Objective: To investigate the prevalence of depressive symptoms and their associated factors among students in Zhejiang Province, so as to provide evidence for targeted prevention strategies. Methods: A stratified cluster random sampling method was used to select 23 829 college students and primary and secondary school students aged 11-22 years in Zhejiang Province from December 2019 to February 2020. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Three machine learning algorithms, including Logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost), were applied to construct predictive models, and key associated factors were identified by comparing model performance. Results: The detection rate of depressive symptoms among students in Zhejiang Province was 19.92%; the rates were 17.20% in boys and 22.87% in girls( χ 2=164.89, P <0.05). The CES-D total score was 9.00(4.00,13.00). Multiple Logistic regression analysis revealed that loneliness had the strongest association with depressive symptoms ( AOR =9.58, 95% CI =8.90-10.30), while bullying exposure ( AOR =4.39, 95% CI =4.02-4.80), female students( AOR =1.81, 95% CI =1.68-1.94)，never eating breakfast ( AOR = 2.34，95% CI =2.00-2.67) and overweight/obesity( AOR =1.10，95% CI =1.08-1.12) were significant associated factors of depressive symptoms among students (all P <0.05). Analysis based on the XGBoost model produced highly consistent results, identifying the above 5 factors as the core features with the highest correlation strength (all P <0.05). Conclusions Female, loneliness, bullying exposure, frequency of weekly breakfast and BMI are strongly associated with depressive symptoms among students. Mental health education for high risk groups should be strengthened, and coordinated prevention efforts between families and schools are recommended.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Immunotherapy has become a pivotal treatment regimen for hepatocellular carcinoma (HCC); however, its efficacy is influenced by various factors. Hepatitis B virus (HBV) infection is one of the primary etiological factors leading to HCC. HBV DNA replication can alter the immune microenvironment through multiple mechanisms, notably by upregulating the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), thereby facilitating tumor immune escape. Paradoxically, this upregulation of PD-1/PD-L1 may enhance the response rate to PD-1/PD-L1 inhibitors and potentiate the antitumor effect. This review aims to summarize current research progress on the relationship between HBV DNA load and the efficacy of PD-1/PD-L1 inhibitors, explore the underlying mechanisms, and provide a scientific basis for promoting personalized treatment strategies for patients with HBV-related HCC.

Objective:To digitally measure the three-dimensional (3D) size of primary tooth crowns and the dimensions of the dental arch in children with individual normal primary dentition, preliminarily obtaining baseline data on the 3D size of primary tooth crowns as well as the length and width of the dental arch, and their influence factors. This study aims to provide a data foundation for the design of reference models for primary dentition.Methods:From May to June 2021, 122 caries-free children aged 3.5-4.5 years with individual normal occlusion were selected from five kindergartens in Haidian District, Beijing. Impressions were taken and plaster models were cast. After preliminary screening, 67 eligible models were scanned to obtain digital dental models. Digital measurement software was used for landmark-based measurements. Parameters included 3D crown dimensions (mesiodistal diameter, buccolingual diameter, and occlusogingival height), dental arch dimensions (length and width at specific regions), and occlusal measurements (overjet and overbite at the primary central incisors, and Bolton index for anterior and full dentition). Gender differences in crown dimensions and bilateral symmetry of homologous teeth, as well as the correlations between arch dimensions and gender, height, weight, and body mass index (BMI) were analyzed.Results:The homonymous teeth of 67 children exhibited strong bilateral symmetry in all 3D dimensions ( P>0.05). Gender differences were observed in the buccolingual dimension for all deciduous molars except for the right mandibular first deciduous molar ( P<0.05). For the occlusogingival dimension, gender differences were found in the right maxillary first and second deciduous molars, left maxillary first deciduous molar, and left mandibular first and second deciduous molars ( P<0.05). For the mesiodistal dimension, only the left mandibular second deciduous molar and right mandibular deciduous canine showed gender differences ( P<0.05). All significant differences above indicated larger dimensions in boys compared to girls. In both maxillary and mandibular arches, the lengths and widths at various locations were significantly larger in boys than in girls ( P<0.05). Univariate correlation analysis revealed that body weight was positively correlated with the width of the terminal plane in both the maxilla and mandible and the total length of the mandibular dental arch, while BMI was positively correlated with the width of the maxillary terminal plane and the widths at all measured sites in the mandible ( P<0.05). Multiple regression analysis demonstrated that, after controlling for relevant variables, BMI was a significant positive predictor for the lengths and widths at various sites of the dental arch ( P<0.05), and height was a positive predictor for dental arch length ( P<0.05), as well as body weight was a positive predictor for the width in the molar region ( P<0.05). Overjet at the primary central incisors was 2.28 (1.57, 2.66) mm, and overbite was 1.13 (0.75, 1.92) mm. The anterior Bolton index was 0.79±0.03, and the overall Bolton index was 0.94±0.03. Conclusions:Primary tooth crowns of individual normal occlusion children demonstrate strong bilateral symmetry in homologous teeth. Most primary molars exhibit gender differences in buccolingual and occlusogingival dimensions, with larger values in boys. Arch dimensions (length and width) are consistently larger in boys.

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

Objective Investigate the expression level of discs large homolog associated protein 5(DLGAP5)in oral squamous cell carcinoma(OSCC)and analyze its effects on cell proliferation,migration,invasion capacity,and the Warburg effect.Methods Bioinformatics analysis was performed to identify the potential therapeutic targets for OSCC.A total of 72 OSCC tissue samples and 40 adjacent non-cancerous tissue samples collected in the First Affiliated Hospital of Shihezi University from 2013 to 2024 were included,and the clinical pathological and prognostic data were collected from patients.Immunohistochemistry assay was applied to detect the protein expression of DLGAP5,and its association with clinical pathological features was analyzed.Kaplan-Meier survival curve was plotted for survival analysis,and Cox regression model was employed to analyze the prognostic factors.The expression of DLGAP5 at mRNA and protein levels was detected in HOK,SCC-9,SCC-15,SCC-25,and CAL-27 cell lines with RT-qPCR and Western blotting,respectively.Four small interfering RNAs(siRNAs)were designed to target the DLGAP5 sequence,and then based on the transfection efficiency,the sequence with optimal silencing effect was selected for subsequent functional studies.After DLGAP5 was silenced in the CAL-27 and SCC-15 cells,Western blotting was applied to detect the expression of hexokinase 2(HK2)and enolase 1(ENO1),CCK-8,scratch healing and Transwell assays were conducted to assess cell proliferation,migration,and invasion capabilities,and glucose,lactate,and ATP detection kits were utilized to determine the glycolytic metabolic levels in OSCC cells.Results Bioinformatics analysis indicates that DLGAP5 is a potential key therapeutic target for OSCC.Experimental validation demonstrated that DLGAP5 was highly expressed in both OSCC tissues and cells(P<0.05).Analysis of clinical pathology and prognostic data revealed that DLGAP5 expression level was significantly correlated with tumor TNM stage,lymph node metastasis,and differentiation grade in OSCC patients,and high DLGAP5 expression was associated with poor prognosis(P<0.05).DLGAP5 silencing resulted in significantly reduced expression of HK2 and ENO1,markedly decreased levels of glycolytic metabolites(P<0.05),and notably declined cell proliferation,migration,and invasion capabilities(P<0.05).Conclusion DLGAP5 is highly expressed in OSCC.Silencing DLGAP5 may inhibit OSCC cell proliferation,migration,and invasion by indirectly regulating the Warburg effect,and the molecule is associated with poor prognosis in the OSCC patients.

Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the effect of physical activity on mortality risk in patients with chronic obstructive pulmonary disease (COPD) in Sichuan Province.Methods:Based on baseline data from 2004 to 2008 from the China Kadoorie Biobank project site in Pengzhou City, Sichuan Province, a total of 8 501 COPD patients aged 30-79 years were enrolled and followed up for a long period to determine mortality outcomes. Quartiles were used to group physical activity levels. The Cox proportional hazards regression model was used to analyze the effect of physical activity level on mortality outcomes.Results:As of December 31, 2017, the cumulative follow-up of the participants totaled 85 600.58 person-years (mean follow-up duration: 10.07 years). During this period, a total of 2 000 deaths were recorded, yielding a cumulative mortality rate of 23.53%. Among these deaths, 665 were attributed to COPD, corresponding to a cumulative mortality rate of 7.82%; and 1 116 were attributed to cardiovascular and cerebrovascular disease (CVD), corresponding to a cumulative mortality rate of 13.13%. The Cox proportional hazards regression model analysis revealed that, after adjusting for confounding factors, total physical activity was associated with a reduced risk of mortality from COPD, CVD, and all causes in patients with COPD. Compared with the low-level group of total physical activity, the medium-high-level group had the lowest risk of COPD mortality, with an HR of 0.39 (95% CI: 0.30-0.49). The high-level group had the lowest risk of CVD death and all-cause death, with HRs of 0.46 (95% CI: 0.37-0.56) and 0.55 (95% CI: 0.48-0.64), respectively. The lowest risk of COPD death and CVD death was found in the medium-high level of work-based physical activity group, with HRs of 0.36 (95% CI: 0.28-0.46) and 0.43 (95% CI: 0.36-0.51), respectively; the risk of all-cause mortality was lowest in the medium-high and high-level groups, with HRs values of 0.53 (95% CI: 0.46-0.61) and 0.53 (95% CI: 0.45-0.61). The risk of COPD death was lowest in the high-level transportation physical activity group, with an HR of 0.66 (95% CI: 0.53-0.83), and the risk of CVD and all-cause death was lowest in the medium-high level group, with HRs of 0.63 (95% CI: 0.53-0.76) and 0.73 (95% CI: 0.64-0.84), respectively. The risk of COPD death and CVD death was the lowest in the high-level domestic physical activity group, with HRs of 0.66 (95% CI: 0.49-0.89) and 0.76 (95% CI: 0.61-0.95), respectively, and the risk of all-cause death was the lowest in the medium-high level group, with an HR of 0.82 (95% CI: 0.72-0.94). There is no statistical association between leisure physical activity and the risk of death from three types of diseases. Conclusions:Total physical activity, including work-based, transportation-based, and domestic physical activity, reduced the risk of COPD, CVD, and all-cause mortality in patients with COPD in Sichuan Province. The magnitude of mortality risk was influenced by the type and level of physical activity.

Objective:To digitally measure the three-dimensional (3D) size of primary tooth crowns and the dimensions of the dental arch in children with individual normal primary dentition, preliminarily obtaining baseline data on the 3D size of primary tooth crowns as well as the length and width of the dental arch, and their influence factors. This study aims to provide a data foundation for the design of reference models for primary dentition.Methods:From May to June 2021, 122 caries-free children aged 3.5-4.5 years with individual normal occlusion were selected from five kindergartens in Haidian District, Beijing. Impressions were taken and plaster models were cast. After preliminary screening, 67 eligible models were scanned to obtain digital dental models. Digital measurement software was used for landmark-based measurements. Parameters included 3D crown dimensions (mesiodistal diameter, buccolingual diameter, and occlusogingival height), dental arch dimensions (length and width at specific regions), and occlusal measurements (overjet and overbite at the primary central incisors, and Bolton index for anterior and full dentition). Gender differences in crown dimensions and bilateral symmetry of homologous teeth, as well as the correlations between arch dimensions and gender, height, weight, and body mass index (BMI) were analyzed.Results:The homonymous teeth of 67 children exhibited strong bilateral symmetry in all 3D dimensions ( P>0.05). Gender differences were observed in the buccolingual dimension for all deciduous molars except for the right mandibular first deciduous molar ( P<0.05). For the occlusogingival dimension, gender differences were found in the right maxillary first and second deciduous molars, left maxillary first deciduous molar, and left mandibular first and second deciduous molars ( P<0.05). For the mesiodistal dimension, only the left mandibular second deciduous molar and right mandibular deciduous canine showed gender differences ( P<0.05). All significant differences above indicated larger dimensions in boys compared to girls. In both maxillary and mandibular arches, the lengths and widths at various locations were significantly larger in boys than in girls ( P<0.05). Univariate correlation analysis revealed that body weight was positively correlated with the width of the terminal plane in both the maxilla and mandible and the total length of the mandibular dental arch, while BMI was positively correlated with the width of the maxillary terminal plane and the widths at all measured sites in the mandible ( P<0.05). Multiple regression analysis demonstrated that, after controlling for relevant variables, BMI was a significant positive predictor for the lengths and widths at various sites of the dental arch ( P<0.05), and height was a positive predictor for dental arch length ( P<0.05), as well as body weight was a positive predictor for the width in the molar region ( P<0.05). Overjet at the primary central incisors was 2.28 (1.57, 2.66) mm, and overbite was 1.13 (0.75, 1.92) mm. The anterior Bolton index was 0.79±0.03, and the overall Bolton index was 0.94±0.03. Conclusions:Primary tooth crowns of individual normal occlusion children demonstrate strong bilateral symmetry in homologous teeth. Most primary molars exhibit gender differences in buccolingual and occlusogingival dimensions, with larger values in boys. Arch dimensions (length and width) are consistently larger in boys.