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

BACKGROUND:Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown. OBJECTIVE:To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique. METHODS:The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.The βvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages. RESULTS AND CONCLUSION:A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with age:age-unspecified bone mineral density[β=0.038,95%confidence interval(CI):1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI:1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI:1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI:0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI:0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI:0.96-1.04,P=0.716).Similar results were obtained from the MR-Egger regression and weighted median estimator analyses.These findings indicate that type 2 diabetes mellitus may be one of the protective factors of bone mineral density,and there is a correlation with age.

Objective:To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD).Methods:A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c. 11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+ PM2_Supporting+ PP3). Conclusion:The c. 11098C>T (p.R3700C) and c. 11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

Objective To investigate the effect of different doses of rocuronium on the monitoring of recurrent laryngeal nerve during endoscopic thyroidectomy.Methods A total of 116 patients undergoing endoscopic thyroidectomy through areolar approach were selected from October 2021 to October 2022,30 males and 86 females,aged 18-64 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ or Ⅱ.All the patients were divided into three groups by random number table method:rocuronium 0.30 mg/kg group(group R1,n=39),rocuronium 0.45 mg/kg group(group R2,n=39),and rocuronium 0.60 mg/kg group(group R3,n=38).After induction of anesthesia,groups R1,R2,and R3 were injected intrave-nously with rocuronium 0.30,0.45,and 0.60 mg/kg,respectively.When the TOF value was 0,the nerve monitoring tracheal catheter was inserted,and the muscle relaxation was monitored throughout the operation.No muscle relaxants were added before the end of the nerve monitoring.The time and amplitude of recurrent laryngeal nerve electromyography(EMG)from intravenous rocuronium to the first occurrence were recorded.The time of intubation and quality of tracheal intubation(Cooper's score),intraoperative special conditions(hypotension,hypertension,bradycardia,tachycardia,intraoperative movement,etc.),postoperative throat pain,hoarseness,and muscle pain were recorded.Results There was no significant difference in the time of first occurrence of recurrent laryngeal nerve EMG among the three groups.Compared with group R1,the recurrent laryngeal nerve EMG amplitude in groups R2 and R3 was significantly decreased for the first occurrence(P＜0.05).Compared with group R1,the time of intubation in groups R2 and R3 was signifi-cantly shortened(P＜0.05).Compared with group R2,the time of intubation in group R3 was significantly shortened(P＜0.05).Compared with group R1,the quality of tracheal intubation in groups R2 and R3 was significantly higher(P＜0.05).Compared with group R1,the incidence of intraoperative and postop-erative laryngeal pain in groups R2 and R3 was significantly lower(P＜0.05).Conclusion During endo-scopic thyroidectomy,compared with rocuronium 0.30 mg/kg,rocuronium 0.45 and 0.60 mg/kg can not only provide good conditions for tracheal intubation,but also monitor recurrent laryngeal nerve signals,and rocuronium 0.60 mg/kg can be intubated for a shorter time.

Objective To establish an artificial intelligence (AI)-assisted platform for detection of parasite eggs, and to evaluate its detection efficiency and accuracy, so as to provide technical supports for elimination of parasitic diseases. Methods A total of 1 003 slides of Enterobius vermicularis, horkworm, Trichuris trichiura, Clonorchis sinensis, Taenia, Ascaris lumbricoides, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski eggs were collected, and converted into digital images with an automatated scanning microscope to create a dataset. Based on the Object Detection platform on the Baidu Easy DL model, an AI-assisted platform for detection of parasite eggs was created through procedures of uploading, labeling, training, evaluation and optimization. Then, 70% of the datasets were randomly selected for model training, and the precision, recall and average accuracy were calculated to evaluate the effectiveness of platform for recognition of parasite eggs. In addition, the platform was deployed on the computer and smart phone terminals for use. Results An AI-assisted platform for detection of parasite eggs was successfully created. If the platform was deployed using the public cloud application programming interface (API), the average accuracy, precision and recall of the platform were 93.42%, 92.55% and 89.32% for recognition of parasite eggs. If the platform was deployed using the offline software development kit (SDK), the average accuracy, precision and recall of the platform were 92.97%, 94.78% and 87.63% for recognition of parasite eggs. In addition, the precision of the platform was 97.00% and 96.23% for identification of Taenia and C. sinensis eggs, respectively. Conclusions The AI-assisted platform for detection of parasite eggs has been successfully created, which is high in the accuracy for recognition of parasite eggs and convenient in use. This platform may provide a powerful technical support for parasitic disease diagnosis.

Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Throughout history,the development of medicine has been accompanied by the embodiment of humanity.In recent years,with the vigorous development of medical humanities,its connotation has been continuously enriched.Intensive care unit(ICU),at the forefront of treatment for critically ill patients,encounters many ethical risks and moral issues.Therefore,humanistic care for patients and the humanistic literacy of medical staff are particularly important.From the perspective of frontline doctors in the ICU,this article briefly discusses the reflection on the cognition of humanistic literacy,medical humanistic education,and humanistic practice within the ICU.

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

Early diagnosis, effective treatment and monitoring of recurrence and metastasis of hepatocellular carcinoma have always been difficult problems for clinicians. MicroRNA (miRNA) plays an important role in hepatocellular carcinoma cells' proliferation, apoptosis, metabolism and other processes, and can be released into body fluids such as blood, urine and saliva. The peripheral blood miRNA in hepatocellular carcinoma can be used as biomarkers for the diagnosis, efficacy assessment, recurrence and metastasis monitoring and prognosis judgment, and may even become therapeutic targets for hepatocellular carcinoma. This article summarizes the research progress of circulating miRNA in peripheral blood as markers for diagnosis and treatment monitoring of hepatocellular carcinoma.