ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Objective:Inflammation has been confirmed to play an important role in the occurrence and development of sudden sensorineural hearing loss（SSNHL）, and the neutrophil-to-lymphocyte ratio（NLR） is a biomarker positively correlated with the degree of inflammation. This study aims to identify the difference in serum NLR between patients with SSNHL and normal population, and to evaluate the predictive efficacy of NLR for the occurrence and prognosis of SSNHL, thereby guiding the clinical diagnosis and treatment of SSNHL. Methods:In this study, 96 patients diagnosed with SSNHL admitted to our department from January 2023 to March 2024 and 96 patients diagnosed with vocal cord polyps admitted to our department during the same period were recruited as a control group. Multivariate Logistic regression was used to evaluate independent related factors, and a nomogram was constructed to predict the probability of SSNHL. The receiver operating characteristic（ROC） curve and calibration curve were used to evaluate the accuracy of prediction. Results:Multivariate logistic regression analysis showed that a high level NLR（OR2.215; 95%CI1.597-3.073; P<0.001） were independently associated with the presence of SSNHL. High age（OR1.036; 95%CI1.009-1.067; P=0.012）, high FIB（OR2.35; 95%CI1.176-4.960; P=0.019） were the risk factor for SSNHL. Incorporating these 3 factors, a forest plot and a nomogram were generated. The ROC curve, nomogram and calibration curve showed that the model had good clinical practicability. A low NLR（OR0.598; 95%CI0.439-0.816; P<0.001） was significantly associated with a favorable prognosis of SSNHL. Conclusion:Elevated NLR can serve as an promising biomarker for assessing the risk of SSNHL. The nomograms calculation model may be utilized as a tool to estimate the probability of SSNHL. Low level NLR is significantly associated with a good prognosis of SSNHL.
Humans ; Neutrophils ; Female ; Male ; Lymphocytes ; Hearing Loss, Sensorineural/blood* ; Hearing Loss, Sudden/diagnosis* ; Middle Aged ; Prognosis ; Nomograms ; ROC Curve ; Adult ; Logistic Models ; Biomarkers/blood* ; Lymphocyte Count ; Inflammation/blood* ; Clinical Relevance

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

OBJECTIVES: To investigate the clinical features and gene mutation characteristics of combined oxidative phosphorylation deficiency type 7 (COXPD7) caused by mutations in the C12orf65 gene, and to enhance the awareness of this disease. METHODS: A child diagnosed with COXPD7 in the Department of Neurology, Children's Hospital Affiliated to Zhengzhou University in 2021 was included, along with 10 patients reported in the literature. All subjects were analyzed for their genotypes and clinical phenotypes. RESULTS: A total of 11 patients with COXPD7 were included, comprising 1 reported in this study and 10 from the literature. Among the 11 patients, 9 had homozygous mutations in the C12orf65 gene, while 2 had compound heterozygous mutations, which were identified as frameshift or nonsense mutations. The age of onset ranged from 1 day to 2 years, and clinical manifestations included optic nerve atrophy and delays in intellectual and motor development. Eight patients exhibited external ophthalmoplegia, and five patients displayed spastic paralysis. Cranial magnetic resonance imaging revealed optic nerve atrophy in all 11 patients, abnormal brainstem signals in 10 patients, and a lactate peak on brainstem magnetic resonance spectroscopy scans in 3 patients. CONCLUSIONS COXPD7 associated with the C12orf65 gene results from homozygous or compound heterozygous mutations, with primary clinical manifestations of optic nerve atrophy and delays in intellectual and motor development. Some patients may also present with spastic paralysis or external ophthalmoplegia. Cranial imaging reveals symmetrical abnormal signals in bilateral basal ganglia and brainstem, and a lactate peak is observed on brainstem magnetic resonance spectroscopy scans.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Oxidative Phosphorylation ; Infant, Newborn

Abstract Upper cross syndrome (UCS) is an abnormal body posture phenomenon. The detection rate of UCS in adolescents is high in China, which has become a serious public health problem threatening the health of adolescents. Exercise therapy has a positive effect on the prevention and treatment of UCS.The article reviews the pathological mechanisms of muscle imbalance, muscle interaction inhibition, and neural control related to the occurrence and development of UCS both domestically and internationally in recent years.And it elucidates the effects and corresponding mechanisms of exercise interventions such as gentle exercise, stretching exercise and physical function training on UCS, so as to provide help for the correction of UCS.

Objective:To analyze the epidemiological characteristics of tick-borne encephalitis (TBE) in Heilongjiang province, to provide a scientific basis for the prevention and control of TBE.Methods:The epidemiological characteristics of TBE were systematically analyzed by the data of TBE cases reported in Disease Surveillance Information Reporting System.Results:A total of 1 127 TBE cases were reported from 2006 to 2020. The average age was 45.8 year, and the case fatality rate was 1.2%. Most TBE cases occurred from April to August, with a peak in June.Conclusions:This research elucidated the epidemiological characteristics of TBE in Heilongjiang province, and provides important basic data for the disease prevention and control.

Objective: To explore the potential classification of 24 hour activity time allocation among college students in Yinchuan and its association with active health levels, so as to provide references for optimizing activity time allocation to enhance active health levels. Methods: From November 18 to December 6, 2024, a stratified cluster random sampling method was used to select 2 422 first and second year college students from full time undergraduate institutions in Yinchuan. The Chinese College Students 24 hour Movement Behaviors Questionnaire (24 h MBQ) and Active Health Behavior Scale were used to assess 24 hour activity time allocation and evaluate active health levels. Latent profile analysis (LPA) was employed to categorize activity types, and a binary Logistic regression analysis was conducted to analyze the relationship between active health levels and activity types. Results: A total of 1 087 students (44.9%) were found of meeting active health standards, and significant statistical differences were found in active health levels across different genders, grades, academic qualities, sources of origin and academic categories ( χ 2= 22.03 , 7.65, 25.50, 10.12, 43.44, all P <0.01). Moreover, significant statistical differences could also be found among college students 24 hour activity time across different genders, ages, grades, sources of origin, academic qualities, and academic categories ( t/Z/H/F=-5.70-111.39, P <0.05).The 24 hour activity time allocation was classified into four types:academic high ( 6.9 %), low activity rest (8.8%), light activity (67.8%), and high activity dynamic (16.4%). Significant statistical differences were observed in activity time allocation categories across different ages, academic qualities and academic categories ( χ 2=15.52-108.46, all P <0.05). Using the high activity dynamic type as a reference, the light activity type ( OR=0.39, 95%CI =0.31-0.50), low activity rest type ( OR=0.10, 95%CI =0.06-0.15), and academic high type ( OR=0.03, 95%CI =0.02-0.07) had lower active health levels among college students (all P <0.01). Conclusion There is a significant difference in 24 hour activity time allocation among college students in Yinchuan, and different activity types are associated with active health levels.

Lactylation, a recently identified post-translational modification of proteins, is induced by lactic acid and can occur at multiple lysine residues in both histone and non-histone proteins. This modification plays a role in disease pathogenesis by affecting transcriptional regulation, mitochondrial metabolism, and immune inflammation. Significant advancements have been made in understanding the mechanisms of lactylation in various ophthalmic diseases, including retinal neovascularization, uveitis, melanoma, and myopia. This paper provides a comprehensive review of the relationship between lactic acid and lactylation, the regulatory mechanisms of lactylation, and the role of lactylation in different ocular diseases. Additionally, it addresses current research limitations and future directions, which is of great significance to elucidate the molecular mechanisms of lactylation in eye diseases and improving the diagnosis and targeted treatment of these conditions.

Objective:To explore differences in dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders based on therapeutic drug monitoring data.Methods:A retrospective analysis was performed; clinical data, including demographic characteristics, therapeutic drug monitoring results, comorbidities, medication details (daily valproic acid dose, concomitant medications), and liver and kidney function indicators, were collected from 633 patients with bipolar disorder or schizophrenia who were hospitalized at Xi'an Mental Health Center and received different valproates from January 2024 to June 2024 (98 patients receiving sodium valproate and 535 receiving magnesium valproate). Clinical data between a sodium valproate group and a magnesium valproate group were compared. Multivariate linear regression was used to identify independent influencing factors for dose-adjusted plasma concentration of valproic acid. Valproic acid daily doses, and plasma concentrations and dose-adjusted plasma concentrations of valproic acid were compared between the two groups, with subgroup analyses conducted by gender and age categories.Results:A total of 658 measurements of plasma valproic acid concentration were obtained in 633 patients, including 104 measurements in the sodium valproate group and 554 in the magnesium valproate group. Significant differences in proportions of comorbidities and concomitant use of olanzapine, quetiapine and clozapine were observed between the sodium valproate group and magnesium valproate group ( P<0.05). After adjusting for age, gender, body mass index, comorbidities, concomitant medications, and liver and kidney function indicators, the type of valproates remained an independent influencing factor for dose-adjusted plasma concentration of valproic acid (adjusted unstandardized B coefficient=13.814, 95% CI: 8.090-19.540, P<0.001). Daily dose in the sodium valproate group (1.0[1.0, 1.0] g/d) was significantly higher than that in the magnesium valproate group (0.5[0.5, 1.0] g/d), and dose-adjusted plasma concentration of valproic acid in the magnesium valproate group (93.00 [75.60, 117.40] [μg/mL]/[g·d]) was statistically higher than that in the sodium valproate group (78.55 [57.90, 90.00][μg/mL]/[g·d], P<0.05). Subgroup analysis revealed that, among patients stratified by genders and ages (<40 years vs. ≥40 years), the daily dose in the sodium valproate group was significantly higher than that in the magnesium valproate group, while the dose-adjusted plasma concentration of valproic acid in the magnesium valproate group was significantly higher than that in the sodium valproate group ( P<0.05). Conclusion:Significant differences in dose-adjusted plasma concentrations of valproic acid are observed among different valproate formulations for the treatment of mental disorders; therefore, therapeutic drug monitoring should be performed in patients when switching valproates to facilitate precise individualized dosage adjustment.