Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

To improve the quality evaluation system of Hibisci Mutabilis Folium, this study established high performance liquid chromatography(HPLC) fingerprints of Hibisci Mutabilis Folium and evaluated the quality differences of medicinal materials from different places of production by chemometrics. Furthermore, a content measurement method of differential components was established based on quantitative analysis of multi-components by single-marker(QAMS). The fingerprints of 17 batches of Hibisci Mutabilis Folium from different places of production were constructed, with a total of 19 common peaks marked and seven components confirmed. The similarity between the sample fingerprints and the reference fingerprints ranged from 0.890 to 0.974. By utilizing principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA), the chemical patterns of fingerprints were identified. Five components that could be used to evaluate the quality differences of Hibisci Mutabilis Folium were screened, namely peak 6(quercetin 3-O-β-robinobioside), peak 7(rutin), peak 9(kaempferol-3-O-β-robinobioside), peak 10(kaempferol-3-O-rutinoside), and peak 14(tiliroside). The relative correction factors of isoquercitrin, kaempferol-3-O-β-robinobioside, kaempferol-3-O-rutinoside, kaempferol-3-O-β-D-glucoside, and tiliroside were measured with rutin as the internal reference. The QAMS method was established for the content measurement of six flavonoids, and the results showed there was no significant difference compared to the results obtained by an external standard method. In summary, the HPLC fingerprints and QAMS method established in the study, demonstrating stability and accuracy, can provide a reference for the overall quality evaluation of Hibisci Mutabilis Folium.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Principal Component Analysis

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective:To analyze the epidemiological characteristics, spatial clustering, and correlation between dental fluorosis detection rates and meteorological factors in children aged 8 - 12 years old in 37 counties (cities, districts, hereinafter referred to as counties) affected by coal-burning-borne endemic fluorosis in Guizhou Province, and to provide a scientific basis for prevention and control of the disease.Methods:Monitoring data on dental fluorosis in children aged 8 - 12 years old from 2019 to 2022 were collected from the National Health Security Information System for Endemic Diseases. Meteorological data, including annual average temperature, annual average precipitation, annual sunshine hours, and annual average relative humidity, were obtained from the Guizhou Provincial Bureau of Statistics. Descriptive epidemiology, analytical epidemiology, and spatial correlation analysis methods were used to analyze the data. Visual maps were created based on the clustering levels of annual dental fluorosis detection rates (high-high, low-low, high-low, low-high). Spatial autocorrelation and meteorological factors were used to analyze the epidemiological characteristics, spatial clustering, and the impact of meteorological factors on dental fluorosis.Results:From 2019 to 2022, a total of 3 649 161 children aged 8 - 12 in the counties affected by coal-burning-borne endemic fluorosis were monitored, and 115 793 children were diagnosed with dental fluorosis, with a detection rate of 3.17%. The detection rates were 4.73% (45 093/954 338) in 2019, 3.35% (31 424/938 445) in 2020, 2.86% (21 727/760 195) in 2021, and 1.76% (17 549/996 183) in 2022, respectively. The dental fluorosis indices were 0.09, 0.07, 0.06, and 0.03, respectively. The number of counties with detection rates > 6% was 7, 5, 5, and 0 in 2019 - 2022, respectively. Dafang County consistently had the highest detection rates, with rates of 10.06% (6 783/67 408), 10.07% (1 955/19 421), 13.54% (4 017/29 667), and 4.83% (3 284/76 206) in 2019 - 2022, respectively. The Moran's I indices for dental fluorosis detection rates were 0.45, 0.53, 0.53, and 0.53 in 2019 - 2022, with Z = 4.29, 5.07, 5.31, and 5.10, respectively ( P < 0.05), indicating global spatial autocorrelation (positive) and spatial clustering of dental fluorosis detection rates. The number of counties with "high-high" clustering of detection rates was 7, 7, 6, and 7 in 2019 - 2022, mainly concentrated in the northwestern region, including Qixingguan District, Nayong County, Dafang County, Zhijin County, and Jinsha County of Bijie City. "Low-high" clustering areas were distributed in Zhongshan District of Liupanshui City in 2019, 2020, and 2022. The detection rate of dental fluorosis was associated with local annual average temperature (°C) and annual precipitation (mm) ( r = - 0.393, - 0.337, P = 0.016, 0.041). Conclusions:From 2019 to 2022, the detection rate of dental fluorosis in children aged 8 - 12 in coal-burning-borne endemic fluorosis areas in Guizhou Province has been decreasing year by year, and it shows spatial clustering. The high clustering area is in the northwest of Guizhou Province, which should be regarded as a key prevention and control area for coal-burning-borne fluorosis in the future. At the same time, areas with lower temperatures and precipitation should also strengthen prevention and control efforts.

Objective:To investigate the curative effect and mechanism of hyperbaric oxygen therapy on nonalcoholic fatty liver disease in mice.Methods:Twenty-one 8-week-old male C57BL/6J mice were divided into three groups: control group (normal diet), model group (high-fat and high-cholesterol diet), and hyperbaric oxygen group (high-fat and high-cholesterol diet + hyperbaric oxygen therapy), with seven mice in each group. The changes in body weight, serum liver enzymes, and blood lipids were compared after treatment between the three groups. Hematoxylin-eosin staining, Oil Red O staining, Sirius red staining, and F4/80 immunohistochemical staining were used to observe the pathological changes in liver tissues. RT-qPCR and Western blot methods were used to detect the expression levels of oxidative stress and inflammatory factors. One-way analysis of variance was used for comparison among the groups.Results:Mice in the hyperbaric oxygen group had significantly improved liver histopathology. The serological levels of alanine aminotransferase, aspartate aminotransferase, and cholesterol were (77.50±13.59) U/L, (156.06±23.68) U/L, and (4.80±0.53) mmol/L, which were significantly lower than those in the model group [(109.43±16.88) U/L, (216.62±18.79) U/L, and (5.86±0.53) mmol/L, P<0.05], and accompanied by lower levels of lipid deposition, macrophage infiltration, and fibrosis. In addition, compared with the model group, the expression of antioxidant stress protein nuclear transcription factor erythroid 2-related factor 2 [(0.30±0.06) and (2.16±1.21), P<0.05] and heme oxygenase-1 [(0.48±0.19) and (1.01±0.18), P<0.05] in liver tissue showed an upward trend following hyperbaric oxygen treatment, which was also validated at the transcriptional level ( P<0.05). Simultaneously, compared with the model group, the mRNA expressions of tumor necrosis factor-α [(2.60±0.71) and (0.66±0.15), P<0.05], interleukin-1β [(2.41±1.01) and (0.78±0.23), P<0.05], and interleukin-6 [(3.61±2.17) and (0.94±0.25), P<0.05] in the liver tissue of mice in the hyperbaric oxygen group were decreased. The tumor necrosis factor-α protein level [(7.50±4.73) and (1.05±0.58), P<0.05] and interleukin-1β [(1.65±0.35) and (1.02±0.02), P<0.05] was reduced following hyperbaric oxygen treatment compared with those in the model group. Conclusion:Hyperbaric oxygen therapy can slow down the progression of nonalcoholic fatty liver disease by regulating the levels of oxidative stress and inflammation in the mice.

Objective:To investigate the distribution of iodine in drinking water in external environment and the iodine nutrition status of key population in Guizhou Province, and to provide a basis for further precise implementation of prevention and control strategy of "adapting to local conditions, providing classified guidance, and scientifically supplementing iodine".Methods:From April to September 2023, a survey on the iodine level of residents' drinking water was conducted in administrative villages (neighborhood committees, hereafter referred to as administrative village) in 88 counties (districts) of 9 cities (prefectures) in Guizhou Province. At the same time, one township (town) was selected from each of the five districts of east, west, south, north and center of each county (district). From each township (town), 40 non-boarding students aged 8 - 10 years old from one primary school and 20 pregnant women were selected. Household edible salt sample and once random urine sample were collected for detection of salt iodine and urinary iodine levels.Results:The survey covered 16 492 administrative villages in 1 481 townships (towns), 88 counties (districts), 9 cities (prefectures) throughout the province. A total of 51 531 samples of residents' drinking water were collected, with a median water iodine level of 1.50 μg/L and a range of 0.01 - 98.70 μg/L. Among them, there were 16 284, 208, and 0 administrative villages with median water iodine levels < 10, 10 - < 40, and 40 - 100 μg/L, respectively, accounting for 98.74%, 1.26%, and 0, respectively. A total of 26 491 samples of household edible salt were collected from children and pregnant women, with a median salt iodine levels of 27.6 mg/kg. The coverage rate of iodized salt was 99.6% (26 395/26 491), and the qualified iodized salt consumption rate was 97.0% (25 708/26 491). And 17 657 urine samples from children and 8 834 urine samples from pregnant women were collected, with median urinary iodine levels of 222.1 and 164.4 μg/L, respectively. There were statistically significant differences in urinary iodine levels among children of different genders and ages ( Z = - 6.08, H = 19.17, P < 0.001). The results of correlation analysis showed that there was no correlation between urinary iodine of children and pregnant women and water iodine ( r = 0.01 0.02, P > 0.05), while urinary iodine of pregnant women was positively correlated with salt iodine ( r = 0.02, P = 0.041). Conclusions:The external environment of Guizhou Province is generally deficient in iodine. Under the universal salt iodization policy, children have sufficient iodine nutrition, and pregnant women have an appropriate level of iodine nutrition. Comprehensive prevention and control measures, mainly based on universal salt iodization, should be continuously carried out to eliminate the harm of iodine deficiency.

Objective To explore the clinical application value of multimodal radiomics in differentiating parotid pleomorphic adenoma(PA)from adenolymphoma(AL).Methods The clinical and imaging data of 68 cases of PA and 52 cases of AL were retrospectively analyzed.All patients underwent ultrasound examination,enhanced CT scan and enhanced MRI scan of the neck before the operation.All patients were randomly divided into training group(n=84)and validation group(n=36)according to the ratio of 7∶3.The 3D Slicer software was used to manually draw the lesion area of the preoperative images and perform radiomics feature extraction.The best feature subset was selected to establish the radiomics model,and the diagnostic efficacy of different models was evaluated by the receiver operating characteristic(ROC)curve.Results The study found that age,gender,and smoking history were effective in differentiating parotid PA from AL,and were used to construct a clinical diagnostic model.Eighteen features were selected through dimensionality reduction to establish the radiomics model.A multimodal combined diagnostic model was then constructed by integrating the radiomics model with gender,age,and smoking history.Compared to the clinical model and the radiomics model,the multimodal combined diagnostic model demonstrated the highest area under the curve(AUC)for distinguishing PA from AL in both the training group and the validation group.Conclusion The combination of radiomics based on neck ultrasound,CT,and MRI with clinical characteristics shows significant clinical application value in the preoperative differentiation of PA and AL.