Osteosarcoma is the most common primary malignant bone tumor, yet treatment modalities and patient outcomes have remained relatively stagnant over the past three decades. Recently, with increasing insights into the molecular characteristics of osteosarcoma, targeted therapies, such as tyrosine kinase inhibitors and cell cycle-related inhibitors, have shown significant progress in both preclinical studies and clinical trials. Checkpoint kinase 1 (CHEK1), a key player in DNA damage response, is involved in various critical biological functions, and the development of its specific inhibitors has gained attention in multiple fields of cancer treatment. Osteosarcoma, comprising multiple subtypes with distinct alterations in cell cycle and DNA damage response mechanisms, particularly exhibits increased sensitivity to CHEK1 inhibitors in p53 mutant cells. Targeting the CHEK1-associated pathway holds promise for improving patient outcomes. Inhibition of ataxia telangiectasia mutated (ATM) and/or ataxia telangiectasia and Rad3-related (ATR) pathways impairs DNA damage repair in osteosarcoma cells, identifying downstream molecules linked to CHEK1 as potential therapeutic targets. Suppression of CHEK1 activity leads to downregulation of related protein expression and inhibits cell proliferation and repair processes, an effect that is notably enhanced when combined with chemotherapeutic agents. Although single-agent chemotherapy often produces limited results, the use of CHEK1 inhibitors such as Prexasertib enhances cytotoxic effects against osteosarcoma cells, either as monotherapy or in combination regimens, demonstrating robust efficacy. Co-administration of CHEK1 inhibitors with other cell cycle modulators or downstream target antagonists could further optimize treatment outcomes. Furthermore, modulating DNA damage response pathways may have implications for immunotherapy. This review systematically summarizes recent research on the CHEK1-related pathway in osteosarcoma and emphasizes that targeting the DNA damage response pathway related to CHEK1 may be a promising strategy for osteosarcoma treatment with broad prospects.

Objective:To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer(MIBC)with intermediate-to-high-risk primary prostate cancer.Methods:From January 2012 to October 2023,the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed.All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study.Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients.For significant influencing factors(pathological T stage,M stage and perineural invasion of bladder cancer),survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors.Results:A total of 32 patients were included in this study.The mean age was(72.5±6.6)years;the median preoperative total prostate specific antigen(tPSA)was 6.68(2.47,6.84)μg/L;the mean preoperative creatinine was(95±36)μmol/L,and the median survival time was 65 months.The majority of the patients(87.5％)had high-grade bladder cancer,53.1％had lymphatic invasion,and 31.3％had perineural invasion.Prostate involvement was observed in 25.0％of the cases,and the positive rate of soft-tissue surgical margin was 37.5％.Multivariate Cox analysis revealed that preoperative creatinine level(HR=1.02,95％CI:1.01-1.04),pathological stage of bladder cancer T3(HR=11.58,95％CI:1.38-97.36)and T4(HR=19.53,95％CI:4.26-89.52)metastasis of bladder cancer(HR=9.44,95％CI:1.26-70.49)and perineural invasion of bladder cancer(HR=6.26,95％CI:1.39-28.27)were independent prognostic factors(P＜0.05).Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3,T4,M1,and perineural invasion were unfavorable factors affecting the patients'survival prognosis(P＜0.05).Conclusion:Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis.High preoperative serum creatinine,T3 or T4 pathological stage of bladder cancer,metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

Purpose BRCA1/2 gene germline variants of the uncertain significance(VUS)are categorized into five clas-ses based on their risk levels,and three classes require regular periodic analysis due to their unclear clinical significance.The aim of this study was to investigate the influence of updating var-iation evidences on the VUS sites and guide clinical diagnosis and treatment.Methods The VUS sites in BRCA1/2 gene were analyzed.971 samples(breast or ovarian cancer)that un-derwent BRCA1/2 germline testing were stored.The VUS sites in BRCA1/2 gene were further reinterpreted by integrating the following evidences,including population frequency database,disease database,computer software prediction,co-segregation evidence,allelic evidence and population cohort evidence to determine whether the variation classification was changed.Results The number of the patients with VUS sites was 142,accounting for 14.6％(142/971).The total number of VUS sites was 128,among which the proportions of missense muta-tion,synonymous mutation,in-frame non-shifted mutation and non-coding region mutation were 70.3％,4.7％,3.1％and 21.9％,respectively.Reinterpretation of VUS sites discovered that 11.7％(15/128)of VUS sites could be downgraded to Class 2,likely benign.Conclusion With the continuous in-creasing evidences of germline variation,the variation classifica-tion of VUS sites will be changed after periodic analysis.

Objective lo explore the application value of medial caudal approach combined with middle page-turning lymphadenectomy in laparoscopic radical right hemicolectomy.Methods Eighty-six patients with right hemicolon cancer admitted to our hospital from May 2019 to May 2020 were selected as the research objects,and they were divided into an observation group of 43 cases and a control group of 43 cases by random drawing.The control group adopts the intermediate approach,and the observation group adopts the medial caudal approach combined with middle page-turning lymphadenectomy.The surgical recovery index,complication rate,serum tumor markers and survival index were compared between the two groups to evaluate the clinical efficacy and safety.Results There were no significant differences between the two groups in the number of lymph nodes removed,the length of the intestinal tube removed,extubation,fluid feeding and hospitalization time,the incidence of postoperative complications(P＞0.05),but the operation time and intraoperative bleeding in the observation group were significantly lower,and the postoperative exhaust time was shorter(P＜0.05).The serum CA19-9 and CEA levels of the two groups after one year decreased,and the serum CA19-9 and CEA levels of the observation group were lower than those of the control group(P＜0.05).The disease-free progression period was prolonged in the observation group(P＜0.05),but there was no difference in survival time.Conclusion The medial caudal approach combined with the middle page-turning lymphadenectomy has higher clinical application value in the laparoscopic radical right hemicolectomy,which is conducive to shortening the operation time and postoperative exhaust time,reducing the amount of intraoperative bleeding and postoperative serum CA19-9 and CEA levels,and improving the disease-free progression period with high safety.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective    To explore whether surgery combined with adjuvant chemotherapy can bring survival benefits to patients with cervical and upper thoracic esophageal squamous cell carcinoma (ESCC). Methods    The clinical data of patients with cervical and upper thoracic ESCC who underwent R0 resection and neck anastomosis in our department from 2006 to 2010 were retrospectively analyzed. Patients received neoadjuvant therapy or adjuvant radiotherapy were excluded. The adjuvant chemotherapy group was given a combination of taxanes and platinum based chemotherapy after surgery; the surgery alone group did not receive adjuvant chemotherapy. The Kaplan-Meier method was used to analyze the survival difference between the adjuvant chemotherapy group and the surgery alone group. Results    A total of 181 patients were enrolled, including 141 (77.9%) males and 40 (22.1%) females, with an average age of 61.0±8.2 years (80 patients aged≤61 years, 101 patients aged>61 years). There were 70 (38.7%) patients of cervical ESCC, and 111 (61.3%) patients of upper thoracic ESCC. Eighty-seven (48.1%) patients underwent postoperative adjuvant chemotherapy, and 94 (51.9%) patients underwent surgery alone, and the basic clinical characteristics were well balanced between the two groups (P>0.05). The median survival time of patients in the adjuvant chemotherapy group and the surgery alone group was 31.93 months and 26.07 months, and the 5-year survival rate was 35.0% and 32.0%, respectively (P=0.227). There was no statistical difference in median survival time between the cervical ESCC and upper thoracic ESCC group (31.83 months vs. 29.76 months, P=0.763). For cervical ESCC patients, the median survival time was 45.07 months in the adjuvant chemotherapy group and 14.70 months in the surgery alone group (P=0.074). Further analysis showed that the median survival time of lymph node negative group was 32.53 months, and the lymph node positive group was 24.57 months (P=0.356). The median survival time was 30.43 months in the lymph-node positive group with adjuvant chemotherapy and 17.77 months in the lymph-node positive group with surgery alone. The survival curve showed a trend of difference, but the difference was not statistically significant (P=0.557). Conclusion    There is no statistical difference in the long-term survival of cervical and upper thoracic ESCC patients after R0 resection. Postoperative adjuvant chemotherapy may have survival benefits for patients with cervical ESCC and upper ESCC with postoperative positive lymph nodes, but the differences are not statistically significant in this setting.

Objective:To explore the role of WeChat platform combined with flipped classroom in improving the working ability of resident doctors in the fever clinic.Methods:A total of 118 resident doctors who rotated in the fever clinic of department of emergency medicine were selected as the study subjects, and they were randomized into experimental group and control group, with 59 people in each group. The experimental group used WeChat platform and flipped classroom teaching, and the control group used traditional teaching. The results of theory assessment, operation performance and questionnaire survey were compared between the two groups. SPSS 26.0 statistical software was used for t test and chi-square test. Results:There was no significant difference in theoretical test scores between the experimental group and the control group ( P>0.05). The experimental group scored (91.61±3.01) points and the control group scored (84.52±4.02) points in operational assessment, with significant differences ( t=-10.85, P<0.05). The results of the satisfaction survey showed that there was no significant difference in teaching time distribution between the two groups, and the experimental group was better than the control group in any other aspects. Conclusion:The use of WeChat platform combined with flipped classroom during the COVID-19 epidemic can improve the level of operational skills of the resident doctors to wear or take off the protective clothing and collect nasopharyngeal swabs, help residents to avoid the infections, and improve the level of daily diagnosis and treatment of fever clinic.

Objective:To analyze the results in clinical application of backtracking full-thickness continuous everting suturing in primary closure of common bile duct after laparoscopic bile duct exploration.Methods:From February 2014 to November 2018 at the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 82 patients with cholecystolithiasis and choledocholithiasis entered into this study. There were 45 males and 37 females, with an average age of 62.7 years. These patients underwent primary closure of common bile duct after laparoscopic bile duct exploration using backtracking full-thickness continuous everting suturing to close the incisions in common bile ducts. Clinical data on surgery, postoperative complications and follow-up were collected and analyzed retrospectively.Results:Primary closure of common bile duct was successfully carried out in all patients. The operation time ranged from 45 to 150 min (average 68.5 min). Intraoperative blood loss ranged from 5 to 150ml (average 18.4 ml). Postoperative bile leakage occurred in 2 patients (2.4%). There were no intra-abdominal or biliary bleeding, severe cholangitis, liver function derangement, abdominal infection or residual stones. Of 77 patients who were followed up (follow-up rate of 93.9%), the follow-up time ranged from 9 to 50 months (median 14 months). On follow-up, 2 patients (2.4%) developed recurrence of choledocholithiasis and 1 patient (1.2%) was diagnosed to have intrahepatic bile duct stones. There were no patients with bile duct stenosis or acute cholangitis.Conclusion:Primary closure of common bile duct with backtracking full-thickness continuous everting suturing has the advantage of reducing postoperative bile leakage in patients after laparoscopic bile duct exploration. The long-term effects of this technique still need further clinical studies.

Purpose: From the perspective of positive psychology, our study aimed to explore depressive symptomsand psychological well-being among Chinese nurses, as well as analyze the impacts of characterstrengths, self-efficacy and social support on the mental health of nurses. Methods: A cross-sectional and descriptive design using five self-reported questionnaires was used toinvestigate a cohort of 4238 nurses during 2018. A structural equation modeling analysis was used toverify a hypothetical model linking character strengths, self-efficacy, social support, depressive symptoms,and psychological well-being. Results: The prevalence of depression among this cohort of Chinese nurses was 58.1%. The mean scoresfor caring, inquisitiveness, and self-control were 19.93 (SD = 2.82), 15.94 (SD = 3.00), and 16.34(SD = 2.95), respectively. The hypothesized model was a good fit of the data (x2/df = 1.77, p = .183, rootmean square error of approximation = 0.04, goodness of fit index = 1.00, comparative fit index = 1.00,TuckereLewis index = 1.00). Except for the path from self-control to depression, the other hypotheticalpaths investigated were statistically significant. Conclusion Character strengths were directly and positively associated with psychological well-being.Inquisitiveness was the strongest direct protective factor for depression. In addition, characterstrengths indirectly alleviated depression and increased psychological well-being through mediatingvariables of social support and self-efficacy. This study should alert nurse managers that more attentionshould be paid to the character strengths and mental health of nurses. This study provides evidence forinterventions based on character strengths as a management strategy to support the mental health ofnurses.

Purpose: From the perspective of positive psychology, our study aimed to explore depressive symptomsand psychological well-being among Chinese nurses, as well as analyze the impacts of characterstrengths, self-efficacy and social support on the mental health of nurses. Methods: A cross-sectional and descriptive design using five self-reported questionnaires was used toinvestigate a cohort of 4238 nurses during 2018. A structural equation modeling analysis was used toverify a hypothetical model linking character strengths, self-efficacy, social support, depressive symptoms,and psychological well-being. Results: The prevalence of depression among this cohort of Chinese nurses was 58.1%. The mean scoresfor caring, inquisitiveness, and self-control were 19.93 (SD = 2.82), 15.94 (SD = 3.00), and 16.34(SD = 2.95), respectively. The hypothesized model was a good fit of the data (x2/df = 1.77, p = .183, rootmean square error of approximation = 0.04, goodness of fit index = 1.00, comparative fit index = 1.00,TuckereLewis index = 1.00). Except for the path from self-control to depression, the other hypotheticalpaths investigated were statistically significant. Conclusion Character strengths were directly and positively associated with psychological well-being.Inquisitiveness was the strongest direct protective factor for depression. In addition, characterstrengths indirectly alleviated depression and increased psychological well-being through mediatingvariables of social support and self-efficacy. This study should alert nurse managers that more attentionshould be paid to the character strengths and mental health of nurses. This study provides evidence forinterventions based on character strengths as a management strategy to support the mental health ofnurses.