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.

AIM: To observe the effect of orthokeratology combined with vision therapy and Clouclip(OCVTC)on myopic children with dysfunctional accommodation.METHODS: A prospective, non-randomized control study was conducted on 99 myopic children(99 eyes)with dysfunctional accommodation at the optometry center were of Langfang Aier Eye Hospital from April 2022 to January 2023. and they selected and divided into three groups: 39 children in OCVTC group, 30 in orthokeratology(Ortho-k)group, and 30 in single vision spectacle lens(SVL)group. The OCVTC group received office-based accommodative therapy for 3 mo and home reinforcement for 3 mo, and Clouclip was used in the first 3 wk to monitor and remind children of eye habits; the accommodative amplitudes and facility were measured at baseline, 3, 6, and 12 mo after treatment.RESULTS: The OCVTC group showed significantly better improvement in accommodative amplitude compared with both the Ortho-k group and the SVL group(all P<0.05), and the Ortho-k group was better than the SVL group at 3, 6, and 12 mo after the intervention(both P<0.05). Similarly, accommodative facility was significantly enhanced in the OCVTC group compared with the other groups at 6 and 12 mo after intervention, and the Ortho-k group was better than the SVL group(all P<0.05). Both accommodative amplitude and facility in the OCVTC group were significantly improved at 3, 6, and 12 mo after the intervention compared with the baseline(all P<0.05). Additionally, 13%(5/39)of cases in the OCVTC group showed a decrease in accommodative amplitude at 12 mo after treatment, with no cases showing a decrease in accommodative facility.CONCLUSION: For myopic patients with dysfunctional accommodation, orthokeratology combining with visual training and Clouclip will enhance accommodative amplitude and facility, and maintain a stable effect over a long time.

Care dependence refers to a complex and comprehensive state of being dependent on others due to the limita-tion of physical functions caused by the disease.Elderly stroke patients are high risk group for care dependence due to decrease in self-care ability caused by their disease characteristics.Therefore,this paper reviews the current research status,influencing factors,and interventions of care dependence,in order to provide reference for increasing attention to the care needs of elderly stroke patients,reducing their dependence,and improving their quality of life.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To explore the prognostic value of MCF in elderly patients with cardiac amy-loidosis using CMR.Methods A retrospective analysis was conducted on 54 elderly patients with cardiac amyloidosis diagnosed in our hospital.All patients underwent CMR imaging.They were di-vided into a survival group of 25 cases and a mortality group of 29 cases based on clinical out-comes.Correlations of MCF with CMR parameters and biochemical indicators were evaluated.Cox regression analysis was performed to identify independent predictors of patient survival.Survival analysis was used to assess the value of MCF in predicting patient prognosis.Results The surviv-al group had significantly higher MCF than the mortality group[(70.63±24.72)％vs(43.59± 13.36)％,P=0.001].As MCF increasing,LVEF level was in an increasing trend,while LVMI,LVGPWT,ECV,and troponin T and NT-proBNP levels showed a decreasing trend.Multivariate Cox regression analysis revealed that MCF was an independent predictor of patient survival(HR=0.922,95％CI:0.866-0.981,P=0.011).Kaplan-Meier survival curve showed that the patients with MCF＞57％had significantly higher survival rates than those with MCF ≤57％(P＜0.01).Conclusion MCF is an effective imaging indicator for evaluating the prognosis of elderly patients with cardiac amyloidosis,which can help identify high-risk patients and guide clinical treatment.

Objective:To analyze the video electroencephalogram (VEEG) and clinical features of simultaneous or sequential onset of childhood absence epilepsy (CAE) and childhood benign epilepsy with centrotemporal spikes (BECTS).Methods:Seven patients with simultaneous or sequential onset of CAE and BECTS admitted to Neurology Center, Beijing Tiantan Hospital from January 2016 to July 2023 were chosen. The clinical features, VEEG, treatments and prognoses of these patients were retrospectively analyzed. PubMed database was searched for articles on simultaneous or sequential onset of CAE and BECTS from January 2002 to July 2023, and studies with 3 or more cases of simultaneous or sequential onset of CAE and BECTS were included. Clinical characteristics of these patients in various studies were compared.Results:(1) The mean onset age in these 7 patients was 6.28 years, ranged from 4 to 8 years. CAE was recorded in 2 patients without clinical manifestation of BECTS during the course of disease progression; simultaneous or sequential onset of CAE and BECTS was recorded in 5 patients. Of the 7 patients, 2 effectively accepted valproate sodium (VPA) monotherapy, and 5 required additional antiepileptic drugs. Although all patients had well-controlled seizures and no developmental delays, 3 had learning disabilities, 3 had attention deficit hyperactivity disorder (ADHD), and 2 had anxiety. Wechsler Intelligence Scale for Children-III (WAIS-III) showed that 1 patient had below average intelligence and 6 had average intelligence. VEEG of all 7 patients showed simultaneous or sequential absence seizures and centrotemporal spikes. (2) Four studies were included in PubMed database. Combined with our study, these 5 sutdies indicated significant differences in onset age in patients with simultaneous or sequential onset of CAE and BECTS ( P<0.05), but no significant differences in simultaneous VEEG manifestations occurred or not and disease comorbidities or not in CAE and BECTS patients ( P>0.05). Conclusion:Patients with simultaneous or sequential onset of CAE and BECTS have different onset age, good overall prognosis and good response to anti-epileptic drugs, and trend to have complicated cognitive impairment.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.