OBJECTIVE To analyze the clinical characteristics and influential factors of drug-induced liver injury （DILI） in children caused by intravenous azithromycin. METHODS Clinical data of 157 DILI pediatric cases caused by intravenous azithromycin， reported by the Hengshui Adverse Drug Reaction Monitoring Center from January 2015 to January 2025， were collected as the observation group. Clinical data of pediatric patients who received intravenous azithromycin but did not develop DILI during the same period at Hengshui People’s Hospital were collected in a 1∶1 ratio to serve as the control group. The clinical classification， severity and prognosis of DILI in pediatric patients from the observation group were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for DILI in children caused by intravenous azithromycin. RESULTS Among 157 DILI cases， 92 cases （58.60%） had hepatocellular injury-type， 51 cases （32.48%） had cholestatic-type， and 14 cases （8.92%） had mixed-type. DILI severity was grade 1 in 117 cases （74.52%）， grade 2 in 33 cases （21.02%）， and grade 3 in 7 cases （4.46%）. Liver function had all recovered after stopping medication and symptomatic treatment. Combined with acetaminophen [OR＝3.769， 95%CI （1.615， 8.235）， P＝0.021]， daily dose of azithromycin＞10 mg/kg [OR＝ 2.237， 95%CI （1.075， 4.655）， P＝0.034] were independent risk factors for DILI in children caused by intravenous azithromycin. CONCLUSIONS Hepatocellular injury-type and cholestatic-type are relatively common in children with DILI caused by intravenous azithromycin， with mild severity being predominant and showing a favorable prognosis. Combination with acetaminophen and daily dose＞10 mg/kg are independent risk factors for azithromycin-induced DILI in children.

Parkinson's disease is a neurodegenerative disease that mostly occurs in middle-aged and elderly people. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra and aggregation of Lewy bodies, resulting in a series of motor symptoms and non-motor symptoms. Depression is the most important manifestation of non-motor symptoms, which seriously affects the quality of life of patients. Clinicians often use antidepressant drugs to improve the depressive symptoms of patients with Parkinson 's disease, but it is still urgent to solve the problems of drug side effects and drug resistance caused by such methods. Repetitive transcranial magnetic stimulation is a safe and non-invasive neuromodulation technique that can change the excitability of the corticospinal tract, induce the release of dopamine and other neurotransmitters, and further improve the depressive symptoms of patients with Parkinson 's disease. Based on this, this paper discusses and summarizes the research progress on the efficacy and potential mechanism of repetitive transcranial magnetic stimulation for improving depression in Parkinson 's disease at home and abroad, in order to provide reference for related clinical application research.
Humans ; Parkinson Disease/psychology* ; Transcranial Magnetic Stimulation/methods* ; Depression/etiology*

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Objective To investigate the effect of subchronic inhalation of toluene diisocyanate (TDI) on oxidative stress damage in rat lung tissue. Methods SPF-grade Sprague-Dawley male rats were randomly divided into 4 groups,the rats were placed in a HOPE-MED 8050A movable poison cabinet in a cage.To observe the ultrastructural and histopathology changes of lung tissue in rats.The levels of reduced glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in lung tissue were detected. The ultrastructural and histopathological changes were examined. The expression levels of HO-1 mRNA and protein were detected by Real-time PCR and Western Blot, respectively. Results The body mass, lung tissue mass, and lung organ coefficient of rats in each dose group were lower than those in the control group (P<0.05), and the body mass of rats in each group increased with the increase of exposure time (P<0.05); The results of lung histopathological examination showed that after TDI exposure,in the high-dose group, pulmonary alveolar wall hyperemia and edema were observed in the lung tissue of rats, alveolar wall thickening was observed, alveolar septa widening, and a large number of red blood cells were seen in the alveolar cavity. The results of ultrastructural examination of lung tissue showed that after TDI exposure, while in the high-dose group, the number of alveolar cells decreased, with unclear cell boundaries and irregular morphology. The levels of MDA in the lung tissue of rats exposed to TDI at various doses were higher than those in the control group (P<0.05), while the levels of GSH, GSH-Px, SOD, and CAT were lower than those in the control group (P<0.05); There was no significant difference in HO-1 gene and protein levels among rats in each group (P>0.05). Conclusion Subchronic inhalation of TDI can cause changes in the pathology and ultrastructure of rat lung tissue, leading to abnormal levels of metabolic enzymes in lung function, thereby inducing oxidative stress damage to the lungs. However, but HO-1 is involved in oxidative stress damage in the lungs induced by TDI.

Objective To analyze the applicability of different risk assessment methods in assessing laboratory benzenes exposure. Methods The work positions exposed to benzenes (benzene, toluene, xylenes) of a chemical catalyst research and development company were selected as the research subjects. An occupational health field survey was conducted, and the benzenes exposure levels of the lab personnel were measured. Qualitative assessment method, comprehensive index method, quantitative assessment method, and occupational hazards classification method were used to evaluate the occupational health risk on benzenes exposure in the laboratory personnel. The applicability of different assessment methods was compared. Results The occupational health engineering protection measures and management system of the company need to be further implemented. The benzene exposure level of benzene hydrogenation laboratory personnel exceeded the national standard, with the exposure concentration of time weighted average (C_TWA) of 5.00 mg/m³ and short term exposure concentration (C_STE) of 10.50 mg/m³. The C_TWA and C_STE of toluene and xylenes exposure were both lower than the minimum quantitative concentrations. The results of different risk assessment methods varied. The qualitative assessment method indicated higher level of occupational health risk of benzenes, while the comprehensive index and hazard classification methods indicated consistent result on lower level of benzenes. For occupational health risk of benzene, the standardized risk ratio (RR) levels corresponding to the qualitative and quantitative assessment methods were both extremely high risk. The RR levels of benzene exposure assessment using the comprehensive index method and the occupational hazards classification method were high, while the corresponding RR levels of exposure to toluene and xylenes were both low. Conclusion Attention should be paid on the health risks of benzene exposure to benzene hydrogenation laboratory personnel. When benzene exposure level is below the national occupational exposure limit, occupational hazards classification method is not recommended for health risk assessment for benzenes. The comprehensive index method is preferable when more comprehensive occupational health information is available, as it provides a more objective and comprehensive evaluation on occupational health risks of benzenes.

Objective To investigate the clinical efficacy of endovascular intervention in the treatment of acute ischemic stroke caused by carotid stump syndrome(CSS).Methods A retrospective analysis was performed for the patients with anterior circulation acute ischemic stroke who underwent endovascular intervention in The First Hospital of Jilin University from August 2018 to October 2022,among whom the patients with acute ischemic stroke caused by CSS were identified,and related data were collected for these patients,including demographic information,risk factors,surgery-related characteristics,and prognosis.Results A total of 23 patients met the diagnostic criteria for CSS,among whom 19 patients achieved successful revascularization and 7 achieved extended Thrombolysis in Cerebral Infarction(eTICI)grade 3.Fourteen patients received concurrent carotid artery stenting.Twelve patients experienced intracranial hemorrhage after surgery,among whom 1 patient experienced symptomatic intracranial hemorrhage(sICH)leading to in-hospital death.On day 90 after onset,8 patients achieved functional independence,with a modified Rankin Scale score of≤2,while 4 patients died within 90 days.Conclusion CSS is a clinical syndrome caused by embolization from the occluded distal portion of the internal carotid artery.Endovascular intervention is an effective method for the treatment of CSS.

Purpose/Significance To analyze the network security risk events monitored by the situational awareness platform of large hospitals,to find out the causes,and to put forward solutions and suggestions for improvement.Method/Process Taking the First Affiliated Hospital of Zhengzhou University as an example,the paper analyzes risk events on the situational awareness platform,screens the risky ter-minals on the hospital intranet,carries out rectification and reinforcement,analyzes the department distribution and causes of risky termi-nals,and puts forward suggestions for improvement.Result/Conclusion The number of risky terminals in medical and technical depart-ments is large,mainly due to the lack of management and the lack of full coverage of antivirus software.Through the rectification and rein-forcement of risky terminals,the number of network security risk events has been significantly reduced.Strengthening the hospital terminal security management,enhancing staff awareness of network security,and strengthening network security protection in different areas can ef-fectively reduce the incidence of hospital network security risk events and improve the hospital network security protection capability.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*