 36 cases of thinner and 9 cases of occlusion of the distal subphrenic paraesophageal vein after surgery, respectively. Cases with esophageal varices disappearance, cases with mild and moderate residual of esophageal varices, cases with severe residual of esophageal varices, cases with recurrence of esophageal varices, cases with esophageal varices bleeding were 7, 70, 9, 4, 4 in the 94 patients after surgery. Cases with esophageal varices disappearance was 7 in the 45 patients with paraesophageal vein, versus 0 in the 49 patients without paraesophageal vein, showing a significant difference between them ( P<0.05). Of 94 patients, 17 cases developed postoperative late portal vein thrombosis and cavernous transformation, 7 cases developed liver cancer, 1 case had hepatic encephalopathy, and 6 cases died. Conclusion:Peri-gastric devascularization without dissociation of esophagus is safe and feasible for the treatment of portal hypertension.

Objective:To analyze the short and mid-term efficacy of aortic valvuloplasty with autopericardium on children with aortic valve diseases.Methods:A total of 26 children with aortic valve diseases (stenosis or regurgitation) who underwent aortic valvuloplasty with autopericardium in Fuwai Central China Cardiovascular Hospital from September 2017 to June 2021 were retrospectively analyzed.The short-term and mid-term follow-up data were collected.The maximum aortic valve pressure gradient, subaortic regurgitation area, left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were compared before and after operation.Paired t test was used to analyze the short-term and mid-term efficacy of aortic valvuloplasty with autopericardium on children with aortic valve diseases. Results:All 26 cases were successfully operated, and there were no deaths and serious complications during the follow-up period of (22.96±6.45) months.There was a significant difference between the preoperative and postoperative maximum aortic valve pressure gradient at 1 month ( t=7.85, P<0.05), 6 months ( t=6.43, P<0.05), 1 year ( t=6.16, P<0.05) and 2 years postoperatively ( t=4.22, P<0.05) in children with aortic stenosis or that combined with mild-to-moderate closure.The follow-up data of 9 children with simple aortic stenosis showed that there was a significant difference between the preoperative (8.87±3.57) cm 2 and postoperative aortic regurgitation area at 1 month ( t=6.85, P<0.05), 6 months ( t=5.13, P<0.05), 1 year ( t=6.62, P<0.05) and 2 years postoperatively ( t=5.41, P<0.05). The LVEDV of 26 children was significantly lower at 6 months[(63.54±27.61) mL], 1 year [(53.61±20.20) mL] and 2 years postoperatively [(64.39±17.78) mL] compared with that of preoperative level[(89.42±45.89) mL]( t=3.89, 4.67, 3.58, all P<0.05). The left ventricular pressure and volume decreased, the enlarged heart was narrowed down, and the geometry of the heart was restored.The LVEF of 26 patients also from (61.65±9.67)% before surgery increased to (67.88±4.69)% 6 months after surgery( t=3.68, P<0.05), and increased to (68.62±4.46)% 1 year after surgery( t=4.01, P<0.05), and increased to (67.55±3.09)% 2 years after operation( t=3.01, P<0.05), and the heart function was improved. Conclusions:Aortic valvuloplasty with autopericardium presents an effective short and mid-term efficacy on children with aortic valve diseases, which prevents or delays the aortic valve replacement.

Objective:To summarize the thoracic and abdominal CT presentations after endoscopic full-thickness resection (EFR) and to analyze its significance in the evaluation and management of postoperative complications.Methods:Data of 82 patients who underwent gastrointestinal EFR at the Endoscopy Center of Zhongshan Hospital, Fudan University and received a chest and/or abdominal CT within 1 week from September 2016 to September 2021 were collected retrospectively. The patients were divided into the intervention group ( n=38) and the control group ( n=44) according to the presence or absence of special postoperative interventions or prolonged hospital stays. The differences in the incidence of abnormal CT presentations between the two groups were analyzed. Risk factors for abnormal CT presentation were explored by multifactorial analysis. Results:Among the 82 patients, the main CT presentations were pneumoperitoneum in 51 patients (62.2%), abdominal and pelvic effusion in 30 patients (36.6%), pneumothorax in 5 (6.1%), pleural effusion in 43 (52.4%), and pulmonary inflammation in 16 (19.5%). The incidence of pelvic and abdominal effusions ( W=637.48, P=0.031) and pleural effusions ( W=622.06, P=0.031) in CT was higher in the intervention group than that in the control group. Age was an independent risk factor for air-related complications after EFR (>60 years old VS ≤60 years old: OR=0.17, 95% CI: 0.05-0.56, P=0.002). Conclusion:CT presentations of pelvic and abdominal effusion and pleural effusion after EFR is of great significance in suggesting complications, while patients with other CT presentations often do not require special intervention or prolonged hospital stay. Postoperative CT in elderly patients is less likely to detect air-related complications.

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus oxiracetam in treating mild vascular dementia (VD) and seek its underlying mechanism. Methods: Ninety-six patients with mild VD were randomized into an observation group and a control group, with 47 cases in the observation group and 49 cases in the control group. The control group received oral oxiracetam capsules for treatment, and the observation group was given additional Tuina treatment. Before and after treatment, the mini-mental state examination (MMSE) was adopted to assess the patient's cognitive function; the activities of daily living (ADL) scale was used to evaluate their ability to conduct daily activities; changes in the serum inflammatory factors and oxidative stress indicators were also detected. Results: After treatment, the serum content of malondialdehyde (MDA) decreased in both groups (P<0.05) and was lower in the observation group than in the control group (P<0.05); the serum contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) increased in both groups (P<0.05) and were higher in the observation group than in the control group (P<0.05); the serum contents of interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-6, and IL-8 declined in both groups (P<0.05) and were lower in the observation group than in the control group (P<0.05). After the intervention, the levels of systolic velocity (Vs) and mean velocity (Vm) of the middle cerebral artery elevated, and the pulsatility index (PI) dropped in patients in the two groups, showing significant intra-group differences (P<0.05); the levels of Vs and Vm in the observation group were higher than those in the control group, and the PI was lower in the observation group than in the control group, showing significant between-group differences (P<0.05). The MMSE and ADL scores increased in both groups after the intervention (P<0.05) and were higher in the observation group than in the control group (P<0.05). Conclusion: In the treatment of mild VD, Tuina plus oxiracetam can improve the cerebral blood supply, ADL, and cognitive function; the mechanism may be associated with the reduction of oxidative stress damages and inflammatory reactions.

Objective:To investigate the positive rates of 2019-nCoV nucleic acid in different specimens from confirmed COVID-19 cases during hospitalization and after discharge.Methods:Patients with confirmed COVID-19 were enrolled from designated hospitals. Nasal swabs, throat swabs, and specimens of stool, urine and blood were collected during hospitalization. After the patients were discharged, nasal swabs, throat swabs and stool specimens were collected during follow-up. Real-time RT-PCR was used to detect 2019-nCoV nucleic acid.Results:This study involved 25 confirmed COVID-19 cases. During hospitalization, all patients tested positive in both nasal and throat swab 2019-nCoV nucleic acid tests, and nine of them (36.00%) were positive in stool specimen test. Urine and blood specimen test results were all negative. Nasal swabs, throat swabs and stool specimens were collected from each patient 7 d and 14 d after discharge. Two patients (8.00%) tested positive for 2019-nCoV nucleic acid again in nasal and throat swab tests on 7 d, while all stool specimen tests were negative. No 2019-nCoV nucleic acid was detected in nasal swabs, throat swabs or stool samples on 14 d.Conclusions:2019-nCoV nucleic acid was detected in stool samples of confirmed COVID-19 cases during hospitalization. Nasal and throat swab nucleic acid tests turned positive again in some patients after discharge.

Objective:To investigate the efficacy and safety of short-term transcatheter arterial chemoembolization （TACE）-radiofrequency ablation （RFA） sequential therapy for advanced hepatocellular carcinoma (HCC).Methods:The clinical data of 117 patients with advanced HCC enrolled in the Central Hospital of Lishui from March 2010 to January 2019 were retrospectively analyzed. All patients received TACE and RFA sequential therapy. The patients were divided into 2 groups including short interval group (interval≤7 d, 61 cases) and long interval group (interval>7 d, 56 cases) according to interval between TACE and RFA. The difference of response rate was analyzed by Wilcoxon test. Kaplan-Meier survival curve was used to calculate the overall survival (OS) time and progression free survival (PFS) time.The risk factors of TACE-RFA sequential therapy were tested using Cox multivariate analysis. The complications in the two groups were compared using χ 2 test. Results:The response rate in the short interval group (72.1%, 43/61) was significantly higher than that in the long interval group (41.1%，23/56) with significant difference ( Z=-2.50, P=0.01). The median PFS in the short interval group (14.9 months) was longer than that in the long interval group (9.1 months). The difference of PFS survival curve between the 2 groups was statistically significant (χ2 =5.90, P=0.01).The median OS in the short interval group (34.7 months) was longer than that in the long interval group (20.3 months). The difference of OS survival curve between the 2 groups was statistically significant (χ2 =6.60, P=0.01). Cox multivariate analysis showed that tumor size [hazard ratio (HR)=2.42, P<0.01], cirrhosis (HR=2.04, P<0.01), interval (HR=0.44, P<0.01), aspartate aminotransferase (HR=1.71, P=0.03) were the independent risk factors for advanced HCC.There were no significant differences in the complication incidence between the 2 groups ( P>0.05). Conclusion:Short-term interval TACE-RFA sequential therapy as a protective factor is efficient and safe for advanced HCC treatment.

Objective To summarize the outcomes and the median follow －up finding of stage 1 surgical approaches of coarctation of aorta(CoA)combined with cardiac anomalies.Methods A retrospective study was per-formed for summarizing the operative and follow－up finding of 82 patients(40 males and 42 females)of CoA combined with cardiac anomalies,who underwent stage 1 repair from February 2013 to December 2016 at the Department of Cardio-vascular Surgery,Henan Provincial People's Hospital.The operative age was ranged from 1 month to 8 years old[mean (11.92 ± 22. 51)months]and the weight was (7.31 ± 6.79)kg. Forty －five cases had ventricular septal defect (VSD)or atrial septal defect (ASD).Septal defect and patent ductus arteriosus were found in 31 patients.CoA was associated with aortic arch hypoplasia in 5 patients.Complex cardiovascular deformity was found in 7 cases.The surgical methods included end－to－end anastomosis,end－to－side anastomosis and patch augmentation of the coarctation seg-ment.Results Seven patients died after operation,3 cases of them died of low cardiac output syndrome amd circulatory failure,1 case died of circulatory failure and respiratory failure,1 patient died of malignant arrhythmia,and 2 cases died of respiratory failure.Postoperative echocardiogram suggested that anastomosis maintained patency in all the patients. The follow－up time was 8 months to 4 years,63 patients were followed up,and follow－up rate was 77%.No death or aneurysm occurred during follow－up period.Recoarctation was found in 5 cases.Conclusions Stage 1 repair for CoA combined with cardiac anomalies is effective,and has low complications during postoperative and median follow－up period.Long－term results need further study.