Objective: To explore the relationship between social jetlag and depressive symptoms in junior high school students, as well as the potential gender differences, so as to provide a reference for developing effective interventions for depressive symptoms and promoting adolescents mental health. Methods: In October 2024, a total of 3 516 students from grades 7 to 9 were recruited from 4 junior high schools in Chongqing Municipality using a combination of cluster sampling and convenience sampling. A questionnaire survey was conducted using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Munich Chronotype Questionnaire (MCTQ). Statistical analyses included the χ 2 test, binary Logistic regression analysis, and stratified Logistic regression analysis. Results: The detection rate of depressive symptoms among the junior high school students was 34.3%. The number of students with social jetlag >2 h was 714 (20.3%), >1-2 h was 1 455(41.4%), and ≤1 h was 1 347(38.3%). Results from the binary Logistic regression analysis showed that compared to the group with social jetlag ≤1 h, the risk of depressive symptoms in the group with social jetlag >2 h was higher ( OR=1.59, 95%CI=1.28-1.98, P <0.01). Gender stratified analysis revealed that among females, the risk of depressive symptoms was higher in the groups with social jetlag of >1-2 h and >2 h compared to the ≤1 h group ( OR = 1.34 and 2.05, 95% CI =1.03-1.75 and 1.48-2.83, both P <0.05). However, among males, the associations were not statistically significant ( OR =1.11 and 1.29, 95% CI =0.86-1.43 and 0.95-1.77, both P >0.05). Conclusions Social jetlag is positively associated with depressive symptoms in junior high school students, demonstrating a threshold effect and gender differences. The findings suggest that reducing social jetlag may decrease the risk of depressive symptoms in adolescents, and targeted intervention measures should be developed considering different gender characteristics.

Objective: To explore the association between various components of sleep quality and the co-occurrence of non-suicidal self-injury (NSSI) behaviors and depressive symptoms among junior high school students, so as to provide evidence for targeted prevention strategies of NSSI and depression. Methods: From May to June 2024, a total of 5 008 junior high school students from 8 schools in 2 districts/counties of Chongqing were selected through a stratified cluster sampling method. The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies Depression Scale (CES-D), and the Adolescent Non suicidal Self injury Assessment Questionnaire (ANSAQ) were used to assess sleep quality, depressive symptoms, and NSSI, respectively. Data were analyzed by using the Chi-square test, Bonferroni correction, and multivariate Logistic regression. Results: Non-NSSI group and depressive symptoms group accounted for 68.11% among junior high school students, NSSI-only group accounted for 4.71%, only depressive symptoms group accounted for 14.94%, and co-occurrence of NSSI and depressive symptoms group accounted for 12.24%. The prevalence of the co-occurrence group was higher in girls (16.39%) than in boys (7.85%) ( χ 2=84.89, P <0.01). After controlling for gender, grade, and boarding status etc., multivariate Logistic regression analysis revealed that five sleep components, including subjective sleep quality, sleep latency, sleep duration, sleep disturbances, and daytime dysfunction, were significantly and positively associated with the co-occurrence of NSSI and depressive symptoms ( OR =1.30-3.86, all P <0.05). The strength of association between these components and the co-occurrence group, in descending order, was: daytime dysfunction ( OR = 2.52), sleep disturbances ( OR =2.36), subjective sleep quality ( OR =1.76), sleep latency ( OR =1.44), and sleep duration ( OR =1.22) (all P <0.01). Conclusions The co-occurrence of NSSI and depressive symptoms is prevalent among junior high school students, with girls being more significantly affected. Sleep disturbances and daytime dysfunction may represent particularly important risk factors. Targeted and prioritized intervention strategies addressing specific sleep components should be developed and implemented to reduce the co-occurrence of NSSI and depressive symptoms in junior high school students.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Acute-on-chronic liver failure （ACLF） refers to severe liver dysfunction that occurs on the basis of chronic liver diseases， and it is characterized by rapid disease progression， poor prognosis， and high mortality rate. In recent years， inflammatory markers have become a research hotspot due to their significant role in assessing the prognosis of ACLF. This article reviews the advances in the application of inflammatory markers in assessing the prognosis of ACLF， such as systemic immune inflammatory index， lymphocyte-white blood cell ratio， neutrophil-lymphocyte ratio， and C-reactive protein， and discusses their clinical value and future research directions， in order to provide a theoretical basis for the early intervention and prognosis management of ACLF patients.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

Colorectal cancer(CRC) is one of the most common malignant tumors worldwide, primarily originating from recurrent inflammatory bowel disease(IBD). Therefore, blocking the inflammation-cancer transformation in the colon has become a focus in the early prevention and treatment of CRC. The inflammation-cancer transformation in the colon involves multiple types of cells and complex pathological processes, including inflammatory responses and tumorigenesis. In this complex pathological process, immune cells(including non-specific and specific immune cells) and non-immune cells(such as tumor cells and fibroblasts) interact with each other, collectively promoting the progression of the disease. In traditional Chinese medicine(TCM), inflammation-cancer transformation in the colon belongs to the categories of dysentery and diarrhea, with the main pathogenesis being cold and heat in complexity. This paper first elaborates on the complex molecular mechanisms involved in the inflammation-cancer transformation process in the colon from the perspectives of inflammation, cancer, and their mutual influences. Subsequently, by comparing the pathogenic characteristics and clinical manifestations between inflammation-cancer transformation and the TCM pathogenesis of cold and heat in complexity, this paper explores the intrinsic connections between the two. Furthermore, based on the correlation between inflammation-cancer transformation in the colon and the TCM pathogenesis, this paper delves into the importance of the interaction between inflammation and cancer. Finally, it summarizes and discusses the clinical and basic research progress in the TCM intervention in the inflammation-cancer transformation process, providing a theoretical basis and treatment strategy for the treatment of CRC with integrated traditional Chinese and Western medicine.
Humans ; Colon/pathology* ; Integrative Medicine ; Animals ; Cold Temperature ; Cell Transformation, Neoplastic/drug effects* ; Medicine, Chinese Traditional ; Hot Temperature ; Inflammation ; Drugs, Chinese Herbal/therapeutic use* ; Colonic Neoplasms/drug therapy*

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*