The prevalence and its associated factors of psychological stress among middle school students in China: pooled evidence from a systematic scoping review.

Psychological issues are of significant concern in present-day society, as poor mental well-being results in depression and suicidal behavior. Understanding the current situation of psychological stress among secondary school students will help policy makers to formulate targeted measures to help them cope with stress, and at the same time evaluate the effectiveness of the existing policies to address the shortcomings and enhance the diversification of interventions. The main purpose of this review was to map the existing evidence on the prevalence and levels of psychological stress among adolescents in China, and to identify the associated risk factors. This review strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was performed spanning Web of Science, PubMed, and Scopus databases. Studies involving only humans and full text in English were selected. Selection was limited to samples from mainland China, Hong Kong, Macau, and Taiwan. Variables were extracted, exploring the factors that affected the mental wellness of Chinese middle school students. A final 15 articles and 1 report were included. The findings revealed psychological stress is prevalent among Chinese middle school population, with the degree of prevalence from low to severe stress levels. Three dimensions of psychological stress affecting Chinese secondary school students: school, family and lifestyle. Within the school, the factors included academic stress, peer relationships etc. Family-related factors were comprised of parent-child relationship, parents' mental health status etc. Lastly, lifestyle-related factors included poor diet, sedentary and inactivity etc. Our findings suggest that policy makers should reduce the excessive emphasis on examination results and focus on the all-round development of students, and that schools should organize a variety of extra-curricular activities to reduce students' stress. Parents should create a harmonious family atmosphere to minimize conflicts and maintain close communication with teachers. Systematic Review Registration: OSF; https://doi.org/10.17605/OSF.IO/HEFCP.

Discrimination between benign and malignant lung lesions using volumetric quantitative dynamic contrast-enhanced MRI.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is considered a promising method in lung lesion assessment. METHODS: Sixty-four patients with single pulmonary lesions (SPLs) received DCE-MRI at 3.0 T. Of them, 49 cases were diagnosed with lung cancer, and 15 with benign pulmonary nodules (8 inflammatory nodules, 5 tuberculosis, and 2 abscesses). SPLs were quantitatively analyzed to determine the pulmonary lesions-related perfusion parameters, including reflux constant (Kep), volume transfer constant (Ktrans), the maximum slope of increase (MaxSlope), extravascular extracellular space volume fraction (Ve), apparent diffusion coefficient (ADC), the initial area in the signal intensity-time curve (IAUGC), and contrast-enhancement ratio (CER). In addition, a Student's t-test was conducted to calculate statistical significance regarding the quantitatively analyzed perfusion parameters in benign SPLs compared to malignant SPLs. The area under (AUC) the receiver operating characteristic (ROC) curve was studied to investigate the performance of perfusion parameters in diagnosing lung cancer. RESULTS: Values of Ktrans, Kep, Ve, MaxSlope, and IAUGC increased within malignant nodules relative to benign nodules (Ktrans: 0.21 ±0.08 vs. 0.73 ±0.40, P = 0.0001; Kep: 1.21 ±0.66 vs. 1.83 ±0.90, P = 0.0163; Ve: 0.24 ±0.08 vs. 0.47 ±0.18, P < 0.0001; MaxSlope: 0.09 ±0.14 vs. 0.28 ±0.29, P = 0.0166; IAUGC: 0.18 ±0.09 vs. 0.55 ±0.34, P = 0.0001). Meanwhile, malignant nodules presented higher ADC than benign nodules (0.0016 ±0.0006 vs. 0.0012 ±0.0003, P = 0.0019). Ktrans and IAUGC showed the best diagnostic performance with AUCs [1.0, 95%CI (0.99-1.0); 0.93, 95%CI(0.85-1.0), respectively]. CONCLUSION: Malignant pulmonary lesions had higher values of Ktrans, Ve, Kep, MaxSlope, and IAUGC compared to benign pulmonary lesions. Overall, perfusion parameters of DCE-MRI facilitate discrimination between benign from malignant pulmonary nodules.

Pelvic floor muscle exercises alleviate symptoms and improve mental health and rectal function in patients with low anterior resection syndrome.

Background: Pelvic floor rehabilitation has been reported to be effective in improving fecal incontinence. The aim of this study was to prospectively evaluate the effectiveness of combined pelvic floor muscle exercises (PFMEs) and loperamide treatment on rectal function and mental health for low anterior resection syndrome (LARS) patients after sphincter-saving operation (SSO) for rectal cancer. Methods: A total of 60 inpatients diagnosed with LARS were enrolled and randomly assigned to one of two groups: patients in Group A (n = 30) were treated with a PFME intervention and those in Group B (n = 30) with a control intervention for 4 weeks. High-resolution anorectal manometry (HRAM) was performed for all LARS patients. Demographic information was collected for all patients, and they subsequently also completed several questionnaires, including the Hospital Anxiety and Depression Scale (HADS), a measure of Wexner score, a measure of stool frequency per day, and the Bristol Stool Form Scale (BSFS). Results: No significant differences between the groups were observed in baseline data. With regard to rectal function, we found significant improvements at week 4 in maximal resting pressure (MRP) (39.93 ± 5.02 vs. 28.70 ± 5.40 mmH2O, p < 0.001) and maximal squeeze pressure (MSP) (132.43 ± 8.16 mmH2O vs. 113.33 ± 9.87 mmH2O, p < 0.001) among Group A patients compared to Group B patients. Additionally, Wexner scores were significantly lower in Group A than in Group B at week 4 (8.10 ± 1.24 vs. 9.87 ± 1.29 ml, p = 0.018), as were stool frequency (6.47 ± 0.90 vs. 7.83 ± 0.93, p < 0.001) and BSFS scores (5.17 ± 0.65 vs. 6.10 ± 0.80, p = 0.020). Notably, HADS scores were also significantly lower in Group A than in Group B at week 4 (8.25 ± 2.36 vs. 10.48 ± 3.01, p < 0.001). Additionally, both anxiety scores (4.16 ± 1.38 vs. 5.33 ± 1.69, p < 0.001) and depression scores (4.09 ± 1.56 vs. 5.15 ± 1.89, p < 0.001) were significantly lower in Group A than in Group B at week 4. Conclusion: Pelvic floor muscle exercises are an effective treatment that can alleviate symptoms and improve rectal function and mental health in patients with low anterior resection syndrome.

Efficacy of mandibular molar distalization by clear aligner treatment. / æ— æ‰˜æ§½éšå½¢çŸ«æ²»å™¨è¿œç§»ä¸‹é¢Œç£¨ç‰™çš„ç–—æ•ˆ.

OBJECTIVES: At present, the research on clear aligner of molar distalization mainly focuses on the upper jaw, while the research on mandibular molars is few.This study aims to evaluate the therapeutic effect of mandibular molars distalization with clear aligner via cone beam CT (CBCT) and Dolphin software. METHODS: Twenty cases of mandibular molars with clear aligner were included according to the inclusion and exclusion criteria. CBCT was taken before treatment (T0) and when the first molar was moved in place (T1). Dolphin software was used to measure the effectiveness of molar distalization. Three-dimensional changes in direction and the impact on the incisors and facial soft and hard tissues were evaluated. RESULTS: The effective rates of crown and root distalization of the second and first mandibular molars were 74%, 49%, and 71%, 47%, respectively. The second and first molars were both the distal buccal cusp with the largest distalization [(2.15 ± 0.91) mm and (1.85±1.09) mm], respectively, with significant difference between the T0 and T1 (P<0.05). The second and first molars were accompanied by depression, distal tilt, and buccal tilt with 1.06 mm, 2.10°, 2.27°, and 0.91 mm, 1.62°, and 1.91°, respectively, with significant differences between the T0 and T1 (all P<0.05). There was no obvious difference between men and women. The mandibular central incisor showed a lip-side movement of 1.02 mm, a depression of 0.82 mm, a mesial incline of 0.66°, and a crown-lip torque of 1.51° after molar distalization, with significant differences between the T0 and T1 (all P<0.001). Only the lower lip thickness increased by 0.1 cm, the length of the lower lip increased by 0.1 cm, and the ANS-ME (distance from anterior nasal spine to submental point) decreased by 0.13 cm, with significant differences between the T0 and T1 (all P<0.05). CONCLUSIONS: Clear aligner can effectively move mandibular molars farther, the crown is more effective than the root, and it is tilted. The second mandibular molar is more effective than the first mandibular molar in its distant displacement and three-dimensional changes. Molar distalization causes minor changes in mandibular incisors and facial soft and hard tissues.

Minor allele of rs55763075 located in MTHFR is associated with the risk of cognitive impairment after anesthesia via modulating miR-34b.

This study aimed to investigate the association between cognitive impairment after general anesthesia and rs55763075 polymorphisms. We enrolled and grouped patients undergoing general anesthesia according to their genotypes of rs55763075 polymorphism. Mini-Mental State Examination (MMSE) scoring was performed to evaluate the cognitive status of patients. Quantitative real-time PCR was carried out to analyze the expression of methylenetetrahydrofolate reductase (MTHFR) mRNA and miR-34b while Western blot was performed to evaluate the expression of MTHFR protein. Furthermore, we studied the effect of rs55763075 polymorphism on the expression of MEHFR via luciferase assay. Accordingly, we found that the MMSE score in GG/GA groups was significantly higher than that in AA group. And a significant reduction of MTHFR mRNA expression was observed in the serum and peripheral blood mononuclear cells (PBMCs) of patients carrying AA genotype compared with the patients carrying GG/GA genotypes. Moreover, the MTHFR expression was much lower in the cultured AA-genotyped cells transfected with miR-34b. Luciferase assay results also showed that miR-34b transfection reduced luciferase activity in the cells carrying A allele but not in cells carrying G allele. In summary, the data of this study showed that minor allele (A) of rs55763075 polymorphisms in the 3'-untranslated region of MTHFR mRNA generated a potential binding site for miR-34b, which led to reduced level of folic acid in the patients carrying the AA genotype. Furthermore, we found that the MMSE score of AA-genotyped patients was lower than that of patients carrying GG/GA genotypes.

UGT1A1 rs4148323 A Allele is Associated With Increased 2-Hydroxy Atorvastatin Formation and Higher Death Risk in Chinese Patients With Coronary Artery Disease.

It is widely accepted that genetic polymorphisms impact atorvastatin (ATV) metabolism, clinical efficacy, and adverse events. The objectives of this study were to identify novel genetic variants influencing ATV metabolism and outcomes in Chinese patients with coronary artery disease (CAD). A total of 1079 CAD patients were enrolled and followed for 5 years. DNA from the blood and human liver tissue samples were genotyped using either Global Screening Array-24 v1.0 BeadChip or HumanOmniZhongHua-8 BeadChip. Concentrations of ATV and its metabolites in plasma and liver samples were determined using a verified ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method. The patients carrying A allele for the rs4148323 polymorphism (UGT1A1) showed an increase in 2-hydroxy ATV/ATV ratio (p = 1.69E-07, false discovery rate [FDR] = 8.66E-03) relative to the value in individuals without the variant allele. The result was further validated by an independent cohort comprising an additional 222 CAD patients (p = 1.08E-07). Moreover, the rs4148323 A allele was associated with an increased risk of death (hazard ratio [HR] 1.774; 95% confidence interval [CI], 1.031-3.052; p = 0.0198). In conclusion, our results suggested that the UGT1A1 rs4148323 A allele was associated with increased 2-hydroxy ATV formation and was a significant death risk factor in Chinese patients with CAD.

Chiral fermion reversal in chiral crystals.

In materials chiral fermions such as Weyl fermions are characterized by nonzero chiral charges, which are singular points of Berry curvature in momentum space. Recently, new types of chiral fermions beyond Weyl fermions have been discovered in structurally chiral crystals CoSi, RhSi and PtAl. Here, we have synthesized RhSn single crystals, which have opposite structural chirality to the CoSi crystals we previously studied. Using angle-resolved photoemission spectroscopy, we show that the bulk electronic structures of RhSn are consistent with the band calculations and observe evident surface Fermi arcs and helical surface bands, confirming the existence of chiral fermions in RhSn. It is noteworthy that the helical surface bands of the RhSn and CoSi crystals have opposite handedness, meaning that the chiral fermions are reversed in the crystals of opposite structural chirality. Our discovery establishes a direct connection between chiral fermions in momentum space and chiral lattices in real space.

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy.

MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.

Preparation of Micro/Nano-Structure Copper-Substituted Hydroxyapatite Scaffolds with Improved Angiogenesis Capacity for Bone Regeneration.

The surface microstructures of calcium phosphate ceramics play an essential role in determining bone regeneration. However, it is difficult to produce micro/nano-structures on the surface of the porous hydroxyapatite (HA) scaffolds. In this study, we successfully developed and fabricated various micro/nano-structured surfaces on the HA scaffolds in copper ion (Cu2+)-containing solutions under hydrothermal conditions. The micro/nano-structures on the surface of the HA scaffolds were controlled by modulating the Cu2+ concentrations during the hydrothermal process. With an increase in the Cu2+ concentration, the surface morphology of the HA scaffolds changed significantly from sphere-like to flower-like, before becoming nano-structures. These findings indicated that the Cu2+ concentration affects the morphologies of calcium phosphate coatings that grow on the HA scaffolds. In vitro endothelial cell (EC) cultures showed that the cell proliferation was significantly enhanced when cultured on the flower-like morphology compared with other morphologies. Furthermore, an in vivo test in New Zealand rabbits demonstrated that the HA scaffold with the flower-like surface resulted in more angiogenesis compared with the control scaffold. This copper-assisted hydrothermal deposition process provides a simple and controllable route for engineering a micro/nano-structured surface on the HA scaffolds, which has benefits in terms of angiogenesis and bone regeneration.

Activation of M1 macrophages in sepsis-induced acute kidney injury in response to heparin-binding protein.

BACKGROUND: In the early stage of sepsis, M1 macrophages result in the production of inflammatory mediators and AKI. Heparin-binding protein (HBP) have been shown to play important roles in sepsis-induced AKI. In this study, we investigate the association of HBP with M1 macrophages in sepsis-induced AKI. METHODS: Male C57BL6 mice were subjected to cecal ligation and puncture (CLP) or sham surgery. Biochemical and histological renal damage was assessed. Macrophage infiltration was assessed by immunohistochemistry. RT-PCR was used to investigate the expression of heparin-binding protein (HBP), the inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) mRNAs. Western blots were performed to assay the tissue levels of HBP, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). RESULTS: High levels of HBP were obviously detected 24 h after sepsis-induced AKI. Heparin inhibited HBP expression during sepsis-induced AKI. The suppression of HBP expression by heparin injection after the establishment of sepsis-induced AKI resulted in a reduction in renal injury severity accompanied with a significant repression of M1 macrophage activation and expression of TNF-α and IL-6. CONCLUSIONS: HBP plays an important role in the initial inflammatory reaction associated with sepsis-induced AKI, presumably by activating M1 macrophages and suppressing TNF-α and IL-6 secretion.

Significant alterations of 6-keto prostaglandin F1a and NO levels in spermatic vein plexus patients with varicocele.

To investigate the level variation of correlative factors between the spermatic vein plexus and peripheral blood in patients with varicocele, a total of 22 patients diagnosed with varicocele were enrolled in the study. All patients were performed a testicular artery-sparing microsurgical varicocelectomy. During the operation, a blood sample from the left spermatic vein plexus and a peripheral blood sample were collected. A radioimmunoassay was used to determine the 6-keto prostaglandin F1a (6-keto-PGF1a ). A colorimetric method was performed to determine the NO. The enzyme immunoassay method was used to determine the creatinine, urea nitrogen, adrenaline, noradrenaline, dopamine and 5-HT. The mean age of all patients was 29.3 ± 7.8 years. Compared with the level of 6-keto-PGF1a and NO in the peripheral blood, 6-keto-PGF1a and NO were significantly increased in left spermatic vein plexus (347.3 (230.8-415.1) versus 99.7 (80.4-119.9) pg/ml and 192.3 ± 178.5 versus 107.1 ± 73.6 µmol/L, p < .05). There were no differences in the level of creatinine, urea nitrogen, adrenaline, noradrenaline, dopamine and 5-HT between the peripheral blood and left spermatic vein plexus (p > .05). The 6-keto-PGF1a and NO concentrations in left spermatic vein plexus were significantly higher than that in peripheral blood patients with varicocele.

Effects of PON1 Gene Promoter DNA Methylation and Genetic Variations on the Clinical Outcomes of Dual Antiplatelet Therapy for Patients Undergoing Percutaneous Coronary Intervention.

INTRODUCTION AND OBJECTIVE: The relationship between either paraoxonase 1 (PON1) gene promoter DNA methylation or genetic variations and bleeding or major adverse cardiac events after dual antiplatelet therapy has been incompletely characterized. We aimed to systematically investigate the role of genetic variations and DNA methylation of the PON1 CpG island promoter on the clinical outcomes of dual antiplatelet therapy for patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). METHODS: This study included 653 patients with CAD undergoing PCI and receiving dual antiplatelet therapy. Genomic DNAs were isolated from whole blood and were genotyped for the three single nucleotide polymorphisms (SNPs) of the PON1 gene. The DNA methylation levels in the PON1 promoter region were determined by bisulfite sequencing or pyrosequencing at five CpG sites (positions -142, -161, -163, -170, and -184 from the transcription start site). Clopidogrel and its metabolites in plasma were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and platelet function analysis was performed using the VerifyNow assay. RESULTS: Statistically significant associations between methylation levels at five PON1 CpG sites and bleeding were observed: -184 [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.96-1.00, p = 0.028]; -170 (OR 0.99, 95% CI 0.97-1.00, p = 0.048); -163 (OR 0.98, 95% CI 0.96-1.00, p = 0.029); -161 (OR 0.98, 95% CI 0.97-1.00, p = 0.026); and -142 (OR 0.98, 95% CI 0.97-1.00, p = 0.042) at a false discovery rate of <5%. Statistical analysis also revealed that aspirin reaction units (ARUs) were significantly associated with PON1 methylation level at CpG site -163 (p = 0.0342). The ARUs of patients with the PON1 126 CC genotype was 527 ± 94, which was higher than the ARUs (473 ± 89) of patients with the 126 CG genotype (p = 0.0163). Multivariate logistic regression analysis indicated that the PON1 methylation level at CpG site -161 (OR 0.95, 95% CI 0.92-0.98, p = 0.002) and the use of angiotensin-converting enzyme inhibitors (OR 0.48, 95% CI 0.26-0.89, p = 0.021) were associated with a decreased risk of bleeding events. CONCLUSIONS: Hypomethylation of CpGs in the PON1 promoter may be a weak, albeit statistically significant, risk factor of bleeding after dual antiplatelet therapy. Further large-scale studies are needed to verify our results.

Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis.

BACKGROUND: The aim of this study was to determine whether neutrophil CD64 (nCD64) combined with procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) can increase the sensitivity and accuracy of neonatal sepsis diagnosis. METHODS: The serum levels of nCD64, CRP, PCT and WBC were detected in 60 patients with neonatal sepsis and 60 patients with non-sepsis. Sensitivity, specificity, positive and negative predictive values, receiver operating characteristic (ROC) area under the curve (AUC), and logistic regression analysis were performed to evaluate the diagnostic value of these markers on neonatal sepsis. RESULTS: Serum levels of nCD64, PCT, CRP and WBC were higher in the sepsis group than non-sepsis group (p<0.001). The sensitivities of nCD64, PCT, CRP and WBC at the recommended cut-off level for all infants were 79.5%, 68.2%, 38.6% and 52.3%, respectively. The best combination was nCD64 and PCT, which obtained sensitivity of 90.9%, largest AUC of 0.922, and a negative predictive value of 89.2%. However by using an optimal cut-off value, the sensitivities of all four biomarkers for the diagnosis of neonatal sepsis were increased to 95.5%. Except for WBC, the birth weight and gestational age had no effects on the diagnostic value of these serum biomarkers. CONCLUSIONS: nCD64 and PCT are better diagnostic biomarkers for early diagnosis of neonatal sepsis as compared to CRP. With the help of optimal cut-off value based on ROC curve and logistic regression analysis, the combination of these biomarkers could improve the sensitivity for the diagnosis of suspected late-onset neonatal sepsis based on common serum biomarkers.

CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer.

BACKGROUND/AIMS: To determine whether the combination of tumor markers (CA72-4, CA125, CA19-9 and CEA) could increase the sensitivity and accuracy for in the diagnosis of gastric cancer (GC). METHODS: This study is a retrospective analysis. A total of 426 patients, including 106 patients with GC, 149 patients with benign gastric diseases and 171 healthy people, who visited Zhejiang Xiaoshan Hospital from January 2011 to December 2013, were measured by serum markers, including CA72-4, CA125, CA19-9 and CEA. Statistical analyses including area under curve (AUC) of receiver operating characteristic (ROC) curve, and logistic regression analysis, were performed to evaluate the diagnostic value of these markers on GC. RESULTS: Serum levels of CA72-4, CEA, CA125 and CA19-9 were higher in the GC group than those in the benign gastric disease group and the healthy control group (P<0.005). The sensitivities of CA72-4, CEA, CA125 and CA19-9 at the recommended cut-off level for all patients were 33.0%, 25.5%, 31.1% and 38.7%, respectively. However, when all four markers were used in combination the sensitivity increased to 66.0%. But by using an optimal cut-off value, the sensitivities of all four markers for the diagnosis of GC were improved. Especially the sensitivity of CEA increased to 73.6% and the sensitivity of the combination of the tumor markers increased to 75.5%. The age and gender had no effects on the diagnostic value of these markers. CONCLUSIONS: With the help of optimal cut-off values based on ROC curve and logistic regression analysis, the combination of these markers could improve the sensitivity for the diagnosis of GC based on common serum tumor markers.

Schisantherin A protects lipopolysaccharide-induced acute respiratory distress syndrome in mice through inhibiting NF-κB and MAPKs signaling pathways.

Acute respiratory distress syndrome (ARDS) is characterized by polymorphonuclear neutrophils (PMNs) adhesion, activation, sequestration and inflammatory damage to alveolar-capillary membrane. Schisantherin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been reported to have anti-inflammatory properties. In the present study, we aimed to investigate the protective effects of schisantherin A on LPS-induced mouse ARDS. The pulmonary injury severity was evaluated 7 h after LPS administration and the protective effects of schisantherin A on LPS-induced mouse ARDS were assayed by enzyme-linked immunosorbent assay and Western blot. The results revealed that the wet/dry weight ratio, myeloperoxidase activity, and the number of total cells, neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) were significantly reduced by schisantherin A in a dose-dependent manner. Meanwhile, pretreatment with schisantherin A markedly ameliorated LPS-induced histopathologic changes and decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in the BALF. In addition, the phosphorylation of nuclear transcription factor-kappaB (NF-κB) p65, inhibitory kappa B alpha (IκB-α), c-jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 induced by LPS were suppressed by schisantherin A. These findings indicated that schisantherin A exerted potent anti-inflammatory properties in LPS-induced mouse ARDS, possibly through blocking the activation of NF-KB and mitogen activated protein kinases (MAPKs) signaling pathways. Therefore, schisantherin A may be a potential agent for the prophylaxis of ARDS.

High levels of glucose induce "metabolic memory" in cardiomyocyte via epigenetic histone H3 lysine 9 methylation.

Diabetic patients continue to develop inflammation and cardiovascular complication even after achieving glycemic control, suggesting a "metabolic memory". Metabolic memory is a major challenge in the treatment of diabetic complication, and the mechanisms underlying metabolic memory are not clear. Recent studies suggest a link between chromatin histone methylation and metabolic memory. In this study, we tested whether histone 3 lysine-9 tri-methylation (H3K9me3), a key epigenetic chromatin marker, was involved in high glucose (HG)-induced inflammation and metabolic memory. Incubating cardiomyocyte cells in HG resulted in increased levels of inflammatory cytokine IL-6 mRNA when compared with myocytes incubated in normal culture media, whereas mannitol (osmotic control) has no effect. Chromatin immunoprecipitation (ChIP) assays showed that H3K9me3 levels were significantly decreased at the promoters of IL-6. Immunoblotting demonstrated that protein levels of the H3K9me3 methyltransferase, Suv39h1, were also reduced after HG treatment. HG-induced apoptosis, mitochondrial dysfunction and cytochrome-c release were reversible. However, the effects of HG on the expression of IL-6 and the levels of H3K9me3 were irreversible after the removal of HG from the culture. These results suggest that HG-induced sustained inflammatory phenotype and epigenetic histone modification, rather than HG-induced mitochondrial dysfunction and apoptosis, are main mechanisms responsible for metabolic memory. In conclusion, our data demonstrate that HG increases expression of inflammatory cytokine and decreases the levels of histone-3 methylation at the cytokine promoter, and suggest that modulating histone 3 methylation and inflammatory cytokine expression may be a useful strategy to prevent metabolic memory and cardiomyopathy in diabetic patients.

Association between polymorphisms of the renin-angiotensin system and coronary artery disease in Chinese patients with type 2 diabetes.

BACKGROUND: The renin-angiotensin system (RAS) is regarded as one of the most important regulatory systems for cardiovascular homeostasis. In this study, we investigated associations of the five genetic polymorphisms in the RAS and presence of coronary artery disease (CAD) in type 2 diabetes. METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. We used the generalised multifactor dimensionality reduction (GMDR) method to identify gene-gene interactions. RESULTS: The D allele in the ACE gene was significantly more frequent in type 2 diabetic patients with CAD (p = 0.04). In multivariate logistic regression analysis, the DD genotype was associated with a significantly increased risk of CAD (p = 0.044). 1675G/A variant in the AT2R gene was found to be associated with CAD in female subjects with type 2 diabetes (p = 0.025). The three other polymorphisms of the RAS do not seem to influence the development of CAD in type 2 diabetes. No significant gene-gene interaction for any combinations of genotypes was found in the GMDR method. CONCLUSION: The DD variant of the ACE gene polymorphism is associated with increased risk of developing CAD in Chinese patients with type 2 diabetes. A slight impact of AT2R 1675G/A polymorphism on CAD was found only in female diabetic patients.

Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers.

AIMS: To assess the effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. METHODS: Fourteen healthy male volunteers (age range 19-25 years) received orally administered bupropion (150 mg) alone and during treatment with G. biloba 240 mg day(-1) (two 60-mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6-catalysed metabolite, hydroxybupropion. RESULTS: Ginkgo biloba extract administration resulted in no significant effects on the AUC(0-infinity) of bupropion and hydroxybupropion. Bupropion mean AUC(0-infinity) value was 1.4 microg.h ml(-1)[95% confidence interval (CI) 1.2, 1.6] prior to G. biloba treatment and 1.2 microg.h ml(-1) (95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC(0-infinity) value was 8.2 microg.h ml(-1) (95% CI 6.5, 10.4) before G. biloba administration and 8.7 microg.h ml(-1) (95% CI 7.1, 10.6) after treatment. The C(max) of hydroxybupropion increased from 221.8 ng ml(-1) (95% CI 176.6, 278.6) to 272.7 ng ml(-1) (95% CI 215.0, 345.8) (P = 0.038) and the t(1/2) of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000). CONCLUSIONS: Ginkgo biloba extract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. Although G. biloba extract treatment appears to reduce significantly the t(1/2) and increase the C(max) of hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally with G. biloba extract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion.

Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers.

BACKGROUND: Ginkgo biloba extract (GBE), the best selling herbal medicine in the world, has been reported to inhibit P-glycoprotein in vitro. However, the effects of GBE on P-glycoprotein activity in humans have not been clarified. OBJECTIVE: To investigate the effects of single and repeated GBE ingestion on the oral pharmacokinetics of talinolol, a substrate drug for P-glycoprotein in humans. METHODS: Ten unrelated healthy male volunteers were selected to participate in a 3-stage sequential study. Plasma concentrations of talinolol from 0 to 24 hours were measured by high-performance liquid chromatography after talinolol 100 mg was administrated alone, with a single oral dose of GBE (120 mg), and after 14 days of repeated GBE ingestion (360 mg/day). RESULTS: A single oral dose of GBE did not affect the pharmacokinetics of talinolol. Repeated ingestion of GBE increased the talinolol maximum plasma concentration (C(max)) by 36% (90% CI 10 to 68; p = 0.025), the area under the concentration-time curve (AUC)(0-24) by 26% (90% CI 11 to 43; p = 0.008) and AUC(0-infinity) by 22% (90% CI 8 to 37; p = 0.014), respectively, without significant changes in elimination half-life and the time to C(max). CONCLUSIONS: Our results suggest that long-term use of GBE significantly influenced talinolol disposition in humans, likely by affecting the activity of P-glycoprotein and/or other drug transporters.