Discrimination and screening of volatile metabolites in atractylodis rhizoma from different varieties using headspace solid-phase microextraction-gas chromatography-mass spectrometry and headspace gas chromatography-ion mobility spectrometry, and ultra-fast gas chromatography electronic nose.

Atractylodis rhizoma is a common bulk medicinal material with multiple species. Although different varieties of atractylodis rhizoma exhibit variations in their chemical constituents and pharmacological activities, they have not been adequately distinguished due to their similar morphological features. Hence, the purpose of this research is to analyze and characterize the volatile organic compounds (VOCs) in samples of atractylodis rhizoma using multiple techniques and to identify the key differential VOCs among different varieties of atractylodis rhizoma for effective discrimination. The identification of VOCs was carried out using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), resulting in the identification of 60 and 53 VOCs, respectively. The orthogonal partial least squares discriminant analysis (OPLS-DA) model was employed to screen potential biomarkers and based on the variable importance in projection (VIP ≥ 1.2), 24 VOCs were identified as critical differential compounds. Random forest (RF), K-nearest neighbor (KNN) and back propagation neural network based on genetic algorithm (GA-BPNN) models based on potential volatile markers realized the greater than 90 % discriminant accuracies, which indicates that the obtained key differential VOCs are reliable. At the same time, the aroma characteristics of atractylodis rhizoma were also analyzed by ultra-fast gas chromatography electronic nose (Ultra-fast GC E-nose). This study indicated that the integration of HS-SPME-GC-MS, HS-GC-IMS and ultra-fast GC E-nose with chemometrics can comprehensively reflect the differences of VOCs in atractylodis rhizoma samples from different varieties, which will be a prospective tool for variety discrimination of atractylodis rhizoma.

Effects of thumb-tack needling combined with sporting on older adult patients with knee osteoarthritis: A randomized active-control clinical trial.

AIM: The aim of this clinical study was to explore the effects of thumb-tack needling combined with sporting (TTNS) therapy on the improvement of pain and joint function in older adult patients with knee osteoarthritis (KOA). METHODS: A total of 120 older adult patients with KOA were randomly assigned to receive TTNS therapy or medicine treatment (Med group) only for 1 month. The patients were followed up for 3 months and clinical efficacies were evaluated using a visual analog scale to assess pain, the Lequesne scoring system to assess motor function, and the Western Ontario and McMaster University Osteoarthritis Index to assess KOA severity. Blood was collected to measure the levels of interleukin-6 and tumor necrotic factor-alpha using enzyme-linked immunosorbent assay. RESULTS: The data suggested that TTNS therapy resulted in a significantly higher clinical efficacy (P = 0.012). Visual analog scale score, Lequesne index, and Western Ontario and McMaster University Osteoarthritis Index of the TTNS group at the time of post-treatment (1 month) and post-follow-up (3 months) were also lower compared with the Med group. Patients in the TTNS group also showed lower levels of serum tumor necrotic factor-alpha and interleukin-6. CONCLUSIONS: TTNS therapy is more efficacious than pharmacological treatment in improving the clinical outcomes of patients with KOA, which suggests its clinical utility in the management of KOA. Geriatr Gerontol Int 2024; 24: 415-420.

Modulation of oxidized low-density lipoprotein-affected macrophage efferocytosis by mitochondrial calcium uniporter in a murine model.

OBJECTIVE: Efferocytosis dysfunction contributes to the progression and rupture of atherosclerotic plaques. Efferocytosis is crucially modulated by intracytoplasmic Ca2+, and mitochondrial calcium uniporter (MCU) complex proteins serve as key channels for regulating Ca2+ concentration. Therefore, it was speculated that MCU may affect the development of atherosclerosis (AS) by regulating efferocytosis. In the present study, we aimed to investigate whether MCU could affect foam cell formation by regulating efferocytosis. METHODS: We stimulated primary macrophages (Møs) using oxidized low-density lipoprotein (ox-LDL) to mimic the atherosclerotic microenvironment and treated them with Ru360, an MCU-specific inhibitor, and UNC1062, an inhibitor of efferocytosis. Additionally, we conducted double staining to determine the Mø efferocytosis rate. We measured the expression of MCU complexes and efferocytosis-associated proteins using western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, we separately detected the Ca2+ level in the cytoplasm and mitochondria (MT) using Fluo-4 AM and Rhod-2 methods. We separately determined the reactive oxygen species (ROS) level in cytoplasm and MT using dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probing method and Mito-SOXTM superoxide indicator staining. Additionally, we conducted the enzyme-linked immunosorbent assay (ELISA) to detect the production of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Oil Red O staining was performed to measure cytoplasmic lipid levels. RESULTS: Ru360 attenuated ox-LDL-induced efferocytosis dysfunction, and attenuated the upregulation of MCU and MCUR1 induced by ox-LDL, and meanwhile attenuated the downregulation of MCUb induced by ox-LDL. Ru360 attenuated the decrease of intracytoplasmic Ca2+ concentration induced by ox- LDL, Ru360 also attenuated the ROS production induced by ox- LDL, attenuated the release of IL-6, IL-18, IL-1ß, and TNF-α induced by ox- LDL, and attenuated the increase of intracytoplasmic lipid content induced by ox-LDL. UNC1062 attenuated the effects of Ru360 in reducing inflammatory cytokines and intracytoplasmic lipid content. CONCLUSIONS: In this study, we found that MCU inhibition modulated intracytoplasmic Ca2+ concentration, improved impaired Mø efferocytosis, and reduced ROS generation. Macrophage efferocytosis removed apoptotic cells and prevented the release of inflammatory factor and foam cell formation, and this can be a potential new therapeutic target for alleviating atherosclerosis.

Ability of artificial intelligence to identify self-reported race in chest x-ray using pixel intensity counts.

Purpose: Prior studies show convolutional neural networks predicting self-reported race using x-rays of chest, hand and spine, chest computed tomography, and mammogram. We seek an understanding of the mechanism that reveals race within x-ray images, investigating the possibility that race is not predicted using the physical structure in x-ray images but is embedded in the grayscale pixel intensities. Approach: Retrospective full year 2021, 298,827 AP/PA chest x-ray images from 3 academic health centers across the United States and MIMIC-CXR, labeled by self-reported race, were used in this study. The image structure is removed by summing the number of each grayscale value and scaling to percent per image (PPI). The resulting data are tested using multivariate analysis of variance (MANOVA) with Bonferroni multiple-comparison adjustment and class-balanced MANOVA. Machine learning (ML) feed-forward networks (FFN) and decision trees were built to predict race (binary Black or White and binary Black or other) using only grayscale value counts. Stratified analysis by body mass index, age, sex, gender, patient type, make/model of scanner, exposure, and kilovoltage peak setting was run to study the impact of these factors on race prediction following the same methodology. Results: MANOVA rejects the null hypothesis that classes are the same with 95% confidence (F 7.38, P<0.0001) and balanced MANOVA (F 2.02, P<0.0001). The best FFN performance is limited [area under the receiver operating characteristic (AUROC) of 69.18%]. Gradient boosted trees predict self-reported race using grayscale PPI (AUROC 77.24%). Conclusions: Within chest x-rays, pixel intensity value counts alone are statistically significant indicators and enough for ML classification tasks of patient self-reported race.

Substance P prevents doxorubicin­induced cardiomyocyte injury by regulating apoptosis and autophagy: In vitro and in vivo evidence.

The function of substance P (SP) in myocardial ischemia is well understood, but its effects on congestive heart failure are unclear. The present study aimed to use in vitro and in vivo approaches to investigate the effects of SP on doxorubicin­induced cardiomyocyte injury. Pathological changes, apoptosis, cardiomyocyte ultrastructure and molecular mechanisms were evaluated in vitro and in vivo. The effects of SP on cell viability of H9c2 myocardial cells were evaluated using the Cell Counting Kit­8 and flow cytometry. B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein (Bax), Beclin­1 and microtubule­associated protein 1A/1B­light chain 3 (LC3) were detected by western blotting. Heart failure in rats was established by intraperitoneal injection of doxorubicin. The in vitro data demonstrated that SP at concentrations of 1 µg/ml inhibited doxorubicin­induced apoptosis of H9c2 cells. Administration of doxorubicin reduced Bcl­2, Beclin­1 and LC3 expression levels in H9c2 cells, while having no effect on Bax levels. Administration of SP to these doxorubicin­treated cells did not affect Bcl­2 or Bax expression, but further reduced Beclin­1 while inhibiting the reduction in LC3 expression. In vivo, food intake was significantly increased in rats in the SP group compared with the model group. Cardiomyocytes in the heart­failure group underwent dysfunctional autophagy as ascertained by transmission electron microscopy. Compared with the heart­failure group, these pathological changes, including loss of striations and vacuolation, were inhibited by SP treatment, which promoted Bax expression, reduced Beclin­1 expression and inhibited the reduction in LC3 expression. Taken together, SP reduced cardiomyocyte apoptosis in doxorubicin­induced cardiomyocyte injury, likely by promoting autophagy, which suggested that SP is a potential therapeutic target for doxorubicin­induced heart failure.

miR-520c-3p regulates IL-1ß-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GAS2.

BACKGROUND: MicroRNAs (miRNAs) have been shown to be associated with osteoarthritis (OA) progression. This study aimed to explore the role of miR-520c-3p in OA progression. METHODS: Expression levels of miR-520c-3p and Growth arrest-specific 2 (GAS2) were detected using quantitative real-time PCR. The proliferation and apoptosis of cells were measured using cell counting kit 8 (CCK8) assay and flow cytometry. Furthermore, the protein levels of apoptosis-related markers, extracellular degradation markers, inflammatory response markers, and GAS2 were tested using quantitative real-time polymerase chain reaction (RT-PCR) and western blot (WB) analysis. In addition, the interaction between miR-520c-3p and GAS2 was examined using dual luciferase reporter assay. RESULTS: GAS2 was highly expressed, and miR-520c-3p was lowly expressed in OA cartilage tissues. miR-520c-3p could promote the proliferation and inhibit the apoptosis and inflammation of OA chondrocytes. miR-520c-3p could be sponged by GAS2, and its inhibitor could reverse the regulation of GAS2 on the biological functions of OA chondrocytes. GAS2 was a target of miR-520c-3p, which was identified by bioinformatic analysis and dual-luciferase reporter assay. Overexpression of GAS2 could inhibit the proliferation and promoted the apoptosis and inflammation of OA chondrocytes. CONCLUSION: Our data showed that miR-520c-3p might regulate the GAS2 to inhibit the progression of OA.

Intramuscular accumulation of pentadecanoic acid activates AKT1 to phosphorylate NCOR1 and triggers FOXM1-mediated apoptosis in the pathogenesis of sarcopenia.

Sarcopenia is an age-associated disorder that results in skeletal muscle loss. Apoptosis and inflammation are the two major contributors to sarcopenia. Emerging evidence has shown that long-chain fatty acids (LCFAs) are implicated in the muscles of sarcopenic animal models. However, it is unknown whether LCFAs are correlated with apoptosis or inflammation in the pathogenesis of sarcopenia. Herein, we found that pentadecanoic acid (PDA), a C15 LCFA, was significantly accumulated in human sarcopenic muscles. In vitro PDA treatment could dose-dependently induce the expression of the transcription factor FOXM1 (forkhead box M1) and several proapoptotic genes, such as PUMA (p53-upregulated modulator of apoptosis), BAX (B-cell/lymphoma 2-associated X) and APAF1 (apoptotic peptidase activating factor 1), thereby causing apoptosis. Mechanically, PDA activated AKT1 (AKT serine/threonine kinase 1) to phosphorylate NCOR1 (nuclear receptor corepressor 1). The phosphorylated NCOR1 disassociated from the NCOR1-FOXM1 transcriptional complex and could not repress FOXM1-mediated transcription, leading to the induction of PUMA. The activated PUMA further triggered downstream apoptotic signaling, including activation of the BAX, APAF1 and caspase cascades, leading to the occurrence of apoptosis. Alkaline phosphatase or knockdown of AKT1 in vitro reversed the FOXM1-mediated apoptotic signaling. Collectively, our results provide new evidence that LCFAs are involved in the pathogenesis of sarcopenia by activating apoptotic signaling. Attempts to decrease the intake of PDA-containing foods or blocking AKT1 may improve the symptoms of sarcopenia.

Risk-Adapted Cutoffs in Colorectal Cancer Screening by Fecal Immunochemical Tests.

INTRODUCTION: Fecal immunochemical tests (FITs) for hemoglobin are increasingly used in colorectal cancer (CRC) screening. The use of uniform positivity thresholds (cutoffs) within screening populations is expected to imply lower positive predictive values (PPVs) and higher numbers of colonoscopies needed (numbers needed to scope [NNSs]) to detect advanced neoplasms among screening participants at lower risk compared with those at higher risk. We aimed to assess such variation and its potential implications in a large screening cohort. METHODS: A quantitative FIT (FOB Gold; Sentinel Diagnostics, Milan, Italy) was conducted in fecal samples collected by 4,332 participants of screening colonoscopy before bowel preparation. Participants were classified into 3 risk groups (low, medium, and high) by tertiles of a previously derived risk-factor-based risk score. We determined the variation of PPVs and NNSs for detecting advanced neoplasms (i.e., CRC or advanced adenoma) when using the same FIT cutoffs and variation of FIT cutoffs that would yield uniform PPVs across risk groups. RESULTS: When a fixed FIT cutoff of 10 µg/g was used, the PPV increased from 23.3% to 41.8% from the low- to the high-risk group, with NNS decreasing from 4.3 to 2.4 (P < 0.001). Similar variations of PPVs and NNSs across risk groups were observed at higher FIT cutoffs. When risk group-specific cutoffs were defined to achieve fixed PPVs of 25%, 30%, and 35% across all risk groups, cutoffs varied from 5.3 to 11.4, 6.5 to 18.7, and 7.5 to 31.0 µg hemoglobin/g feces, respectively, between high- and low-risk groups (P < 0.05 for all differences). DISCUSSION: Using risk-adapted cutoffs may help to achieve target levels of PPV and NNS and might be an option to consider for personalized FIT-based CRC screening.

The clinical significance of myeloid-derived suppressor cells in dengue fever patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients. METHODS: This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1-2, 3-4, 5-6, 7-8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis. RESULTS: The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = - 0.317, p < .001), CD8+ T cell number (rho = - 0.361, p < .001), "programmed cell death protein 1" (PD-1) (rho = - 0.347, p < .001), "T cell immunoglobulin domain and mucin domain-3" (Tim3) (rho = - 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and "regulated upon activation normal T-cell expressed and secreted" (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024). CONCLUSIONS: Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.

Outcomes at follow-up of negative colonoscopy in average risk population: systematic review and meta-analysis.

OBJECTIVE: To review and summarise the evidence on the prevalence of colorectal adenomas and cancers at a follow-up screening colonoscopy after negative index colonoscopy, stratified by interval between examinations and by sex. DESIGN: Systematic review and meta-analysis of all available studies. DATA SOURCES: PubMed, Web of Science, and Embase. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings. ELIGIBILITY CRITERIA: Studies assessing the outcome of a follow-up colonoscopy among participants at average risk for colorectal cancer with a negative previous colonoscopy (no adenomas). RESULTS: 28 studies were identified, including 22 cohort studies, five cross sectional studies, and one case-control study. Findings for an interval between colonoscopies of one to five, five to 10, and more than 10 years were reported by 17, 16, and three studies, respectively. Summary estimates of prevalences of any neoplasm were 20.7% (95% confidence interval 15.8% to 25.5%), 23.0% (18.0% to 28.0%), and 21.9% (14.9% to 29.0%) for one to five, five to 10, and more than 10 years between colonoscopies. Corresponding summary estimates of prevalences of any advanced neoplasm were 2.8% (2.0% to 3.7%), 3.2% (2.2% to 4.1%), and 7.0% (5.3% to 8.7%). Seven studies also reported findings stratified by sex. Summary estimates stratified by interval and sex were consistently higher for men than for women. CONCLUSIONS: Although detection of any neoplasms was observed in more than 20% of participants within five years of a negative screening colonoscopy, detection of advanced neoplasms within 10 years was rare. Our findings suggest that 10 year intervals for colonoscopy screening after a negative colonoscopy, as currently recommended, may be adequate, but more studies are needed to strengthen the empirical basis for pertinent recommendations and to investigate even longer intervals. STUDY REGISTRATION: Prospero CRD42019127842.

Head-to-Head Comparison of the Performance of 17 Risk Models for Predicting Presence of Advanced Neoplasms in Colorectal Cancer Screening.

OBJECTIVES: Many risk scores have been proposed to predict presence of advanced colorectal neoplasms, but a comprehensive comparison conducted in the same population is sparse. The aim of this study was to evaluate and directly compare the diagnostic performance of published risk prediction models for advanced colorectal neoplasms. METHODS: Data were drawn from 2 cohorts of subjects undergoing screening colonoscopy in Germany, i.e., KolosSal (n = 16,195) and BliTz (n = 7,444). Absolute risks and relative risks were generated for the presence of at least 1 advanced neoplasm, taking the lowest risk group as the reference group. Performance of risk models was assessed by the area under the receiver operating characteristic curve (AUC) and compared by the net reclassification improvement. RESULTS: The 2 cohorts included 1,917 (11.8%) and 848 (11.4%) participants with advanced neoplasm, respectively. Absolute risks were mostly between 5% and 10% among participants in the lowest risk group and between 15% and 20% among participants in the highest risk group, and relative risks mostly ranged from 2.0 to 4.0 across the risk models in both cohorts. The AUCs ranged from 0.58 to 0.65 in KolosSal and from 0.57 to 0.61 in BliTz for all risk scores. Compared to models with lower AUC, classification was significantly improved in most models with higher AUC. DISCUSSION: Risk models for advanced colorectal neoplasms generally yielded modest discriminatory power, despite some variation in performance between models. Future studies should evaluate the performance of these risk models in racially diverse populations and investigate possible extensions, such as combination with polygenic risk scores.

Risk Scores for Predicting Advanced Colorectal Neoplasia in the Average-risk Population: A Systematic Review and Meta-analysis.

OBJECTIVES: A systematic review and meta-analysis was performed to summarize the available evidence on risk scores for predicting advanced colorectal neoplasia (advanced adenomas and cancer) in average-risk and asymptomatic populations undergoing screening colonoscopy. METHODS: PubMed, EMBASE, and Web of Science databases were searched up to 28 March 2018. Studies that developed or validated a risk score to predict the risk of advanced colorectal neoplasia were included. Two reviewers independently extracted study characteristics including diagnostic performance indicators and assessed risk of bias and applicability in the included studies. Meta-analyses were conducted to determine the overall discrimination of risk scores evaluated by more than 1 study. RESULTS: A total of 22 studies including 17 original risk scores were identified. Risk scores included a median number of 5 risk factors. Factors most commonly included were age, sex, family history in first-degree relatives, body mass index and smoking. The area under the receiver operating characteristic curve of risk scores ranged from 0.62 to 0.77 in the individual studies and from 0.61 to 0.70 in the meta-analyses. CONCLUSIONS: Although the majority of available risk scores had relatively weak discriminatory power, they may be of some use for risk stratification in CRC screening. Rather than developing more risk scores based on environmental risk factors, future research should focus on exploring possibilities of enhancing predictive power by combining risk factor data with novel laboratory matters, such as polygenetic risk scores.

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. DATA SOURCES: PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. METHODS: Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. RESULTS: A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I2 = 71%, P = 0.0005). CONCLUSION: Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

The association between the environmental endocrine disruptor bisphenol A and polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between bisphenol A (BPA) and polycystic ovary syndrome (PCOS). METHODS: A systematic review and meta-analysis using STATA software for observational studies. RESULTS: Nine studies involving 493 PCOS patients and 440 controls were included in this review. The meta-analysis demonstrated that PCOS patients had significantly higher BPA levels compared with control groups (standardized mean difference (SMD): 2.437, 95% confidence interval (CI): (1.265, 3.609), p < .001). For studies of serum samples detected by enzyme-linked immunosorbent assay (ELISA), subgroup analyses according to ethnicity, body mass index (BMI), sample size, detection method (high-performance liquid chromatography (HPLC) and ELISA), PCOS-to-control ratio and study quality displayed that high BPA levels were significantly associated with Caucasian PCOS patients (SMD: 0.615, 95% CI: (0.308, 0.922), p < .001), high BMI (SMD: 0.512, 95% CI: (0.180, 0.843), p = .002), high quality (SMD: 0.624, 95% CI: (0.391, 0.856), p < .001), and high HOMA-IR (SMD: 0.467, 95% CI: (0.121, 0.813), p = .008). CONCLUSIONS: Serum BPA may be positively associated with women with PCOS and BPA might be involved in the insulin-resistance and hyperandrogenism of PCOS. More evidence from high quality studies, advanced detection methods, and larger cohorts for observational trials are needed to further confirm the association between BPA and PCOS.

Androgen alleviates neurotoxicity of ß-amyloid peptide (Aß) by promoting microglial clearance of Aß and inhibiting microglial inflammatory response to Aß.

AIMS: Lower androgen level in elderly men is a risk factor of Alzheimer's disease (AD). It has been reported that androgen reduces amyloid peptides (Aß) production and increases Aß degradation by neurons. Activated microglia are involved in AD by either clearing Aß deposits through uptake of Aß or releasing cytotoxic substances and pro-inflammatory cytokines. Here, we investigated the effect of androgen on Aß uptake and clearance and Aß-induced inflammatory response in microglia, on neuronal death induced by Aß-activated microglia, and explored underlying mechanisms. METHODS: Intracellular and extracellular Aß were examined by immunofluorescence staining and Western blot. Amyloid peptides (Aß) receptors, Aß degrading enzymes, and pro-inflammatory cytokines were detected by RT-PCR, real-time PCR, and ELISA. Phosphorylation of MAP kinases and NF-κB was examined by Western blot. RESULTS: We found that physiological concentrations of androgen enhanced Aß42 uptake and clearance, suppressed Aß42 -induced IL-1ß and TNFα expression by murine microglia cell line N9 and primary microglia, and alleviated neuronal death induced by Aß42 -activated microglia. Androgen administration also reduced Aß42 -induced IL-1ß expression and neuronal death in murine hippocampus. Mechanistic studies revealed that androgen promoted microglia to phagocytose and degrade Aß42 through upregulating formyl peptide receptor 2 and endothelin-converting enzyme 1c expression, and inhibited Aß42 -induced pro-inflammatory cytokines expression via suppressing MAPK p38 and NF-κB activation by Aß42 , in an androgen receptor independent manner. CONCLUSION: Our study demonstrates that androgen promotes microglia to phagocytose and clear Aß42 and inhibits Aß42 -induced inflammatory response, which may play an important role in reducing the neurotoxicity of Aß.

[A preliminary investigation of relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease].

OBJECTIVE: To preliminarily investigate the relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease. METHODS: One hundred and twenty-six children with congenital heart disease undergoing surgical treatment were enrolled as subjects. The serum level of apelin was determined before surgery and at 7 days after surgery. The ratio of pulmonary artery systolic pressure to aortic systolic pressure (Pp/Ps) was calculated before extracorporeal circulation. According to the Pp/Ps value, patients were classified into non-pulmonary arterial hypertension (PAH) group, mild PAH group, moderate PAH group, and severe PAH group. Pulmonary artery mean pressure was estimated by echocardiography at 7 days after surgery. RESULTS: The non-PAH group had the highest serum level of apelin before and after surgery, followed by the mild PAH group, moderate PAH group, and severe PAH group (P<0.05). All groups had significantly increased serum levels of apelin at 7 days after surgery (P<0.05). The serum level of apelin was negatively correlated with pulmonary artery pressure before surgery (r=-0.51, P<0.05) and at 7 days after surgery (r=-0.54, P<0.05). CONCLUSIONS: The decrease in serum apelin level is associated with the development of pulmonary hypertension in children with congenital heart disease. The significance of serum apelin in predicting the development and degree of pulmonary hypertension in children with congenital heart disease deserves further studies.

Lipase-catalyzed hydrolysis of linseed oil: optimization using response surface methodology.

Lipase-catalyzed hydrolysis of linseed oil was investigated. Four commercially available microbial lipases of Lipase AY, Lipozyme RMIM, Lipozyme TLIM, and Novozym 435 were used. Among these tested lipases, Lipase AY exhibited the best hydrolysis effeciency to linseed oil. The effect of reaction variables was also evaluated and optimized using response surface methodology. A second-order regression for the Box-Behken design was used to study the effect of five independent variables, such as, temperature, pH, oil-aqueous phase ratio, enzyme load, and reaction time, on the hydrolysis of linseed oil. The optimal conditions were as follows: temperature 33°C, pH 5.80, oil-aqueous phase ratio 0.90 (w/w), enzyme load 1.20% (relative to the weight of total substrates), and reaction time 3.33 h. Under these conditions, the hydrolysis ratio of linseed oil was 93.92±0.54%.

[One-stage complete correction of 52 cases infantile aortic coarctation or interrupted aortic arch associated with intracardiac anomalies].

OBJECTIVE: To sum up one-stage complete correction of infantile aortic coarctation (CoA) or interrupted aortic arch (IAA) associated with intracardiac anomalies through median sternotomy. METHODS: The clinical data of 52 infants with CoA or IAA associated with intracardiac anomalies from May 2004 to March 2010 was analyzed. There were 32 male and 20 female, aged from 25 d to 7 months with a mean of (2.03 ± 0.15) months, weighted from 2.5 to 8.0 kg with a mean of (3.9 ± 0.5) kg. All of intracardiac defect were corrected by self-arcula cordisand. Forty cases with CoA were underwent by operative techniques, including resection with end to side anastomosis, extended end to side anastomosis (n = 34), and vertical incision and cross joint (n = 3). Three cases of pseudo-CoA were cut and ductus arteriosus or ligamentum arteriosus and dissected arch. Twelve cases of IAA were underwent by extended end to side anastomosis. RESULTS: The time of cardiopulmonary bypass was (98 ± 41) min, and all patients hemorrhaged (78 ± 13) ml during operation. One case of IAA associated with double outlet right ventricle died after 43 d post-operation because of left bronchial stenosis. The other patients were in good condition. The rate of aneurysm formation was 11% in 1 to 6 years' follow-up. CONCLUSIONS: One-stage complete correction of infantile CoA or IAA associated with intracardiac anomalies through median sternotomy yields excellent intermediate surgical results. This operative approach is beneficial, not only with shorten period of therapy and loss operative cost.

[Myocardial protection of cold autoblood cardioplegia in infants with congenital heart disease].

OBJECTIVE: To study the effects of cold autoblood cardioplegia on oxygen free radicals in the myocardium in infants who underwent cardiopulmonary bypass and to explore the possible mechanism of myocardial protection of autoblood cardioplegia. METHODS: Thirty infants with acyanotic congenital heat disease (CHD) (weight< or =8 kg) were randomized to receive cold crystalloid, cold blood or cold autoblood cardioplegia (n=10 each group) during cardiopulmonary bypass. The biopsy samples were taken from the right atrium just before heart arrest and after heart self-recovery for the measurement of malonaldehyde (MDA) and superoxide dismutase (SOD) contents. The time and the rate of the heart self-recovery to sinus rhythm, and the incidence of ventricular fibrillation were recorded during operation. The cardiac index (CI) and the dependence of positive inotropic drugs were monitored after operation. RESULTS: Before the operation, there were no significant differences in myocardial MDA (0.87+/-0.14, 0.88+/-0.11 and 0.86+/-0.15 nmol/mg prot, respectively) and SOD contents (61.3+/-3.4, 69.2+/-3.1 and 64.4+/-4.2 U/g, respectively) among the crystalloid, the blood and the autoblood cardioplegia groups. After operation, the myocardial MDA content increased (3.12+/-0.21, 2.93+/-0.27 and 1.67+/-0.15 nmol/mg prot, respectively) and SOD content (42.6+/-2.3, 44.6+/-3.1 and 57.7+/-2.1 U/g, respectively) decreased significantly in the three groups (P<0.05 or 0.01). The autoblood cardioplegia group had lower myocardial MDA content and higher SOD content than the crystalloid and the blood cardioplegia groups (P<0.05). The time of heart self-recovery was shortened and the dependence of positive inotropic drugs were reduced in the autoblood cardioplegia group compared with the crystalloid and the blood cardioplegia groups (P<0.05). Post-operational CI in the autoblood cardioplegia group was significantly higher than that in the blood and the crystalloid cardioplegia groups. There were significant differences in the time of heart self-recovery, the dependence of positive inotropic drugs and the CI between the blood and the crystalloid cardioplegia groups (P<0.05 or 0.01). CONCLUSIONS: Cold autoblood cardioplegia reduces oxygen free radicals in the myocardium, thus providing myocardial protections in infants undergoing cardiopulmonary bypass.