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 clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95％CI 0.758～0.918),0.774(95％CI 0.656～0.892),and 0.700(95％CI 0.589～0.810),respectively,and the value of their combined model was 0.899(95％CI 0.811～0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71％and 86.52％,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P＜0.001,95％CI 0.140～0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.

Objective: To compare the clinical effects of endoscopic thyroidectomy using a modified gasless transsubclavian approach and the traditional neck approach for unilateral papillary thyroid carcinoma (cN0). Methods: The clinical data of 135 patients with cN0 papillary thyroid carcinoma who underwent unilateral thyroidectomy in the Department of Thyroid Surgery, the First Hospital of Jilin University from October 2020 to November 2022 were retrospectively analyzed. There were 37 males and 98 females, aging (43.2±8.8) years (range: 21 to 59 years). There were 51 cases using the modified gasless transsubclavian approach (TS group) and 84 cases using the traditional neck approach (TN group). Comparative analyses were performed between the operative results of the 2 groups by t-test, Wilcoxon rank sum test, and χ² test. Results: All endoscopic operations were successfully completed without conversion to the traditional neck approach. Compared to the TN group, the TS group had a longer operation time (M(IQR)) (73.5 (22.5) minutes vs. 90.0 (30.0) minutes, Z=-5.831, P<0.01), more postoperative drainage (60 (25) ml vs. 95 (45) ml, Z=-6.275, P<0.01), higher hospitalization costs (22 687 (3 488) yuan vs. 26 652 (2 431) yuan, Z=-6.944, P<0.01), and a higher rate of parathyroid autotransplantation (15.5% (13/84) vs. 60.8% (31/51), χ²=29.651, P<0.01). There was no significant difference in the total exposure rate of the central compartment, postoperative hospitalization time, the number of dissected lymph nodes, the number of metastatic lymph nodes, C-reactive protein ratio before and after operation, and preoperative and postoperative parathyroid hormone (all P>0.05). Conclusions: Endoscopic thyroidectomy using the modified gasless transsubclavian approach is safe for cN0 papillary thyroid carcinoma, with longer operating time, more postoperative drainage, higher hospitalization costs, and moredifficulty in preserving the inferior parathyroid gland in situ compared to traditional open surgery.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

In order to establish an infectious clone for CDV-3, a commercial vaccine strain of canine distemper virus for mink, to provide reference for the studies of pathogenesis and novel vaccine development of CDV. Thirteen pairs of primers were used to amplify the full-length genome of CDV-3 strain. Five long fragments were obtained based on single restriction site analysis of the whole genome of CDV-3 by RT-PCR. Five fragments were successively inserted into the multiple clone sites in the modified eukaryotic vector of pcDNA3.2 by restriction enzymes and splicing. Meanwhile, the hammerhead ribozyme and hepatitis delta virus ribozyme sequences were added to the beginning of F1 fragment and the ending of F5 fragment, respectively. Then, the full-length cDNA recombinant plasmid of CDV-3 was obtained and named as pcDNA3.2-CDV-3. In addition, three helper plasmids, expressing the N protein, P protein and L protein of the CDV-3 strain respectively, were constructed. The 293T cells were transfected with the full-length cDNA recombinant plasmid and three helper plasmids by Lipofectamine™ 2000. At 3 days post transfection, the supernatant was added to the monolayer of Vero cells to observe the typical syncytium of CDV. Indirect immunofluorescence and artificial label identification of recombinant virus rCDV-3 were conducted after the occurrence of lesions. Finally, the growth characteristics of wtCDV-3 and rCDV-3 were compared after passaging of rCDV-3. The identification of the full-length cDNA recombinant plasmid and three helper plasmids by restriction enzyme digestion and sequencing were consistent with expected. The Vero cells infected with the recombinant rCDV-3 showed typical syncytic. The identification of indirect immunofluorescence and labeled marker, and observation under electron microscope proved that the rCDV-3 was indeed rescued from the recombinant plasmid of pcDNA3.2-CDV-3. In comparison of the virus titers of wtCDV-3, rCDV-3 replicated massively and rapidly and reached the maximize virus titer of 10⁷·⁶⁶⁷ TCID₅₀/mL within 36 h post infection (p.i.) in Vero cells, while wtCDV-3 grew gradually to 10⁶·⁶⁶⁷ TCID₅₀/mL at 72 h p.i. in Vero cells. This reverse genetic system of CDV-3 strain has been established successfully, to provide reference for the studies of pathogenesis and novel vaccine development of CDV.
Animals ; Chlorocebus aethiops ; Clone Cells ; DNA, Complementary ; Distemper Virus, Canine/genetics* ; Plasmids/genetics* ; Vero Cells

OBJECTIVE：To develop a method for simultaneous determination of 5 components in classical formula Huaihua san，including rutin ，naringin，neohesperidin，quercetin and pulegone. METHODS ：HPLC wavelength switching method was adopted. The determination was performed on Cosmosil C 18 column with mobile phase consisted of acetonitrile- 0.05％ phosphoric acid solution （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelengths were set at 257 nm for rutin ，283 nm for naringin and neohesperidin ，254 nm for quercetin ，252 nm for pulegone ，respectively. The column temperature was set at 30 ℃， and sample size was 10 μL. RESULTS：The linear range was 21.7-2 170 μg/mL for rutin，46-4 600 μg/mL for naringin，22.3- 2 230 μg/mL for neohesperidin，0.96-96 μg/mL for quercetin，2.7-270 μg/mL for pulegone（all r＞0.999），respectively. RSDs of precision，stability（24 h）and reproducibility tests were all lower than 2％（n＝6）. Average recoveries were 100.70％，99.31％， 101.10％，100.03％ and 99.63％（all RSD ＜2％，n＝9）. Among 3 batches of Huaihua san samples ，the contents of above 5 components were 20.055-22.615，25.557-27.806，11.428-13.250，0.350-0.478，2.372-4.011 mg/g，respectively. CONCLUSIONS ： Established method is simple ，accurate and reproducible ，and could be used for the simultaneous determination of 5 components in Huaihua san.

The aim of this study was to evaluate the safety and immunogenicity of the first domestic ACYW135 meningococcal conjugate vaccine and a control vaccine named AC group meningococcal conjugate vaccine for 3 months (90-119 days) infants. From February 2017 to June 2018, a randomized, blinded, and similar vaccine-controlled clinical trial design was adopted at the Henan Vaccine Clinical Research Base. The subjects were 3 months old healthy infants, a total of 720, based on a 1∶1 ratio. The random allocation table for entry was randomly assigned to the experimental group and the control group. According to the 3, 4, and 5 month-old vaccination procedures, the subjects were vaccinated with test vaccine (ACYW135 group meningococcal conjugate vaccine) and control vaccine (group A group C meningococcal polysaccharide conjugate vaccine), of which 720 were given the first dose, 696 were given the second dose (test group: 346; control group: 350), and 692 were given the third dose (test group: 344; Control group: 348). The overall adverse reaction rate of the test vaccine was 21.90% (230 cases), which was lower than the 32.04% (339 cases) of the control vaccine (<0.001). The incidence of systemic adverse reactions was 19.52% (205 cases), which was lower than that of the control vaccine (27.69%) (293 cases) (<0.001). The local adverse reaction rate was 3.04% (32 cases), which was lower than the control group (7.84%) (83 cases) (<0.001). The graded adverse reaction test vaccine was 0.57% (6 cases), which was lower than the control group of 2.36% (25 cases) (<0.001). The positive conversion rate of anti-bacterial serum antibodies showed that there was no significant difference between the test vaccine group A (91.42%), C (88.76%) and the control vaccine (92.92%) (87.02%) (>0.05). Group Y and W135 was 88.17% (298 cases), 99.41% (336 cases), respectively. The GMT results showed that the test vaccine group A was 56.24, the control vaccine was 57.43 (>0.05); the group C test vaccine (43.53) was higher than the control group (27.28) (<0.001). The group Y and W135 are 89.22 and 140.66, respectively. Among them, the proportion of the group C GMT antibody ≥ 1∶128 for test vaccine (31.07%, 105 cases) was higher than the control vaccine (16.22%, 55 cases) (<0.001). ACYW135 group meningococcal conjugate vaccine has more safety and immunogenicity after application to 3 month old infants.
Antibodies, Bacterial ; Humans ; Infant ; Meningococcal Vaccines ; adverse effects ; immunology ; Vaccines, Conjugate

The liver is one of the most easily metastasized target organs of many malignant tumors and the proportion of metastatic tumors is higher than that of intrahepatic primary tumors. The existence of liver metastases is an important factor in the treatment of malignant tumors. Therefore, the detection and characterization of liver metastases are particularly important. The main imaging methods for hepatic metastases include ultrasound (US), computed tomography(CT), magnetic resonance imaging(MRI), positron emission computed tomography (PET/CT) and PET/MRI. In this paper, the advantages and limitations of the above imaging methods in the diagnosis of liver metastasis are analyzed, and the application progress of various imaging methods is emphasized.

Objective To investigate the relationship between preoperative albumin-to-alkaline phosphatase ratio and overall survival (OS) after radical cystectomy of bladder cancer.Methods The clinical date of patients with bladder cancer who underwent radical cystectomy and urinary diversion and confirmed by pathology from Jan 2007 to Dec 2015 were analyzed retrospectively,with 140 cases undergoing laparoscopic surgery and 26 cases undergoing open surgery.There were 148 males and 18 females,aged was 33-85 years,with an ayerage ageof (65.1 ± 9.4) years.There were 55 cases of cutaneous ureterostomy,96 cases of Brick diversior with ileum,and 15 cases of ileal neobladder.The AAPR range 0.03-1.67,with an average 0.62 ± 0.23,and body mass index (BMI) was 16.79-32.65 kg/m2,with an average of (24.00 ± 3.32) kg/m2.There were 33 cases with hydronephrosis and 133 no hydronephrosis,31 cases with hypertension and 135 cases no hypertension,and 14 cases with diabetes and 152 cases no diabetes.Four cases were classified as grade0,65 cases as grade 1,86 cases as grade 2,and 11 cases as grade 3.Based on the preoperative AAPR(0.62 ±0.23),they were divided into three groups,with 55 cases in the low AAPR (0.42 ± 0.09) group,55 cases in the middle AAPR (0.58 ± 0.05) group,and 56 cases in the high AAPR (0.86 ± 0.21)group.Cox proportional hazards regression methodology were used to evaluate the relationship between preoperative AAPR and overall survival.Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test.Results 166 patients were followed up for 1-144 months,with a median of 63 months,and 71 cases died and 95 survived.The median serum AAPR level in all cases was 0.59 (range 0.03-1.67).Results of univariate Cox regression model revealed that AAPR(HR =0.09,95％ CI 0.022-0.391,P =0.001),high AAPR (HR=0.40,95％CI0.216-0.742,P=0.003),age (HR =2.42,95％ CI 1.294-4.531,P =0.006),tumor size (HR =2.11,95％ CI 1.112-4.014,P =0.023),pT3 stage (HR=8.93,95％CI3.173-25.114,P＜0.001),pT4 stnge(HR =10.39,95％ CI 3.110-34.707,P ＜0.001),pN1 stage(HR =2.80,95％ CI 1.422-5.531,P =0.003),pN3 stage (HR =17.06,95％ CI2.192-132.863,P =0.007),pathological grade (HR =0.30,95％ CI 0.113-0.817,P =0.019),hydronephrosis (HR =2.36,95 ％ CI 1.406-3.939,P =0.001),adjuvant chemotherapy (HR =2.66,95％ CI 1.674-4.247,P ＜ 0.001)were associated with OS.Compared with patients in the lowest of AAPR,the risk for death in the highest AAPR group decreased about 59％ (HR =0.406,95％ CI 0.200-0.822,P =0.012)after adjustment for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy in multiple Cox regression models.Each unit increase in the AAPR was associated with about 80％ decreased risk of death (HR =0.199,95％ CI 0.051-0.779,P =0.020) after adjusting for the confounding variables.After adjusting for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy,the curve fitting results showed that with the increase of AAPR,the risk of death decreased and the overall survival prolonged.Consistent with the linear trend test results,the relationship between AAPR and OS is linear.Conclusions AAPR was associated with overall survival of patients who underwent radical cystectomy of bladder cancer.

Objective To investigate the effect of tail vein transplantation of human amniotic mesenchymal stem cells (hAMSCs) with different transforming growth factor (TGF)-β expressions on recovery of sciatic nerve function in peripheral nerve xenotransplantation mice.Methods The hAMSCs were isolated from amnion membranes by healthy mother donors and identified by fluorescence activated cell sorter.The up-regulated and down-regulated TGF-β lentiviral plasmids were constructed and transfected into the purified hAMSCs;hAMSCs with stable up-regulated or down-regulated TGF-β expression were constructed.The sciatic nerves of C57BL/6 mice were isolated and cut out,and sciatic nerves of SD rats were isolated and transplanted into the sciatic nerve defected C57BL/6 mice to construct peripheral nerve xeno-transplanted mice models;these mice models were divided into 4 groups (n=10)according to random number table:control group,hAMSCs treatment group,high-expressed TGF-βhAMSCs treatment group,and low-expressed TGF-β hAMSCs treatment group;one d before modeling,phosphate buffer saline (PBS) or hAMSCs re-suspension were drawn with a syringe and slowly pushed into the tail veins of mice for transplantation treatment;14 d after treatment,DigGait analysis system was used to evaluate the recovery of sciatic nerve function in each group of mice.Result Fourteen d after treatment,the sciatic nerve function index (SFI) of the high-expressed TGF-β hAMSCs treatment group (-25.820±0.286) was significantly higher than that of the low-expressed TGF-β hAMSCs treatment group (-33.413±0.920) and hAMSCs treatment group (-30.755±0.421,P＜0.05).Conclusion The tail vein transplantation of hAMSCs with TGF-β high expression can effectively improve the sciatic nerve function in peripheral nerve xenotransplantation mice,which may be a new breakthrough in the treatment of peripheral nerve defects.