OBJECTIVE To assess the safety profile of sintilimab in combination with chemotherapy for the treatment of cholangiocarcinoma. METHODS The data of patients with cholangiocarcinoma from January 1st， 2021 to December 31st， 2022 were collected and divided into control group （29 cases） and observation group （18 cases） based on different medication regimens. Patients in the control group were treated with Gemcitabine hydrochloride for injection+Cisplatin for injection or Oxaliplatin for injection， the observation group was treated with Sintilimab injection based on the control group. Patients in each group underwent blood routine， liver and kidney function， biochemical and other examinations before and after each treatment cycle to observe the occurrence of adverse drug reactions. The correlation of adverse drug reactions with drugs was evaluated with Naranjo’s scale. RESULTS The correlation between blood toxicity and drug use was deemed “probable” in both groups； however， the observation group exhibited a significantly higher score， indicating a stronger correlation. In the control group， hepatotoxic reactions were classified as “suspicious” whereas in the observation group， they were categorized as “probable”. The correlation of gastrointestinal symptoms between the two groups was considered “possible”. Systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity and renal toxicity were all classified as having a “suspicious” correlation with drug use. The total incidence of blood toxicity in the observation group was significantly higher than control group （P＝0.014）. There was no statistically significant difference in the total incidences of hepatotoxic， gastrointestinal symptoms， systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity， renal toxicity， or the incidence of grade 3 or higher blood toxicity， hepatotoxic between the two groups （P＞0.05）. For the patients experiencing adverse drug reactions， the symptoms were alleviated following drug discontinuation or symptomatic supportive treatment. No fatalities occurred during the treatment period. CONCLUSIONS Sintilimab combined with chemotherapy may significantly increase the risk of blood toxicity in patients with cholangiocarcinoma， especially thrombocytopenia， but the adverse reactions are within a controllable range， and the overall safety is good.

BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female

The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

Objective To analyze the cognition level of health care workers(HCWs)and the management status of various levels of medical institutions towards allergy reactions to commonly used antimicrobial agents.Methods HCWs and clinical pharmacists who were related to the diagnosis and treatment of antimicrobial agents in 14 medical institutions of city-level and autonomous prefectures in Gansu Province were randomly selected for a questionnaire survey.The survey contents included respondents'basic information,criteria for judging antimicrobial allergy,awareness on procedures related to antimicrobial allergy,and antimicrobial management level of different levels of medical institutions.Results A total of 8 670 valid questionnaires from HCWs were collected,including 3 300 phy-sicians,5 024 nurses and 328 pharmacists.160,775,2 123 and 5 612 HCWs were with senior,associate,interme-diate and junior professional titles,respectively.87.66％of the HCWs received relevant training on antimicrobial management in the past two years,the proportion of HCWs from different levels of medical institutions who have received training on antimicrobial management in the past two years was statistically significant different(x2=42.668,P＜0.001).HCWs with senior professional titles had the highest proportion of receiving relevant training(93.75％),there was a statistically significant difference in the proportion of receiving antimicrobial management training among HCWs with different professional titles in the past two years(x2=69.782,P＜0.001).50.98％of HCWs were not clear about penicillin allergy,and most of whom were with junior professional titles,accounting for 68.52％.25.19％of HCWs expressed uncertainty about whether patients with penicillin allergy could use cephalosporins,225 of whom were with associate professional titles,accounting for 29.03％of the total number of HCWs with associate profe-ssional titles.6.11％of HCWs had no experience in skin test procedure;46.94％of HCWs expressed that their medical institutions had no or unclear about whether their medical institutions had an antimicrobial allergy assess-ment team.Conclusion HCWs'judgment on allergy reactions to commonly used antimicrobial agents and aware-ness on antimicrobial application is not high enough,and the overall management level of antimicrobial allergy in all levels of medical institutions is poor.The popularity of antimicrobial allergy assessment teams is not high,and there is an urgent need to strengthen supervision,management,training,et al.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To explore the prospective associations between physical activity and incident ischemic stroke in adults.Methods:Data of China Kadoorie Biobank study in Tongxiang of Zhejiang were used. After excluding participants with cancers, strokes, heart diseases and diabetes at baseline study, a total of 53 916 participants aged 30-79 years were included in the final analysis. The participants were divided into 5 groups according to the quintiles of their physical activity level. Cox proportional hazard regression models was used to calculate the hazard ratios ( HR) for the analysis on the association between baseline physical activity level and risk for ischemic stroke. Results:The total physical activity level in the participants was (30.63±15.25) metabolic equivalent (MET)-h/d, and it was higher in men [(31.04±15.48) MET-h/d] than that in women [(30.33±15.07) MET-h/d] ( P<0.001). In 595 526 person-years of the follow-up (average 11.4 years), a total of 1 138 men and 1 082 women were newly diagnosed with ischemic stroke. Compared to participants with the lowest physical activity level (<16.17 MET-h/d), after adjusting for socio-demographic factors, lifestyle, BMI, waist circumference, and SBP, the HRs for the risk for ischemic stroke in those with moderate low physical activity level (16.17-24.94 MET-h/d), moderate physical activity level (24.95-35.63 MET-h/d), moderate high physical activity level (35.64-43.86 MET-h/d) and the highest physical activity level (≥43.87 MET-h/d) were 0.93 (95% CI: 0.83-1.04), 0.87 (95% CI: 0.76-0.98), 0.82 (95% CI: 0.71-0.95) and 0.76 (95% CI: 0.64-0.89), respectively. Conclusion:Improving physical activity level has an effect on reducing the risk for ischemic stroke.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Osteonecrosis of the femoral head(ONFH)is a common orthopedic disease,and hip preservation surgery has high clinical value in the early stages of ONFH,especially for young and middle-aged patients.However,the repair of ONFH is heterogeneous,leading to inter-individual variations in the efficacy of hip preservation.Currently,the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation,making it difficult to achieve precise repair.Smart responsive materials have good biocompatibility and self-feedback capability.By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems,new possibilities are provided for the precise repair of ONFH.This paper reviews the research progress of smart responsive materials at home and abroad.Based on the response principles of various materials and the repair characteristics of ONFH,the application prospects of various smart responsive materials such as reactive oxygen species-responsive,fluid shear stress-responsive,and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH,providing new ideas for the precise treatment of ONFH.

Objective To construct a risk prediction model for healthcare-associated infection(HAI)in stroke pa-tients,accurately and effectively screen out potential high-risk groups,and formulate targeted preventive interven-tions to reduce the occurrence of infection.Methods Stroke patients in the"Henan Stroke Cohort"in 2019-2021 were selected as the study objects,and relevant clinical data were collected as the main analysis data for model con-struction and internal validation.The relevant data of stroke patients in three hospitals that had never participated in the cohort construction from January to September 2022 were randomly selected as a test set for external validation of the risk prediction model.The main analysis data were randomly divided into a training set and a test set,and a risk prediction model was constructed based on logistic regression,artificial neural network(ANN)algorithm,extreme gradient boosting algorithm and random forest algorithm,respectively.Multiple indicators were used to evaluate the prediction performance of the model,and the optimal model was externally validated based on the test set data.Results The infection rate of stroke patients was 20.6％in the main analysis data and 56.4％in the test set data.The accuracy of the risk prediction model based on logistic regression was 91.2％,the area under the re-ceiver operating characteristic(ROC)curve(AUC)was 0.938,the precision rate,recall rate,specificity,and the F1 score were 0.851,0.695,0.968,and 0.765,respectively.The accuracy rate,precision rate,specificity and AUC of the logistic risk prediction model and the ANN risk prediction model were all significantly better than other models,while the recall rate and F1 score of the logistic risk prediction model were slightly better than the ANN risk prediction model.The logistic risk prediction model had excellent prediction performance in external validation.Conclusion HAI risk prediction model of stroke patients based on logistic regression can better screen out high-risk stroke patients with infection risk,and can contribute to formulate targeted preventive interventions to reduce the occurrence of infection.