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:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

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 investigate the expression of Acyl-CoA synthetase long-chain family member 4(ACSL4)in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.Methods Clinical samples of liver cancer and adjacent normal liver tissues were examined for malondialdehyde(MDA)contents and for expressions of mRNA and protein expressions of ACSL4 and proliferating cell nuclear antigen(PCNA)using RT-qPCR and Western blotting.Human liver cancer Huh-7 cells were treated with Erastin(a ferroptosis inducer),Fer-1(a ferroptosis inhibitor),or both,and the changes in expression levels of MDA,ACSL4 and PCNA were detected,and the cell proliferation was assessed with plate cloning assay.Results MDA contents were lower and ACSL4 and PCNA expressions were higher significantly in liver cancer tissues than in adjacent liver tissues.In Huh-7 cells,Erastin treatment significantly inhibited mRNA and protein expressions of ACSL4 and PCNA,suppressed cell proliferation,and increased MDA contents.Fer-1 alone did not produce significant effect on cell viability but reversed the effect of Erastin on ACSL4 and PCNA expressions,cell proliferation and MDA contents.Conclusion ACSL4 level is significantly overexpressed in liver cancer.Erastin increases MDA contents and down-regulates ACSL4 expression,thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells,and these effects can be reversed by Fer-1.

Objective To investigate the expression of Acyl-CoA synthetase long-chain family member 4(ACSL4)in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.Methods Clinical samples of liver cancer and adjacent normal liver tissues were examined for malondialdehyde(MDA)contents and for expressions of mRNA and protein expressions of ACSL4 and proliferating cell nuclear antigen(PCNA)using RT-qPCR and Western blotting.Human liver cancer Huh-7 cells were treated with Erastin(a ferroptosis inducer),Fer-1(a ferroptosis inhibitor),or both,and the changes in expression levels of MDA,ACSL4 and PCNA were detected,and the cell proliferation was assessed with plate cloning assay.Results MDA contents were lower and ACSL4 and PCNA expressions were higher significantly in liver cancer tissues than in adjacent liver tissues.In Huh-7 cells,Erastin treatment significantly inhibited mRNA and protein expressions of ACSL4 and PCNA,suppressed cell proliferation,and increased MDA contents.Fer-1 alone did not produce significant effect on cell viability but reversed the effect of Erastin on ACSL4 and PCNA expressions,cell proliferation and MDA contents.Conclusion ACSL4 level is significantly overexpressed in liver cancer.Erastin increases MDA contents and down-regulates ACSL4 expression,thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells,and these effects can be reversed by Fer-1.

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.

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.