ObjectiveTo investigate the prevalence and associated factors of malocclusion among preschool children in Fengxian District, Shanghai, and to provide a scientific basis for local medical and public health departments to formulate targeted interventions. MethodsA cross-sectional study was conducted from September to December 2024. A total of 1 172 children aged 3‒5 years were recruited from 10 kindergartens across 5 townships in Fengxian District, using stratified cluster random sampling method. Clinical examinations were conducted to record occlusal parameters such as the relationship of the second deciduous molars, canine teeth relationship, anterior overbite and overjet, anterior and posterior crossbite, and crowded dentition. A questionnaire survey was performed to the parents to collect information on factors influencing malocclusion, including genetic predisposition, poor oral habits, dietary patterns, and sleep-related breathing conditions. Data were statistically analyzed using IBM SPSS Statistics 27 software, with chi-square test for categorical data and binary logistic regression analysis for influencing factors. ResultsThe overall prevalence of malocclusion among 3‒5-year-old children in Fengxian District of Shanghai was 70.73%, with no statistically significant differences between genders (P>0.05). Deep overbite accounted for the highest proportion (49.66%), followed by Angle Class Ⅱ malocclusion of the second deciduous molars (17.83% on the left, 19.11% on the right), midline deviation (13.23%), anterior crossbite (6.74%), and crowding of the maxillary and mandibular anterior teeth (16.38% for the maxillary dentition, 17.58% for the mandibular dentition). Multivariate analyses showed that habitual mouth breathing during the day (OR=0.509, P=0.009) and morning dry mouth upon waking (OR=1.455, P=0.023) were independent influencing factors for malocclusion. ConclusionThe prevalence of malocclusion is relatively high among preschool children in Fengxian District, Shanghai,with deep overbite being the dominant trait. Sleep-related breathing conditions (such as habitual mouth breathing during the day and morning dry mouth) is an important influencing factor for malocclusion. Public health authorities should strengthen oral health education and promote the correction of bad habits to reduce the prevalence of malocclusion and improve children’s oral health.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective:The study aimed to analyze the risk variables influencing the prognosis of patients with sepsis-associated delirium (SAD) in the Intensive Care Unit (ICU) and build a prediction nomogram.Methods:This was a retrospective cohort study that includes patients with SAD in the Medical Information Mart for Intensive CareⅢ database (MIMIC-Ⅲ) database as training cohort, and patients who were hospitalized in the First Hospital of Jiaxing from January 2021 to September 2022 as validation cohort. Inclusion criteria: (1) age≥18 years old; (2) being admitted to the ICU for the first time; (3) the length of ICU stay≥24 h; (4) consistent with the diagnosis of sepsis; (5) the diagnosis of delirium was identified by CAM-ICU questionnaire. The general information, vital signs, past medical history and laboratory examination results of the patients were collected, and the outcome was 28-day mortality. Multiple logistic regression was used to identify independent influencing factors and the nomogram was constructed. The validity of the prediction model was determined using multiple indicators, including calibration curve, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and Hosmer-Lemeshow test.Results:A total of 250 patients were included in the training cohort and 154 patients were in the validation cohort. The multiple logistic regression demonstrated that age ( OR=1.057, 95% CI: 1.030-1.084, P<0.001), respiratory frequency ( OR=1.117, 95% CI: 1.037-1.202, P=0.003), lactic acid ( OR=1.137, 95% CI:1.011-1.279, P=0,032), hemoglobin ( OR=0.983, 95% CI: 0.970-0.997, P=0.020), SOFA score ( OR=1.184, 95% CI: 1.070-1.309, P=0.001) were independent risk factors associated with the 28-day mortality of patients with SAD. The AUC of the nomogram created by the five factors above was 0.773 (95% CI: 0.705-0.841), and the Hosmer-Lemeshow test showed that the model was a good fit ( P=0.875). The DCA curve indicates that the model has potential net benefit. The AUC was 0.864 (95% CI: 0.799-0.928) in the validation cohort, and the Hosmer-Lemeshow test showed that the model was a good fit ( P=0.488). The DCA curve indicates that the model of the validation cohort had potential net benefit. Conclusion:The prediction model based on age, respiratory frequency, lactate, hemoglobin, and SOFA scores shows valuable capability of predicting the prognosis of patients with SAD, which could help clinicians identify risk factors at first time and make earlier intervention.

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
Child ; Male ; Humans ; Female ; Child, Preschool ; Adolescent ; Crohn Disease ; Inflammatory Bowel Diseases ; Colon ; Inflammation ; Colonoscopy ; Glycoproteins ; Wnt Proteins

Objective:To explore the relationship between affective temperament and the severity of depressive symptoms in medical college students.Methods:From October to November 2021, a questionnaire survey was conducted among 1 780 medical undergraduates from two medical colleges in Anhui Province.The Chinese version of temperament scale of Memphis, Pisa, Paris and San Diego autoquestionnaire (TEMPS-A) and the Chinese version of the Beck depression inventory (BDI-Ⅱ) were used to evaluate the affective temperament and depressive symptoms of medical college students, respectively.SPSS 23.0 software was used for statistical analysis of the data.Ordinal Logistic regression model was used to analyze the impact of affective temperament characteristics on the severity of depressive symptoms.Results:The detection of depressive symptoms among medical college students was 6.4% with mild depression, 7.4% with moderate and severe depression and 86.2% without depression.The scores of cyclothymic, depressive, irritable, hyperthymia and anxious temperaments in TEMPS-A were significantly different among medical college students with different levels of depressive symptoms (all P<0.05). There were statistically significant differences in the detection rates of depression symptoms among medical college students with different typical affective temperament characteristics(all P<0.05). Ordinal Logistic regression model analysis showed that typical cyclothymic temperament ( OR=5.05, 95% CI: 3.68-6.94), typical depressive temperament ( OR=7.69, 95% CI: 4.64-12.86), typical hyperthymia temperament ( OR=0.30, 95% CI: 0.15-0.58), and typical anxious temperament ( OR=2.41, 95% CI: 1.75-3.32) were influencing factors for the severity of depressive symptoms in medical college students. Conclusion:Affective temperament, especially typical depressive temperament, typical cyclothymic temperament and typical anxious temperament can affect the severity of depressive symptoms in medical college students.

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Humans ; Mice ; Animals ; Caco-2 Cells ; beta Catenin/metabolism* ; Culture Media, Conditioned/pharmacology* ; Tight Junctions/metabolism* ; Intestinal Mucosa ; Inflammatory Bowel Diseases ; Tight Junction Proteins/metabolism* ; Inflammation/metabolism* ; Fibroblasts/metabolism* ; Mice, Inbred C57BL ; Glycoproteins/metabolism* ; Wnt Proteins/pharmacology* ; Frizzled Receptors/metabolism*

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.
Humans ; Inflammasomes ; Endothelial Cells ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammation ; Sleep Apnea, Obstructive ; Nucleotides

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.
Humans ; Inflammasomes ; Endothelial Cells ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammation ; Sleep Apnea, Obstructive ; Nucleotides

Objective To investigate the relationship between body composition and serum lipids and uric acid among adults in Maonan, and to analyze the effect of body composition changes on blood lipid and uric acid. Methods Totally 584 Maonan adult volunteers in Maonan village of Maonan Autonomous County in Guangxi, the age from 20 to 80 were recruited. The height was measured by the personal height tester; the body composition was measured by the ANITAMC-180 instrument; and the blood lipids and blood uric acid were measured by the Hitachi 7600 instrument. The obtained data were statistically analyzed by SPSS 20. 0. Results The age,height, weight, free fat mass, muscle mass, presumptive bone mass, body water, proptein,extracellular water, intracellular water, and waist-to-hip ratio were greater in Maonan men than in women (P<0. 05). However, whereas male fat content, body fat rate, and subcutaneous fat content were smaller than those of female (P < 0. 01). The total prevalence of hyperuricemia and hyperlipidemia in Maonan nationality was 13. 9% and 28. 4%, respectively. The prevalence of hyperuricemia and hyperlipidemia in males was higher than in females. In males, the body mass, body mass index, free fat mass, fat mass, muscle mass, presumptive bone mass, protein, extracellular water, body fat rate, visceral fat content, subcutaneous fat content and waist-hip ratio of the hyperlipidemia group were higher than the normal group (P<0. 05); and in females, the age, body mass index, fat mass, body fat rate, visceral fat content and waist-hip ratio of the hyperlipidemia group were higher than the normal group. In male, The body mass, free fat mass, presumptive bone mass, body water, extracellular water of the hyperuricemia group were higher than the normal group (P<0. 05); In females, the age, body mass, body mass index, fat mass, extracellular water, body fat ratio, muscle mass, visceral fat content, subcutaneous fat content, and waist-hip ratio of the hyperuricemia group were higher than the normal group. Conclusion The detection rate of hyperlipidemia and hyperuricemia in males of Guangxi Maonan nationality is all higher than that in females. The body composition is significant differences between the normal adults and the patients with hyperlipidemia and hyperuricemia of Maonan nationality in Guangxi.