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.

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.

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To explore the association between uric acid and new-onset chronic kidney disease (CKD) in middle-aged and elderly hypertensive patients.Methods:This was a retrospective cohort study. Middle-aged and elderly hypertensive patients who had attended at least two annual health examinations at Yongshun Community Health Service Center in Tongzhou District, Beijing, from June 2016 to December 2020 were enrolled. The time interval between the two physical examinations was three years. The first physical examination time served as the baseline, and the second as the end of follow-up. Based on the uric acid level at baseline, the participants were divided into the normal uric acid group and the hyperuricemia group. The relevant clinical data of the participants were collected. The endpoint of the study was new-onset CKD. A multivariate logistic regression model was used to analyze the association between uric acid and new-onset CKD in hypertensive patients.Results:A total of 2 472 middle-aged and elderly hypertensive patients with an average age of (62.43±7.02) years were included. Of these, 733(29.7%) were male. There were 710 patients with hyperuricemia (hyperuricemia group) and 1 762 patients with normal uric acid levels (normal uric acid group).After adjusting for age, sex, body mass index (BMI), systolic blood pressure, diabetes mellitus, estimated glomerular filtration rate (eGFR), and uric acid-lowering treatment, multivariate logistic regression analysis showed that combined with hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001). The results of multivariate logistic analysis showed that elevated uric acid level was an independent risk factor for new-onset CKD in both male and female middle-aged and elderly hypertensive patients (both P<0.05), and there was no sex interaction ( P for interactio n>0.05). The results of multivariate logistic analysis showed that the combination of asymptomatic hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001), and there was no gender interaction ( P for interactio n>0.05). Conclusions:Hyperuricemia is an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients, and elevated uric acid levels increase the risk of new-onset CKD in both male and female patients. Moreover, asymptomatic hyperuricemia may increase the risk of new-onset CKD.

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

In recent years，with the increase in environmental pollution，organisms are exposed to more internal and external oxidative stress factors than ever before.Nuclear factor erythroid 2-related factor 2（nuclear factor erythroid 2-related factor 2，NRF2），as a core transcription factor in response to oxidative stress，maintains cellular redox homeostasis by inducing the expression of various antioxidant factors.The nasal cavity，as the "gateway" of the respiratory tract，is often accompanied by oxidative stress（oxidative stress，OS）damage，leading to the occurrence of allergic rhinitis（allergic rhinitis，AR）.Recent studies have revealed some associations between the NRF2 signaling pathway and the mechanism of AR development.Activation of NRF2 provides a potential protective effect against AR，and some natural NRF2 activators have shown therapeutic potential in clinical experiments.Therefore，this article briefly reviews the relationship between NRF2 and AR，aiming to provide a new therapeutic target and perspective for the treatment of AR.
NF-E2-Related Factor 2/metabolism* ; Humans ; Rhinitis, Allergic/metabolism* ; Signal Transduction ; Oxidative Stress

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.