Objective To utilize a comprehensive two-sample Mendelian randomized analysis for determining the causal relation-ship between immune cells and heart failure.Methods Immune cell data were collected from the genome-wide association analysis da-tabase,while the data of heart failure were obtained from the FinnGen database.The inverse variance weighted method,MR-Egger re-gression method,weighted median method,and weighted model method were employed to analyze the causal relationship between immune cells and heart failure.Comprehensive sensitivity analysis was utilized to verify the robustness,heterogeneity,and level pleiotropy of the results.The Stsiger test was applied to determine whether there was a reverse causal relationship between heart failure and immune cells.Results A total of 2557single nucleotide polymorphisms(SNP)were obtained from 731 immune cells.A total of 25 immunophenotypes were identified as having a causal function before the adjustment.After Bonferroni adjustment,only three results retained statistical signifi-cance.The inverse variance weighted analysis showed that there was a significant causal relationship between the absolute lymphocyte count and the increased risk of heart failure(HF)(OR=1.199,95％CI:1.104-1.302,P=1.70 × 10-5).The absolute count of T cells(OR=1.186,95％CI:1.095-1.284,P=2.84×10-5),and the absolute count of plasma-like dendritic cells(OR=1.137,95％CI:1.056-1.224,P=0.0007)were positively correlated with HF.The Stsiger test did not detect a causal relationship between heart failure and immune cells.Conclusion There exists a causal relationship between immune cells and the risk of heart failure.

Objective To investigate the effects of taurine-upregulated gene 1(TUG1)on the biological functions of human um-bilical vein endothelial cells(HUVEC)such as apoptosis,proliferation,and migration after oxygen-glucose deprivation/reoxygenation(OGD/R)injury.Methods HUVEC were treated with OGD/R to establish a cell model injured by OGD/R.Small interfering RNA si-lencing TUG1(si-TUG1)and its negative control(si-NC)were transfected,and the cells were divided into the control group,OGD/R group,OGD/R+si-NC group,and OGD/R+si-TUG1 group.PCR was used to detect the expression level of TUG1 in HUVEC;flow cytometry was used to detect cell apoptosis;CCK-8 assay was used to detect cell proliferation;wound-healing assay was used to detect cell migration;immunofluorescence was used to detect the expression of CD31 in HUVEC;and Western blot was used to detect the expres-sion of nuclear proliferation antigen(PCNA)protein.Results The PCR results showed that the expression level of TUG1 in OGD/R group cells was significantly higher than that in the control group(P＜0.05);si-TUG1 transfection can significantly reduce the expres-sion level of TUG1 in HUVEC(P＜0.05);the apoptosis rate of HUVEC in the si-TUG1 group was significantly lower than that in the si-NC group(P＜0.05);The cell proliferation,cell migration,immunofluorescence intensity of CD31,and the expression levels of PC-NA protein in the si-TUG1 group were higher than those in the si-NC group(P＜0.05).Conclusion Inhibiting TUG1 can significant-ly reduce the apoptosis of HUVEC under OGD/R conditions,and increase the biological functions of HUVEC,such as proliferation,mi-gration,and tubular ability.

Objective To investigate the expression of long non-coding RNA maternally expressed gene 3(lncRNA MEG3)and autophagy in the liver of copper-loaded rats treated with Gandouling(GDL)and to explore its mechanism of action in attenuating liver fi-brosis.Methods Ten SD rats were taken as the normal group,and another 50 were divided into model groups,penicillamine group,GDL low dose group,GDL medium dose group,and GDL high dose group,with 10 rats in each group.The liver fibrosis model of rats with copper-loaded Wilson's Disease was established by gavage of copper sulphate pentahydrate.HE and Masson's staining were used to observe liver pathological morphology.ELISA was used to detect the levels of hyaluronic acid(HA),and laminin(LN),type Ⅲ procol-lagen(PC-Ⅲ),and type Ⅳ collagen(C-Ⅳ).A biochemical kit was used to detect the activity of alanine aminotransferase(ALT)and azelaic acid aminotransferase(AST).Western blot was used to detect the expression of alpha-smooth muscle actin(α-SMA)and collagen type Ⅰ(Col-Ⅰ).RT-qPCR was used to detect the expression of Beclin-1 and lncRNA Meg3mRNA.Immunofluorescence was used to detect the expression of Beclin-1 and LC3-Ⅱ.Results Compared with the normal group,rats in the model group showed collagen fiber deposition in liver tissue,increased levels of HA,LN,PC-Ⅲ,C-Ⅳ,α-SMA,Col-Ⅰ,liver injury,decreased ex-pression of lncRNA Meg3,and increased levels of key markers of autophagy,Beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).After administration of GDL and penicillamine,comparing to the model groups,the levels of AST,LN,Col-Ⅰ,and Beclin-1 showed a trend of reduction in both GDL low,medium,and high dose groups and penicillamine group(P＜0.01).The levels of C-Ⅳ,and α-SMA were decreased in the GDL medium,low,and high dose group and the penicillamine group,with a significant re-duction in the GDL medium and high dose group(GDL low dose group:P＜0.05,GDL middle-high dose group:P＜0.01).Moreover,the reduced expression of lncRNA Meg3 was reversed,and the level of lncRNA Meg3 was increased in the GDL middle-high dose group and the penicillamine group(P＜0.01).Pathological section results indicated that the degree of liver fibrosis was reduced in rats after GDL intervention,and the effect of GDL was obvious in the high dose group.Conclusion GDL alleviated liver fibrosis,and the mecha-nism may be related to the regulation of autophagy expression by lncRNA Meg3.

Objective To evaluate the morphological differences of the glenoid fossa in adult patients with Angle's Class Ⅱ maloc-clusions.Methods The cone-beam computed tomography(CBCT)images of bilateral temporomandibular joints in 82 patients with av-erage mandibular angle were selected.The patients were divided into 4groups including skeletal class Ⅰ with Angle's Class Ⅱ division 1,skeletal class Ⅰ with Angle's Class Ⅱ division 2,skeletal class Ⅱ with Angle's Class Ⅱ division 1 and skeletal class Ⅱ with Angle's Class Ⅱ division 2.Angular and linear measurements of the glenoid fossa were evaluated and the differences among the groups were statis-tically analyzed.Results The functional articular eminence inclination(AEI-BFL)showed statistical differences between skeletal classⅠ and skeletal class Ⅱ groups with the same occlusal relationship and between the two Angle's Class Ⅱ groups with the same sagittal skele-tal relationships(P＜0.05),while the anatomical articular eminence inclination(AEI-TRL)showed no statistical differences among groups(P＞0.05).The width of the glenoid fossa(GFW),the depth of the glenoid fossa(GFD),the ratio of the GFW to the GFD(GFW/GFD)showed no statistical differences among different groups(P＞0.05).Conclusion The morphology of the glenoid fossa re-vealed differences in the Angle's Class Ⅱ with skeletal class Ⅰ and class Ⅱ patients.

Objective Acute liver injury(ALI)exacerbates the condition of patients with severe acute pancreatitis(SAP)and neg-atively affects their prognosis.Recent studies have highlighted the crucial role of chaperone-mediated autophagy(CMA)in regulating liver injury.This study aims to explore the effects of CMA on the pathophysiologic mechanisms of SAP-induced acute liver injury(SAP-ALI).Methods A SAP rat model was established via retrograde injection of 5％sodium taurocholate into the biliary-pancreat-ic duct.Rats were randomly divided into the sham operation(Sham)group,SAP group,CMA activator(AR7)control group,and AR7+SAP treatment group.After 24hours,serum amylase(AMY),liver function,and oxidative stress-specific markers were meas-ured.HE staining was used to evaluate the pathological injury in the pancreatic and liver tissues.The expression levels of lysosomal-as-sociated membrane protein 2 A(LAMP2A),GAPDH,keleh-like ECH-associated protein 1(Keap1),and nuclear factor E2-related factor 2(Nrf2)proteins and LAMP2A,Nrf2mRNA were analyzed by Western blot,immunofluorescence staining,and qRT-PCR.Results AR7 pretreatment significantly improved liver function(P＜0.05),alleviated the pathological damage to the pancreas and liver and enhanced the antioxidant stress capacity(P＜0.05)of SAP-ALI rats.The downregulation of LAMP2A(P＜0.05)and accumula-tion of the CMA substrate GAPDH(P＜0.05)indicated CMA dysfunction in SAP-ALI.Furthermore,AR7-induced upregulation of CMA promoted the activation of the Keap1/Nrf2 pathway in liver(P＜0.05),contributing to its antioxidative effect.Conclusion Our study demonstrates that CMA dysfunction is involved in the pathological process of SAP-induced acute liver injury.AR7-induced CMA reactivation regulates the Keap1/Nrf2 antioxidant pathway,providing protection against SAP-induced acute liver injury in rats.

Objective To investigate the correlation between the triglyceride-glucose(TyG)index,its derivatives in combination with obesity indicators and the risk of albuminuria in patients with type 2diabetes mellitus(T2DM).Methods T2DM inpatients who were hospitalized in the Department of Endocrinology from January 2020 to March 2023 were consecutively collected as study subjects,and divided into the group with no albuminuria(n=246)and the group with albuminuria(n=221).Spearman correlation analysis was used to analyze the correlation between TyG index,its derivative index and clinical indicators,and multivariate Logistic regression was used to analyze the correlation between TyG index,its derivative indexes and albuminuria.Results The TyG index and its derived indices[TyG-body mass index(TyG-BMI),TyG-waist-to-hip ratio(TyG-WHR),TyG-waist-to-height ratio(TyG-WtHR)]were significantly higher in the albuminuric group of patients with T2DM than in the group without albuminuria(all P＜0.001).The inci-dence of albuminuria gradually increased with increasing tertile groupings of all four indicators(all P＜0.001).In multivariate Logistic regression analysis,after correcting for screened risk factors,the TyG index(OR=1.50,95％CI:1.07-2.08,P=0.019),TyG-BMI(OR=1.01,95％CI:1.00-1.01,P=0.009),TyG-WHR(OR=1.45,95％CI:1.12-1.88,P=0.005),and TyG-WtHR(OR=1.39,95％CI:1.00-1.91,P=0.048)were the independent risk factors for albuminuria.For categorical variables,using the 1st quartile group(Q1)as a control group,the 3rd quartile group(Q3)of all four indices were all risk factors for albuminuria,whereas the Q3group of TyG-WHR was more significantly associated with albuminuria compared to the TyG index alone and the other de-rived indices(OR=2.55,95％CI:1.44-4.51,P=0.002).Conclusion In patients with T2DM,both TyG index and its derivatives combined with obesity indicators were significantly associated with albuminuria,and in patients with higher index levels,the risk of albu-minuria was higher in patients with high levels of TyG-WHR compared with single TyG index and other derivatives.Therefore,TyG-WHR may be a novel biological indicator to predict the development of DKD in T2DM patients.

Objective To analyze the sensitization spectrum of common inhaled allergens for respiratory allergic diseases in Mento-ugou district of Beijing,and explore the safety of domestic intradermal test reagents.Methods A total of 19 kinds of inhaled allergen re-agents were used to conduct intradermal test in patients with suspected or definite respiratory allergic diseases(bronchial asthma or allergic rhinitis with bronchial asthma)who visited Department of Respiratory and Critical Care Medicine,Beijing Jingmei Group General Hospital from January 2018 to October 2021.The trends of age,gender and distribution of allergens were compared,and the safety of domestic in-tradermal test reagents were observed.Results A total of 4775 patients were conducted,the positive rate of intradermal test was 52％(2483/4775);the top 5 inhaled allergen positive rates were indoor dust with 29.78％(1422/4775),summer and autumn pollen Ⅰ with 28.06％(1340/4775),dust mite with 23.54％(1124/4775),kochia scoparia with 20.52％(980/4775),spring pollen Ⅱ with 18.03％(861/4775).The positive rate of intradermal test decreased with the increase of age.Patients with respiratory allergic diseases often combined a variety of substances allergy.Before and after CO VID-19 infection,the positive rate of allergens decreased significantly after scientific protection.Adverse effect was observed in 7 patients,the severity of the adverse reaction was all level Ⅰ.Conclusion The inhaled allergens are mainly dust,pollen and dust mite.The main allergens have not changed significantly from 2018 to 2021.Scien-tific protection can effectively reduce the incidence of allergic diseases.Domestic intradermal reagents has high safety and can serve the clinic well.

Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P＜0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P＜0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P＜0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P＜0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.

Objective To analyze the influencing factors of malnutrition in patients with lung cancer undergoing chemotherapy,and construct a predictive nomogram model according to the results.Methods A retrospective analysis was made on 100 patients with lung cancer who received postoperative chemotherapy in our hospital from March 2022 to April 2024.After all the patients had completed five cycles of chemotherapy,the incidence of malnutrition was counted.According to the nutritional evaluation results,the patients were divid-ed into two groups:well-nourished group and malnourished group.The clinical data of patients were compared and the related influen-cing factors were screened by Logistic regression analysis.The nomogram model for risk prediction of malnutrition risk of lung cancer pa-tients undergoing chemotherapy was constructed,and the predictive value and fitting degree of the model were evaluated by drawing the re-ceiver operating characteristic(ROC)curve and calibration curve.Results There were 29 cases of malnutrition in 100subjects,and the other 71 patients had normal nutritional status.Among the general data with significant differences between the two groups,TNM is stageⅣ(OR=2.275,95％CI:1.242-4.169),Accompanied by digestive system adverse reactions(OR=2.142,95％CI:1.133-4.050),Low albumin(OR=2.601,95％CI:1.370-4.937),Low hemoglobin(OR=2.697,95％CI:1.483-4.903),Low prealbumin(OR=2.686,95％CI:1.460-4.941)is a risk factor for malnutrition in patients with lung cancer undergoing chemotherapy(P＜0.05).Based on the above related risk factors,a nomogram model was established to predict the occurrence of malnutrition in patients with lung cancer undergoing chemotherapy.ROC curve analysis showed that the AUC value and 95％CI of the model for predicting malnutrition in patients with lung cancer undergoing chemotherapy were 0.972 and 0.918-0.995.The calibration curve results show that the nomogram model has a good fitting degree.Conclusion TNM is stage Ⅳ,accompanied by digestive system adverse reactions,low KPS score before chem-otherapy and low levels of albumin,hemoglobin and prealbumin are all related risk factors for malnutrition in patients with lung cancer un-dergoing chemotherapy.The nomograph model based on this is also of high predictive value.

Objective To explore the therapeutic effect of corosolic acid on melanoma and its possible molecular mechanisms.Methods Melanoma B16 cells and A375 cells were cultured and divided into control group(0μmol/L),low concentration corosolic acid group(5μmol/L),medium concentration corosolic acid group(10μmol/L),and high concentration corosolic acid group(20μmol/L).According to the grouping,the two types of cells were intervened with corresponding concentrations of corosolic acid.Then,the cell prolif-eration activity was detected by colony formation assay,the cell migration ability was detected by scratch assay,and the cell invasion abili-ty was detected by Transwell assay.Western blot analysis was performed to detect the expression levels of transforming growth factor-β1(TGF-β1),mothers against DPP hom 2(Drosophila)(SMAD2),SMAD3,phosphorylated SMAD2(p-SMAD2),phosphorylated SM3(p-SMAD3),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),and Bcl-2 associated death promoter(Bad)in cells.Immunofluorescence staining was used to detect the expression levels of N-cadherin and Vimentin in cells.For response experi-ments,TGF-β1 recombinant protein was added to the cell culture system of the corosamic acid treated groups as described above.Results Compared with the blank group cells,intervention with different concentrations of corosolic acid significantly inhibited the prolif-eration,migration,and invasion activities of B16 cells and A375 cells,showing a concentration-dependent effect.Additionally,corosol-ic acid intervention led to a significant decrease in the expression levels of TGF-β1,p-SMAD2,p-SMAD3,Bcl-2,N-cadherin,and Vimentin proteins within melanoma cells,while significantly increasing the expression levels of Bax and Bad proteins.However,there was no significant change in the expression levels of SMAD2 and SMAD3 proteins.After adding recombinant TGF-β1 protein,the inhibi-tory effect of corosolic acid on melanoma cells was partially reversed.Conclusion Corosolic acid can significantly inhibit the prolifera-tion,migration,and invasion activities of melanoma cells,and this is related to its inhibition of the TGF-β1/SMAD2/3 pathway.