OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.

OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.

Objective To evaluate the impact of the growth speed of cerebral infarction on the occurrence of symptomatic intracranial hemorrhage(sICH)in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods The clinical data of patients with acute ischemic stroke(AIS),who received mechanical thrombectomy at the First Affiliated Hospital of Soochow University of China from June 2016 to December 2022,were retrospectively analyzed.After thrombectomy,the patients were divided into sICH group and non-sICH group according to Heidelberg criteria.The clinical data and imaging findings were compared between the two groups.Multivariate logistic regression analysis was used to identify the independent risk factors for sICH after thrombectomy,and the area under the receiver operating characteristic curve(AUC)was used to evaluate the efficacy of the growth speed of cerebral infarction in predicting sICH.Results A total of 218 patients were enrolled in this study,sICH group had 23 patients and non-sICH group had 195 patients.The differences in NIHSS score,collateral circulation status,core infarction volume,and growth speed of cerebral infarction between the two groups were statistically significant(all P＜0.05).Multivariate logistic regression analysis showed that rapid growth speed of cerebral infarction was an independent risk factor for sICH occurring after mechanical thrombectomy.For predicting sICH,the sensitivity and specificity of the growth speed of cerebral infarction were 78.3％and 69.7％respectively,with an AUC of 0.751 and a predicted value of 7.6 mL/h.Conclusion The rapid growth speed of cerebral infarction is a predictive factor for sICH occurring after mechanical thrombectomy in patients with acute anterior circulation ischemic stroke.The risk of sICH becomes higher after mechanical thrombectomy when the growth speed of cerebral infarction is faster than 7.6 mL/h.

Objective:To analyze the occurrence characteristics of heat-related diseases in the 19th Hangzhou Asian Games beach volleyball events, strengthen the ability of prevention and early identification of heat-related diseases, and provide reference for the holding of large-scale outdoor events in summer and reasonable allocation of medical resources.Methods:The medical insurance of heat-related diseases of relevant personnel in the beach volleyball competition from September 19 to September 28, 2023 was retrospectively analyzed, and the incidence of heat-related diseases in the personnel involved in Asia was analyzed.Results:During the beach volleyball competition in Ningbo Region of the Hangzhou Asian Games, a total of 103 people were provided with health services in the medical service field (61 people had mild discomfort due to excessive outdoor temperature; Other cold, minor injury, bandage 42 people); Medical services provided 44 times (4 referrals). Among them, 11 cases were sports injury and trauma (29.5%), 11 cases were heat stroke and other related symptoms (25%), 6 cases were sunburn (13.6%), 10 cases were oral diseases of five senses (22.8%), 4 cases were upper respiratory tract infection (9.1%).Conclusions:The holding of large-scale outdoor events in summer should focus on heat-related diseases, and it is necessary to effectively do the corresponding planning work in advance in terms of reasonable allocation of medical resources and targeted training of professionals.

Objective: To analyze the relationship between serum lactic acid value and risk of death in patients with extensive burn during shock stage and the related influencing factors. Methods: Clinical data of 127 patients (111 males and 16 females) with extensive burn admitted to Institute of Burn Research of the First Affiliated Hospital of Army Medical University from January 2009 to December 2013 and Department of Plastic Surgery and Burns of the Affiliated Hospital of Southwest Medical University from January 2016 to December 2018, who met the admission criteria, were retrospectively analyzed. The patients aged 21 to 62 years, with total burn area more than 50% total body surface area. All patients were treated with antishock therapy after admission. (1) According to the treatment outcome, the patients were divided into survival group (n=98) and death group (n=29). The gender, age, total burn area, partial-thickness burn area, full-thickness burn area, abbreviated burn severity index (ABSI), admission time after injury, number of patients with inhalation injury, number of patients with acute renal failure, and serum lactic acid values on admission and at post admission hour (PAH) 12, 24, 36, and 48 were recorded. (2) According to the optimal positive cut-off value of serum lactic acid 48 hours after admission, the patients were divided into high lactic acid group and normal lactic acid group. Age, gender, total burn area, indexes at PAH 48 including urea nitrogen, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total serum bilirubin, alkaline phosphatase (ALP), albumin, white blood cell count, platelet count, lymphocyte count, prothrombin time (PT), hematocrit value, oxygenation index, respiratory index (RI), the alveolar-arterial oxygen partial pressure difference, mean arterial pressure (MAP) at PAH 48, the average urine volume within 48 hours after admission, the total volume of intravenous fluid infusion within 48 hours after admission, the volume of fluid infusion per kilogram of body mass within the first 24 hours after admission, the volume of fluid infusion per one percent of body surface area per kilogram of body mass within the first 24 hours after admission, the volume of urine per kilogram of body mass per hour within the first 24 hours after admission, and the percentage of hospital death were recorded. Data were processed with t test, chi-square test, and Fisher′s exact probability test. Cox regression analysis was used to screen independent risk factors affecting the prognosis of patients. Receiver operating characteristic curve (ROC) of serum lactic acid value at PAH 48 of 127 patients was drawn to predict patients′ death and determine the optimal positive cut-off value. Multivariate logistic regression analysis was used to screen independent risk factors causing increase of serum lactic acid. Results: (1) There were significantly statistical differences in total burn area, full-thickness burn area, and ABSI of patients between survival group and death group (t=6.257, 4.476, 5.727, P<0.01), while other indexes between the two groups were close. (2) The serum values of lactic acid of patients in death group on admission and at PAH 12, 24, 36, and 48 were (4.00±0.28), (4.50±0.26), (4.02±0.31), (3.48±0.22), (3.40±0.19) mmol/L, respectively, which were significantly higher than those in survival group [(3.30±0.21), (3.20±0.19), (2.33±0.17), (1.85±0.18), (1.50±0.09) mmol/L, t=14.552, 29.603, 38.133, 40.648, 74.973, P<0.05 or P<0.01]. (3) Cox regression analysis showed that the serum value of lactic acid at PAH 48 was the independent risk factor affecting the prognosis of patients, with risk ratio of 1.853 and 95% confidence interval of 1.342-2.559, P<0.01. (4) The total area under ROC of serum value of lactic acid at PAH 48 to predict death of 127 patients was 0.811, with 95% confidence interval of 0.699-0.924, P<0.01. The optimal positive cut-off value of serum value of lactic acid was 1.75 mmol/L, with sensitivity of 75.0% and specificity of 79.5% for predicting death. (5) There were significantly statistical differences in total burn area, ALT, AST, ALP, PT, total serum bilirubin, total volume of intravenous fluid infusion within 48 hours after admission, volume of fluid infusion per kilogram of body mass within the first 24 hours after admission, and percentage of hospital deaths of patients between high lactic acid group (n=34) and normal lactic acid group (n=93), t=3.592, 6.797, 10.367, 2.089, 2.880, 4.517, 2.984, 4.044, χ²=58.498, P<0.05 or P<0.01, while other indexes were close between the two groups. (6) Multivariate logistic regression analysis showed that AST and total serum bilirubin were independent risk factors for increase of serum lactic acid, with odds ratios of 1.021 and 1.064 and 95% confidence intervals of 1.001-1.040 and 1.001-1.132, P<0.05. Conclusions Serum value of lactic acid at PAH 48 can independently predict the death of patients with extensive burns. Liver injury is an important risk factor causing hyperlacticemia during burn shock stage. Widespread increase of vascular permeability and large amount of fluid resuscitation are the core factors leading to aggravation of abdominal organ injury.

AIM:To investigate the regulation mechanism for insufficient KChIP 2 expression induces Ito,f downregulation and arrhythmogene-sis in cardiac hypertrophy .METHODS:Bidirectional manipulations of MG 53 expression were performed by adenoviral overexpression of MG53 or knockdown of MG53 with RNA interference in neonatal rat ventricular myocytes with or without PE stimulation .Ito,f was re-corded with patch clamp in whole-cell mode 48 h after adenoviral transfection .Then the WT or MG53 knockout ( MG53 -/-) mouse model of left ventricular hypertrophy induced by transverse aortic constriction ( TAC) were used to detect the susceptibility to ventricu-lar arrhythmia.RESULTS: Here, we show muscle-specific MG53 regulates KChIP2 expression and Ito,f densities, where they are downregulated in hearts from MG53 knockout mice and MG53 knockdown rat cardiomyocytes , but upregulated in MG53 overexpressed cells.MG53 expression is decreased in phenylephrine ( PE)-induced cardiomyocyte hypertrophy and restoration of MG 53 rescues PE-induced downregulation of KChIP2 and Ito,f.Furthermore, MG53 is decreased in a mouse model of hypertrophy induced by transverse aortic constriction and ablation of MG 53 increases the susceptibility to ventricular arrhythmia by exaggerating Ito,f remodeling.CON-CLUSION:These findings establish MG53 as a novel regulator of Ito,f and its central role in arrhythmogenesis in hypertrophy .

Objective To establish the model of acute spinal infarction, to evaluate the relative factors affecting results in spinal embolization, and to provide the theorial basis with the preoperative embolization of spinal tumors. Methods Through the SAE of the lumbar arteries, the neuro function of the posterior legs of dogs, MRI findings, and pathologic changes of the spinal specimen were observed in 12 dogs. The embolizing agents was gelfoam(GF). Results The significant ischemia changes of spinal column and the corresponding muscles at the occluding spinal after embolizing more than one segmental arteries occurred in 9 dogs, but there were no paraplegia or obvious changes in 3 dogs having been embolized single lumbar arteries no matter they sent out the radiculomedullary artery(RA) or not. Paraplegia occurred in one dog after embolizing the multisegmental arteries. Conclusion (1) The method of SAE in dog can be used to set up the experimental model of the acute ischemia of spine. (2)The occlusion in single segmental arteries can not result in the infarction of the whole spine. (3)The serious complication may result from embolizing multisegmental spinal arteries (especially sending out RA) (4) The protecting embolization should be carried out in order to decrease the reaction during SAE in spine.