This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over

AIM To investigate the protective effects of verbascoside on D-galactose-induced liver injury in mice and its underlying mechanisms.METHODS C57BL/6J mice were randomly assigned to the normal group,the model group,the vitamin E group(100 mg/kg),and the low-dose and high-dose verbascoside groups(40,80 mg/kg),with 10 mice in each group.Simultaneous administration of medicine and subcutaneous injection of D-galactose(600 mg/kg)went on among the groups except the normal group for 8 weeks.Serum ALT,AST,ALP activities,along with TBil levels were measured using biochemical kits.Hepatic GSH,MDA concentrations,as well as SOD and GSH-Px activities were quantified.Liver pathological morphology was evaluated by HE staining,while hepatic fibrosis area was assessed using Sirius red staining.Western blot analysis determined hepatic expression of IL-6,IL-1β,TNF-ɑ,TLR4,NF-κB p65,IκBɑ and p-IKBɑ proteins.RESULTS Compared to the model group,the groups treated with vitamin E or verbascoside demonstrated significantly reduced body weight(P＜0.05,P＜0.01);increased hepatic index(P＜0.05,P＜0.01);decreased serum activities of ALT,AST and ALP alongsided reduced TBil levels(P＜0.05,P＜0.01);attenuated pathological damage of liver tissue and fibrosis severity;reduced hepatic MDA level(P＜0.05,P＜0.01);and elevated GSH level with enhanced SOD and GSH-Px activities(P＜0.05,P＜0.01).Furthermore,the high-dose verbascoside group showed significantly decreased hepatic expressions of IL-6,IL-1 β,TNF-ɑ,TLR4,NF-κB p65,and p-IKBɑ/IKBɑ proteins(P＜0.05,P＜0.01).CONCLUSION Verbascoside improves D-galactose-induced liver injury through its antioxidant activity,anti-inflammatory effects,and suppression of the TLR4/NF-κB signaling pathway.

AIM To investigate the protective effects of verbascoside on D-galactose-induced liver injury in mice and its underlying mechanisms.METHODS C57BL/6J mice were randomly assigned to the normal group,the model group,the vitamin E group(100 mg/kg),and the low-dose and high-dose verbascoside groups(40,80 mg/kg),with 10 mice in each group.Simultaneous administration of medicine and subcutaneous injection of D-galactose(600 mg/kg)went on among the groups except the normal group for 8 weeks.Serum ALT,AST,ALP activities,along with TBil levels were measured using biochemical kits.Hepatic GSH,MDA concentrations,as well as SOD and GSH-Px activities were quantified.Liver pathological morphology was evaluated by HE staining,while hepatic fibrosis area was assessed using Sirius red staining.Western blot analysis determined hepatic expression of IL-6,IL-1β,TNF-ɑ,TLR4,NF-κB p65,IκBɑ and p-IKBɑ proteins.RESULTS Compared to the model group,the groups treated with vitamin E or verbascoside demonstrated significantly reduced body weight(P＜0.05,P＜0.01);increased hepatic index(P＜0.05,P＜0.01);decreased serum activities of ALT,AST and ALP alongsided reduced TBil levels(P＜0.05,P＜0.01);attenuated pathological damage of liver tissue and fibrosis severity;reduced hepatic MDA level(P＜0.05,P＜0.01);and elevated GSH level with enhanced SOD and GSH-Px activities(P＜0.05,P＜0.01).Furthermore,the high-dose verbascoside group showed significantly decreased hepatic expressions of IL-6,IL-1 β,TNF-ɑ,TLR4,NF-κB p65,and p-IKBɑ/IKBɑ proteins(P＜0.05,P＜0.01).CONCLUSION Verbascoside improves D-galactose-induced liver injury through its antioxidant activity,anti-inflammatory effects,and suppression of the TLR4/NF-κB signaling pathway.

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.
Male ; Female ; Humans ; Risk Factors ; Diabetes Mellitus/epidemiology* ; Mortality, Premature ; Smoking ; Cost of Illness ; China/epidemiology* ; Global Burden of Disease

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

OBJECTIVE: To study the mechanism of Shengmai Injection (SMI, ) on anti-sepsis and protective activities of intestinal mucosal barrier. METHODS: The contents of 11 active components of SMI including ginsenoside Rb1, Rb2, Rb3, Rd, Re, Rf, Rg1, Rg2, ophioposide D, schisandrol A and schisantherin A were determined using ultra-performance liquid chromatography. Fifty mice were randomly divided into the blank, the model, the low-, medium- and high-dose SMI groups (0.375, 0.75, 1.5 mL/kg, respectively) by random number table, 10 mice in each group. In SMI group, SMI was administrated to mice daily via tail vein injection for 3 consecutive days, while the mice in the blank and model groups were given 0.1 mL of normal saline. One hour after the last SMI administration, except the blank group, the mice in other groups were intraperitoneally injected with lipopolysaccharide (LPS) saline solution (2 mL/kg) at a dosage of 5 mL/kg for development of endotoxemia mice model. The mice in the blank group were given the same volume of normal saline. Inflammatory factors including interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), interleukin (IL)-2 and IL-10 were measured by flow cytometry. Myosin light-chain kinase (MLCK), nuclear factor κB (NF-κB) levels, and change of Occludin proteins in jejunum samples were analyzed by Western blot. RESULTS: The decreasing trends of INF-γ, TNF-α and IL-2 were found in serum of SMI treatment groups. In SMI-treated mice, the content of Occludin increased and MLCK protein decreased compared with the model group (P<0.05 or P<0.01). The content of cellular and nuclear NF-κB did not change significantly (P>0.05). CONCLUSION SMI may exert its anti-sepsis activity mainly through NF-κB-pro-inflammatory factor-MLCK-TJ cascade.
Animals ; Drug Combinations ; Drugs, Chinese Herbal ; Mice ; NF-kappa B/metabolism* ; Occludin ; Saline Solution ; Sepsis/drug therapy* ; Tumor Necrosis Factor-alpha/metabolism*

Objective: Predictive models were used to evaluate the impact of common risk factors on the number of cardio-cerebrovascular deaths and the probability of premature death. Methods: Using the data for China estimated by the Global Burden of Disease study 2015 (GBD 2015), we calculated the population attribution fraction (PAF) of risk factors. The proportional change model was used to estimate the number of unattributable deaths by 2030, and to predict the number of deaths, mortality, standardized mortality and probability of premature death by 2030. Results: According to the natural change trend of risk factors from 1990 to 2015, the number of deaths and mortality would reach 6.12 million and 428.53/100 000 by 2030, with an increase of 59.92% and 52.87%. By 2030, the probability of premature death from cardio-cerebrovascular diseases among Chinese aged 30-70 years old would continue to decline, from 11.43% to 11.28% for men, and from 5.79% to 4.43% for women. If the goals of all included risk factors were reached by 2030, 2 289 200 cardio-cerebrovascular deaths would be avoided. If only the exposure to a single risk factor was achieved by 2030, blood pressure, total cholesterol, and fine particulate matter exposure were the three most important factors affecting cardio-cerebrovascular deaths, which would reduce 1 332 800, 609 100 and 306 800 deaths, respectively. Among the involved risk factors, the control of blood pressure would mostly decrease the number of deaths due to ischemic heart disease and hemorrhagic stroke, about 677 300 and 391 100 deaths, accordingly. Conclusion: The control of risk factors is of great significance in reducing deaths and probability of premature death due to cardio-cerebrovascular diseases. If the control targets of all risk factors could be achieved by 2030, the burden of cardio-cerebrovascular diseases would be reduced greatly.
Adult ; Aged ; Blood Pressure ; Cerebrovascular Disorders/epidemiology* ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Mortality, Premature ; Risk Factors