BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Objective:To investigate the value of the virtual monoenergetic image (VMI) obtained by a new dual-layer detector spectral CT combined with metal artifact reduction algorithms(O-MAR) in reduction of different types of artifacts caused by 125I seeds implantation and in improvement of the post-operative CT image quality. Methods:This was a cross-sectional study. Thirty-five patients who underwent dual-layer detector spectral CT scanning of the chest and abdomen after 125I seeds implantation were retrospectively included at the First Affiliated Hospital of Zhengzhou University from March to September 2022. The spectral data were collected and reconstructed into conventional CT image (CI), VMI image (50-150 keV, 20 keV/level), CI+O-MAR image, and VMI+O-MAR image (50-150 keV, 20 keV/level). The artifacts′ removal effects and image quality improvement in each group were evaluated. Two slices with the strongest artifacts were selected for analysis for each patient, resulting in a total of 70 slices. Objective indicators including artifact index (AI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of soft tissue regions affected by artifacts were measured and calculated. Subjective indicators including the overcorrected artifacts and new artifacts, the different forms of artifacts, the diagnosis of artifacts, and the image quality were assessed. One-way analysis of variance was used for comparisons among multiple groups. Paired t test was used to compare the quantitative indicators between the combined O-MAR group and the non-O-MAR group. Kappa statistics was used to evaluate the consistency between observers. Results:In high/low-density artifacts (ROI H/L), the AI values in all groups showed decrease with increasing VMI keV. In artifact-affected tissue (ROI T), SNR of the CI/VMI (70-150 keV)+O-MAR group were significantly higher than those of the CI/VMI group ( P<0.05), CNR of the CI/VMI(50-150 keV)+O-MAR group were significantly higher than those of the CI/VMI group ( P<0.05). Both overcorrection and new artifacts mainly presented in VMI 50 keV and VMI 70 keV groups; Compared with VMI (50-70 keV) group, significantly less numbers of overcorrection and new artifacts were found in VMI (50-70 keV)+O-MAR group ( P<0.05); regarding the comparison of artifact types, with the VMI keV increasing, the number of a-type banded artifacts gradually decreased on images with high-density artifacts, reaching a minimum of 3 in the VMI 150 keV+O-MAR group; while the number of e-type artifacts with little or no artifacts increased, with the highest number of 23 in the VMI 150 keV+O-MAR group. The total number of high-density artifacts in each type decreased with increasing VMI keV. As VMI keV increased, the diagnostic and image quality scores of high-density artifacts in each group were significantly higher than those of low-density artifacts in the VMI+O-MAR group ( P<0.05). Conclusions:VMI combined with O-MAR can significantly improve the objective and subjective image quality of follow-up CT imaging after 125I seed implantation, enhancing lesion visibility and diagnostic confidence. Additionally, VMI+O-MAR showed more pronounced correction effect on high-density artifacts.

Objective To investigate the predictive value of urinary exosomal microRNA(miR)-29 c in the clinical outcome of organ-and non-organ-confined bladder urothelial carcinoma(BUC).Methods From January 2017 to March 2022,152 patients with BUC were recruited from the Department of Urology in our hospital as a validation set.In addition,126 non-cancer controls were selected from the physical examination center of our hospital.The expression level of urinary exosomal miR-29c was detected by real-time quantitative PCR.Results In the validation set,urinary exosomal miR-29c level in BUC patients was significantly lower than that in non-cancer control group(P＜0.05),while urinary exosomal miR-17-5p level and miR-590-5p level were not significantly different(P＞0.05).The area under ROC curve of urinary exosomal miR-29c for the diagnosis of BUC was 0.969(95％CI:0.953～0.986),and the corresponding sensitivity and specificity were 92.1％and 90.2％,respectively.In subtype analysis,urinary exosomal miR-29c levels were further reduced in patients with non-organ-confined BUC compared with patients with organ-confined BUC(P=0.009).Overall survival(OS),disease-free survival(DFS)and disease-specific survival(DSS)were longer in the urinary exosomal miR-29c high expression group(P＜0.05).Conclusion Low levels of urinary exosomal miR-29c are an adverse prognostic factor for survival in patients with BUC,and are promising as a predictor of adverse clinical outcomes of organ-and non-organ-confined BUC.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

Objective:To explore the clinical effect and safety of extended debridement combined with BAM bone-induced artificial bone repair in the treatment of Cierny-Mader type IV osteomyelitis.Methods:From January 2021 to December 2022, 106 patients with Cierny-Mader type IV osteomyelitis who were treated with allogeneic bone mixed with autologous bone in department of orthopedics of Sichuan Orthopedic Hospital were retrospectively selected as the study subjects. Among them, 54 patients who were combined with BAM bone-induced artificial bone mixed with autologous bone repair were included in observation group, and 52 patients who only received allogeneic bone mixed with autologous bone repair were enrolled as control group. The clinical related indicators (bone healing time, fracture healing time), clinical efficacy (Johner-Wruh tibial shaft fracture evaluation standard) at 1 year after surgery, inflammatory factors (white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin), limb function (American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AH)) and bone healing degree before surgery and at 1 year after surgery were compared between both groups. Chi-square test was used to compare the enumeration data between groups, and the independent sample t test was performed to compare the measurement data with normal distribution between groups.Results:At 1 year after surgery, the clinical healing indicators of bone healing time and fracture healing time and inflammatory factors such as WBC, ESR, CRP and procalcitonin with (21.19±2.16) weeks, (11.35±1.01) weeks, (6.15±0.73)×10 9/L, (9.10±1.05) mm/h, (8.09±1.11) mg/L and (0.05±0.01) μg/L in observation group were significantly shorter or lower than (24.32±2.39) weeks, (12.29±1.27) weeks, (7.86±0.89)×10 9/L, (10.10±1.32) mm/h, (9.26±1.23) mg/L and (0.08±0.01) μg/L in control group,and the differences were statistically significant ( t values were 7.08, 4.23, 10.83, 4.33, 5.15, and 15.44, respectively; all P<0.001). The clinical effective rate (85.19%(46/54)), AOFAS-AH score((84.83±12.17) points) and bone healing probability (94.44%(51/54)) were higher than (67.31%(35/52)), (79.17±11.25) points and 80.77% (42/52) in control group,with statistically significant differences (statistical values were χ2=4.70, t=2.48, and χ2=4.60, respectively; P values were 0.030, 0.015, and 0.032, respectively). Conclusion:Expanded debridement combined with BAM bone-induced artificial bone repair can effectively promote the bone tissue healing in patients with Cierny-Mader type IV osteomyelitis, relieve the inflammatory response, and improve the limb function, and it has good clinical efficacy and high safety.

Objective:To explore the effect of the isolated organ laparoscopic simulation training teaching mode in laparoscopic partial nephrectomy training.Methods:A 39-hour in vitro organ laparoscopic simulation training for 12 urologists who had previously participated in laparoscopic basic technique training but had not independently completed laparoscopic partial nephrectomy in Peking Union Medical College Hospital. The training was conducted twice a week for 3 months from April to June 2022. Five modules, namely ultrasonic knife separation training, ultrasonic knife cutting training, vascularization training, blunt separation training, and partial nephrectomy and wound closure training, were used to provide targeted training for the decomposition of laparoscopic partial nephrectomy, and each training item was assessed and scored according to the scoring rules. At the same time, a questionnaire was used to find out the level of confidence of the 12 physicians in completing the operation and each step in the procedure, so as to assess the changes in the operational skills and psychological quality of the physicians before and after training using paired t-tests or Wilcoxon paired rank sum tests. Results:After the training, the assessment scores of operations in all surgeons were significantly improved. The training scores of ultrasonic knife separation training, ultrasonic knife cutting training, blood vessel nudity training, blunt separation training, and partial nephrectomy and traumatic suture improved from (8.5±0.3), (6.9±0.3), (4.2±0.4), (6.6±0.4), and (5.6±0.7) to (9.8±0.2), (9.6±0.3), (9.3±0.2), (9.4±0.3), and (9.8±0.2), respectively( P<0.05). The average operation time for the partial renal excision and traumatic suture training improved from (47.5±5.8) minutes to (21.6±5.1) minutes( t=18.72, P<0.001). At the same time, self-confidence in completing the operation was also significantly improved from 2(1, 3) before the training to 4(4, 4) after the training ( Z=-3.002, P =0.003). Conclusions:After laparoscopic simulation training with isolated organs, physicians with no previous experience in partial nephrectomy can become proficient in all steps of the procedure, complete the resection of the renal tumor and suturing of the wound within 30 minutes, and gain confidence in the operation of all steps of partial nephrectomy.