Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures. This study explores the neural and behavioral effects of tTIS on the superior colliculus (SC), a region involved in eye movement control, in mice. Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation. In vivo experiments, including Ca²⁺ signal recordings and eye movement tracking, showed that tTIS effectively modulates SC neural activity and induces eye movements. A significant correlation was found between stimulation frequency and saccade frequency, suggesting direct tTIS-induced modulation of SC activity. These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements, highlighting its potential for neuroscientific research and therapeutic applications.
Animals ; Superior Colliculi/physiology* ; Transcranial Direct Current Stimulation/methods* ; Eye Movements/physiology* ; Male ; Mice ; Mice, Inbred C57BL

AIM:To analyze the expression of se-creted phosphoprotein 1(SPP1)and programmed cell death-ligand 1(PD-L1)in SMARCA4-deficient non-small cell lung cancer,and to provide a scientif-ic basis for the study of the follow-up treatment of this rare pathological type of lung cancer.METH-ODS:The clinical and pathological characteristics of 12 patients with this disease were analyzed retro-spectively,and the patients were divided into two groups of adenocarcinomas and poorly differentiat-ed carcinomas according to their morphological characteristics,and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups.RESULTS:SPP1 expression was detect-ed in all patients and Its expression level was signif-icantly higher in the poorly differentiated carcino-ma group compared with the adenocarcinoma group(P=0.015);PD-L1 expression was found in 6/7 patients(5 cases were not measured),compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carci-noma group(P=0.048)and the PD-L1 difference be-tween the two groups suggested that the results were similar to those of SPP1.CONCLUSION:SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1.It was more pronounced in patients with poorly differenti-ated carcinoma.There may be a positive correla-tion between SPP1 and PD-L1 expression in SMAR-CA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies.

Objective:To investigate the mechanism by which histone deacetylase 6 (HDAC6) exerts immune protective effects in Chlamydia trachomatis respiratory tract infection. Methods:Wild-type (WT) C57BL/6 mice and HDAC6 gene knockout (HDAC6 -/-) mice were used to establish mouse models of Chlamydia muridarum ( Cm) respiratory infection by nasal inhalation of Cm. qPCR and Western blot were used to detect the relative expression of HDAC6 in lung tissues of WT mice after Cm infection. Intracellular factor staining was used to detect the percentages and absolute numbers of CD4 + T cell subsets (Th1, Th17 and Th2 cells)in mouse lung tissues after infection. The levels of IL-4 in spleen cell culture supernatants were measured by ELISA. One-way or two-way analysis of variance (ANOVA) was used for statistical analysis. Results:Cm respiratory tract infection significantly promoted the expression of HDAC6 at both mRNA and protein levels in lung tissues of WT mice ( P<0.001). HDAC6 -/- mice lost more weight than WT mice and took longer to recover to the normal level. Chlamydia load ( P<0.001 and P<0.05) and pathological damage ( P<0.05 and P<0.000 1) in lung tissues were more serious in HDAC6 -/- mice than in WT mice at 7 and 14 d after infection. Neither the percentage nor the absolute number of Th1 (CD4 + IFN-γ + T) and Th17 (CD4 + IL-17 + T) cells showed significant differences between WT and HDAC6 -/- mice, while the percentage and absolute number of Th2 (CD4 + IL-4 + T) cells increased in HDAC6 -/- mice ( P<0.05 and P<0.01). Moreover, in HDAC6 -/- mice, the expression of IL-4 mRNA increased ( P<0.000 1) and the level of IL-4 in the splenic cell culture supernatants increased ( P<0.01). Conclusions:HDAC6 plays an immune protective role in Cm infection. It can reduce the susceptibility of host to Cm respiratory tract infection and alleviates the pathological damage in lung tissues by inhibiting the immune response of Th2 cells.

Objective:To explore the correlation between weekend moderate-to-vigorous physical activity(MVPA), weekday sedentary behavior(SB)and the risk of frailty in the elderly population monitored by wearable devices, and to provide a scientific basis for lifestyle interventions for frailty in the elderly.Methods:This study was based on the data of the UK Biobank from 2013 to 2015.A cross-sectional study design was adopted, and 33, 212 elderly people aged 60 and above with complete physical activity monitoring data were selected.The Frailty Index(FI)constructed by the deficit accumulation method was used to assess the frailty status.The correlation between the combined effect of weekday SB and weekend MVPA and the frailty status was analyzed, and the differences between genders were explored.Results:There were significant differences in physical activity indicators among the elderly with different frailty statuses.As the degree of frailty increased, the MVPA-related indicators showed a downward trend, while the weekday SB time gradually increased.There were sex differences in physical activity patterns and frailties.Compared with women, men had longer SB time on weekdays, lower metabolic equivalent of weekly MVPA consumption, and higher MVPA time on weekends, but the frailties index of women was slightly higher than that of men.After adjusting for confounding factors, the frailty risks for men and women in the subgroup with the lowest weekday SB and the highest weekend MVPA duration decreased by 46.9% and 59.8%, respectively( P<0.001)when compared to the highest-risk group. Conclusions:Based on the monitoring data from wearable devices, elderly individuals who reduced their SB time during weekdays and increased their MVPA time on weekends were associated with a lower risk of frailty, especially among women; which providing a new perspective for lifestyle-based intervention strategies for frailty among the elderly.

Ovarian cancer is one of the three major malignant tumors in the female reproductive system,and its development and pro-gression involves multiple genes and stages.Circular RNA is a special type of non-coding RNA with a closed circular structure and plays an important regulatory role in cancer.The article comprehensively introduces the role of circular RNA in the proliferation,migra-tion,and invasion of ovarian cancer cells and summarizes the potential value of circular RNA.The article reviews the use of circular RNA as a liquid marker to monitor cancer progression and summarizes the situation of regulating chemotherapy resistance.This article provides a new idea for the diagnosis and treatment of ovarian cancer.

Gastric cancer is one of the most common malignant tumors in the digestive system, characterized by high incidence and mortality rates. In recent years, with the rapid develop-ment of molecular immunology, the application of immune checkpoint inhibitors (ICIs) in neoadju-vant therapy has significantly improved pathological response rates and survival outcomes for patients with resectable locally advanced gastric cancer. The authors systematically review current research progress on combination strategies involving immune checkpoint inhibitors in neoadjuvant therapy for locally advanced gastric cancer, aiming to provide an evidence for optimizing individua-lized therapeutic regimens.

Objective:To investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.

Objective To investigate the effect of joint end micro fracture treatment combined with arthroscopy on the long-term effect of ankle joint fusion and the effects on perioperative oxidative stress and complications.Methods 108 patients with end-stage ankle arthritis with internal and external inversion angles with ≤20° matching baseline data from February 2021 to April 2023 were selected.Among them,54 patients underwent arthroscopic ankle fusion as arthroscopic group,54 patients were treated with joint end microfracture combined with arthroscopic ankle joint fusion as improved group.The surgical indexes,perioperative oxidation indexes[malondialdehyde(MDA),total oxidation state(TOS),oxidative stress index(OSI)before surgery,1 d after surgery and 3 d after surgery]and antioxidant indexes[glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),total antioxidant capacity(TAC)before surgery,1 d after surgery and 3 d after surgery]of the two groups were compared.Visual analogue scale(VAS score),American Orthopaedic Foot and Ankle Society(AOFAS score),before surgery,6 months after surgery and 1 year after surgery,excellent and good rate and complications were compared between the two groups,and fusion time and AOFAS score at 1 year after surgery of patients with different internal and external inversion angles were compared between the two groups.Results The intraoperative blood loss in the improved group was less than that in the arthroscopic group,postoperative hospital stay in the improved group was shorter than that in the arthroscopic group,the differences were statistically significant(P＜0.05).The MDA,TOS and OSI levels in the improved group were lower than those in the arthroscopic group on day 1 and day 3 after operation,the differences were statistically significant(P＜0.05).The GSH-Px,SOD and TAC levels in the improved group were significantly higher than those in the arthroscopic group at 1 and 3 days after surgery,the differences were statistically significant(P＜0.05).The VAS score and AOFAS score at 6 months and 1 year after surgery in the improved group were not significantly different from those in the arthroscopic group(P＞0.05).Comparison of the excellent rate of patients in the two groups,the difference was not statistically significant(P＞0.05).The total complication rate of the improved group was significantly lower than that of the arthroscopic group,the difference was statistically significant(P＜0.05).There was no significant difference in AOFAS scores between patients with 10°～20° and patients with＜10° at 1 year after surgery(P＞0.05).The fusion time of patients with internal and external inversion angles 10°～20° was longer than that of patients with＜10°(P＜0.05).Conclusion Joint end microfracture treatment combined with arthroscopy ankle fusion for end-stage ankle arthritis with ≤20° internal and external varus can avoid bone grafting and osteotomy with satisfactory efficacy,and has advantages in reducing intraoperative bleeding and complications,alleviating perioperative oxidative stress,and accelerating postoperative recovery.However,when internal and external varus malformations are obvious,the time of osseous fusion can be prolonged.