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.

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.

BACKGROUND:Reactive oxygen species is a double-edged sword in the development of periodontitis and the regeneration of periodontal tissue.Low concentration of reactive oxygen species induces the differentiation of periodontal fibroblasts,and excessive reactive oxygen species will cause damage to periodontal tissue.In the process of inflammation,the accumulation of reactive oxygen species in periodontal tissue induces damage to cells and tissues through a variety of signaling pathways or through redox reactions. OBJECTIVE:To review the double-edged sword effect of reactive oxygen species in periodontitis and periodontal tissue regeneration,thereby providing potential targets and treatment ideas for the clinical treatment of periodontitis and periodontal tissue regeneration. METHODS:Databases of CNKI and PubMed were searched for relevant articles published from April 1990 to April 2023 with the key words of"periodontal tissue engineering,periodontal defect,regeneration of periodontal tissue,chronic periodontitis,reactive oxygen species,oxidative stress,antioxidative stress,oxidative injuries,free radicals,reactive nitrogen species"in Chinese and English,respectively.By reading the titles and abstracts,repetitive studies or irrelevant literatures were excluded.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Reactive oxygen species are a kind of free radicals with high reactivity.When bacteria invade,reactive oxygen species are released in large quantities by the respiratory explosion of neutrophils and play a double-edged sword role in the body through their redox reactions or as pleiotropic physiological signal transmitters.In periodontitis,low concentrations of reactive oxygen species can kill invading pathogenic bacteria,but high concentrations of reactive oxygen species promote the secretion of inflammatory factors through JNK,RANK,Wnt/β-Catenin and other pathways,promote immune damage or directly damage tissues through oxidative reactions or through other ways to aggravate periodontitis.In the process of periodontal tissue regeneration,low concentrations of reactive oxygen species can promote the proliferation and differentiation of periodontal ligament stem cells through Nrf2 and other pathways and can promote the secretion of vascular endothelial growth factor to promote vascular regeneration.This provides seeds and a nutrient environment for periodontal tissue regeneration,which is extremely important for promoting periodontal tissue regeneration.However,high concentrations of reactive oxygen species will reduce the activity of periodontal ligament stem cells and damage endothelial cells,which are not conducive to vascular regeneration.This will inhibit wound healing and periodontal tissue regeneration.Therefore,it is important to explore the role of reactive oxygen species in the development of periodontitis and periodontal tissue regeneration and to discover the potential mechanism of its action and to explore the appropriate concentration for its role in reducing periodontal inflammation and promoting periodontal tissue regeneration for the future treatment of periodontitis and periodontal tissue regeneration in clinical practice.Using reactive oxygen species as a target to explore ways to reduce periodontal inflammation and promote periodontal ligament stem cell activity and vascular regeneration may become a clinically effective method for treating periodontitis and promoting periodontal tissue regeneration.

Objective To explore the oral mucosal manifestations of Sweet's syndrome and provide a reference for its early detection and correct diagnosis.Methods The oral mucosal manifestations of a 60-year-old female patient with Sweet's syndrome are described in detail,followed by a discussion of the related literature.Results The patient had skin erythema of both lower extremities,which was accompanied by oral mucosal ulceration and pain for 3 days.The patient presented with mild cutaneous lesions and diffuse large-scale erosion in the oral mucosa with obvious pain.During the onset of the disease,the patient was accompanied by fever with a temperature of 38.5℃.After visiting the Department of Stomatology,laboratory tests showed an increase in C-reactive protein(35.2 mg/L)and an accelerated erythrocyte sedimentation rate(77.00 mm/h).Scattered red plaques and mild tenderness were observed in the knees and lower limbs.Histopathological examination of the skin lesions revealed scattered infiltration of immature neutrophils across the entire dermis.The patient responded well to glucocorticoid therapy.According to the clinical signs and labo-ratory examination,combined with the lesion histopathological results,a diagnosis of Sweet's syndrome was given.The patient was administered 1 mL compound Betamethasone injection only once intramuscularly.In the meantime,the pa-tient was asked to gargle with compound chlorhexidine solution and topically apply recombinant bovine basic fibroblast growth factor solution to the damaged mucosa three times a day for 1 week.After 4 days of medication,the patient's body temperature had returned to normal and the oral lesions were significantly reduced.After 2 weeks,the erythema in the leg and knee had almost all subsided,and the oral mucosal lesions had disappeared.The patient was followed up 6 months after treatment,with no recurrence of skin lesions.After 2 years of follow-up,the disease was stable with no re-currence.A review of the relevant literature shows that Sweet's syndrome is a rare inflammatory reactive dermatosis with unknown etiology,which can be divided into three clinical types:specific,tumor-related,and drug-induced.The male/female prevalence ratio is 1:4.The salient clinical manifestations are abrupt onset of painful erythematous plaques or nodules most commonly involving the extremities,often accompanied by pyrexia,elevated neutrophil count,elevation of the erythrocyte sedimentation rate,and positive C-reactive protein.The use of glucocorticoids is the most common treatment for this disease,and most patients see a rapid improvement in skin lesions;however,some may experience infection or recurrence after withdrawal.Some patients with Sweet's syndrome are accompanied by oral lesions,but cases of oral mucosal damage have been rarely reported,and this condition is easily misdiagnosed.Conclusion Oral mucosal lesions may be extraterritorial manifestations of Sweet's syndrome,and the patient's systemic condition should be comprehensively considered.Skin biopsy should be completed as soon as possible to make a clear diagnosis,so as not to delay the disease.J Prev Treat Stomatol Dis,2024,32(8):620-624.

Objective To investigate the inhibitory effects of magnesium citrate(MgCit)on oxidative stress in chronic renal failure(CRF).Methods SD rats were divided into CRF model group,MgCit groups(375 and 750 mg/kg),normal control group,and MgCit control group(750 mg/kg).The morphology of mitochondria in thoracic artery vascular smooth muscle cells(VSMCs)was observed by transmission electron microscopy.The content of superoxide dismutase(SOD)and malonaldehyde(MDA)in rat aorta and plasma was detected by the kit.The VSMCs were divided into normal control group,CRF model group,and MgCit groups(1.5 and 3 mmol/L).The levels of superoxide anion(DHE)and apoptosis were quantitatively detected by flow cytometry.Results Compared with the control groups,the mitochondria were swollen and the cristae fractured or disappeared in the model group;MgCit intervention could reduce mitochondrial swelling,but not cristae fracture.In the model group,SOD level in aorta and plasma decreased(P＜0.05)while MDA level increased(P＜0.05).MgCit intervention could increase SOD in aorta and plasma,but decrease MDA level(P＜0.05).In the CRF environment,the DHE content of VSMCs and apoptosis in CRF model group increased(P＜0.05).MgCit intervention could decrease DHE content and inhibit apoptosis(P＜0.05).Conclusion MgCit inhibits oxidative stress levels in vivo and in vitro in CRF.

Objective:To develop a genotyping method for the Junior blood type and report on a rare blood type with Jr(a-).Methods:Healthy O-type RhD+ volunteer donors of the Shenzhen Blood Center from January to May 2021 ( n=1 568) and a pedigree with difficult cross-matching ( n=3) were selected as the study subjects. Serological methods were used for proband′s blood type identification, unexpected antibody identification, and antibody titer determination. Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used for typing the proband′s RHD gene. ABCG2 gene coding region sequencing and a PCR-SSP genotyping method were established for determining the genotypes of the proband and his family members and screening of Jra antigen-negative rare blood type among the 1 568 blood donors. Results:The proband′s ABO and RhD blood types were respectively determined as B and partial D (RHDDVI.3/RHD01N.01), Junior blood type Jra antigen was negative, and plasma had contained anti-D and anti-Jra. Sequencing of the ABCG2 gene revealed that the proband′s genotype was ABGG201N.01/ABGG201N.01 [homozygous c. 376C>T (p.Gln126X) variants], which is the most common Jr(a-) blood type allele in the Asian population. Screening of the voluntary blood donors has detected no Jr(a-) rare blood type. Statistical analysis of the heterozygotes suggested that the allelic frequency for ABCG2*01N.01 (c.376T) was 0.45%, and the frequency of Jr(a-) rare blood type with this molecular background was about 0.2‰. Conclusion:A very rare case of partial DVI.3 type and Jr(a-) rare blood type has been identified. And a method for identifying the Junior blood type through sequencing the coding regions of the ABCG2 gene and PCR-SSP has been established.

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.

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.