Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Objective　This study aims to investigate and compare the clinical characteristics and prognostic factors among primary liver cancer (PLC) patients who had hepatitis B virus (HBV)-induced cirrhosis associated with liver cancer, alcoholic cirrhosis associated with liver cancer, or both HBV and alcoholic cirrhosis associated with liver cancer. 　　　Methods　Inpatients diagnosed with PLC admitted to the First Affiliated Hospital of Fujian Medical University between January 2010 and September 2020 were enrolled and divided into three groups based on the etiology. The follow-up period ends in October 2024. Survival analyses were performed using Kaplan-Meier curves, univariate analysis, and multivariate Cox regression. Results　During the study period, 45 cases of alcoholic cirrhosis associated liver cancer (ALD group), and 71 cases of hepatitis B combined with alcoholic cirrhosis associated liver cancer (HBV+ALD group) were enrolled. At the same time, 73 patients with hepatitis B cirrhosis associated liver cancer (HBV group) during the same period were randomly selected with a ratio of about 1∶1.5, totaling 189 cases. And 183 (96.8%) of the patients were male and 6 (3.2%) were female. The age was (55.93±10.20) years. 109 deaths (57.7%) were recorded. The median survival times were 12 months for the entire cohort, 55 months for HBV group, 36 months for ALD group and 11 months for HBV+ALD group. And the 10-year death rate was 42.5% in HBV group, compared to 66.7% in ALD group and 67.6% in HBV+ALD group. In this study, 93 patients chose either the surgical resection or the radiofrequency ablation as their treatments. The recurrence rate was 69.9%, the median recurrence time was 8 months and the median overall survival time was 39 months. Univariate Cox regression identified that etiology of HBV and ALD, alpha-fetoprotein (AFP)>1 200 ng/mL, Child-Pugh class B and C, Barcelona Clinic Liver Cancer (BCLC) stages of C and D and curative therapies such as surgery and radiofrequency ablation were significantly correlated with overall survival (all P<0.05). Multivariate Cox regression revealed that patients with both HBV and ALD (HR=1.750，95%CI: 1.107-2.765，P=0.017), AFP>1 200 ng/mL (HR=1.649，95%CI: 1.060-2.564，P=0.027), and BCLC stages of C and D (HR=3.404，95%CI: 2.254-5.142，P<0.001) were independent risk factors of mortality in PLC patients with cirrhosis. Conclusions　Among HBV, ALD and HBV+ALD groups, the HBV+ALD group had the shortest median survival time and the highest overall mortality rate, suggesting that alcohol consumption and HBV infection may accelerate the progression of PLC with cirrhosis and worsen its prognosis. HBV infection combined with alcoholic consumption, AFP>1 200 ng/mL, and BCLC stages of C and D were independent risk factors for mortality in PLC patients with cirrhosis.

Human keratinocyte growth factor-1 (hKGF-1), a member of the fibroblast growth factor (FGF) family, plays crucial roles in organ development, cell proliferation, wound healing, and tissue repair, representing one of the most effective and specific growth factors for skin repair. However, obtaining recombinant hKGF-1 remains challenging due to its universally low expression efficiency in vitro. This study employs the Bombyx mori baculovirus expression system to establish a technological platform that utilizes the economically important insect Bombyx mori as a bioreactor for high-efficiency and low-cost expression and production of recombinant human keratinocyte growth factor 1 (hKGF-1) protein, ultimately achieving high-level expression of hKGF-1 in Bombyx mori ovary cell line (BmN). In this study, we optimized the hKGF-1 sequence based on the codon preference of baculovirus. By fusing hKGF-1 with polyhedrin (highly expressed in this system) and adding extra promoters and enhancers, we significantly improved the expreesion level of hKGF-1 in Bombyx mori cells. The results demonstrated that the aforementioned strategies significantly enhanced the expression level of hKGF-1 in Bombyx mori cells. SDS-PAGE and Western blotting results revealed that the highest hKGF-1 expression (accounting for 8.7% of total cellular protein) was achieved when the Polh promoter was combined in tandem with the P6.9 promoter and hKGF-1 was fused with a 15-residue polyhedrin fragment for co-expression. The optimal harvest time was determined to be 120 h post transfection. This study achieved the efficient expression of hKGF-1 in Bombyx mori cells, establishing an ideal technological platform for the industrial utilization of recombinant hKGF-1. The developed methodology not only provides valuable technical references for the production of other growth factors and complex proteins, but also demonstrates significant implications for employing silkworms as bioreactors for recombinant human protein expression.
Bombyx/metabolism* ; Animals ; Baculoviridae/metabolism* ; Humans ; Fibroblast Growth Factor 7/biosynthesis* ; Recombinant Proteins/genetics* ; Cell Line ; Genetic Vectors/genetics*

Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.

Prior to clinical application,reliability of percutaneous ventricular assist devices(pVAD)requires to be tested systematically.Currently,there's a lack of dedicated reliability testing equipment and methodologies for pVAD.Considering the structural and functional aspects of percutaneous ventricular assist devices,this study conducts research on pVAD reliability test engineering.Test setups,clinical conditions,failure modes,effects analysis,and evaluation models have been investigated.A highly feasible methodological approach for percutaneous ventricular assist device reliability assessment has been formed.This study offers valuable insights into standardizing their reliability evaluation in clinical settings.

Objective:To summarize the clinical characteristics in of different antibody subtypes in of patients with antisynthetase syndrome (ASS) complicated with interstitial lung disease (ILD).Methods:A retrospective analysis was conducted on 132 ASS-ILD patients at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People′s Hospital), encompassing a period from December 2019 to June 2023. The data included were basic demographic information, clinical features, laboratory test results, chest computed tomography (CT) scans, and pulmonary lung function tests. Patients were categorized into distinct subtypes based on anti-aminoacyl tRNA synthetase (ARS) antibodies. Statistical analysis was performed using a t-test for comparing means between two samples with equal variance, the Mann-Whitney U test for non-normally distributed continuous data, and the chi-square ( χ2) test or Fisher′s exact test for categorical variables. Results:The most prevalent subtype of anti-synthetase antibody was anti-histidine antibody (Jo-1), accounting for 60 of 132 cases (45.5%), followed by anti-glycine-based tRNA synthetase antibody (EJ) (33/132, 2 5.0%), anti-tRNA synthase antibody (PL-7) (26/132, 19.7%), anti-alanine-based tRNA synthetase antibody (PL-12) (7.6%, 10/132), anti-isoleucine-tRNA synthase antibody (OJ) (3/132, 2.2%). The presence of anti-Ro-52 antibodies was significantly associated with rapidly progressive ILD. In patients with different subtypes of ASS-ILD, the presence of anti-Jo-1 antibodies is was positive in 28 cases (46.7%), and the combination of infection is was more common than in other groups ( χ2=0.15, P=0.047). The group with positive anti-EJ antibodies has had a significant decline in lung function, and cough is was more common in 31 cases (93.9%) than in other groups ( P<0.05); the group with positive anti-PL-12 antibodies has had a more pronounced decline in lung function than other groups ( P<0.05), and fever (7 cases, 70.0%) wais more common than in other groups ( χ2=0.02, P=0.022). Conclusion:Anti-Jo-1, Anti-PL-7, and Anti-PL-12 antibodies were are observed more frequently in patients with ILD. Furthermore, a significant deterioration in lung function was is observed in patients testing positive for anti-PL-12 and anti-EJ antibodies.

Objective To optimize the simulation of the pathological characteristics and seizure behavior of medial temporal lobe epilepsy(MTLE),we aimed to establish a chronic epilepsy model of MTLE by unilateral,single hippocampal injection of kainic acid(KA)via stereotactic surgery,and to validate this epilepsy model in terms of behavior,electrophysiology,and pathology.Methods A total of 22 healthy C57BL/6 wild-type male mice were divided randomly into a control group(n=6)and an experimental group,which received KA injections(n=16).Both groups underwent microinjection of equal doses of saline or KA in the hippocampal CA3 area via stereotactic surgery.One week later,all mice were implanted with electrodes in the hippocampal CA3 area to facilitate electroencephalogram(EEG)recording.Seizure frequency and duration were analyzed statistically.The chronic epilepsy model was assessed in terms of behavior,electrophysiology,and pathology.Results No mice in the control group experienced seizures,while all surviving mice in the experimental group developed seizures.Adult model mice exhibited chronic spontaneous seizure behaviors,such as staring,chewing,head and facial muscle twitching,and limb spasms.Two mice died as a result of the surgery,four mice died during the acute seizure phase,and ten model mice were successfully established.EEG recordings showed epileptiform changes consistent with MTLE.Immunofluorescence staining revealed neuronal loss in the CA3 area and astrocytic changes,consistent with characteristic pathological changes of hippocampal sclerosis.Conclusions The model constructed by single unilateral intrahippocampal KA injection demonstrated several advantages such as being time-efficient,easy to operate,and reproducible.This model exhibited EEG,behavioral,and neuropathological changes similar to human MTLE,making it valuable for studying effective treatments for temporal lobe epilepsy and serving as an ideal animal model for predicting outcomes of epilepsy surgery.

Objective To investigate the association between milk fat globule-epidermal growth factor 8(MFG-E8)and Alzheimer disease(AD).Methods The Alzheimer's Disease Neuroimaging Initiative database was used,and a multiple linear regression analysis was used to investigate the association of MFG-E8 with the pathological markers of AD and brain structure and perform subgroup analyses.The mixed-effects model was used to investigate the longitudinal changes in MFG-E8 with AD pathological markers and brain structure,and a mediation analysis was used to investigate the potential association of MFG-E8 with AD pathology and brain structure.Results A total of 377 individuals were en-rolled in the study.The level of MFG-E8 was positively correlated with the concentrations of amyloid β-protein 42(Aβ42),tau protein,and phosphorylated tau protein in cerebrospinal fluid,and subgroup analyses showed that the correlation of MFG-E8 with the concentrations of AD pathological markers and lateral ventricular volume in male individuals,the elderly popula-tion,and the individuals carrying the APOE4 gene was consistent with that in the overall population.Longitudinal studies showed that during follow-up,the increase in MFG-E8 level was significantly associated with enlarged lateral ventricle volume.In addition,MFG-E8 could alter lateral ventricle volume by affecting the level of Aβ42.Conclusion MFG-E8 is associated with AD and may influence lateral ventricular volume through AD pathological markers.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.