BACKGROUND: Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment. METHODS: Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models. RESULTS: Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin ( OMD ), apolipoprotein A4 ( APOA4 ), and insulin like growth factor binding protein 6 ( IGFBP6 ) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells. CONCLUSIONS Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD , APOA4 , and IGFBP6  may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.
Machine Learning ; Humans ; Computational Biology/methods* ; Biomarkers/metabolism* ; Diabetes Mellitus, Type 2/genetics* ; Animals ; Mice ; Gluconeogenesis/physiology* ; Gene Expression Profiling ; Transcriptome/genetics* ; Gene Regulatory Networks/genetics* ; Clinical Relevance

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Transcatheter aortic valve replacement(TAVR)has emerged as a promising therapeutic alternative for addressing aortic valve-related pathologies.However,the occurrence of rapid arrhythmias linked to TAVR procedures is progressively drawing scrutiny.Presently,pharmacologic interventions constitute the mainstay of managing atrial arrhythmias related to TAVR,while the potential of ablation as a viable treatment modality remains undefined.Notably,in cases where the arrhythmia's genesis is presumed to be intricately linked to the prosthetic valve,the practicality and safety of ablation procedures remain unverified.Our institution has successfully ventured into radiofrequency ablation for a distinctive patient presenting with this intricate condition,thereby tentatively affirming the efficacy and safety of catheter ablation administered on the surface of prosthetic valves.

Objective:To investigate the characteristics of thalassemia gene types in children in Liuzhou,Guangxi.Methods:A total of 822 children suspected thalassemia aged from 1 day to 14 years who were admitted to our hospital from January 2019 to April 2022 were collected.Gap-PCR and PCR combined with reverse dot blot hybridization were used to detect α-and β-thalassemia genes.Results:Among 822 children,561 thalassemia carriers were detected,with a detection rate of 68.25％.Among them,303 cases were detected with α-thalassemia,and the most common genotype was--SEA/αα(163 cases),followed by-α3.7/αα(37 cases)and αcsα/αα(26 cases),44 cases with HbH disease.240 cases were detected with β-thalassemia,with a detection rate of 29.20％,and the most common genotype was βCD41-42/β N(112 cases),followed by βCD17/βN(75 cases)and βIVS-Ⅱ-654/β N(11 cases),11 cases with moderate to severe β-thalassemia.18 cases were detected with α β-thalassemia,with a detection rate of 2.19％,and--SEA/αα complex βCD41-42/βN was the most common genotype(4 cases).In Zhuang and Han populations,the detection ratio of-α3.7α/αα in α-thalassemia was the same(both 12.50％).While,the other main types such as--SEA/αα,αCSα/αα and-α4.2α/αα had certain differences.In β-thalassemia,CD41-42 and CD17 were the main genotypes detected in Han and Zhuang.Conclusion:In Liuzhou of Guangxi autonomous region,α-thalassemia is the main type in children,with a detection rate of 68.25％,and--SEA/αα is the most common genotype in mild thalassemia,followed by βCD41-42/βN.The detection rate of moderate to severe α-and β-thalassemia is relatively high.There are certain differences in the distribution of thalassemia among different ethnic groups.

Purpose: Polyacrylamide hydrogel (PAHG), which had been used widely for breast augmentation, has been banned for more than 15 years. Patients who had been injected PAHG for breast augmentation need evacuation surgery to remove as much as possible. To provide a series of diagnosis and treatment process MRI and intraoperative color Doppler ultrasound are combined for maximal removal of PAHG. Methods: The patients who received evacuation surgery in Peking University Third Hospital from 2010 to 2022 after PAHG injection for breast augmentation were included in this research. MR scanning was performed preoperatively and postoperatively in some of these patients and color Doppler ultrasound was applied to help evacuate PAHG intraoperatively. The mean clearance rate of PAHG was calculated according to the MRI outcomes. Results: Two hundred and 4 patients had received evacuation surgery after PAHG injection for breast augmentation with an average age of 42.8 years and an average body mass index of 21.2 kg/m 2 . The average PAHG retention time was 13.5 years. Among them, 52 patients underwent pre- and postoperative MRI scanning. The mean three-dimensional (3D) volume of PAHG was 684.8 mL (range, 350.0–1,123.9 mL), and the average residual 3D volume of PAHG was 53.7 mL (range, 12.4–98.3 mL). The mean clearance rate was 92.1%. Conclusion MRI and intraoperative color Doppler ultrasound can provide effective and precise location information of PAHG for evacuation surgery, which is a reliable method to ensure the maximal removal of PAHG.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
Male ; Humans ; Androgens/therapeutic use* ; Receptors, Androgen/genetics* ; Prognosis ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Cell Line, Tumor ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Gene Expression Regulation, Neoplastic

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*