Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

Objective To study the relationship between serum insulin-like growth factor-1 (IGF-1) and resistin levels and osteoporosis in patients with type 2 diabetes mellitus (T2DM). Methods This study was conducted on 306 T2DM patients admitted to Baoding No.2 Central Hospital from January 2018 to January 2022. According to the detection results of bone mineral density, the patients were divided into osteoporosis group (T≤-2.5) and non-osteoporosis group (T>-2.5). The differences in IGF-1, resistin and bone mineral density were compared between the two groups. Pearson correlation analysis was used to analyze the correlation between serum IGF-1 and resistin levels and bone mineral density in patients with osteoporosis. Receiver operating characteristic (ROC) curve was applied to evaluate the application value of IGF-1 and resistin in predicting osteoporosis in patients with T2DM. Patients with T2DM complicated with osteoporosis were followed up for 2 years, and the occurrence of fractures was assessed. After univariate analysis, multivariate logistic regression analysis was applied to screen the risk factors for fractures in T2DM patients with osteoporosis. Results The incidence rate of osteoporosis in patients with T2DM was 53.59% (164/306). The IGF-1 level and bone mineral density level in the osteoporosis group were lower than those in the non-osteoporosis group, while the level of resistin was higher than that in the non-osteoporosis group (P<0.05). Serum IGF-1 in patients with osteoporosis was positively correlated with bone mineral density, and serum resistin was negatively correlated with bone mineral density (P<0.05). The AUC, sensitivity and specificity of combination of IGF-1 and resistin in predicting osteoporosis were 0.888, 82.93% and 62.68% respectively, which were all higher than those of single factor prediction (P<0.05). The 164 T2DM patients with osteoporosis were followed up for two years, and 15 patients developed fragility fractures, with the incidence of fracture of 9.15% (15/164). Multivariate analysis showed that hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1, and high resistin were risk factors for fractures in patients with T2DM complicated with osteoporosis (P<0.05). Conclusion For patients with T2DM, the incidence rates of osteoporosis and fractures are high. The levels of IGF-1 and resistin are closely related to bone mineral density, which can be combined to predict osteoporosis. Hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1 and high resistin are risk factors for fractures in T2DM patients with osteoporosis. It is necessary to carry out targeted preventive measures in clinical practice to reduce the incidence rate of fractures.

To investigate the levels and clinical significance of serum microRNA ( miR) -146a, miR-145, T-helpertype17 (Th17)/regulatory T cell (Treg) in children with respiratory syncytial virus (RSV) infectious pneumonia. The clinical data of 200 children with RSV infectious pneumonia admitted to Nantong Maternal and Child Health Hospital from June 2020 to June 2023 were retrospectively collected as the study group. At the same time, 200 children with mycoplasma pneumonia were selected as the common pneumonia group and 200 healthy children were selected as the healthy group. The levels of serum inflammatory factors [interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α)] were detected by enzyme-linked immunosorbent assay. The expression levels of serum miR-146a and miR-145 were detected by RT-qPCR. The levels of Th17/Treg were detected by flow cytometry. The levels of miR-146a, miR-145, Th17/Treg and serum inflammatory factors were compared among the three groups. Pearson method was used to analyze the correlation between miR-146a, miR-145, Th17/Treg and serum inflammatory factors in children with RSV infectious pneumonia. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia. The results showed that in the study group, miR-146a (2.01±0.58), miR-145 (1.81±0.46), Th17/Treg (1.09±0.31), IL-6 (7.82±2.11) ng/L and TNF-α (9.82±2.96) ng/L were higher than those in the common pneumonia group miR-146a (1.49±0.42), miR-145 (1.43±0.31), Th17/Treg (0.77±0.24), IL-6 (5.89±1.32) ng/L, TNF-α (7.34±2.32) ng/L and healthy group miR-146a (1.25±0.19), miR-145 (1.19±0.16), Th17/Treg (0.38±0.09), IL-6 (4.52±1.04) ng/L, TNF-α (5.39±1.07)ng/L. The levels of the above indexes in the common pneumonia group were higher than those in the healthy group, and the differences were statistically significant ( F=183.543, 175.938, 617.182, 226.657, 193.459, P<0.05). In the study group, IFN-γ (14.18±3.25) pg/ml was lower than that in the control group (19.52±5.13) pg/ml, but higher than that in the healthy group (9.77±2.40) pg/ml, and the difference was statistically significant ( F=335.432, P<0.05). Pearson correlation analysis showed that miR-146a, miR-145 and Th17/Treg were positively correlated with IL-6 and TNF-α ( P<0.05), but negatively correlated with IFN-γ ( P<0.05). ROC curve results showed that the area under the curve (AUC) of miR-146a, miR-145 and Th17/Treg in the diagnosis of RSV infectious pneumonia was 0.767, 0.762 and 0.790, respectively, while the combined detection of the three was 0.904. In conclusion, the levels of miR-146a, miR-145 and Th17/Treg are highly expressed in children with RSV infectious pneumonia, and are closely related to the inflammatory response of children. The combined detection of the three may have certain application value in the auxiliary diagnosis of RSV infectious pneumonia.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

To investigate the levels and clinical significance of serum microRNA ( miR) -146a, miR-145, T-helpertype17 (Th17)/regulatory T cell (Treg) in children with respiratory syncytial virus (RSV) infectious pneumonia. The clinical data of 200 children with RSV infectious pneumonia admitted to Nantong Maternal and Child Health Hospital from June 2020 to June 2023 were retrospectively collected as the study group. At the same time, 200 children with mycoplasma pneumonia were selected as the common pneumonia group and 200 healthy children were selected as the healthy group. The levels of serum inflammatory factors [interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α)] were detected by enzyme-linked immunosorbent assay. The expression levels of serum miR-146a and miR-145 were detected by RT-qPCR. The levels of Th17/Treg were detected by flow cytometry. The levels of miR-146a, miR-145, Th17/Treg and serum inflammatory factors were compared among the three groups. Pearson method was used to analyze the correlation between miR-146a, miR-145, Th17/Treg and serum inflammatory factors in children with RSV infectious pneumonia. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia. The results showed that in the study group, miR-146a (2.01±0.58), miR-145 (1.81±0.46), Th17/Treg (1.09±0.31), IL-6 (7.82±2.11) ng/L and TNF-α (9.82±2.96) ng/L were higher than those in the common pneumonia group miR-146a (1.49±0.42), miR-145 (1.43±0.31), Th17/Treg (0.77±0.24), IL-6 (5.89±1.32) ng/L, TNF-α (7.34±2.32) ng/L and healthy group miR-146a (1.25±0.19), miR-145 (1.19±0.16), Th17/Treg (0.38±0.09), IL-6 (4.52±1.04) ng/L, TNF-α (5.39±1.07)ng/L. The levels of the above indexes in the common pneumonia group were higher than those in the healthy group, and the differences were statistically significant ( F=183.543, 175.938, 617.182, 226.657, 193.459, P<0.05). In the study group, IFN-γ (14.18±3.25) pg/ml was lower than that in the control group (19.52±5.13) pg/ml, but higher than that in the healthy group (9.77±2.40) pg/ml, and the difference was statistically significant ( F=335.432, P<0.05). Pearson correlation analysis showed that miR-146a, miR-145 and Th17/Treg were positively correlated with IL-6 and TNF-α ( P<0.05), but negatively correlated with IFN-γ ( P<0.05). ROC curve results showed that the area under the curve (AUC) of miR-146a, miR-145 and Th17/Treg in the diagnosis of RSV infectious pneumonia was 0.767, 0.762 and 0.790, respectively, while the combined detection of the three was 0.904. In conclusion, the levels of miR-146a, miR-145 and Th17/Treg are highly expressed in children with RSV infectious pneumonia, and are closely related to the inflammatory response of children. The combined detection of the three may have certain application value in the auxiliary diagnosis of RSV infectious pneumonia.

Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

Objective To explore the effect of cannabinoid receptor 2(CB2)on orthodontic tooth movement(OTM)rate and periodontal tissue reconstruction of pressure area in mice.Methods Thirty CB2-/-male mice and thirty littermate control WT male mice were individually accepted the orthodontic appliance at their age of 6 weeks.The mice were respectively scarified at 3 days,7 days,14 days and 21 days after the operation.Then the tooth movement distance was examined through the stereomicroscope.Hematoxylin-eosin staining was performed to explore the biological responses of periodontium at the distal mesial root pressure area.Anti-tartrate acid phospha-tase staining was performed to calculate the number and distribution of osteoclasts at the distal mesial root pressure area,and MMP-9 was evaluated by immunohistochemistry to examine the number of MMP-9(+)monocytes and multinucleated cells in the same district as the TRAP staining.Results Compared with those WT mice at 3,7,14 and 21 days,OTM distance showed a gradual increased tendency according with experimental time over 21 days.The widths of periodontal ligament on the pressure side were markedly greater in CB2-/-mice than WT mice at 7,14 and 21 days(P＜0.000 1).The numbers of TRAP positive osteoclasts were significantly greater in CB2-/-mice than those in WT mice at 14 days of OTM(P＜0.001).MMP-9 immunohistochemical staining showed that the number of MMP-9(+)monocytes and multinucleated cells was more in CB2-/-mice than that in WT mice at 14 days of OTM(P＜0.05).Conclusion The absence of CB2 accelerates orthodontic tooth movement under or-thodontic force.The absence of CB2 reinforces bone resorption in orthodontic tooth movement compressive area dur-ing orthodontic tooth movement.

Background Nonylphenol (NP) is a typical phenolic endocrine disruptor, and there are significant differences in NP concentration in different regions and water types. Objective To investigate the concentration of NP in three types (river, lake, and reservoir) of water sources in Hubei Province, and assess its ecological risk and population health risk. Methods Fifteen sampling points were set up at four river water sources (Liangtingshan Waterworks, Baishazhou Waterworks, Dijiao Waterworks, and Zongguan Waterworks), one lake water source (Liangzi Lake), and one reservoir water source (Fushui Reservoir). Water samples were collected from the 15 sampling points in June 2019 (wet season), October 2019 (level season), and December 2019 (dry season), respectively. The NP concentration in water samples was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry, and the differences in NP concentration among groups were compared using variance analysis. The ecological risk and the health risk of NP were evaluated using risk quotient (RQ) and non-carcinogenic risk index (NCRI), respectively. Results The detection rate of NP was 100%, with an average concentration of (18.10±15.00) ng·L⁻¹ (5.45-92.71 ng·L⁻¹). The average concentrations of NP during the level, wet, and dry seasons were (11.52±5.31) ng·L⁻¹, (23.86±22.08) ng·L⁻¹, and (18.93±9.51) ng·L⁻¹, respectively, and the maximum concentrations were 24.62 ng·L⁻¹, 92.71 ng·L⁻¹, and 42.38 ng·L⁻¹, respectively. The variance analysis showed no statistical difference in the NP concentration in the samples from rivers, lakes, and reservoirs in different periods (P>0.05). Only the water samples from the water source serving the Zongguan Waterworks showed an RQ (0.19) greater than 0.1 during the wet season, indicating a moderate risk. The RQ values of other water samples were all less than 0.1, indicating an overall relatively low ecological risk. The highest NCRI values during the level, wet, and dry seasons were 0.1459, 0.5492, and 0.2511, respectively, all less than 1, indicating an acceptable health risk level. Conclusion The NP concentrations in all water sources in this study are at a relatively low level, which poses an acceptable risk level to human health.

Objective: To investigate the prevalence of frailty and its influencing factors among the elderly, so as to provide the evidence for prevention and control of frailty. Methods: The elderly population at ages of 65 years and older were selected from 14 administrative villages or communities in Wuzhong District, Suzhou City, Jiangsu Province, using the random cluster sample method from July to November, 2022. Demographic information, smoking and alcohol consumption were collected through questionnaire surveys. Physical activity, sleep quality and frailty were evaluated using the International Physical Activity Questionnaire-Short, Pittsburgh Sleep Quality Index and the FRAIL Scale, respectively. Factors affecting frailty among the elderly were evaluated using a multinomial logistic regression model. Results: A total of 8 782 elderly peolple were surveyed, including 4 259 males (48.50%) and 4 523 females (51.50%). The median age was 71.00 (interquartile range, 8.00) years. There were 2 145 cases with pre-frailty (24.42%) and 189 cases with frailty (2.15%). Multinomial logistic regression analysis showed that age (75-<85 years, OR=1.330, 95%CI: 1.186-1.492; ≥85 years, OR=2.452, 95%CI: 1.882-3.195), smoking (current smoking, OR=0.838, 95%CI: 0.714-0.983), physical activity level (low, OR=1.161, 95%CI: 1.010-1.333) and sleep quality (poor, OR=2.248, 95%CI: 1.822-2.774) were associated with pre-frailty; age (75-<85 years,OR=2.629, 95%CI: 1.921-3.596; ≥85 years, OR=3.067, 95%CI: 1.621-5.801), educational level (junior high school and above, OR=0.488, 95%CI: 0.298-0.798), body mass index (underweight, OR=1.848, 95%CI: 1.023-3.337; obesity, OR=1.798, 95%CI: 1.180-2.740), smoking (quit smoking, OR=1.787, 95%CI: 1.007-3.171; current smoking, OR=0.448, 95%CI: 0.242-0.830), alcohol consumption (yes, OR=0.532, 95%CI: 0.291-0.972), physical activity level (low, OR=2.757, 95%CI: 1.646-4.616) and sleep quality (poor, OR=3.911, 95%CI: 2.438-6.273) were associated with frailty. Conclusion Older, low physical activity level, poor sleep quality, underweight and obesity are associated with frailty of the elderly.

Objective: To explore the association of tobacco/alcohol-excessive Internet usage and insufficient sleep with depressive symptoms among middle school students, so as to provide a reference for improving mental health of middle school students. Methods: In accordance with the cluster random sampling method, a total of 18 484 middle school students in Shanghai were surveyed from September to November 2022. Tobacco/alcohol-excessive Internet usage and sleep duration with depressive symptoms were assessed using the relevant scale items included in the questionnaire of Surveillance for Common Disease and Health Risk Factors among Students. The χ 2 test was used for inter group comparison, Logistic regression analysis and likelihood ratio test were used to analyze the independent and aggregated associations of tobacco/alcohol-excessive Internet use and insufficient sleep wiht depressive symptoms. Results: Self reported rates of tobacco/alcohol-excessive Internet usage, insufficient sleep and depressive symptoms among adolescents were 14.7%, 73.5% and 16.3%, respectively. Tobacco/alcohol-excessive Internet usage ( OR=2.69, 95%CI =2.44-2.97) and insufficient sleep ( OR=1.76, 95%CI =1.58-1.95) were associated with depressive symptoms ( P <0.05). Compared to middle school students with no tobacco/alcohol-excessive Internet usage and sufficient sleep, those with both tobacco/alcohol-excessive Internet usage and insufficient sleep showed the higher rate of depressive symptoms ( OR=4.71, 95%CI =4.08-5.44, P <0.05). Further stratified analysis results showed that, compared to the boys and the high school students, the separate and joint association of tobacco/alcohol-excessive Internet usage and insufficient sleep with depressive symptoms were more pronounced in the girls and the middle school students [ OR (95% CI ) for tobacco/alcohol-excessive Internet usage were 3.09 (2.68-3.56) and 4.74 (3.86-5.83), respectively; OR (95% CI ) for insufficient sleep were 1.86 (1.60-2.17) and 2.00 (1.58-2.53), respectively; and the OR (95% CI ) for the joint association were 6.05 (5.01-7.31) and 9.15 (6.98-11.99), respectively, P <0.05]. Conclusions Tobacco/alcohol-excessive Internet usage and insufficient sleep are associated with depressive symptoms in middle school students. Prevention and control strategies for adolescent mental health should be developed with consideration of health related behaviors, and also need to be tailored by focusing on gender and grade differences.