Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P＜0.05,P＜0.001),but did not up-regulate the expression of Beclin1(P＞0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P＜0.05,P＜0.05,P＜0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulated the expression of Beclin1(P＞0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulate the expression of Beclin1(P＞0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.

Objective To explore the potential causal links between micronutrient levels and the risk of immune-mediated inflammatory skin disease(IMID).Methods Leveraging publicly accessible genome-wide association study(GWAS)datasets,fifteen specific micronutrients were identified as exposure variables,while four prevalent IMID:Psoriasis,atopic dermatitis,urticaria,and alopecia areata were designated as study outcomes.Robust instrumental variables were meticulously selected to facilitate the Mendelian randomization analysis.The main assessment used the inverse-variance weighting(IVW)method,complemented by an assortment of Mendelian randomization methodologies,inclusive of MR-Egger,weighted median estimate(WME)and weighted mode(WM).Rigorous sensitivity analyses were conducted to bolster the robustness of the findings.Results Vitamin D exhibited a significant inverse association with the risk of psoriasis(OR=0.996,P=0.001,95％CI:0.994-0.998),corroborated by consistent trends across WME,MR-Egger,and WM methods.Phosphorus demonstrated a positive correlation with urticaria risk(OR=5.634,95％CI:1.792-17.711,P=0.003),with findings in alignment with WME and WM methods.Copper was found to be positively associated with atopic dermatitis risk(ORIVW=1.234,P=0.0007,95％CI:1.092-1.394),and vitamin E levels were significantly related to the risk of urticaria(OR=26.643,P=0.013,95％CI:1.981-358.333).Sensitivity analysis did not show heterogeneity and pleiotropy(P＞0.05).Conclusion The study establishes a causal relationship between vitamin D levels and the risk of psoriasis,suggesting that augmenting vitamin D intake could be a viable dietary intervention for psoriasis prevention.These findings offer novel insights into the preventative and therapeutic strategies for IMID.

Objective To investigate the protective effect of valeric acid on Doxorubicin-induced myocardial injury in mice.Methods C57BL/6J mice and AC16 cells were randomly divided into control group,injury group,and low-,medium-,and high-dose valeric acid groups.Doxorubicin was used to treat mice and myocardial cells to establish myocardial injury models.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes of myocardial tissue in mice,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of myocardial injury markers and inflammatory factors in mice from each group.Cell counting kit was used to detect the viability of myocardial cells in each group,and spectrophotometry was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the serum and myocardial cells in mice from each group.Reactive oxygen species(ROS)fluorescence probe was used to detect the levels of reactive oxygen species in each group,and flow cytometry was used to detect the apoptosis rate of each group.Western blot was used to detect the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)proteins in myocardial tissue and myocardial cells of mice from each group.Results Compared with the injury group,the myocardial injury in the low-,medium-,and high-dose valeric acid groups was ameliorated,the levels of myocardial injury markers gradually decreased,the levels of SOD in the body,and the expression levels of Nrf2 and HO-1 proteins gradually increased,and the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Compared with myocardial cells in the injury group,the viability of myocardial cells,the levels of SOD,and the expression levels of Nrf2 and HO-1 proteins in the low-,medium-,and high-dose valeric acid groups gradually increased,while the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Conclusion Valeric acid can inhibit inflammation and oxidative stress to improve Doxorubicin-induced myocardial injury,which may be related to the activation of Nrf2/HO-1 signaling pathway by valeric acid.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective:To investigate the relationship between dynamic alterations in serum albumin (ALB) concentrations and clinical outcomes in hospitalized surgical patients, thus providing a basis for optimizing clinical management strategies.Methods:This study utilized data from a prospective observational cohort study on nutritional status among 7 122 elderly hospitalized patients across 34 tertiary hospitals in 18 Chinese cities. A total of 1 714 surgical patients hospitalized for 7-30 days with complete data were included. Standardized protocols were used to collect demographic data, clinical outcomes, and a range of laboratory results, including nutritional and hematological parameters. Heterogeneous effects of ALB on clinical outcomes were explored. Receiver operating characteristic (ROC) curves were used to determine cutoff values for infection-related complications. Correlation analyses and multiple linear regression models were used to identify independent predictors of the absolute change in ALB (?ALB).Results:Among the surgical patients, 69.7% (1 195/1 714) experienced a decline in ALB levels during their hospital stay, which was significantly associated with the occurrence of both infection- and non-infection-related complications. Simultaneously, a marked decrease in ALB was also significantly correlated with changes in nutritional and inflammatory status during hospitalization, worsening of gastrointestinal symptoms at discharge, and functional activity abnormalities (all P<0.05). ?ALB exhibited a close association with outcome variables such as infection-related complications. Based on the incidence of infection-related complications, a cutoff value for ALB was calculated, dividing patients into a high-risk group ( n=179) and a low-risk group ( n=1 535), and a statistically significant difference in the incidence of infection-related complications was found between these two groups ( P<0.05). Correlation analysis and multiple linear regression modeling revealed that female gender, a higher baseline ALB level, a poorer baseline inflammatory status, an exacerbation of inflammatory status, larger alterations in platelet-to-lymphocyte ratio, and the presence of infection-related complications were predictive factors for a decline in ALB levels among surgical patients during their hospital stay. Conclusions:?ALB serves as a critical indicator of the inflammatory-nutritional interplay, with its magnitude of decline effectively predicting clinical outcomes and nutritional status changes and guiding multidisciplinary interventions in surgical patients.

Objective To determine the expression of glucose transporter 1(GLUT1)in lung adenocarcinoma tissues and its effects on cancer cell proliferation,migration,invasion,and cell cycle progression.Methods Prognostic signature genes related to butyrate metabolism in lung adenocarcinoma were screened based on the TCGA-LUAD and GEO databases.Western blot,qPCR,and immunohistochemistry(IHC)were used to detect GLUT1 expression levels.After transfecting A549 and H1299 lung adenocarcinoma cell lines with GLUT1-specific siRNA,CCK-8 assay,colony formation assay,scratch assay,and Transwell assay were performed to investigate the effects of GLUT1 silencing on cell proliferation,clonogenic potential,migration,and invasion,respectively.Flow cytometry was used to analyze cell cycle changes.Results GLUT1 expression was significantly higher in lung adenocarcinoma tissues than normal tissues(P＜0.05).Inhibition of GLUT1 significantly reduced the proliferation,clono-genicity,migration,and invasion abilities of A549 and H1299 cells(P＜0.05).Knockdown of GLUT1 significantly suppressed the expression of CyclinD1 and CDK6,and increased the proportion of cells in the G1 phase(P＜0.05).Conclusion GLUT1 is highly expressed in lung adenocarcinoma tissues and influences patient prognosis by regulating cell cycle progression and pro-liferation,suggesting its potential as a novel therapeutic target for lung adenocarcinoma.

Objective:To investigate the relationship between dynamic alterations in serum albumin (ALB) concentrations and clinical outcomes in hospitalized surgical patients, thus providing a basis for optimizing clinical management strategies.Methods:This study utilized data from a prospective observational cohort study on nutritional status among 7 122 elderly hospitalized patients across 34 tertiary hospitals in 18 Chinese cities. A total of 1 714 surgical patients hospitalized for 7-30 days with complete data were included. Standardized protocols were used to collect demographic data, clinical outcomes, and a range of laboratory results, including nutritional and hematological parameters. Heterogeneous effects of ALB on clinical outcomes were explored. Receiver operating characteristic (ROC) curves were used to determine cutoff values for infection-related complications. Correlation analyses and multiple linear regression models were used to identify independent predictors of the absolute change in ALB (?ALB).Results:Among the surgical patients, 69.7% (1 195/1 714) experienced a decline in ALB levels during their hospital stay, which was significantly associated with the occurrence of both infection- and non-infection-related complications. Simultaneously, a marked decrease in ALB was also significantly correlated with changes in nutritional and inflammatory status during hospitalization, worsening of gastrointestinal symptoms at discharge, and functional activity abnormalities (all P<0.05). ?ALB exhibited a close association with outcome variables such as infection-related complications. Based on the incidence of infection-related complications, a cutoff value for ALB was calculated, dividing patients into a high-risk group ( n=179) and a low-risk group ( n=1 535), and a statistically significant difference in the incidence of infection-related complications was found between these two groups ( P<0.05). Correlation analysis and multiple linear regression modeling revealed that female gender, a higher baseline ALB level, a poorer baseline inflammatory status, an exacerbation of inflammatory status, larger alterations in platelet-to-lymphocyte ratio, and the presence of infection-related complications were predictive factors for a decline in ALB levels among surgical patients during their hospital stay. Conclusions:?ALB serves as a critical indicator of the inflammatory-nutritional interplay, with its magnitude of decline effectively predicting clinical outcomes and nutritional status changes and guiding multidisciplinary interventions in surgical patients.

Objective To determine the expression of glucose transporter 1(GLUT1)in lung adenocarcinoma tissues and its effects on cancer cell proliferation,migration,invasion,and cell cycle progression.Methods Prognostic signature genes related to butyrate metabolism in lung adenocarcinoma were screened based on the TCGA-LUAD and GEO databases.Western blot,qPCR,and immunohistochemistry(IHC)were used to detect GLUT1 expression levels.After transfecting A549 and H1299 lung adenocarcinoma cell lines with GLUT1-specific siRNA,CCK-8 assay,colony formation assay,scratch assay,and Transwell assay were performed to investigate the effects of GLUT1 silencing on cell proliferation,clonogenic potential,migration,and invasion,respectively.Flow cytometry was used to analyze cell cycle changes.Results GLUT1 expression was significantly higher in lung adenocarcinoma tissues than normal tissues(P＜0.05).Inhibition of GLUT1 significantly reduced the proliferation,clono-genicity,migration,and invasion abilities of A549 and H1299 cells(P＜0.05).Knockdown of GLUT1 significantly suppressed the expression of CyclinD1 and CDK6,and increased the proportion of cells in the G1 phase(P＜0.05).Conclusion GLUT1 is highly expressed in lung adenocarcinoma tissues and influences patient prognosis by regulating cell cycle progression and pro-liferation,suggesting its potential as a novel therapeutic target for lung adenocarcinoma.

Objective To investigate the protective effect of valeric acid on Doxorubicin-induced myocardial injury in mice.Methods C57BL/6J mice and AC16 cells were randomly divided into control group,injury group,and low-,medium-,and high-dose valeric acid groups.Doxorubicin was used to treat mice and myocardial cells to establish myocardial injury models.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes of myocardial tissue in mice,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of myocardial injury markers and inflammatory factors in mice from each group.Cell counting kit was used to detect the viability of myocardial cells in each group,and spectrophotometry was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the serum and myocardial cells in mice from each group.Reactive oxygen species(ROS)fluorescence probe was used to detect the levels of reactive oxygen species in each group,and flow cytometry was used to detect the apoptosis rate of each group.Western blot was used to detect the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)proteins in myocardial tissue and myocardial cells of mice from each group.Results Compared with the injury group,the myocardial injury in the low-,medium-,and high-dose valeric acid groups was ameliorated,the levels of myocardial injury markers gradually decreased,the levels of SOD in the body,and the expression levels of Nrf2 and HO-1 proteins gradually increased,and the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Compared with myocardial cells in the injury group,the viability of myocardial cells,the levels of SOD,and the expression levels of Nrf2 and HO-1 proteins in the low-,medium-,and high-dose valeric acid groups gradually increased,while the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Conclusion Valeric acid can inhibit inflammation and oxidative stress to improve Doxorubicin-induced myocardial injury,which may be related to the activation of Nrf2/HO-1 signaling pathway by valeric acid.

Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P＜0.05,P＜0.001),but did not up-regulate the expression of Beclin1(P＞0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P＜0.05,P＜0.05,P＜0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulated the expression of Beclin1(P＞0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulate the expression of Beclin1(P＞0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.