Objective Chronic obstructive pulmonary disease(COPD)is a global respiratory disorder characterized by chron-ic inflammation and airflow limitation.Dysregulation of lipid metabolism plays a pivotal role in its progression.This study aimed to explore the expression of the lipid metabolism-related gene GRIM-12 in COPD,and assess the therapeutic potential of its in-hibitor,Danthron.Methods Gene expression datasets GSE10006 and GSE11784 from the Gene Expression Omnibus(GEO)were analyzed to identify GRIM-12 as a lipid metabolism-related gene upregulated in the small airway epithelium(SAE)of COPD patients.Human airway epithelial cells(16HBE)were stimulated in vitro with cigarette smoke extract(CSE)to evaluate GRIM-12 expression and the regulatory effects of Danthron.IL-6 level was assessed by using enzyme-linked immunosorbent assay(ELISA),while reactive oxygen species(ROS)level was quantified via fluorescence probe assays.The involvement of the Nrf2/HO-1 signaling pathway was also investigated.Results GRIM-12 expression was significantly upregulated in the SAE of COPD patients and in CSE-treated 16HBE cells.Molecular docking analysis showed that Danthron had a high binding affinity with GRIM-12,and inhibited its function through hydrogen bonding and hydrophobic interaction.Danthron treatment significantly suppressed CSE-induced GRIM-12 overexpression in v itro,reduced IL-6 secretion,and attenuated ROS production,alleviated oxidative stress and inflammatory responses.Mechanistic studies further revealed that Danthron enhanced cellular antioxidant defenses by activating Nrf2/HO-1 signaling pathway,thereby mitigating CSE-induced oxidative damage and inflammation.It is proved that Danthron regulated COPD-related pathological changes by targeting and inhibiting GRIM-12 expression.Conclusion Danthron effectively alleviates oxidative stress and inflammation in COPD by GRIM-12 expression inhibition and Nrf2/HO-1 signaling pathway activation,offering a promising therapeutic strategy for COPD management.

Objective To investigate the potential causal relationship between autoimmune liver diseases(AILD)and type 1 diabetes(T1D)based on two-sample Mendelian randomization(TSM R)method.Methods Genome-wide association study(GWAS)data were obtained from the Open GWAS database.Forward Mendelian randomization analysis was performed with three types of AILD as exposures and T1D as the outcome,while reverse analysis was conducted with T1D as the exposure and three types of AILD as outcomes.Single nucleotide polymorphism(SNP)that was significantly associated with the exposure was selected as instrumental variable(IV).The inverse variance weighting(IVW)method was employed as the primary analytical ap-proach to explore the bidirectional causal relationships between AILD and T1D.Sensitivity analyses,including heterogeneity tests and horizontal pleiotropy tests,were conducted to ensure the robustness of the results.Results The IVW analysis indica-ted that primary biliary cholangitis(PBC)increased the risk of T1D(OR=1.14,95％CI:1.082-1.201,P=9.41 ×10-7),while no significant associations was observed for primary sclerosing cholangitis(PSC)and autoimmune hepatitis(AIH)with T1D(PSC:OR=1.058,95％CI:0.966-1.159,P=0.223;AIH:OR=0.992,95％CI:0.953-1.033,P=0.706).Conversely,T1D was associated with an increased risk of PBC(OR=1.272,95％CI:1.143-1.416,P=1.024×10-5)and PSC(OR=1.246,95％CI:1.072-1.448,P=0.004),but not AIH(OR=1.032,95％CI:0.931-1.144,P=0.551).Conclusion This study demon-strates a bidirectional causal relationship between PBC and T1D,and T1D also increases the risk of PSC.These findings provide new insights and directions for future research into the molecular mechanisms underlying these associations.

Objective To investigate the effect of Danshou decoction on autophagy,proliferation and apoptosis of human villous trophoblast cell HTR-8/Svneo by regulating the mTOR/S6K pathway.Methods HTR-8/Svneo cells were divided into control,Danshou decoction low-dose(Danshou decoction-L,100 μmol/mL),medium-dose(Danshou decoction-M,150 μmol/mL),high-dose(Danshou decoction-H,200 μmol/mL),the mTOR pathway activator MHY1485(100 nmol/mL),and Danshou decoction-H+M HY1485 groups.After 24 hours of treatment,cell proliferation,apoptosis,invasion,and migration were detected by using CCK-8,flow cytometry,Transwell,and wound healing assays.Autophagosome changes were observed,and the expres-sion levels of LC3,p62,Beclin1 mRNA and mTOR/S6K pathway related proteins were detected.Results Compared with the control group,the proliferation rate,invasion rate,migration rate,the proportions of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression reduced,and the apoptosis rate and p62 mRNA expression increased in Danshou decoction group at different dosages.The proliferation rate,invasion rate,migration rate,the proportion of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression increased,and the apoptosis rate and p62 mRNA expression decreased in the MHY1485 group(all P＜0.05).Compared with the Danshou decoc-tion-H group,the proliferation rate,invasion rate,migration rate,the proportion of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression increased,and the apoptosis rate and p62 mRNA expression decreased in the Danshou decoction-H+M HY1485 group(all P＜0.05).Conclusion Danshou decoction inhibits autophagy and proliferation,and induces apoptosis of human villous trophoblast cell HTR-8/Svneo by regulating the mTOR/S6K pathway.

Objective To investigate the inhibitory effects of aggregation protein(Agrin)and scaffold protein(Rapsyn)on the inflammatory responses of microglia and macrophages in injured spinal cord tissue of SD rats through activation of α4β2 nic-otinic acetylcholine receptor(α4β2 nAChR).Methods A spinal cord injury(SCI)model was established by using 4-week-old SD rats.Microglia was cultured,follo wed by incubation with Agrin and Rapsyn.Flow cytometry was utilized to detect changes in markers such as microglia and macrophages,while Co-IP was employed to detect the interaction between the two proteins.The qRT-PCR and IHC were used to identify changes in inflammatory cell marker expression in the spinal cord tissue of SCI models after lentivirus injection.Results The number of microglia and macrophages increased significantly from Day 1 to Day 14 after SCI(all P＜0.01),with the most substantial increase observed from Day 3 to Day 7.The qRT-PCR analysis revealed that in-flammatory microglial cytokine(CD68)and soluble inflammatory cytokines(IL-1β and CCL3)were upregulated after SCI.After injection of lentivirus expressing Agrin and Rapsyn,both A and R groups exhibited a slight reduction in the upregulation of these markers during the observation period of 0-1 week,whereas the A/R group demonstrated a significant reduction in their upregulation(all P＜0.01).IHC analysis indicated that the number of labeled microglial cells in the A/R group was notably lower than that in either A group or R group(all P＜0.01).Conclusion After SCI,Agrin and Rapsyn activate α4β2 nAChR and has inhibitory effects on microglia and inflammatory macrophages,which may block or slow down the progression of spinal cord injury.

Objective To explore the possibility of mutual regulation between TRiC/CCT complex(TCP-1 ring complex/chaperonin containing TCP-1)and mTOR complex 1(mechanistic target of rapamycin complex 1).Methods co-immunoprecipi-tation and Western blot were adopted to explore the interaction between TRiC/CCT complex and mTORC1.Rapamycin was used to inhibit the activity of mTORC 1.Soluble and insoluble cell protein samples were prepared,and the changes in protein ex-pression levels of TRiC/CCT complex-assisted folding were compared.The changes were observed via non-denaturing gel elec-trophoresis to explore the influences of mTORC1 on the integrity of TRiC/CCT complex.The CCT2 or CCT5 gene in HEK-293T cells was silenced by lentivirus-mediated shRNA to explore the influences of TRiC/CCT complex on the expression of key components of mTORC1 and the phosphorylation level of downstream substrates.Results Interaction between each subunit of TRiC/CCT complex and mTORC1 was proved by co-immunoprecipitation experiment.The activity of mTORC1 was inhibited by rapamycin.Expression levels of β-actin,β-Tubulin,and STAT3 insoluble proteins were not significantly increased,and the molecular size of the complex did not change significantly in the non-denaturing electrophoresis gel,indicating that mTORC1 had no regulative effect on formation of TRiC/CCT complex.CCT2 or CCT5 was silenced in HEK-293T.The protein expres-sion levels of mTOR,Raptor,and mLST8 were decreased,and the phosphorylation levels of p70S6K and Akt were decreased,re-vealing that the TRiC/CCT complex had a regulative effect on mTORC1 and downstream molecules.Conclusion The protein expression level of each component of mTORC1 was regulated by TRiC/CCT complex,thus affecting the phosphorylation level and activity status of the downstream substrates.

Objective To explore the value of intravoxel incoherent motion diffusion weighted imaging(IVIM)in preopera-tive diagnosis of microvascular invasion(MVI)in hepatocellular carcinoma(HCC).Methods A retrospective analysis was con-ducted on the imaging data of 38 hepatocellular carcinoma patients who underwent surgical resection at Hunan Medical College General Hospital from 2019 to 2022.According to postoperative pathology results,they were divided into MVI positive group and MVI negative group.The apparent diffusion coefficient(ADC)of DWI parameters,the true diffusion coefficient(D),perfu-sion related diffusion coefficient(D),and perfusion score(f)of IVIM parameters were measured before surgery in HCC pa-tients.The risk factors affecting the occurrence of MVI in HCC were analyzed,and the diagnostic efficacy of subject operating characteristic curve(ROC)was evaluated for MVI.Results The ADC and D values of the MVI positive group were lower than those of the negative group,with statistical differences(both P＜0.05).The area under the D-value curve(AUC),specificity,and sensitivity were 0.741,68％,and 94％,respectively.The area,specificity,and sensitivity under the ADC value curve were 0.714,50％,and 88％,respectively,The area under the curve for the combined diagnosis of MVI by two indicators was 0.832,with a sensitivity of 94％and a specificity of 77％.Conclusion The IVIM parameter D value and DWI parameter ADC value can help to predict microvascular infiltra-tion in hepatocellular carcinoma before surgery,and the diagnostic efficacy of D value is superior to ADC value.IVIM imaging can im-prove the accuracy of preoperative prediction of microvascular invasion in hepatocellular carcinoma.

Tacrolimus(FK506)is the most widely utilized calcineurin inhibitors(CNIs)and serves as the first-line agent in immunosuppressive treatment regimens.FK506 has a narrow therapeutic index,and its pharmacokinetics exhibit significant vari-ability both between and within individuals.High-dose exposure to FK506,whether administered long-term or short-term,can result in nephrotoxicity.Proximal tubule cells in kidney are the only cells that are capable of metabolizing CNIs,and these cells are believed to play a central role in the development of toxicity associated with this class of drugs.The mechanism underlying renal tubular toxicity induced by FK 506 is complex,involving factors such as cellular oxidative stress,inflammatory responses,metabolic dysfunction of renal tubular cells,apoptosis,and the renin-angiotensin system.Despite extensive research,the patho-genesis of FK506-induced tubular toxicity remains incompletely understood.Therefore,this article aims to review the research progress concerning the pathogenesis of tacrolimus-related renal tubular toxicity,as well as its prevention and treatment,to pro-vide a reference for clinical practice and future research.

Objective To compare the complications,etiology,and clinical manifestations between pediatric patients with heart valve disease undergoing surgical treatment.Methods A retrospective analysis was conducted on the clinical data of 169 pediatric patients aged 0-14 years diagnosed with heart valve abnormalities at Wuhan Union Hospital from January 2019 to October 2022.Patients were divided into two groups based on whether they received surgical intervention for valve abnormali-ties:the surgical treatment group and the medical treatment group.Results There were significant differences in age,type and grade of heart failure,club-finger,pneumonia and cough,cardiac morphology,arrhythmia,ventricular septal width and left ven-tricular ejection fraction(all P＜0.05).Univariate and multivariate binary logistic regression analyses revealed that left ventricu-lar ejection fraction(OR=1.206,95％CI:1.072-1.357,P＜0.05)was an independent risk factor for the surgical treatment group.Conclusion The clinical manifestations of heart valve abnormalities in children are often atypical.Clinicians should ac-tively evaluate the etiology based on clinical symptoms and echocardiographic findings,and develop individualized treatment strategies,either surgical or medical,to prevent the progression of severe heart disease.

Currently,there is a paucity of efficacious treatments for acute kidney injury(AKI),and existing therapeutic ap-proaches primarily aim to mitigate symptoms and enhance patient outcomes.Platelets,a vital element of the circulatory system,are characterized by their abundance and multifaceted functions.Moreover,several studies have documented platelet infiltration within the kidneys during A KI,revealing elevated expression levels of platelet activation markers such as P-selectin,RANTES,and integrin α Ⅱ bβ3.This suggests that platelet activation occurs in A KI and may influence the progression of the disease.Furthermore,preliminary findings from both clinical and animal model studies indicate that antiplatelet therapy could re-duce tissue damage and protect renal function in AKI resulting from various etiologies.This review aims to elucidate the role of platelets in the pathophysiology of AKI by synthesizing current researches,while also investigating the potential of antiplatelet therapy as a novel approach for the management of AKI,thereby offering new diagnostic and therapeutic strategies.

Renal anemia is a common complication of chronic kidney disease(CKD).It not only reduces patients'quality of life and accelerates the progression of kidney disease,but also increases the risk of all-cause mortality in CKD patients.This arti-cle reviews studies related to the pathogenesis of renal anemia,with the aim of offering novel ideas for the prevention and inter-vention of renal anemia in clinical practice.