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.

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 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.

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.

Objective:To investigate the normal reference values of spinal bone mineral density measured by quantitative computed tomography (QCT) and the differences of bone mineral density (BMD) in different regions of in Chinese adult males.Methods:Men who underwent low-dose CT lung scan for cancer screening in regions of Northeast, North, East, South, Central and Southwest of China from January 2018 to December 2019 were selected. And the lumbar vertebrae BMD values in the male subjects were measured by the QCT system (Mindways Software, Inc.). The mean BMD values and their decline rates were calculated at an age interval of 10 years, and the prevalence of osteoporosis was calculated according to the American College of Radiology spine QCT osteoporosis diagnostic criteria.Results:A total of 50 682 males with a mean age of (50.22±12.79) years (ranged 20 to 98 years) were included in this study. The peak BMD of (173.11±28.56) mg/cm 3 in the healthy Chinese adult male population appeared in the age group of 20 to 29 years and then declined with age. Before the age of 70 years, the BMD was relatively higher in males in South China, and it was lower in Central China and Southwest China, and it was intermediate in Northeast, North and East of China, with statistically significant differences. There was no significant differences in BMD in the males in the two age groups of 70 to 79 years and 80 and older among the regions in China. The overall decline rate of spinal BMD in Chinese males under QCT was about 46.92% over the lifetime, and it declined obviouslyin the 40-49 age group. The overall prevalence of osteoporosis in Chinese male population aged 50 years and above was approximately 11.42%, with the highest prevalence in Southwest China and Central China (14.72% and 13.87%, respectively) and the lowest in North China and South China (8.53% and 7.71%, respectively). Conclusions:A reference of lumbar spine BMD values for healthy males in China based on QCT is established. BMD values were highest in South China and Lowest in Central China.

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.

Objective:To use quantitative computed tomography (QCT) technology to measure the bone mineral density of the spine of the Chinese healthy population, and to explore its correlation with hemoglobin and serum albumin.Methods:The data in this study came from the China Health Quantitative CT Big Data Project (China Biobank). The spine bone density was measured by using QCT Pro Image Analysis System and all cooperating centers used the European spine phantom (NO.145) for quality control. Total of 50 053 healthy persons who met the criteria for entry were selected as the research subjects. The subjects were divided into 7 groups according to age. The general data, spine bone density, serum albumin, hemoglobin of the subjects were collected. The single-factor analysis of variance, Pearson correlation analysis and multi-classification logistic regression model were applied to analyze the correlation between bone density and hemoglobin and serum albumin.Results:The bone mineral density of healthy people decreased with age ( P<0.05), and there were significant differences in hemoglobin, serum albumin and body mass index (BMI) among different age groups (all P<0.05). Linear correlation analysis showed that there were positive correlation between bone mineral density and hemoglobin in healthy males in different age groups ( r=0.086, 0.101, 0.076, 0.090, 0.072, 0.123, 0.100, all P<0.01). There were negative correlation between bone mineral density and hemoglobin in certain age groups in women (40-49 years group: r=-0.027; 70-79 yearsgroup: r=-0.077; both P<0.05). And corelation were found between bone mineral density and serum levels of albumin in certain age groups of healthy subjects (among men, 30-39 years group: r=-0.048; 40-49 years group, r=-0.027; 70-79 years group, r=-0.051; among women, 30-39 years group: r=-0.044; 40-49 years group, r=-0.042; 50-59 years group, r=-0.086; 70-79 years group, r=-0.070; all P<0.05). After adjusting for age and BMI, the multi-category logistic regression analysis showed that the hemoglobin level was protective factor of normal bone density ( OR=1.022, 95% CI:1.017-1.027) and decreased bone density ( OR=1.012, 95% CI:1.007-1.016) in healthy males, and the serum albumin was risk factor for normal bone density ( OR=0.926, 95% CI:0.905-0.948) and decreased bone density ( OR=1.006, 95% CI:0.951-1.011) in healthy women. Conclusion:There is a correlation between bone mineral density and hemoglobin and serum albumin in Chinese healthy population. Hemoglobin is a protective factor for bone mineral density in men, and serum albumin is a risk factor for bone mineral densityin women.

Objective:To investigate the relationship between abdominal visceral adipose tissue (VAT) and cardiometabolic risk (CMR) through quantitative computed tomography (QCT).Methods:The present study included 76226 participants. Abdominal fat areas were measured using the QCT Pro Model 4 system. Cardiometabolic indices were collected, including systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterols CMR score was the sum of abnormal blood pressure, fasting glucose, triglyceride, and high-density lipoprotein cholesterol. Restricted cubic spline and ordered logistic regression models were applied.Results:The mean age was 50±13 years and the percentage of men was 58.8%. The level of VAT area was higher in men than in women (191.7±77.1 cm 2 vs 116.4±56.2 cm 2, P<0.0001 for all). After adjustment for age, the cardiometabolic indices except high-density lipoprotein cholesterol increased with increasing VAT area. When VAT area was 300 cm 2, age-adjusted odds ratios and 95% confidence intervals of a CMR score ≥ 1 were 14.61 (13.31, 16.04) for men and 5.46 (4.06, 7.36) for women, and the age-adjusted probability of a CMR score ≥ 3 was 31.7% for men and 31.3% for women. Conclusions:QCT-derived VAT is closely related to CMR. The findings suggest that measurement of visceral fat is recommended for the management of abdominal obesity in subjects who agree to undergo lung cancer screening via low-dose CT without additional radiation exposure.

Objective:To analyze the etiological characteristics and molecular epidemiological correlation of five cases of typhoid fever during the same period in yantai city.Methods:Six S. Typhis strains were isolated from 5 typhoid patients and epidemiological samples in Yantai city in 2018. The onset time of the cases were from May 26, 2018 to July 24, 2018, distributed in Shuidao Town of Muping District, Dengzhou Street of Penglai District, Donglai Street of Longkou District, Wenhua Street of Muping District and Fulaishan Street of zhifu District. S. Typhis strains were analyzed by conventional bacterial isolation method and XbaⅠ/BlnⅠ double-enzyme digestion pulse-field gel electrophoresis (PFGE). Meanwhile, ViaB virulence gene detection and 27 common antibiotics sensitivity tests were conducted to study the etiology of S. Typhis.Results:Six strains of S. Typhi were isolated from 5 patients and the domestic egg of one patient, which were divided into 4 PFGE patterns by PFGE-XbaⅠ and PFGE-BlnⅠ and among which 3 strains had the same PFGE patterns.One multi-drug resistant strain (foreign patient), one single-drug resistant strain (patient with a history of provincial retention), and one completely sensitive strain were detected. The three strains of the same PFGE pattern exhibit the same drug-sensitive phenotype which were intermediate against aminoglycosides and quinolones and susceptibility against the other antibiotics.All of the strains carried the ViaB virulence factor except the strain from the foreign patient.Conclusion:Local S. Typhi is susceptibility or intermediate against antibiotics commonly used in clinic.Sporadic cases of typhoid fever and typhoid imported infections still need attention.