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 mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

Objective:To investigate the efficacy and safety of nerve decompression surgery through the lateral-rectus approach for sacral plexus nerve injury after sacral fracture fixation.Methods:A retrospective study was conducted to analyze the 10 patients with combined sacral plexus nerve injury after sacral fracture fixation who had been admitted to Department of Orthopedics, Xiangya Hospital between May 2022 and May 2023. There were 2 males and 8 females with an age of 16.5 (15.0, 26.3) years. At the time of injury, the patients had been clearly diagnosed as sacral fracture combined with sacral plexus nerve injury. By the Denis classification of sacral fractures: 7 cases of type Ⅱ and 3 cases of type Ⅲ; sacral plexus nerve injury sites: 1 case of L 4, 8 cases of L 5, 7 cases of S 1, and 2 cases of S 2. All of them were treated with reduction and internal fixation via the posterior approach within 2 weeks after injury, but after surgery their manifestations of sacral plexus nerve injury still persisted which were confirmed by CT, magnetic resonance imaging and neuromuscular electromyography. Therefore, at (4.0±2.3) months after internal fixation, all patients were treated with nerve decompression surgery through the lateral-rectus approach. The operative time, intraoperative bleeding, length of hospitalization, Gibbons nerve damage score and neurological recovery at the last follow-up were recorded. Results:In the 10 patients, the operative time was (112.0±21.5) min, intraoperative bleeding (215.0±91.3) mL, and length of hospitalization 7.0 (6.0, 8.5) d. Intraoperatively, sacral plexus nerve compression was found in 9 cases (6 cases of nerve compression and pulling due to fracture displacement, 3 cases of nerve entrapment due to soft tissue scar adhesion), and 1 case of nerve root avulsion injury. No other intraoperative complications occurred. The 10 patients were followed up for (9.2±2.3) months after surgery. At the last follow-up, the Gibbons score for the 10 patients improved from preoperative 3.0 (3.0, 3.3) points to 1.0 (1.0, 2.0) point, and their British Medical Research Council (BMRC) nerve injury grading was improved from the preoperative grade 0.0 (0.0, 1.3) to grade 3.5 (2.8, 4.0) (1 case of M5, 4 cases of M4, 4 cases of M3, and 1 case of M2).Conclusion:The lateral-rectus approach is effective and safe for exploration and decompression of the sacral plexus nerve in patients combined with sacral plexus nerve injury despite sacral fracture fixation.

Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

ObjectiveTo investigate the current status of cognition and attitude towards hospice care among medical staff in Liaocheng，analyze the related influencing factors，and to provide reference for further development of hospice care services. MethodsUsing the method of convenient sampling，404 medical staff from all levels of hospitals in Liaocheng were selected as the research subjects from January to June 2022 to conduct a questionnaire survey on the cognition and attitude towards hospice care.Statistical methods were used to analyze the related influencing factors. ResultsThe knowledge score of hospice care among medical staff in Liaocheng was （13.02 ± 4.10），with an average score rate of 65.10%.The score of attitude was （38.67 ± 5.64），with an average score rate of 64.50%.Age （41~50 years old），having received education and training，treated or cared for patients in the middle and late stages，and understanding ethics and morality，as well as cultural customs were significantly positively correlated with knowledge scores.Age （> 50 years old），professional title （deputy senior professional title），position （medical treatment），and experience in treating or caring for patients in the middle and late stages were positively related to attitude scores. ConclusionThe cognition and attitude towards hospice care among medical staff in Liaocheng were at a moderate level.Strengthening the construction of a standardized hospice care system is helpful to improve the cognition and attitude level towards hospice care among medical staff.

Objective:Type H blood vessels are a subtype of bone-specific microvessels(CD31hiEmcnhi)that play an important regulatory role in the coupling of angiogenesis and osteogenesis.Despite reports on the distinct roles of type H and L vessels under physiological and pathological bone conditions,their genetic differences remain to be elucidated.This study aims to construct a competitive endogenous RNA(ceRNA)network of key gene for differencial expression(DE)in type H and L vascular endothelial cells(ECs)through integrated bioinformatic methods. Methods:We downloaded relevant raw data from the ArrayExpress and the Gene Expression Omnibus(GEO)database and used the Limma R-Bioconductor package to screen for DE lncRNAs,DE miRNAs,and DE mRNAs between type H and L vascular ECs.A total ceRNA network was constructed based on their interactions,followed by refinement using protein-protein interaction(PPI)networks to select upregulated and downregulated key genes.Enrichment analysis was performed on these key genes.Random validation was conducted using flow cytometry and real-time RT-PCR. Results:A total of 1 761 DE mRNAs,187 DE lncRNAs,and 159 DE miRNAs were identified,and a comprehensive ceRNA network was constructed based on their interactions.Six upregulated(Itga5,Kdr,Tjp1,Pecam1,Cdh5,and Ptk2)and 2 downregulated(Csf1r and Il10)key genes were selected via PPI network to construct a subnetwork of ceRNAs related to these key genes.Upregulated key genes were mainly enriched in negative regulation of angiogenesis and vascular apoptosis.Results from flow cytometry and real-time RT-PCR were consistent with bioinformatics analysis. Conclusion:This study proposes a ceRNA network associated with upregulated and downregulated type H and L vascular ECs based on selected key genes,providing new insights into the regulatory mechanisms of type H and L vascular ECs in bone metabolism.

Objective:To compare the clinical efficacy of robot-assisted pedicle screw placement with visualization technology and conventional robot-assisted pedicle screw placement, and analyze the accuracy and safety of robot-assisted pedicle screw placement with visualization.Methods:This retrospective study analyzed data from 60 patients (39 males and 21 females) with an average age of 51.03±18.04 years (range 12-78 years) who underwent open spinal pedicle screw fixation surgery for thora columbar diseases at the Orthopedic Department of the First Affiliated Hospital of China Medical University between August 2020 and September 2022. The cases included 25 cases of spinal stenosis, 15 cases of lumbar fractures, 7 cases of thoracic fractures, 3 cases of lumbar spondylolisthesis, and 10 cases of spinal deformities. 30 patients underwent solid pedicle screw placement using robot-assisted visualization technology (visualization group), while the remaining 30 patients received hollow pedicle screw placement using conventional robot-assisted technology (conventional group). After screw placement, "O"-arm X-ray scans were performed for verification, and screw placement accuracy was evaluated based on the Gertzbein-Robbins standard. The study recorded and compared the time required for screw placement, number of fluoroscopy sessions, and perioperative complications between the two groups to provide a comprehensive assessment of surgical outcomes.Results:There were no significant differences in age and gender between the two groups ( P>0.05). In the visualization group, a total of 178 pedicle screws were placed, with 172 screws (96.6%) achieving satisfactory placement, while the conventional group placed 254 pedicle screws, with 240 screws (94.5%) achieving satisfactory placement. The difference in accuracy rates between the two groups was not statistically significant (χ 2=1.087, P=0.297). The visualization group required a mean of 2.60±1.03 fluoroscopy sessions during surgery, significantly less than the conventional group's mean of 5.57±2.12 sessions ( t=-6.860, P=0.001). Moreover, the visualization group had a shorter mean screw placement time of 13.23±3.68 minutes compared to the conventional group's mean of 24.68±15.75 minutes ( t=-3.870, P=0.040). All patients in both groups completed the surgery without postoperative complications such as infection, hematoma, or nerve root injury. Conclusion:The technique of robot-assisted pedicle screw placement with visualization effectively preserves the high precision achieved in conventional robotic surgery. With its advantage of real-time monitoring for screw position, it reduces the intraoperative fluoroscopy times and shortens the screw placement time, thereby further enhancing surgical efficiency.

Objective:To investigate the impact of age,various hormonal levels,and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction(ED).Me-thods:A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography(CDDU)and intracavernosal injection test(ICI)at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023.Data were managed and processed using SPSS 29.0,and a multivariable Logistic regression analysis was conducted.Results:A total of 700 ED patients were included,with 380 showing negative ICI results and 320 positive.In the study,84 patients had a peak systolic velocity(PSV)＜25 cm/s,while 616 had PSV ≥ 25 cm/s;202 patients had end-diastolic velocity(EDV)＞5 cm/s,and 498 had EDV ≤5 cm/s.264 patients had ab-normal PSV and/or EDV results,and 436 had normal results for both.Patients with vascular ED had sig-nificantly lower estrogen levels(t=-3.546,P＜0.001),lower testosterone levels(t=-2.089,P=0.037),and a higher rate of hyperglycemia(x2=12.772,P=0.002)compared with those with non-vascular ED.The patients with arterial ED were older(t=3.953,P＜0.001),had a higher rate of hyperglycemia(x2=9.518,P=0.009),and a higher estrogen/testosterone ratio(t=2.330,P=0.020)compared with those with non-arterial ED.The patients with mixed arteriovenous ED had higher age(t=3.567,P＜0.001),lower testosterone levels(t=-2.288,P=0.022),a higher rate of hyperglycemia(x2=12.877,P=0.002),and a larger estrogen/testosterone ratio(t=2.096,P=0.037)compared with those with normal findings.Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED(OR=1.009,95％CI:1.004-1.014),and glucose 7.0 mmol/L was a risk factor(OR=0.381,95％CI:0.219-0.661).Older age was a risk factor for arte-rial ED(OR=0.960,95％CI:0.938-0.982).Additionally,older age(OR=0.976,95％CI:0.958-0.993)and glucose levels of 5.6-6.9 mmol/L(OR=0.591,95％CI:0.399-0.876)were also risk fac-tors for mixed arterio-venous ED.Conclusion:Hyperglycemia and aging may impair penile cavernous body vascular function,while higher levels of estrogen may have a protective effect on it.

Surgical robot is the national strategic diagnostic and therapeutic equipment research focus,get a number of scientific research institutes,colleges and universities and enterprises pay extensive attention to the design and development of a variety of surgical robots,and registration declaration.This article explores the critical technologies of surgical robots and key areas for optimizing their performance,including kinematic positioning errors,pose errors,feedback model errors,image recognition positioning errors,path planning,and safety aspects.The findings not only provide a scientific basis for future standardization research on surgical robots but also offer significant theoretical and practical references for the research,manufacturing,and registration processes in the medical robotics industry.