BackgroundIn recent years， the incidence of depression among adolescents has been increasing steadily， posing a serious threat to their physical and mental health and even leading to severe consequences such as self-harm and suicide. At the same time， the detection rate of subclinical depression symptoms among adolescents is even higher. Although these symptoms do not meet the clinical diagnostic criteria， they have significantly affected their quality of life， and their persistence over time may further develop into depression. Therefore， in-depth exploration of adolescent depression symptoms and the predictive factors holds significant practical significance and research value. However， up to now， no large-scale investigation and research on depression symptoms among children and adolescents has been conducted in Inner Mongolia Autonomous Region. ObjectiveTo understand the prevalence of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region， in order to provide references for formulating scientific and effective prevention strategies and intervention measures. MethodsBy using the cluster stratified random sampling method， 6 281 students from the third grade of primary school to the second grade of high school in 12 leagues and cities of Inner Mongolia Autonomous Region were selected in March 2024. A self-designed questionnaire and the Self-rating Depression Scale （SDS） were used for on-site investigation. ResultsA total of 6 058 （96.45%） children and adolescents completed the valid questionnaire survey， and 2 728 cases （45.03%） were found to have depressive symptoms. There were statistically significant differences in the detection rates of depressive symptoms among children and adolescents of different genders， ages， whether they were only children， different family types， family monthly income， parents' educational levels， and whether the mother was employed （χ²=33.769， 40.618， 48.593， 29.972， 142.648， 195.999， 168.190， 5.445， P<0.05 or 0.01）.The results of the Logistic regression analysis showed that for children and adolescents， being female， aged between 12 and 16， over 16 years old， not being an only child， living in a reconstituted family， having a monthly family income of less than 5 000 yuan， and having parents with an education level of primary school or below were predictors of depressive symptoms （OR=1.241， 1.427， 1.273， 1.177， 1.549， 1.278， 1.462， 1.417， 1.514， 1.929， 1.660， 1.528， P<0.05 or 0.01）. ConclusionThe detection rate of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region is relatively high. Factors that may predict depressive symptoms in children and adolescents include female gender， ages between 12 and 16， ages over 16 years old， non-only children， families with a restructured structure， monthly family income of less than 5 000 yuan， and parents with an education level of primary school or below. ［Funded by Science and Technology Planning Project of the Inner Mongolia Autonomous Region （number， 2022YFSH0119）］

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

ObjectiveTo investigate the mechanism by which Shengjiang Pingchuan Zhike pills （SPZP） alleviate airway injury in the rat model of cough variant asthma （CVA） via regulating autophagy through activating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like autophagy activating kinase 1 （ULK1） signaling pathway based on transcriptomics， thus providing experimental evidence for the clinical application of SPZP. MethodsForty SPF-grade SD rats were enrolled in the present study and randomly via the random number table method assigned into four groups： a blank group， a model group， a SPZP （2 160 mg·kg^-1·d^-1） group， and a positive drug （montelukast sodium， MTL， 0.9 mg·kg^-1·d^-1）group， with 10 rats in each group. After one week of adaptive feeding， the rat model of cough variant asthma （CVA） was established by two-week sensitization with ovalbumin （OVA） and aluminium hydroxide， followed by capsaicin atomization challenge. Rats in the blank group received an equal volume of normal saline during modeling. Upon successful modeling， rats in the SPZP group and positive drug group were administrated with SPZP suspension and MTL solution， respectively， while those in the blank and model groups received the same dose of normal saline by gavage. The whole intervention lasted for 21 consecutive days. After the intervention， general behaviors of rats in each group were observed. Pulmonary function indicators were subsequently detected. Hematoxylin-eosin （HE） staining was performed to visualize the pathological morphology of the lung tissue， and periodic acid-Schiff （PAS） staining was adopted to evaluate airway mucus secretion. Transcriptomic sequencing was conducted to screen differentially expressed genes in the lung tissue across groups. The levels of inflammatory cytokines including interleukin （IL）-4， IL-5， immunoglobulin E （IgE）， and interferon-γ （IFN-γ） in the bronchoalveolar lavage fluid （BALF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence staining was used for detecting the co-localization of autophagy-related protein Beclin-1 and phosphorylated mammalian target of rapamycin （p-mTOR）. Transmission electron microscopy was employed to count autophagosomes and observe mitochondrial morphological changes in the lung tissue. Western blot assay was utilized to measure the expression levels of AMPK/mTOR/ULK1 axis-related proteins， including AMPK， phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， mTOR， phosphorylated mammalian target of rapamycin （p-mTOR）， ULK1， and phosphorylated Unc-51-like autophagy activating kinase 1 （p-ULK1） as well as the autophagy biomarkers Beclin-1 and selective autophagy adaptor protein p62 in lung specimens. ResultsCompared with the blank group， the model group exhibited markedly elevated cough frequency accompanied by wheezing and stridor， dull fur， poor mental activity， diminished motor activity， accelerated respiratory rate， and weakened sensory response and mobility to external stimuli， accompanied by a declining tendency of body mass. Meanwhile， the model group exhibited decreased dynamic lung compliance， increased airway resistance （P<0.01）， severe pathological damage and excessive mucus secretion in the lung tissue （P<0.01）， and elevated levels of IL-4， IL-5， and IgE and declined level of IFN-γ in the BALF （P<0.01）. Ultrastructural observation revealed damaged mitochondrial morphology and a sharp reduction in the number of autophagosomes in the lung tissue. In addition， the expression of p-AMPK， p-ULK1， and Beclin-1 were downregulated， whereas p-mTOR and p62 were highly expressed （P<0.05， P<0.01） in the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses demonstrated significant enrichment of AMPK， mTOR， and autophagy-related pathways. Compared with the model group， both the positive drug group and SPZP group obtained visible improvements in general behavioral manifestations and obvious recovery of pulmonary function indicators （P<0.05）， alleviated pulmonary pathological lesions and suppressed excessive airway mucus secretion （P<0.05）， recovered levels of inflammatory cytokines in the BALF （P<0.05）， restored mitochondrial morphology， increased autophagosomes， upregulated expression levels of p-AMPK， p-ULK1， and Beclin-1， and downregulated expression levels of p-mTOR and p62 （P<0.05）. ConclusionSPZP can effectively ameliorate airway inflammation and improve the pulmonary function in the rat model of CVA by activating the AMPK/mTOR/ULK1 signaling pathway， enhancing autophagy in the lung tissue， and inhibiting excessive airway mucus secretion and immune inflammatory imbalance.

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

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Objective: To investigate the prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective To investigate the high-risk factors associated with acute postoperative hypertension (APH) following laparoscopic sleeve gastrectomy(LSG) in obese patients and to establish a predictive model. Methods A retrospective analysis was conducted on clinical data and laboratory parameters of obese patients who underwent LSG at Department of Metabolic Surgery in our hospital from August 2021 to December 2023. Logistic-LASSO regression analysis was used to identify independent risk factors for APH. A nomogram predictive model was developed based on these factors. The predictive performance and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, Bootstrap resampling, calibration curve, Hosmer-Lemeshow (H-L) test, decision curve analysis (DCA), and clinical impact curve (CIC). Results The incidence of APH was 55.90%. Body mass index (BMI), platelet count, globulin, uric acid, sodium, fibrinogen, fasting blood glucose, and preoperative diastolic pressure had potential predictive value. Among them, BMI (OR=1.066, 95% CI: 1.003-1.137, P=0.046), platelet count (OR=0.994, 95% CI: 0.998-0.999, P=0.027), fibrinogen (OR=1.943, 95% CI: 1.128-3.479, P=0.02), and preoperative diastolic blood pressure (OR=0.953, 95% CI: 0.918-0.985, P = 0.006) were identified as independent high-risk factors. The area under the curve (AUC) of the nomogram was 0.783 (95% CI: 0.711-0.855), with a sensitivity of 0.817 and a specificity of 0.689. The AUC based on Bootstrap resampling was 0.776 (95% CI: 0.702-0.849). The H-L test yielded P>0.05, and the calibration curve showed good model fit. Both DCA and CIC demonstrated favorable screening efficiency. Conclusions BMI, platelet count, fibrinogen, and preoperative diastolic blood pressure are independent high-risk factors for APH following LSG. The developed nomogram model exhibits good predictive performance and clinical applicability, providing a valuable tool for early screening and prevention of APH in LSG patients.