To investigate the clinical characteristics and prognosis of extracranial malignant rhabdoid tumor (eMRT) in children, and to provide a reference for the clinical treatment of this disease.

Objective Uranium compounds are critical materials in the nuclear industry, and their mining, processing, and use pose occupational exposure risks. Epidemiological studies have shown that uranium exposure can impair health, with acute uranium poisoning primarily causing structural and functional damage to the kidneys. Currently, the molecular mechanisms underlying uranium-induced kidney injury remain unclear, and traditional biological models used in toxicological research are inadequate for simulating the human microenvironment. This study employed a human kidney organoid model system to elucidate the nephrotoxic mechanisms of uranyl ions, providing a scientific basis for the prevention and control of uranium poisoning. Methods Kidney organoids were constructed using the human embryonic stem cell line H1 and exposed to solutions with different uranyl ion concentrations. Morphological observation, ATP detection, reactive oxygen species detection, apoptosis assay, and untargeted metabolomics analysis were performed. Mechanisms of toxicity were further explored through KEGG pathway enrichment analysis. Results Uranium exposure led to structural damage in the organoids, accompanied by a dose-dependent decrease in ATP levels, accumulation of reactive oxygen species, and increased apoptosis rate. After 24-hour exposure to 300 μmol/L uranium, significantly disturbed differential metabolites and five core metabolic pathways were identified. Conclusion Uranium induces oxidative stress, mitochondrial dysfunction (ATP reduction), and metabolic disorder (disruption of phospholipid/amino acid metabolism), which synergistically cause DNA damage, apoptosis, and/or necrosis. These findings provide new insights into the mechanisms of uranium-induced kidney injury and support the development of prevention and control strategies.

OBJECTIVES: To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure. METHODS: We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified via PPI analysis. Molecular docking between the core targets and quercetin was performed using PyMOL and AutoDock Tools. In a heart failure model established in H9C2 cardiomyocytes by treatment with isoproterenol, the effect of quercetin on the expressions of the MAPK signaling pathway was tested. RESULTS: A total of 60 intersecting targets were identified. Enrichment analysis revealed that quercetin may inhibit heart failure through the MAPK signaling pathway. The core genes, including AMPK3 and BCL-2, were identified as potential key regulators in quercetin-mediated improvement of heart failure. Cellular experiments demonstrated that quercetin significantly reduced isoproterenol-induced apoptosis of cardiomyocytes in a dose-dependent manner and obviously decreased the Bax/Bcl-2 ratio and the expression levels of caspase-3, ERK and p38 in the cells. CONCLUSIONS Quercetin improves heart failure possibly by inhibiting cardiomyocyte apoptosis through the MAPK signaling pathway.
Quercetin/pharmacology* ; Myocytes, Cardiac/drug effects* ; Heart Failure/metabolism* ; Apoptosis/drug effects* ; MAP Kinase Signaling System/drug effects* ; Rats ; Animals ; Isoproterenol

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

Objective Investigating the effect and mechanism of resveratrol on cardiac function in exercise-induced fatigue rats by regulating mitochondrial energy metabolism.Methods Forty-eight healthy male Sprague Dawley rats(6～8 weeks old)were selected and divided randomly into a blank control(C)group,resveratrol administration(R)group,exercise-induced fatigue(E)group,and exercise-induced fatigue+resveratrol administration group(ER)(n=12 rats per group).Rats in the E and ER groups were subjected to weight-bearing 5％of their body weight for 60 minutes each day and exercise for 6 days per week for 6 weeks.Rats in the R and ER groups received resveratrol 50 mg/kg by gavage,1 hour after exercise.The biochemical kit was used to detect the indicators of motor fatigue,myocardial injury and mitochondrial energy metabolism enzymes in rat myocardium.The mRNA expression levels of myocardial energy metabolism related regulatory factors were detected by real-time fluorescent quantitative PCR(RT-qPCR).Results Plasma levels of blood urea nitrogen(BUN)and creatine kinase(CK)were significantly increased in rats in group E compared with group C(P＜0.05,P＜0.05),CK-MB and cTnI activity were also significantly increased(P＜0.01,P＜0.05),while activity levels of myocardial cytochrome C oxidase(COX)and succinate dehydrogenase(SDH)were significantly reduced(P＜0.01,P＜0.05).mRNA expression levels of the mitochondrial energy metabolism-related genes silent information regulator 1(SIRT1),peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α),and estrogen receptor-related receptor α(ERRα)were also significantly reduced(P＜0.01,P＜0.01,P＜0.01).Serum levels of BUN and CK were significantly decreased in the ER group compared with group E(P＜0.05,P＜0.05),while CK-MB and cTnI activities were significantly decreased(P＜0.05,P＜0.05),myocardial COX and SDH activities were significantly increased(P＜0.01,P＜0.05),and SIRT1,PGC-1α and ERRα mRNA levels were also significantly increased(P＜0.05,P＜0.01,P＜0.01).Conclusions Resveratrol can effectively activate the sirtuin 1/peroxisome proliferator-activated receptor γ coactivator 1α/estrogen-related receptor α signaling pathway,improve myocardial energy metabolism in exercise-fatigued rats,and protect against myocardial injury.

Objective To compare the safety and efficacy of directional atherectomy with anti-restenosis therapy(DAART,drug-coated balloon)versus conventional balloon angioplasty(bare-metal stent,BMS)in elderly patients with femoropopliteal artery disease.Methods A retrospec-tive cohort study was conducted on 116 elderly patients undergoing endovascular intervention due to femoropopliteal artery disease in our hospital between May 2016 and September 2019,divided into DAART group(57 cases)and BMS group(59 cases).Results No statistical differences were observed between the DAART and BMS groups in terms of age,risk factors,distribution of Ruth-erford classification,lesion length,lesion type,lesion location,Global Limb Anatomic Staging Sys-tem grade,infra-popliteal runoff status,or preoperative ankle-brachial index(P＞0.05).However,the BMS group had significantly larger proportion of chronic limb-threatening ischemia than the other group(P＜0.05).Both groups achieved a 100％success rate of surgery.The DAART group obtained obviously higher primary patency rates at 1 and 2 years than the BMS group(90.4％vs 75.0％,76.3％vs 57.3％;P＜0.045).There were no significant differences in the rate of freedom from target lesion revascularization at 1 and 2 years between the two group(96.1％vs 88.8％,91.6％vs 77.7％;P＞0.05).In 2 years of follow-up,the incidence of major adverse events was 10.0％(5 cases)in the DAART group and 20.8％(12 cases)in the BMS group,but no obvious difference(P＞0.05).Conclusion DAART demonstrates superior mid-term efficacy than BMS in treating femoropopliteal artery disease in elderly patients.However,comprehensive preoperative assessment is essential to optimize individualized treatment strategies for this population.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

Objective:To investigate the current use of ulinastatin in the treatment of critically ill children by pediatricians in China.Methods:A anonymous questionnaire survey was conducted among 147 pediatric critical care physicians from 36 hospitals across 16 provinces,autonomous regions,and municipalities in China.The survey content consists of three parts: respondents' basic information, the application status of ulinastatin, and the clinical indicators referenced for evaluating the use of ulinastatin. Descriptive statistical analysis was performed on the collected data.Results:Among the 147 respondents,99.32%(146/147) were from tertiary hospitals；72.11%(106/147) worked in specialized ICUs,and 4.08%(6/147)in emergency medicine departments.A total of 68.03%(100/147) of the physicians reported using ulinastatin in clinical practice.The main diseases for which ulinastatin was used were pancreatitis(26.40%),sepsis and septic shock(23.76%),capillary leak syndrome(21.78%),acute respiratory distress syndrome(8.91%),and disseminated intravascular coagulation(6.27%).A total of 90.00% of physicians combined ulinastatin with other medications,including glucocorticoids(26.82%),albumin(23.51%),plasma(17.22%),and immunoglobulins(13.58%). Clinical indicators referenced during ulinastatin use included elevated interleukin(IL)-6(76.87%),tumor necrosis factor-α(44.22%),IL-8(31.97%),IL-1(19.73%),IL-18(10.20%),blood lactate(59.18%),decreased serum albumin levels(70.07%),increased pleural or peritoneal effusion(67.35%),skin and mucosal edema(65.31%),and elevated thrombomodulin among the four coagulation parameters(58.50%).Conclusion:Ulinastatin is mainly used for the treatment of critical illnesses such as pancreatitis and sepsis.Most physicians combine ulinastatin with other drugs,such as glucocorticoids and albumin.Clinical indicators commonly referenced when using ulinastatin include elevated IL-6,increased lactate,and increased pleural effusion,which suggest a high inflammatory state and endothelial damage.

Objective Investigating the effect and mechanism of resveratrol on cardiac function in exercise-induced fatigue rats by regulating mitochondrial energy metabolism.Methods Forty-eight healthy male Sprague Dawley rats(6～8 weeks old)were selected and divided randomly into a blank control(C)group,resveratrol administration(R)group,exercise-induced fatigue(E)group,and exercise-induced fatigue+resveratrol administration group(ER)(n=12 rats per group).Rats in the E and ER groups were subjected to weight-bearing 5％of their body weight for 60 minutes each day and exercise for 6 days per week for 6 weeks.Rats in the R and ER groups received resveratrol 50 mg/kg by gavage,1 hour after exercise.The biochemical kit was used to detect the indicators of motor fatigue,myocardial injury and mitochondrial energy metabolism enzymes in rat myocardium.The mRNA expression levels of myocardial energy metabolism related regulatory factors were detected by real-time fluorescent quantitative PCR(RT-qPCR).Results Plasma levels of blood urea nitrogen(BUN)and creatine kinase(CK)were significantly increased in rats in group E compared with group C(P＜0.05,P＜0.05),CK-MB and cTnI activity were also significantly increased(P＜0.01,P＜0.05),while activity levels of myocardial cytochrome C oxidase(COX)and succinate dehydrogenase(SDH)were significantly reduced(P＜0.01,P＜0.05).mRNA expression levels of the mitochondrial energy metabolism-related genes silent information regulator 1(SIRT1),peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α),and estrogen receptor-related receptor α(ERRα)were also significantly reduced(P＜0.01,P＜0.01,P＜0.01).Serum levels of BUN and CK were significantly decreased in the ER group compared with group E(P＜0.05,P＜0.05),while CK-MB and cTnI activities were significantly decreased(P＜0.05,P＜0.05),myocardial COX and SDH activities were significantly increased(P＜0.01,P＜0.05),and SIRT1,PGC-1α and ERRα mRNA levels were also significantly increased(P＜0.05,P＜0.01,P＜0.01).Conclusions Resveratrol can effectively activate the sirtuin 1/peroxisome proliferator-activated receptor γ coactivator 1α/estrogen-related receptor α signaling pathway,improve myocardial energy metabolism in exercise-fatigued rats,and protect against myocardial injury.

Objective:To investigate the current use of ulinastatin in the treatment of critically ill children by pediatricians in China.Methods:A anonymous questionnaire survey was conducted among 147 pediatric critical care physicians from 36 hospitals across 16 provinces,autonomous regions,and municipalities in China.The survey content consists of three parts: respondents' basic information, the application status of ulinastatin, and the clinical indicators referenced for evaluating the use of ulinastatin. Descriptive statistical analysis was performed on the collected data.Results:Among the 147 respondents,99.32%(146/147) were from tertiary hospitals；72.11%(106/147) worked in specialized ICUs,and 4.08%(6/147)in emergency medicine departments.A total of 68.03%(100/147) of the physicians reported using ulinastatin in clinical practice.The main diseases for which ulinastatin was used were pancreatitis(26.40%),sepsis and septic shock(23.76%),capillary leak syndrome(21.78%),acute respiratory distress syndrome(8.91%),and disseminated intravascular coagulation(6.27%).A total of 90.00% of physicians combined ulinastatin with other medications,including glucocorticoids(26.82%),albumin(23.51%),plasma(17.22%),and immunoglobulins(13.58%). Clinical indicators referenced during ulinastatin use included elevated interleukin(IL)-6(76.87%),tumor necrosis factor-α(44.22%),IL-8(31.97%),IL-1(19.73%),IL-18(10.20%),blood lactate(59.18%),decreased serum albumin levels(70.07%),increased pleural or peritoneal effusion(67.35%),skin and mucosal edema(65.31%),and elevated thrombomodulin among the four coagulation parameters(58.50%).Conclusion:Ulinastatin is mainly used for the treatment of critical illnesses such as pancreatitis and sepsis.Most physicians combine ulinastatin with other drugs,such as glucocorticoids and albumin.Clinical indicators commonly referenced when using ulinastatin include elevated IL-6,increased lactate,and increased pleural effusion,which suggest a high inflammatory state and endothelial damage.