Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To observe the effect of warming needle therapy combined with Tuina(Chinese therapeutic massage)on the clinical symptoms and anxiety state of patients with cervical vertigo accompanied by anxiety. Methods:Seventy patients with cervical vertigo accompanied by anxiety state were divided into an observation group and a control group using the random number table method,with 35 patients in each group.In addition to disease education,the observation group was treated with warming needle therapy and Tuina 3 times a week,and the control group was treated with betahistine mesylate tablets orally 3 times a day.Both groups were treated for 4 weeks.The changes in the scores of the evaluation scale for cervical vertigo(ESCV),self-rating anxiety scale(SAS),and Hamilton anxiety rating scale(HAMA)were compared between the two groups after treatment. Results:One case in the observation group dropped out due to failure to cooperate with the treatment during the study.In the treatment group,the total effective rate and the cured plus markedly effective rate were 94.1%and 50.0%,respectively,and 88.6%and 8.6%in the control group,respectively;the differences between the two groups were statistically significant(P<0.05).After treatment,the ESCV,SAS,and HAMA scores of both groups decreased significantly compared with those before treatment(P<0.01),and the scores of the observation group were lower than those of the control group(P<0.01 or P<0.05). Conclusion:Warming needle therapy combined with Tuina can significantly improve the clinical symptoms of patients with cervical vertigo accompanied by anxiety state.

Objective To explore the protective effect and mechanism of modified Buyang Huanwu Decoction and Shenqi Dihuang Decoction on diabetic kidney disease(DKD)mice based on the regulation of VEGF-C/VEGFR3 pathway inhibiting lymphangiogenesis.Methods Twenty-four male db/db mice were randomly divided into model group,Chinese medicine group(modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction,crude drug 24.44 g·kg-1)and western medicine group(Irbesartan,13.5 mg·kg-1),with eight mice in each group.Eight db/m mice were selected as control group.Intragastric administration was given once a day for 12 consecutive weeks.Fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),urinary albumin/creatinine ratio(ACR)and kidney index were measured.The pathological changes of renal tissue were observed by HE and Masson staining.The expressions of fibronectin(FN),type I collagen(Col I),Vimentin,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),vascular endothelial growth factor receptor 3(VEGFR3),vascular endothelial growth factor-C(VEGF-C),lymphatic endothelial hyaluronic acid receptor 1(LYVE-1),podoplanin(PDPN),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in renal tissue were detected by immunohistochemistry.The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were detected by Western Blot.The mRNA expressions of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were detected by Real-time PCR.Results Compared with the control group,the levels of serum FBG,TG,TC,ACR and kidney index in the model group were significantly increased(P＜0.05).Glomerular hypertrophy,mesangial matrix increased,basement membrane thickening,cystic cavity narrowing,renal tubular epithelial cell degeneration and necrosis,interstitial infiltration of a large number of inflammatory cells,renal tubular atrophy;the level of renal fibrosis was significantly increased(P＜0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the expression of VEGF-C protein in cytoplasm and the expression of VEGFR3 and PDPN protein around renal tubular capillaries were significantly up-regulated(P＜0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly up-regulated(P＜0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly increased(P＜0.05).Compared with the model group,the levels of serum TG,TC and ACR in the Chinese medicine group were significantly decreased(P＜0.05).Renal tissue injury was improved to varying degrees,renal inflammatory cell infiltration was reduced to a certain extent,and renal tissue fibrosis was significantly reduced(P＜0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the protein expression of VEGF-C in cytoplasm and the protein expressions of VEGFR3 and PDPN around renal tubular capillaries were significantly down-regulated(P＜0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly down-regulated(P＜0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly decreased(P＜0.05).Conclusion Modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction can reduce the level of inflammation and fibrosis in renal tissue of DKD mice,and its mechanism may be related to the regulation of VEGF-C/VEGFR3 pathway to inhibit lymphangiogenesis.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To describe the baseline characteristics of the subjects enrolled in the China Quantitative CT (QCT) big data program in 2018—2019.Methods:Based on baseline data from the Chinese health big data project from January 2018 to December 2019 from the eligible enrolled population, measurements of bone mineral density (BMD) and visceral adipose tissue (VAT) were performed using Mindways′ QCT Pro Model 4 system. The baseline data of age, gender, regional distribution, height, weight, abdominal circumference, blood pressure, blood routine and blood biochemical tests were analyzed. And the single factor analysis of variance (ANOVA) was used to check the age related trend of BMD and VAT in both genders.Results:After screening the inclusion exclusion criteria and outliers of the main indicators, 86 113 people were enrolled in the project. The enrollment rate was 92.47%, including 35 431 (41.1%) women and 50 682 (58.9%) men, and the ratio of men to women was 1.43. The mean age was (50.3±12.7) years in all the subjects, and it was (50.2±12.8) years and (50.4±12.5) years in men and women, respectively, and there was no statistical difference between the two genders ( P>0.05). Total of 43 833 people were enrolled in east China, it was the largest group by region (50.90%), it was followed by central China (16 434 people, 19.08%), and the number of people enrolled in Northeast China was the lowest (2 914 people, 3.38%). The rate of completing of health information indicators related to the main outcome of the study were all above 70%, and there were significant differences between men and women (all P<0.05). The mean BMD was (139.33±46.76) mg/cm 3 in women, (135.90±36.48) mg/cm 3 in men, which showed a decreasing trend with age in both gender (both P<0.001); the mean intra-abdominal fat area was (116.39±56.23) cm 2 in women, (191.67±77.07) cm 2 in men, and there was an increasing trend with age in both men and women (both P<0.001). Conclusions:There are gender differences in BMD and VAT measured by QCT with different age tendency, and there are gender differences in health information index. Regional factors should also be taken into account for regional differences in the inclusion of data.