ObjectiveTreadmill exercise intervention was evaluated for its effects on addictive behavior, learning and memory, and hippocampal neuroinflammation in methamphetamine (MA)-addicted mice, and transcriptomic screening was performed to identify candidate molecules involved in exercise-mediated attenuation of MA-related neuronal injury. MethodsTwo-month-old male C57BL/6 mice were randomly assigned to four groups: control (C), exercise control (CE), methamphetamine (M), and methamphetamine plus exercise (ME). Mice in the M and ME groups received intraperitoneal injections of MA (1 mg/kg) once daily for 7 consecutive days to establish the addiction model, whereas mice in the C and CE groups received equal volumes of saline. Subsequently, mice in the CE and ME groups underwent treadmill exercise at 12 m/min for 60 min/d for 2 weeks. Conditioned place preference (CPP), the Y-maze, and the Morris water maze (MWM) were used to assess addictive behavior, spatial recognition memory, and spatial learning and memory, respectively. Hippocampal neuronal ultrastructure was examined by transmission electron microscopy (TEM), and microglia-related responses were evaluated by immunofluorescence staining for ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampal CA1 region. Previously generated and publicly available RNA-seq data from brain tissue of the C, M, and ME groups were reanalyzed, with three biological samples per group. Differentially expressed genes (DEGs) were re-screened using the criteria of P<0.05 and fold change>1.5 or <0.67, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. NLR family CARD domain containing 5 (Nlrc5) was further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot was used to determine the protein expression of NLRC5, nuclear factor kappa B (NF‑κB), interleukin-1β (IL-1β), postsynaptic density-95 (PSD-95), and synaptophysin. ResultsTreadmill exercise significantly attenuated MA-induced conditioned place preference and improved learning and memory performance in both the Y-maze and MWM tests. Exercise increased exploration time and distance in the novel arm of the Y-maze, shortened escape latency, and increased the number of platform crossings in the MWM. Average swimming speed during the probe trial did not differ significantly among groups, suggesting that the MWM differences were not attributable to obvious differences in swimming performance. TEM revealed that MA exposure induced mitochondrial swelling, disrupted cristae, reduced organelle abundance, and nuclear envelope abnormalities in hippocampal neurons, whereas these ultrastructural changes were alleviated after exercise. Immunofluorescence staining showed that MA increased Iba-1 fluorescence intensity in the hippocampal CA1 region, while treadmill exercise significantly reduced this change. Transcriptomic analysis identified 160 DEGs associated with MA exposure and 58 DEGs associated with exercise intervention, with 9 overlapping DEGs. KEGG enrichment analysis showed that MA-related DEGs were enriched in the NOD-like receptor signaling pathway. Among the overlapping DEGs, Nlrc5, which was downregulated after MA exposure and restored following exercise intervention, was selected as a candidate gene for further validation. RT-qPCR confirmed that treadmill exercise reversed the MA-induced decrease in Nlrc5 mRNA expression. Western blot analysis further showed that treadmill exercise increased NLRC5, PSD-95, and synaptophysin protein expression while reducing NF-κB and IL-1β expression. ConclusionTwo weeks of treadmill exercise attenuated MA-induced conditioned place preference and ameliorated learning and memory impairment, alleviated hippocampal neuroinflammation and neuronal ultrastructural damage, and restored the expression of synapse-related proteins. Transcriptomic screening combined with molecular validation demonstrated that exercise intervention was accompanied by restoration of NLRC5 expression, reduced NF‑κB and IL-1β expression, and increased PSD-95 and synaptophysin expression. These findings suggest that NLRC5 may represent a candidate molecule involved in exercise-mediated amelioration of MA-related neuronal injury. However, the present results mainly demonstrate coordinated changes in NLRC5 expression, inflammatory indicators, and cognitive outcomes rather than a direct causal relationship, and the specific role of NLRC5 requires further functional validation.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the correlation of monocyte count(MONO)to high density lipopro-tein-cholesterol(HDL-C)ratio(MHR)and systemic immune-inflammation index(SII)with diabetic retinop-athy(DR).Methods Patients with type 2 diabetes mellitus(T2DM)admitted to the hospital from June 2020 to May 2023 were selected as the research objects.According to the presence or absence of DR,the patients were divided into non-retinopathy group(NDR group)and DR Group.The differences in basic information,blood routine,and biochemical indexes between the two groups were analyzed,and the MHR and SII were cal-culated.Multivariate Logistic regression was used to analyze the risk factors for DR.Spearman correlation a-nalysis was used to analyze the correlation between risk factors and DR.The receiver operating characteristic(ROC)curve was used to evaluate the value of MHR and SII in predicting DR in T2DM patients.Results A total of 291 T2DM patients were enrolled,including 135 patients in the NDR group and 156 patients in the DR group.Compared with the NDR group,duration of diabetes was significantly prolonged(P<0.05),glycosy-lated hemoglobin(HbA1c),creatinine,fasting plasma glucose(FPG),total cholesterol(TC),platelet count(PLT),MHR and SII were increased(P<0.05),and high density lipoprotein-cholesterol(HDL-C)was de-creased(P<0.05)in the DR Group.Spearman correlation analysis showed that DR was positively correlated with duration of diabetes,FPG,HbA1c,PLT,MHR and SII(P<0.05),and negatively correlated with HDL-C(P<0.05).Multivariate Logistic regression analysis showed that gender(OR=0.151,95%CI 0.052-0.432,P<0.001),history of heavy drinking(OR=7.199,95%CI 2.845-18.216,P<0.001),duration of di-abetes(OR=1.570,95%CI 1.354-1.821,P<0.001),HbA1c(OR=1.218,95%CI 1.013-1.464,P=0.036),MHR(OR=1.054,95%CI 1.028-1.080,P<0.001)and SII(OR=1.002,95%CI 1.001-1.003,P=0.002)were independent influencing factors for DR patients.ROC curve analysis showed that the area un-der the curve(AUC)of MHR and SII in predicting the development of T2DM to DR was 0.696 and 0.567,re-spectively.The AUC of MHR and SII combined in predicting DR was 0.702.Conclusion MHR and SII are closely related to the incidence of DR,and both have certain predictive value for DR,and the predictive value of the combined of MHR and SII is higher.

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.
Humans ; Hypospadias/surgery* ; Male ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Child, Preschool ; Child ; Postoperative Complications/etiology* ; Urethra/surgery* ; Plastic Surgery Procedures/methods* ; Surgical Flaps ; Penis/surgery* ; Treatment Outcome ; Infant

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.