Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

This study aims to reveal the correlation between the pharmacokinetics(PK) and pharmacodynamics(PD) of multiple components in Epimedii Folium-Chuanxiong Rhizoma and clarify the pharmacodynamic material basis and mechanism of this herb pair in treating osteoarthritis. The Hulth method was used to establish the rat model of osteoarthritis and plasma was collected at various time points after drug administration. The plasma concentrations of multiple components were measured. Enzyme-linked immunosorbent assay(ELISA) was used to measure the plasma concentrations of matrix metalloproteinase(MMP)-3, MMP-13, interleukin-1β(IL-1β), nitric oxide(NO), and tumor necrosis factor-α(TNF-α) as pharmacodynamic indicators. Self-defined weighting coefficients were used to calculate the PK and PD data, and a Sigmoid E_(max) fitting model was used to evaluate the synergistic effect of the compatibility of Epimedii Folium-Chuanxiong Rhizoma. The PK-PD models for Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma were E=(1.926×C~(2.652))/(0.136 6~(2.652)+C~(2.652)), E=(1.618×C~(345.2))/(0.118 4~(345.2)+C~(345.2)), and E=(2.305×C~(2.786))/(0.240 3~(2.786)+C~(2.786)), respectively. The E_(max) of Epimedii Folium-Chuanxiong Rhizoma was larger than those of the two herbal medicines alone. The EC_(50) of the herb pair was lower than the sum of Epimedii Folium and Chuanxiong Rhizoma alone. The concentrations of MMP-3, MMP-13, IL-1β, NO, and TNF-α were correlated with mass concentrations of multiple components in Epimedii Folium and Chuanxiong Rhizoma, and the compatibility was better than single use. Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma may play a role in the treatment of osteoarthritis by inhibiting MMP-3, MMP-13, IL-1β, NO, and TNF-α.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Osteoarthritis/metabolism* ; Epimedium/chemistry* ; Interleukin-1beta/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Nitric Oxide/blood* ; Humans ; Rhizome/chemistry*

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

OBJECTIVE To explore the early detection of large vestibular aqueduct syndrome(LVAS)in children by applying several audiological indicators.METHODS Ninety-two children with hearing loss(aged 1-70 months)were enrolled and divided into an LVAS group(45 cases)and a control group(47 cases).Eleven audiological indicators were statistically analyzed:lateral of hearing loss,the degree of hearing loss,configuration of hearing loss;ABR air-conduction threshold;ABR air-bone gap;ASSR average threshold;ASSR thresholds at 0.5,1,2,and 4 kHz;and tympanogram type.Indicators showing significant two-group differences were used to construct a visualized multifactorial linear prediction model using the R language.RESULTS Nine indicators demonstrated statistically significant differences between groups(P<0.05):laterality,configuration of hearing loss,ABR air-conduction threshold,ASSR average threshold,ASSR thresholds at all frequencies(0.5,1,2,4 kHz),and tympanogram type.A prediction model was established.When the total model score ranged between 200 and 240 points,the predicted LVAS risk probability was 0.1 to 0.99.The consistency index(C-index)was 0.85,indicating good predictive ability of the model.CONCLUSION The identified nine audiological indicators are valuable for the early detection of LVAS in children.The developed model can estimate LVAS risk.After refinement,this model holds potential to support early clinical diagnosis and intervention.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.