Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

Aim To study the possibility of luteolin(LUT)as a new drug of traditional Chinese medicine and its improving effect on glucose and lipid metabo-lism and liver oxidative stress injury in db/db mice,and to explore the possible mechanism.Methods AI was used to predict the drug toxicity,evaluate the phys-ical and chemical properties and segment the molecular structure of LUT.Molecular docking was used to verify the binding ability of LUT with Nrf2 and HMOX1;db/m mice were divided into the group C,and db/db mice were randomly divided into the T,L,M,H and P groups.The body weight and FBG changes were ob-served within 12 weeks of intervention.The expres-sions of FBG,HbA1c,Fins,TC,TG,HDL-C,LDL-C were detected.The pathomorphological changes and steatosis of mouse liver were observed by HE and oil red O staining.The expression of MDA,SOD and GSH-Px in liver was detected by Kit.The protein and mRNA expressions of Nrf2 and HMOX1 were detected by immunohistochemistry,WB and qPCR.Results AI algorithm predicted the safety and easy synthesis of LUT.LUT intervention had no significant effect on the body weight of db/db mice.After 12 weeks,compared with the group C,the livers of mice in group T showed disordered structure of hepatic lobules,irregular ar-rangement of hepatocytes,and a large number of fat vacuoles and lipid droplets in the cytoplasm.Compared with the group T,LUT intervention could improve the pathological changes of liver,reduce the expression of FBG,HbA1c,fins,TC,TG,LDL-C,MDA,improve the level of HOMA-IR,and upregulate the activities of SOD and GSH-Px.Molecular docking results showed LUT had strong binding with Nrf2 and HMOX1,and could increase the expression of Nrf2 and HMOX1.Conclu-sion LUT can correct the disorder of glucose and lip-id metabolism in db/db mice,and improve the level of oxidative stress in liver of mice through Nrf2/HMOX1 pathway,which has the development prospect as a new Chinese medicine for the treatment of T2DM.

The aim of this study was to understand the internal genetic diversity and population history dynamics of ticks in Inner Mongolia,to provide data for designing effective vector control programs and revealing ticks'transmission mechanisms.From 2022 to 2023,the manual collection method was used to collect samples in Inner Mongolia.The 16S rDNA and COI gene sequences of ticks were used to identify Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus,and analyze the sequence characteristics and genetic diversity within the populations.Base composition analysis indicated that the average A+T content of the 16S rDNA gene and CO I gene in the three ticks was significantly higher than that of C+G.Moreover,22 haplotypes of the COI gene and 12 haplotypes of the 16S rDNA sequence were identified in Hyalomma marginatum.Eleven haplotypes were identified according to the COI gene,and nine haplotypes were identified according to the16S rDNA sequence of Haemaphysalis concinna.Two haplotypes were identified on the basis of the COI gene,and six haplotypes were identified on the basis of the 16S rDNA sequence of Ar gas persicus.The minimum 16S rDNA haplotype diversity was 0.264 for Ar gas persicus and 0.579 for the other two species.The nucleotide diversity of the three tick species was less than 0.05.Tajima's val-ue and Fu's Fs value of the neutrality test were negative.Base saturation substitution analysis indicated that neither of the two genes in the three tick species reached saturation.The phylogenetic tree revealed that Hyalomma marginatum,Haema physalis concinna,and Ar gas persicus in Inner Mongolia independently aggregated into branches.In conclusion,the base content of Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus genes in Inner Mongolia was consist-ent with the characteristics of insect mitochondrial DNA content.Furthermore,the three tick populations showed rapid evolu-tionary population expansion,and the phylogeny of three tick species showed independent aggregation into clades,with no pop-ulation isolation.

The aim of this study was to understand the internal genetic diversity and population history dynamics of ticks in Inner Mongolia,to provide data for designing effective vector control programs and revealing ticks'transmission mechanisms.From 2022 to 2023,the manual collection method was used to collect samples in Inner Mongolia.The 16S rDNA and COI gene sequences of ticks were used to identify Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus,and analyze the sequence characteristics and genetic diversity within the populations.Base composition analysis indicated that the average A+T content of the 16S rDNA gene and CO I gene in the three ticks was significantly higher than that of C+G.Moreover,22 haplotypes of the COI gene and 12 haplotypes of the 16S rDNA sequence were identified in Hyalomma marginatum.Eleven haplotypes were identified according to the COI gene,and nine haplotypes were identified according to the16S rDNA sequence of Haemaphysalis concinna.Two haplotypes were identified on the basis of the COI gene,and six haplotypes were identified on the basis of the 16S rDNA sequence of Ar gas persicus.The minimum 16S rDNA haplotype diversity was 0.264 for Ar gas persicus and 0.579 for the other two species.The nucleotide diversity of the three tick species was less than 0.05.Tajima's val-ue and Fu's Fs value of the neutrality test were negative.Base saturation substitution analysis indicated that neither of the two genes in the three tick species reached saturation.The phylogenetic tree revealed that Hyalomma marginatum,Haema physalis concinna,and Ar gas persicus in Inner Mongolia independently aggregated into branches.In conclusion,the base content of Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus genes in Inner Mongolia was consist-ent with the characteristics of insect mitochondrial DNA content.Furthermore,the three tick populations showed rapid evolu-tionary population expansion,and the phylogeny of three tick species showed independent aggregation into clades,with no pop-ulation isolation.

Aim To study the possibility of luteolin(LUT)as a new drug of traditional Chinese medicine and its improving effect on glucose and lipid metabo-lism and liver oxidative stress injury in db/db mice,and to explore the possible mechanism.Methods AI was used to predict the drug toxicity,evaluate the phys-ical and chemical properties and segment the molecular structure of LUT.Molecular docking was used to verify the binding ability of LUT with Nrf2 and HMOX1;db/m mice were divided into the group C,and db/db mice were randomly divided into the T,L,M,H and P groups.The body weight and FBG changes were ob-served within 12 weeks of intervention.The expres-sions of FBG,HbA1c,Fins,TC,TG,HDL-C,LDL-C were detected.The pathomorphological changes and steatosis of mouse liver were observed by HE and oil red O staining.The expression of MDA,SOD and GSH-Px in liver was detected by Kit.The protein and mRNA expressions of Nrf2 and HMOX1 were detected by immunohistochemistry,WB and qPCR.Results AI algorithm predicted the safety and easy synthesis of LUT.LUT intervention had no significant effect on the body weight of db/db mice.After 12 weeks,compared with the group C,the livers of mice in group T showed disordered structure of hepatic lobules,irregular ar-rangement of hepatocytes,and a large number of fat vacuoles and lipid droplets in the cytoplasm.Compared with the group T,LUT intervention could improve the pathological changes of liver,reduce the expression of FBG,HbA1c,fins,TC,TG,LDL-C,MDA,improve the level of HOMA-IR,and upregulate the activities of SOD and GSH-Px.Molecular docking results showed LUT had strong binding with Nrf2 and HMOX1,and could increase the expression of Nrf2 and HMOX1.Conclu-sion LUT can correct the disorder of glucose and lip-id metabolism in db/db mice,and improve the level of oxidative stress in liver of mice through Nrf2/HMOX1 pathway,which has the development prospect as a new Chinese medicine for the treatment of T2DM.