Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.