OBJECTIVES: To investigate the effects of Naoluo Xintong Decoction (NLXTD) on proliferation of rat brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and role of the HIF-1α/VEGF pathway in mediating its effect. METHODS: Using a BMEC model of OGD/R, we tested the effects of 10% NLXTD-medicated rat serum, alone or in combination with 2ME2 or 10% NAKL, on cell proliferation, migration, tube-forming ability and permeability using CCK-8 assay, Transwell chamber assay, tube formation assay and permeability assay. Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis, and the expressions of HIF-1α, VEGFR2, Notch1, ERK and P-ERK1/2 proteins were detected with Western blotting. RESULTS: OGD/R injury significantly decreased viability of BMECs. NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation, migration and tube formation ability, but these effects were strongly attenuated by application of 2ME2. NLXTD treatment also significantly increased the percentages of VEGF- and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α, VEGFR2, Notch1 and P-ERK1/2. CONCLUSIONS NLXTD promotes proliferation, migration, and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Rats ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Glucose ; Brain/blood supply* ; Cells, Cultured ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective To observe the value of deep learning combine with radiomics based on MRI for evaluating H3 K27 status of midline gliomas.Methods Totally 127 patients with diffuse midline glioma H3 K27-altered(H3-DMG)and 127 patients with midline glioblastoma(GBM)without H3 K27 mutation were retrospectively enrolled.The patients were randomly divided into training set(n=204)and test set(n=50)at the ratio of 8:2.U-Net neural network visual and radiomics features of tumors were extracted based on MRI,and a deep learning radiomics model was established,its value for evaluating H3 K27 status was observed.Results Based on training set,0.500 was obtained as the security score partition value for the model classification task.In test set,the median safety score of the obtained deep learning radiomics model for evaluating H3 K27 status of H3-DMG and GBM was 0(0,0)and 0.999(0.616,1.000),respectively,for the former was lower than for the latter(Z=-5.114,P＜0.001).The sensitivity,specificity,accuracy and area under the curve of deep learning radiomics model for evaluating H3 K27 status in training set was 93.14％,81.37％,87.25％and 0.953(95％CI[0.923,0.976]),respectively,while was 88.00％,80.00％,84.00％and 0.922(95％CI[0.829,0.986])in test set,respectively.Conclusion Deep learning radiomics based on MRI could accurately evaluate H3 K27 status of midline gliomas.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

OBJECTIVE: To investigate the effects of Naoluo Xintong Decoction (NLXTD) on pyroptosis and angiogenesis of brain microvascular endothelial cells (BMECs) and explore the possible mechanisms in rats with oxygen-glucose deprivation/ reperfusion (OGD/R). METHODS: Rat BMECs with or without caspase-1 siRNA transfection were cultured in the presence of 10% medicated serum from NLXTD-treated rats (or blank serum) and exposed to OGD/R. CCK-8 assay, Transwell chamber assay, and tube formation assay were used to assess proliferation, migration, and tube-forming abilities of the cells. The activity of lactate dehydrogenase (LDH) in the culture supernatant was determined using a commercial assay kit, and the levels of inflammatory factors IL-1β and IL-18 were detected with ELISA. The cellular expressions of pro-caspase-1, caspase-1, NLRP3, Gasdermin D, and angiogenesis-related proteins VEGF and VEGFR2 were detected using Western blotting. RESULTS: The BMECs showed obvious injuries after OGD/R exposure. Compared with the blank serum, the medicated serum significantly improved the cell viability, migration ability, and lumen-forming ability (P < 0.01) and lowered the levels of IL-1β and IL-18 and the LDH release (P < 0.01) of the cells with OGD/R exposure. Western blotting showed that in the BMECs exposed to OGD/R, the medicated serum strongly upregulated the expression of VEGF and VEGFR2 proteins (P < 0.01) and reduced the protein expressions of pro-caspase-1, caspase-1, NLRP3, and Gasdermin D (P < 0.01), and transfection of the cells with caspase-1 siRNA further promoted the expressions of VEGFR2 protein in the cells (P < 0.01). CONCLUSION NLXTD can improve the proliferation, migration, and tube- forming ability and promote angiogenesis of BMECs with OGD/R injury probably by inhibiting the caspase-1/Gasdermin D pathway in pyroptosis, alleviating cell injury, and upregulating the expressions of VEGF and VEGFR2.
Animals ; Rats ; Endothelial Cells ; Caspase 1 ; Gasdermins ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein ; Vascular Endothelial Growth Factor A ; Reperfusion Injury ; Brain ; Angiogenic Proteins ; Glucose

ObjectiveTo investigate the protective effect and underlying mechanism of Gandou Fumu decoction （GDFMT） on renal fibrosis in a mouse model of Wilson's disease. MethodSixty adult male toxic milk （TX） mice were randomly divided into a model group， high-， medium-， and low-dose GDFMT groups， and a positive control （penicillamine） group， and another 12 wild-type mice were assigned to the normal group. The high-， medium-， and low-dose GDFMT groups were administered GDFMT at 13.92， 6.96， 3.48 g·kg^-1， respectively， and the positive control group received penicillamine at 0.1 g·kg^-1， while the model and normal groups were given an equal volume of 0.9% saline solution by gavage once a day for 4 consecutive weeks. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of blood urea nitrogen （BUN）， creatinine （CRE）， type Ⅲ procollagen （PC-Ⅲ）， and type Ⅳ collagen （C-Ⅳ） in the serum. Histological changes in the mouse kidneys were examined by hematoxylin-eosin （HE） and Masson's trichrome staining. Immunofluorescence was used to assess the protein expression of leptin， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription （STAT） in renal cells. Real-time polymerase chain reaction （Real-time PCR） was performed to analyze the mRNA expression levels of leptin， leptin receptor（OB-R）， JAK2， and STAT. Western blot was used to detect the expression of transforming growth factor-β₁ （TGF-β₁） and monocyte chemoattractant protein-1 （MCP-1）. ResultCompared with the normal group， the model mice exhibited a significant increase in BUN， CRE， PC-Ⅲ， and C-Ⅳ levels （P<0.01）. Compared with the model group， the high- and medium-dose GDFMT groups and the penicillamine groups showed significant decreases in these parameters （P<0.05， P<0.01）， with the high-dose GDFMT group demonstrating the most significant reduction （P<0.01）. The histological examination of renal tissue revealed fibrosis in the model group， while the fibrotic damage was mitigated to varying degrees after drug intervention， with improvement in fibrosis. Immunofluorescence results showed that leptin， JAK2， and STAT3 protein expression levels were significantly upregulated in the renal fibrosis of the model group. After GDFMT intervention， the fluorescence intensity decreased， with the high-dose GDFMT group showing the lowest intensity. Real-time PCR results demonstrated that leptin， OB-R， JAK2， and STAT3 mRNA expression levels were significantly elevated in the model group compared with those in the normal group， while the high- and medium-dose GDFMT groups and the penicillamine group showed significant reductions in their expression levels （P<0.05， P<0.01）. Western blot analysis revealed that TGF-β₁ and MCP-1 expression levels were significantly increased in the model group （P<0.01）， and the high- and medium-dose GDFMT groups exhibited significant reductions in their expression levels （P<0.01）. ConclusionGDFMT can alleviate renal fibrosis damage in TX mice， and its mechanism of action may be related to the regulation of leptin and the JAK/STAT signaling pathway.

Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m^-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m⁻² may be more sensitive to compound hot extreme.

Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L⁻¹, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L⁻¹ respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.