Exploration of the molecular mechanism of tea polyphenols against pulmonary hypertension by integrative approach of network pharmacology, molecular docking, and experimental verification.

Pulmonary hypertension, a common complication of chronic obstructive pulmonary disease, is a major global health concern. Green tea is a popular beverage that is consumed all over the world. Green tea's active ingredients are epicatechin derivatives, also known as "polyphenols," which have anti-carcinogenic, anti-inflammatory, and antioxidant properties. This study aimed to explore the possible mechanism of green tea polyphenols in the treatment of pulmonary hypertension using network pharmacology, molecular docking, and experimental verification. A total of 316 potential green tea polyphenols-related targets were obtained from the PharmMapper, SwissTargetPrediction, and TargetNet databases. A total of 410 pulmonary hypertension-related targets were predicted by the CTD, DisGeNET, pharmkb, and GeneCards databases. Green tea polyphenols-related targets were hit by the 49 targets associated with pulmonary hypertension. AKT1 and HIF1-α were identified through the FDA drugs-target network and PPI network combined with GO functional annotation and KEGG pathway enrichment. Molecular docking results showed that green tea polyphenols had strong binding abilities to AKT1 and HIF1-α. In vitro experiments showed that green tea polyphenols inhibited the proliferation and migration of hypoxia stimulated pulmonary artery smooth muscle cells by decreasing AKT1 phosphorylation and downregulating HIF1α expression. Collectively, green tea polyphenols are promising phytochemicals against pulmonary hypertension.

Interleukin-22: a potential therapeutic target in atherosclerosis.

BACKGROUND: Atherosclerosis is recognized as a chronic immuno-inflammatory disease that is characterized by the accumulation of immune cells and lipids in the vascular wall. In this review, we focus on the latest advance regarding the regulation and signaling pathways of IL-22 and highlight its impacts on atherosclerosis. MAIN BODY: IL-22, an important member of the IL-10 family of cytokines, is released by cells of the adaptive and innate immune system and plays a key role in the development of inflammatory diseases. The binding of IL-22 to its receptor complex can trigger a diverse array of downstream signaling pathways, in particular the JAK/STAT, to induce the expression of chemokines and proinflammatory cytokines. Recently, numerous studies suggest that IL-22 is involved in the pathogenesis of atherosclerosis by regulation of VSMC proliferation and migration, angiogenesis, inflammatory response, hypertension, and cholesterol metabolism. CONCLUSION: IL-22 promotes the development of atherosclerosis by multiple mechanisms, which may be a promising therapeutic target in the pathogenesis of atherosclerosis.

[Effects of ulinastatin on coagulation in children after cardiopulmonary bypass].

OBJECTIVE: To study the effects of ulinastatin on coagulation in children who underwent open-heart surgery with cardiopulmonary bypass (CPB). METHODS: Fifty children who underwent open-heart surgery for ventricular septal defect were randomly divided into two groups: ulinastatin treatment and control. Before CPB, ulinastatin (1.0×10(4) U/kg) was added to CPB priming fluid only in the ulinastatin treatment group. Activated partial thromboplasin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and international normalized ratio (INR) were measured both before and at 1 hr, 6 hrs and 24 hrs after CPB. RESULTS: The PT in the ulinastatin group was more prolonged than in the control group at 1 hr after CPB (18.7 ± 0.7 s vs 15.5 ± 0.5 s) and 6 hrs after CPB (17.5 ± 0.6 s vs 15.0 ± 0.6 s). The APTT in the ulinatatin group was also significantly more prolonged than in the control group at 6 hrs after CPB (38.7 ± 3.1 s vs 35.3 ± 3.1 s) and 24 hrs after CPB (34.2 ± 3.0 s vs 31.1 ± 2.6 s). CONCLUSIONS: Ulinastatin may prolong PT and APTT after CPB, and thus affects coagulation in children.

Prognostic Significance of Triglyceride-Glucose Index for Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Insulin resistance (IR) represents a critical regulator in the development and progress of coronary artery disease (CAD). Triglyceride-glucose (TyG) index, a novel surrogate biomarker of IR, has been implicated in several cardiovascular diseases. Accordingly, we conduct a meta-analysis to elucidate the relationship between TyG index and adverse cardiovascular events in patients with CAD. Methods: To identify the studies examining the predictive capacity of the TyG index for adverse cardiovascular events in the setting of CAD, we performed a comprehensive literature retrieval of Scopus, PubMed, EMBASE, and Web of Science, from the inception of databases to October 5, 2021. We pooled the adjusted hazard ratio (HR) along with 95% CI using a random-effects model. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including all-cause death, cardiovascular death (CV death), myocardial infarction (MI), stroke, hospitalization for unstable angina or heart failure, and revascularization. The secondary outcomes were all-cause death, CV death, MI, stroke, and revascularization. Additionally, we conducted subgroup analyses stratified by diabetes status, age, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), category of TyG index, sample size, follow-up duration, and study design. Results: About 12 studies involving 28,795 patients with CAD were finally taken into the quantitative analysis. Our findings showed that there was a 2.14-fold higher risk of MACEs among CAD populations in the highest TyG group compared with those in the lowest TyG group (HR: 2.14, 95% CI: 1.69-2.71, P < 0.001). A greater risk of MACEs was observed in participants with higher BMI than those with lower BMI (P = 0.03 for interaction). In the analysis of secondary outcomes, we also observed a markedly increased risk of MI, stroke, and revascularization in the highest TyG group compared with the lowest TyG group. No evidence of a significant association between TyG index and CV mortality or all-cause mortality in patients with CAD was identified. Conclusions: The elevated TyG index is a promising predictive factor of adverse cardiovascular events in patients with CAD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021228521.

A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

Background: Previous studies had reported increased circulating concentrations of growth differentiation factor-15 (GDF-15) in chronic heart failure (CHF), suggesting the potential prognostic significance of GDF-15 in this setting. To verify the relationship between the circulating GDF-15 levels and prognosis of CHF patients, we conducted an updated evidence-based meta-analysis. Methods: A comprehensive literature retrieval of PubMed, EMBASE, and Cochrane library was performed to collect the qualified studies that analyzed the prognostic value of GDF-15 in CHF from the inception of these online databases to September 25, 2021. The hazard ratio (HR) calculated for logGDF-15 of all-cause death and the related 95% confidence interval (CI) in multivariate analysis were used to measure the effect size. Additionally, subgroup analyses stratified by characteristics of the study participants were conducted for incremental evidence of GDF-15 in CHF with different clinical status. Results: A total of ten eligible studies involving 6,244 CHF patients were finally taken into the quantitative analysis. Results in the random-effects model indicated that there was an increased risk of 6% in all-cause mortality with a per 1LnU increase in baseline GDF-15 concentration (HR: 1.06, 95% CI: 1.03-1.10, P < 0.001). In stratified analyses, the association of GDF-15 with risk of all-cause mortality was found among chronic ischemic HF patients (HR:1.75, 95%CI: 1.24-2.48, P = 0.002), while the association was not found among chronic nonischemic HF patients (HR:1.01, 95%CI: 1.00-1.02, P = 0.219). Conclusion: The elevated GDF-15 is associated with an increased risk of all-cause mortality in CHF, especially, among CHF patients with ischemic etiology. The circulating GDF-15 might be a prognostic indicator in CHF patients. Registration Number: https://www.crd.york.ac.uk/PROSPERO; CRD42020210796.

DTI-based radiomics signature for the detection of early diabetic kidney damage.

OBJECTIVE: To explore whether a radiomics signature based on diffusion tensor imaging (DTI) can detect early kidney damage in diabetic patients. MATERIALS AND METHODS: Twenty-eight healthy volunteers (group A) and thirty type 2 diabetic patients (group B) with micro-normoalbuminuria, a urinary albumin-to-creatinine ratio (ACR) < 30 mg/g and an estimated glomerular filtration rate (eGFR) of 60-120 mL/(min 1.73 m2) were recruited. Kidney DTI was performed using 1.5T magnetic resonance imaging (MRI).The radiologist manually drew regions of interest (ROI) on the fractional anisotropy (FA) map of the right kidney ROI including the cortex and medulla. The texture features of the ROIs were extracted using MaZda software. The Fisher coefficient, mutual information (MI), and probability of classification error and average correlation coefficient (POE + ACC) methods were used to select the texture features. The most valuable texture features were further selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A LASSO regression model based on the radiomics signature was established. The diagnostic performance of the model for detecting early diabetic kidney changes was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Empower (R), R, and MedCalc15.8 software were used for statistical analysis RESULTS: A total of 279 texture features were extracted from ROI of the kidney, and 30 most valuable texture features were selected from groups A and B using MaZda software. After LASSO-logistic regression, a diagnostic model of diabetic kidney damage based on texture features was established. Model discrimination evaluation: AUC = 0.882 (0.770 ± 0.952). Model calibration evaluation: Hosmer-Lemeshow X2 = 5.3611, P = 0.7184, P > 0.05, the model has good calibration. CONCLUSION: The texture features based on DTI could play a promising role in detecting early diabetic kidney damage.

Rapid determination of sulfonamides in chicken using two-dimensional online cleanup mode with three columns coupled to liquid chromatography-tandem mass spectrometry.

A novel method based on online cleanup mode combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established. After an automated sample cleanup system with aqueous gel column, sulfonamides in chicken were detected in multiple reaction monitoring (MRM) mode. The total run time of the system, which included automated extraction, analytical chromatography and re-equilibration, was within 30 min. Different experimental processes containing extraction, purification, separation, and detection have been evaluated respectively to obtain optimized parameters. The developed method was fully validated and the efficient and superior performance of the developed method was demonstrated. The method produced linear results for all sulfonamides from 1 to 10 ng g-1 with a linearity >0.99. The intra-day precision of the method was <8.45% while the inter-day precision was <9.11%. The matrix effect was 77.5% to 105.1%. The recovery was in the range of 72.66% to 116.7% for all sulfonamides. The limit of quantitation in the chicken was 0.6 ng g-1 and the limit of detection was 0.2 ng g-1. Compared with traditional procedures, the automated sample clean-up strategy could significantly shorten the analysis time and offer higher detectability, with the advantage of sufficient sensitivity. Also, the use of gel chromatography column employed the water phase and reduced the organic reagent to achieve the level of green chemistry.

A clinical and molecular analysis of a patient with Emanuel syndrome.

Emanuel syndrome (ES) is the most frequent type of recurrent non­Robertsonian translocation that is characterized by numerous anomalies. Over 100 patients with ES have been described in the literature. The phenotype of this syndrome varies but often consists of facial dysmorphism, microcephaly, severe intellectual disability, developmental retardation, congenital heart disease and genital anomalies. The present study describes a 2­year­old boy with multiple malformations, including facial dysmorphism, severe intellectual disability, growth retardation, congenital heart disease, cleft lip and palate, genital malformation (micropenis), amblyopia, thymic dysplasia and hearing impairment. The karyotype of the patient was 47,XY,+del(22)(q13), and the maternal karyotype was 46,XX,t(11;22)(q25;q13),9qh­,15p+. Single­nucleotide polymorphism­array analysis of the proband indicated a partial duplication of chromosomes 22 and 11 at 22q11.1­q11.21 and 11q23.3­q25, respectively, which confirmed the diagnosis of ES. To date, no cases of ES have been reported in mainland China. The present case further emphasizes the necessity and importance of high­resolution techniques for genetic diagnosis and for subsequent genetic counseling. The present study contributed to the phenotypic delineation of ES and confirmed the first ES patient in mainland China.

Acrylamide in thermal-processed carbohydrate-rich foods from Chinese market.

Acrylamide content in food market in China was determined with the goal to evaluate related health concern. In this survey, products of rice, potato corn, wheat as well as dried fruit slices and instant foods were analysed. All these types of thermal-processed carbohydrate-rich foods were frequently consumed in China. They were purchased from markets in Zhejiang province and analysed using a liquid chromatography tandem/mass spectrometry method. Acrylamide was detected in 94.3% of 105 investigated samples, ranging from 10 to 3649 µg/kg with an average value of 231 µg/kg and a median of 114 µg/kg. In this study, high levels were found in potato products (564 ± 285 µg/kg), corn products (524 ± 187 µg/kg) and instant foods (180 ± 35 µg/kg) while low levels were measured in rice products (82 ± 17 µg/kg), wheat products (96 ± 29 µg/kg) and dried fruit slices (83 ± 13 µg/kg).