Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective:To analyze the endoscopic and clinicopathological characteristics of Helicobacter pylori ( HP)-negative early gastric cancer (EGC). Methods:A retrospective study was conducted on data of patients who were diagnosed as having EGC at the Affiliated Hospital of Qingdao University between June 2013 and March 2024. Cases meeting the diagnostic criteria for HP-negative status were included. Endoscopic findings and histopathological features of HP-negative EGC were systematically analyzed. Results:Among 698 EGC patients, 29 (4.2%) were identified as HP-negative. The age at diagnosis was 59.9±10.0 years, with marked female predominance (69.0%, 20/29 VS 31.0% males, 9/29). A body mass index ≥24 kg/m 2 was observed in 69.0% (20/29). Regarding therapeutic approaches, endoscopic submucosal dissection was performed in 89.7% (26/29). Among the 29 patients with a total of 30 lesions, the majority were localized to the middle third of the stomach (40.0%, 12/30), or the upper third (36.7%, 11/30). Differentiated-type accounted for 73.3% (22/30) among the histological types, including 13 oxyntic gland adenoma (OGA) / gastric adenocarcinoma of fundic-gland type (GA-FG) (upper third: 7; middle third: 6), and 2 gastric adenocarcinomas of fundic-gland mucosa type (GA-FGM) (both upper third). White-light endoscopy revealed polypoid or small submucosal tumor-like protrusions with whitish or erythematous discoloration and characteristic branching dilated vessels on the surface. Among the OGA/GA-FG lesions, 8 exhibited indistinct demarcation lines (DL). Additionally, both GA-FGM lesions demonstrated poorly defined DL. Three gastric adenocarcinomas of foveolar-type (GA-FV) were identified (upper/middle/lower third: 1 each), with 2 presenting as erythematous elevated masses. Five signet ring cell carcinomas (upper/middle/lower third: 1/3/1) exhibited flat or shallow depressed morphology with whitish or erythematous discoloration under white-light endoscopy; 3 exhibited well-demarcated borders. Four pyloric gland adenocarcinomas and three poorly differentiated tubular adenocarcinomas showed no significant differences in endoscopic features on white-light and narrow-band imaging compared to HP-positive EGC. No intestinal-type adenocarcinomas were identified. Conclusion:HP-negative EGC exhibit distinct endoscopic and clinicopathological characteristics, including female predominance and frequent differentiated histology, and upper/middle-third localization of elevated lesions, primarily OGA/GA-FG.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Objective:To summarize the long-term efficacy of nicotinamide in treating pediatric early-onset progressive encephalopathy with brain edema and (or) leukoencephalopathy-2 (PEBEL2) caused by NAXD gene variation .Methods:This was a case report conducted from February 2019 to January 2025. The long-term efficacy of nicotinamide was observed by following up a child with PEBEL2 who received the treatment in the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University. The clinical data included changes in skin lesions, neurological symptoms. The modified Rankin scale (mRS) was used to evaluate the recovery of neurological function.Results:A boy was diagnosed with PEBEL2 caused by NAXD gene variation via genetic testing at Beijing Children′s Hospital Affiliated to Capital Medical University in February 2019, when he was 4 years and 6 months of age. Immediately after diagnosis, nicotinamide treatment was initiated at an initial dose of 100 mg/d, which was increased by 100 mg per week and gradually increased to 500 mg/d; meanwhile, other therapeutic drugs were gradually discontinued. After 1 year and 8 months of treatment, the child′s skin lesions had completely resolved; at the 2-year follow-up, dystonia in both upper limbs and swallowing dysfunction was alleviated significantly; by 2.5-year follow-up, his cognitive function also showed improvement. When the child was treated with 500 mg/d for 3 years, a rash appeared around the mouth. After the dose was reduced to 250 mg/d, the rash resolved, and the dose of 250 mg/d was maintained until the last follow-up. At the last follow-up in January 2025, the child was 10 years and 5 months of age. His mRS score decreased from 5 (before treatment) to 4. During the 6-year of continuous nicotinamide treatment, the child′s condition remained stable without progression. Drug-related skin rashes occurred, but no severe drug-related adverse reactions were observed.Conclusions:PEBEL2 is a treatable mitochondrial disease. Nicotinamide treatment can effectively improve skin lesions and neurological symptoms in PEBEL2 patients, and the long-term administration demonstrates a favorable safety profile.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Hypoxia-related diseases,such as altitude sickness,acute lung injury,and heart failure,have emerged as significant public health challenges worldwide and are strongly associated with increased mortality risks.These conditions tend to cause functional impairment and structural alterations in multiple organs,primarily due to inadequate oxygen supply or the inability of tissues to utilize oxygen effectively.To elucidate the pathophysiological mechanisms underlying hypoxia-associated diseases and to explore potential therapeutic strategies,researchers have employed animal models to conduct extensive mechanistic studies and drug development trials.In this review,we provide a comprehensive overview of the methods used to construct animal models for various hypoxia-related diseases.We made a thorough evaluation of the strengths,weaknesses,limitations,and applicability of each approach.In particular,we focus on modeling strategies for key pathologies such as altitude sickness,acute lung injury,pulmonary hypertension,and heart failure,discussing their respective advantages and restrains.Furthermore,we examined the potential application of gene editing technologies in optimizing animal models,especially its role in enhancing the accuracy and reproducibility of the models.The integration of these advanced technologies holds great promise for developing animal models with improved specificity and simulation of key features of diseases,which will serve as a solid foundation for basic research,drug screening,and preclinical trials concerning hypoxia-related diseases.Herein,we present a systematic summary and future outlook of animal models for hypoxia-related diseases,ultimately providing theoretical support for developing clinical treatment strategies and improving patient outcomes.

AIM:To investigate the association between single nucleotide polymorphisms(SNPs)in the silent information regulator 1(SIRT1)gene and breast cancer risk in the Han Chinese population.METHODS:A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled.Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci,rs3740051,rs3758391,rs12778366 and rs2394443.The Hardy-Weinberg equilibrium(HWE)was analysed using the chi-square test.Multivariate logistic regression was employed to analyze the correlation be-tween each SNP and breast cancer susceptibility,as well as the relationship between the rs3758391 genotype and the clini-copathological characteristics of breast cancer in Han Chinese women.SHEsis software was used to assess linkage disequi-librium and haplotypes of the selected SNPs.The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot.An additional 150 Han Chinese women with breast cancer and 150 healthy controls were en-rolled,and SIRT1 protein expression was assessed using immunohistochemistry.Logistic regression was performed to as-sess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer.Kaplan-Mei-er website was used to determine the association between SIRT1 expression and patient prognosis.RESULTS:All four SNP loci conformed to the HWE test(P>0.05).The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly re-duced the risk of breast cancer compared with the TT genotype(TT vs TC:ORadj=0.348,95%CI:0.157～0.773,Padj=0.010;TT vs TC+CC:ORadj=0.381,95%CI:0.179～0.811,Padj=0.012),and correlated with earlier disease course(stage I/II),smaller tumor volume,and higher SIRT1 protein expression levels(P<0.05).SIRT1 expression was signifi-cantly lower in breast cancer tissues,and low SIRT1 expression was associated with larger tumor size,lymph node metasta-sis,and reduced recurrence-free survival(P<0.05).CONCLUSION:The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women,potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression.In addition,SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.

Objective To investigate the effect of intravenous lidocaine on postoperative fatigue syndrome(POFS)in patients undergoing laparoscopic resection for gastric carcinoma.Methods A total of 80 patients who underwent elective laparoscopic resection for gastric carcinoma at Xuzhou Central Hospital between September 2023 and June 2024 were enrolled.Inclusion criteria included age 18～75 years,ASA physical status classificationⅠ～Ⅲ,body mass index(BMI)of 18.5～27.9 kg/m2,preoperative Christensen score≤4,and estimated operation time≤4 hours.Patients were randomly allocated into either the lidocaine group(Group L)or the saline group(Group C)using a random number table,with 40 patients in each group.Group L received an intravenous infusion of lidocaine at a dose of 1.5 mg·kg?1 over 15 minutes,initiated 30 minutes before anesthesia induction.If no adverse reactions occurred,lidocaine was maintained at a rate of 1.5 mg/(kg·h)throughout the surgery until its conclusion.Group C received an equivalent volume of normal saline administered in the same manner.The Christensen score and Visual Analogue Scale(VAS)scores were recorded on postoperative days 1,3,5,and 7,and the time-weighted average(TWA)of the Christensen score was calculated.Postoperative inflammatory markers were measured,and additional outcomes including extubation time,post-anesthesia care unit(PACU)stay duration,postoperative nausea and vomiting(PONV),consumption of rescue analgesics,time to first flatus and defecation,and length of hospital stay were also documented.Results Compared with Group C,the TWA of the Christensen score in Group L decreased by 0.44 points(95％CI:0.11～0.76;P<0.05).The VAS scores were significantly lower in Group L on postoperative days 1 and 3(P<0.05).Levels of IL-6 and TNF-α at the end of surgery and 24 hours after surgery were also lower in Group L(P<0.05).The time to first flatus and defecation was significantly shorter in Group L(P<0.05).There were no significant differences between the two groups regarding extubation time,PACU stay duration,incidence of PONV,postoperative consumption of remedial analgesic drugs,or length of hospital stay(P>0.05).Conclusion Intravenous lidocaine may improve POFS in patients following laparo-scopic resection for gastric carcinoma by attenuating inflammatory responses,alleviating pain,and facilitating gastrointestinal function recovery,while maintaining a favorable safety profile.