Design and synthesis of pseudo-rutaecarpines as potent anti-inflammatory agents via regulating MAPK/NF-κB pathways to relieve inflammation-induced acute liver injury in mice.

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.7 macrophage. The results of the anti-inflammatory efficacy and action mechanism of compounds 7l and 8c indicated that they significantly reduced the release of IL-6, IL-1ß and TNF-α. Further studies revealed that they can strongly inhibit the activation of NF-κB and MAPK signal pathways. The LPS-induced acute liver injury mice model studies not only confirmed their anti-inflammatory efficacy in vivo but also could effectively relieve the liver injury in mice. The results suggest that compounds 7l and 8c might serve as lead compounds to develop therapeutic drugs for treatment of inflammation.

PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage.

BACKGROUND: The purpose of this study was to investigate the potential involvement of pyruvate kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH). METHODS: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46. RESULTS: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH. The increased expression of PKM2 was mainly co-localized with glial fibrillary acidic protein (GFAP)+ astrocytes and ionized calcium binding adaptor molecule-1 (IBA-1)+ microglia. Furthermore, we observed a notable increase in the nuclear translocation of PKM2 in glial cells following ICH. TEPP-46 treatment significantly reduced PKM2 nuclear translocation, and effectively attenuated glial activation and brain injury, and improved functional recovery of mice with ICH. RNA-seq data indicated that 91.1% (205/225) of differentially expressed genes (DEGs) were down-regulated in the TEPP-46 treated groups compared with the vehicle-treated groups in ICH brains. Furthermore, bioinformatic analyses revealed that these down-regulated DEGs were involved in a variety of biological processes, including autophagy and metabolic processes. In addition, the majority of these downregulated DEGs had a primary high expression in neurons, with subsequent expression seen in endothelial cells, microglia, and astrocytes. CONCLUSIONS: These results indicate that increased PKM2 nuclear translocation promotes the activation of glial cells after ICH, hence aggravating ICH-induced brain damage, and aggravates the brain injury induced by ICH. This highlights a potential therapeutic target for inhibiting glial activation to attenuate brain injury after ICH.

Exploring the Oxidative Stress Regulation of Mice with Hyperglycemia by Lactiplantibacillus plantarum SCS4.

The aim of this study was to evaluate the effects of Lactiplantibacillus plantarum SCS4 (L. plantarum SCS4) on oxidative stress in streptozocin-induced hyperglycemic mice. After establishment of the hyperglycemic model, control group mice were gavaged daily with phosphate-buffered saline, while different experimental groups (AG, BG, and CG) mice were gavaged with L. plantarum SCS4 suspension, cellular inclusion suspension, and inactivated inclusion suspension for 10 weeks, respectively. Compared with the model group (MG) group, the results showed that fasting blood glucose levels in BG and CG groups decreased, and postprandial 2-h blood glucose levels in BG groups decreased, whereas glucose tolerance improved. Meanwhile, ROS and MDA levels in serum of AG mice were decreased significantly (P < 0.05). Compared with the MG group, serum levels of GPx, HO-1, and NQO1 were increased in the BG group, whereas serum levels of CAT, HO-1, and GSH were increased in the CG group. Our results indicate that L. plantarum SCS4 can alleviate oxidative stress induced by hyperglycemia, and there may be synergistic effects among the different treatments.

Combined effect of menopause and cardiovascular risk factors on death and cardiovascular disease: a cohort study.

BACKGROUND: Observational studies suggest that early menopause is associated with increased risk of death and cardiovascular disease (CVD); however, the results of these studies have been inconsistently. We aimed to assess the association of menopause with death and CVD and whether this association was modified by cardiovascular risk factors. METHODS: The study population was women age 35-64 years living in two communities of Beijing who were enrolled in the Chinese Multi-provincial Cohort Study in 1992. Participants were followed until first cardiovascular event, death, or the end of follow-up (2018). Self-reported age at menopause was recorded. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of death and CVD after adjusting for baseline covariates of age, family history of CVD, and white blood cell count, as well as time-varying covariates of menopause, use of oral estrogen, and conventional risk factors. Additionally, we assessed the combined effect of age at menopause and risk factors on the primary endpoint. RESULTS: Of 2104 eligible women, 124 died and 196 had a first CVD event (33 fatal CVD and 163 non-fatal CVD). Compared with women who experienced menopause at age 50-51 years, the risk of death was higher in women with menopause at age 45-49 years (HR 1.99, 95% CI 1.24-3.21; P = 0.005), and the risk of ischemic stroke was higher in women with menopause at age < 45 years (HR 2.16, 95% CI 1.04-4.51; P = 0.04) and at age 45-49 years (HR 2.05, 95% CI 1.15-3.63; P = 0.01). Women who had menopause before age 50 years and at least one elevated risk factor at baseline had a higher risk of death (HR 11.10, 95% CI 1.51-81.41; P = 0.02), CVD (HR 3.98, 95% CI 1.58-10.01; P = 0.003), ischemic CVD (HR 4.53, 95% CI 1.63-12.62; P = 0.004), coronary heart disease (HR 8.63, 95% CI 1.15-64.50; P = 0.04), and stroke (HR 2.92, 95% CI 1.03-8.29; P = 0.04) than those with menopause at age 50-51 years and optimal levels of all risk factors. CONCLUSIONS: Earlier menopause may predict death and ischemic stroke. Furthermore, there is a combined effect of earlier menopause and elevated risk factors on death and CVD.

Association between body mass index, waist circumference, and age at natural menopause: a population-based cohort study in Chinese women.

The purpose of the study was to investigate whether premenopausal body mass index (BMI) and waist circumference (WC) influence age at menopause. A total of 2116 women aged 35-64 years from two communities of the CMCS Beijing cohort were recruited in 1992 and followed up to 2018. Of 1439 premenopausal women at baseline, 6 women data were missing. Finally, 1433 women were included for analysis. Overweight was defined as BMI 24-27.99 kg/m2. Central obesity was defined as WC ≥80 cm. Age at menopause was categorized as <45 years, 45-49 years, 50-51 years (reference), and >51 years. Multinomial logistic regression models were used to estimate relative odds ratios (RORs) and 95% confidence intervals (CIs). Compared to women with normal weight and normal WC, overweight women with normal WC had higher risk of menopause at >51 years (ROR 1.64, 95% CI 1.10-2.45; P = .01); and overweight women with central obesity had higher risk of menopause at not only >51 years (ROR 1.82, 95% CI 1.13-2.93; P = .01) but also <45 years (ROR 3.13, 95% CI 1.20-8.43; P = .02) and 45-49 years (ROR 2.76, 95% CI 1.71-4.46; P < .001). When overweight women combine with central obesity, the risk of early menopause will increase in some of them.

Sensitivity of a Ratio Vegetation Index Derived from Hyperspectral Remote Sensing to the Brown Planthopper Stress on Rice Plants.

Remote sensing end-products related to vegetation have potential applications in monitoring the health of crops. The sensitivity of a spectral index to crop stress determines its application prospect. Our aim in this study was to explore the sensitivity of a ratio vegetation index (RVI) to identify the damage caused by brown planthoppers (BPHs) on rice plants, and to evaluate the potential application of hyperspectral end-products to monitor population size of BPH. Different numbers of the second-instar nymphs were released onto potted rice at the tillering stage. The plants were exposed to BPH for two, four, six, and eight days, and reflectance from the damaged rice was measured using a hyperspectral spectroradiometer. Measurements were done again two, four, and six days after exposure (recover days), and then the spectral index RVI746/670 was compared among rice plants infested with different numbers of BPH. The relationships between RVI746/670, the number of BPH and exposure day were simulated by linear and curve models. BPH damage resulted in a decreased spectral index RVI746/670 of rice plants. RVI746/670 well indicated the damage of rice plants caused by six⁻eight BPH nymphs per plant in six⁻eight days, but the index could not identify the damage of these nymphs in two days. The RVI746/670 showed a two⁻four-day delay to indicate a slight BPH damage. The spectral index RVI746/670 could indicate the physiologic compensation of plants for the feeding of BPH and the post-effect of BPH damage on rice. The RVI746/670 of rice showed a quadratic curve relation with the number of BPH nymphs and a quadratic or linear relation with the exposure day. The recover day had no significant effects on RVI746/670. The RVI746/670 (Y) could be simulated by a quadratic surface model based on the number of BPH (N) and exposure day (T): Y = 3.09427 + 0.59111T + 0.44296N - 0.03683T² - 0.03035N² - 0.08188NT (R² = 0.5228, p < 0.01). In summary, the spectral index RVI746/670 of rice is sensitive to damage caused by BPH.

Chemical Compositions and Antioxidant Activities of Essential Oils Extracted from the Petals of Three Wild Tree Peony Species and Eleven Cultivars.

The aim of this study was to investigate the essential oil (EO) compositions and antioxidant activities from petals of three wild tree peony species (Paeonia delavayi, P. lutea, and P. rockii) and eleven P. suffruticosa cultivars from different cultivar groups. The EOs yields varied from 0.63% to 1.25% (v/v) among samples when using supercritical CO2 extraction. One hundred and sixty-three components were detected by GC/MS; and among them, linalool oxide, (Z)-5-dodecen-1-yl acetate, nonadecane, (Z)-5-nonadecene, heneicosane, phytol, and linoleic acid ethyl ester were dominant. According to hierarchical cluster analysis, principal component analysis and correspondence analysis, P. lutea, P. delavayi, and 'High Noon' were clustered in a group described as having a refreshing herbal-like note due to high rates of phytol and linalool oxide. Notably, P. lutea and P. delavayi also had strong DPPH and ABTS radical scavenging activities. These results suggest that P. lutea and P. delavayi are the most promising candidates as useful sources of fragrances and natural antioxidants.

Chemometric Classification of Different Tree Peony Species Native to China Based on the Assessment of Major Fatty Acids of Seed Oil and Phenotypic Characteristics of the Seeds.

In the present study, we quantitatively measured five major fatty acids (FA) in seed oil using gas chromatography/mass spectrometry (GC/MS) and examined four phenotypic characteristics of the seeds from 19 populations from nine wild tree peony species native to China. The results showed that the unsaturated FAs contents were dominant, of which α-linolenic acid (ALA), linoleic acid, and oleic acid (OA) contents ranged from 14.84 to 42.54 g/100 g, 7.33 to 19.66 g/100 g, and 15.07 - 35.31 g/100 g crude oil, respectively. The phenotypic seed characteristics, such as thousand seed weight (244.01 - 1772.91 g), seed volume (91.31 - 1000.79 mm3 ), weight rate of kernel and coat (1.29 - 3.62) and oil extraction ratio (20.32 - 34.69%), dramatically varied. Based on the contents of the five FAs, the nine species were classified into two groups. The species belonging to subsection Vaginatae were arranged in cluster I and were characterized by high ALA content. Cluster II, consistent with subsection Delavayanae, had a high OA content. From horizontal and vertical perspectives, the natural distribution areas of these two groups were different, reflecting differences in the FA contents and phenotypic seed characteristics. In conclusion, the FAs composition could be used as a chemotaxonomic marker for tree peony species.

[Determination of R(-)- isomer in repaglinide tablets by capillary electrophoresis].

OBJECTIVE: To develop a capillary electrophoresis system for enantiomeric impurity test of repaglinide. METHODS: An uncoated fused silica capillary (50 µm×50 cm, with an effective length of 41 cm) was used. The running buffer was composed of 30 mmol/L NaH2PO4 and 5 mg/ml carboxymethyl-ß-cyclodextrin(pH 3.5). RESULTS: Linear range was 2.00-80.00 µg/ml (correlation coefficient was 0.9993). The average recovery rate was 92.5% to 105.0%. CONCLUSION: The method is simple, accurate and sensitive and it can be used for determination of enantiomeric impurities in repaglinide tablet.

[Determination of enantiomeric impurity in levocetirizine tablets by capillary electrophoresis].

OBJECTIVE: To determine enantiomeric impurity in levocetirizine tablets by using capillary electrophoresis. METHODS: The effects of pH and the concentrations of sulfated-Β-cyclodextrin (S-Β-CD) and buffer salt on chiral resolution were examined with S-Β-CD as chiral selector. RESULTS: A good enantioseparation of cetirizine was achieved with 30 mmol/L NaH2PO4 buffer solution (pH 7.0) containing 20 g/L of S-Β-CD. CONCLUSION: The method developed in the study is sensitive and reliable for determination of enantiomeric impurity in levocetirizine tablets.

Validation of the iHealth Track upper-arm blood pressure monitor KN-550BT in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020).

OBJECTIVE: To validate the iHealth Track KN-550BT oscillometric upper-arm blood pressure monitor in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020). METHODS: Participants were recruited and the same left-arm sequential method was used for blood pressure measurement according to the ISO 81060-2:2018+AMD1:2020. The validation results were assessed following the protocol and the Bland-Altman scatterplot was used to show the difference between the test device and reference results. RESULTS: A total of 89 qualified participants were included in the final analysis. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference readings was -1.22 ±â€…5.76 mmHg and -0.08 ±â€…4.40 mmHg for systolic and diastolic blood pressure, respectively. For Criterion 2, the mean ± SD of the differences between the test device and reference readings per participant was -1.22 ±â€…5.06 mmHg and -0.08 ±â€…3.84 mmHg for systolic and diastolic blood pressure, respectively. CONCLUSION: The iHealth Track KN-550BT upper-arm blood pressure monitor passed all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020) and can be recommended for clinical use and self-measurement in general population.

Geographic differences in psychological symptoms, sleep quality, and quality of life in patients with inflammatory bowel disease: A multicenter study in China.

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.

[An evaluation of the impact of cerebrovascular disease deaths on life expectancy in China].

OBJECTIVE: To evaluate the impact of cerebrovascular death on the life expectancy of Chinese residents in recent years and explore the difference in the subgroups. METHODS: Life expectancy and cause-elimination life expectancy were calculated by standard life table techniques using the adjusted mortality data from the Death Surveillance Data Sets in 2005 and 2010 provided by the National Disease Surveillance System. Decomposition method was used to quantitatively evaluate the impact of cerebrovascular disease. RESULTS: The life expectancy of Chinese residents was 73.23 years old in 2010. The loss of life expectancy caused by cerebrovascular death was 2.26 years in 2010, with about 97% of that came from the elimination of deaths in the residents aged over 40 years old. Compared with 2005, the reduction of cerebrovascular deaths contributed to a total of 0.04 years increase in the life expectancy of Chinese residents in 2010, with 0.45 years for urban residents. However, for the rural residents, cerebrovascular death increased and caused 0.12 years decrease of life expectancy. CONCLUSIONS: The impact of cerebrovascular death on the life expectancy of Chinese residents is still great. Significant difference is showed between the urban and rural areas with reduction in the urban but increase in the rural. The life expectancy is likely to be further increased by reducing cerebrovascular death in the Chinese residents aged over 40 years old.

[Clustering of cardiovascular risk factors and hypertension control status among hypertensive patients in the outpatient setting].

OBJECTIVE: To investigate the status of the clustering of cardiovascular risk factors and hypertension control among hypertensive patients in the outpatient setting in China. METHODS: This multi-center cross-sectional study was carried out from June to December 2009. Study patients were consecutively recruited from 46 hypertension outpatient clinics in 22 provinces, autonomous regions, and municipalities of China according to identical inclusion criteria. More than 100 consecutive patients should be recruited in each outpatient clinic, and 5206 hypertensive outpatients were included. The patients were examined by questionnaires, physical examinations, and biochemical analyses. Risk factors were defined according to the 2010 Chinese guidelines for the management of hypertension. RESULTS: In this patient cohort, dyslipidemia was found in 61.5% (3203/5206), obesity in 56.0% (2917/5206), and impaired glucose regulation in 27.8% (1449/5206) patients. The prevalence of smoking was 34.9% (910/2605) in male hypertensive patients, 88.9% (4630/5206) hypertensive patients had at least one of the above-mentioned four risk factors and 17.4% (906/5206) had three or more risk factors. Only 4.1% (211/5206) hypertensive outpatients were classified as low cardiovascular risk patients, 72.5% (3774/5206) hypertensive outpatients were classified as high or very high cardiovascular risk patients. The general blood pressure control rate was 44.3% (2304/5206), which was higher in the age group of ≥ 65 years than in those of 35-44 years [51.3% (818/1596) vs. 29.6% (160/541), P < 0.01], higher in low-risk patients than in high-risk patients [65.4% (138/211)vs. 41.9% (1581/3774), P < 0.01] and higher in patients under regular therapy ( ≥ 9 months per year) than in those of irregular therapy (< 6 months per year) [50.7% (1744/3442)vs. 30.0% (391/1305), P < 0.01]. CONCLUSION: Clustering of cardiovascular risk factors, especially dyslipidemia and obesity, is common, and cardiovascular risk is high while blood pressure control rate is low among hypertensive outpatients in China.

[Impact of gender on lipoprotein-associated phospholipase A2 activity and association with known cardiovascularrisk factors].

OBJECTIVE: To explore the impact of gender on lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity and association with known cardiovascular risk factors. METHODS: Participants in this study were recruited from Beijing sub-cohort from the Chinese Multi-provincial Cohort Study (CMCS) database. A total of 1471 participants with complete laboratory data were included in the study (688 male). Lp-PLA(2) activity was determined by colorimetric assay kit.Lp-PLA(2) activity level and correlation between Lp-PLA(2) activity and known risk factors were compared between men and women. RESULTS: (1) Lp-PLA(2) activity was higher in males than in females [(22.73 ± 8.52) nmol·min(-1)·ml(-1) vs.(20.01 ± 8.06) nmol·min(-1)·ml(-1), P < 0.01].(2) Age, waist circumference, systolic blood pressure, diastolic blood pressure and the prevalence of hypertension were higher in males than in females, while total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were higher in females than in males (P < 0.05 or P < 0.01).(3)Pearson correlation showed that Lp-PLA(2) activity was correlated with lipids ( total cholesterol, LDL-C, HDL-C, and triglyceride), blood pressure (systolic blood pressure and diastolic blood pressure), and adiposity associated parameters (waist circumference and body mass index) in males (all P < 0.01) and was correlated with lipid level (total cholesterol, LDL-C, HDL-C, and triglyceride) and age in females( P < 0.05 or P < 0.01). Correlations with variables associated with obesity or blood pressure in females were much weaker than those in males (in females, r = 0.02-0.08; in males, r = 0.10-0.16).(4)After adjustment for age, waist circumference, systolic blood pressure, glucose, LDL-C, HDL-C, triglyceride and high sensitivity C-reactive protein by multiple logistic regression model, Lp-PLA(2) activity was still significantly higher in males than in females (OR = 1.72, 95% confidence interval = 1.34-2.21, P < 0.01). CONCLUSIONS: Lp-PLA(2) activity and association with known cardiovascular risk factors differed in males and females. The gender difference in Lp-PLA(2) activity still presents after adjustment for known cardiovascular risk factors in this cohort.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia.

Transient receptor potential vanilloid 1 (TRPV1) ion channel is a classic analgesic target, but antagonists of TRPV1 failed in clinical trials due to their side effects like hyperthermia. Here we rationally engineer a peptide s-RhTx as a positive allosteric modulator (PAM) of TRPV1. Patch-clamp recordings demonstrate s-RhTx selectively potentiated TRPV1 activation. s-RhTx also slows down capsaicin-induced desensitization of TRPV1 in the presence of calcium to cause more calcium influx in TRPV1-expressing cells. In addition, our thermodynamic mutant cycle analysis shows that E652 in TRPV1 outer pore specifically interacts with R12 and K22 in s-RhTx. Furthermore, we demonstrate in vivo that s-RhTx exhibits long-lasting analgesic effects in noxious heat hyperalgesia and CFA-induced chronic inflammatory pain by promoting the reversible degeneration of intra-epidermal nerve fiber (IENF) expressing TRPV1 channels in mice, while their body temperature remains unaffected. Our results suggest s-RhTx is an analgesic agent as a PAM of TRPV1.

Metabolomics Analysis of Electroacupuncture Pretreatment Induced Neuroprotection on Mice with Ischemic Stroke.

The brain metabolic changes caused by the interruption of blood supply are the initial factors of brain injury in ischemic stroke. Electroacupuncture (EA) pretreatment has been shown to protect against ischemic stroke, but whether its neuroprotective mechanism involves metabolic regulation remains unclear. Based on our finding that EA pretreatment significantly alleviated ischemic brain injury in mice by reducing neuronal injury and death, we performed a gas chromatography-time of flight mass spectrometry (GC-TOF/MS) to investigate the metabolic changes in the ischemic brain and whether EA pretreatment influenced these changes. First, we found that some glycolytic metabolites in the normal brain tissues were reduced by EA pretreatment, which may lay the foundation of neuroprotection for EA pretreatment against ischemic stroke. Then, 6[Formula: see text]h of cerebral ischemia-induced brain metabolic changes, especially the enhanced glycolysis, were partially reversed by EA pretreatment, which was manifested by the brain levels of 11 of 35 up-regulated metabolites and 18 of 27 down-regulated metabolites caused by cerebral ischemia significantly decreasing and increasing, respectively, due to EA pretreatment. A further pathway analysis showed that these 11 and 18 markedly changed metabolites were mainly involved in starch and sucrose metabolism, purine metabolism, aspartate metabolism, and the citric acid cycle. Additionally, we found that EA pretreatment raised the levels of neuroprotective metabolites in both normal and ischemic brain tissues. In conclusion, our study revealed that EA pretreatment may attenuate the ischemic brain injury by inhibiting glycolysis and increasing the levels of some neuroprotective metabolites.

[The association between the changes in triglyceride levels and the risk of incident type 2 diabetes mellitus: a 15 years followed-up results from the Chinese Multi-provincial Cohort Study].

OBJECTIVE: To explore the 15-years change in fasting TG level and the accumulative incidence of type 2 diabetes mellitus (T2DM) from 1992 to 2007, and to assess the association between the change in TG level and the accumulative onset risk of T2DM. METHODS: A total of 11 387 subjects aged 35 - 64 years were recruited from 6 provinces in China in the baseline survey in 1992, and were followed-up for cardiovascular disease till 2007. In 2007, 9184 subjects were successfully followed-up and 5966 subjects entered into the second examination. Totally 5408 participants, who were free of diabetes at baseline and had complete information for both check ups, were included in this analysis. Fasting TG levels were categorized into three groups: < 1.70 mmol/L, 1.70 - 2.25 mmol/L and ≥ 2.26 mmol/L. The association between 15-years change in TG level and the accumulative onset risk of T2DM was assessed by logistic regression analysis. RESULTS: In 1992, the mean level of TG was 1.49 mmol/L in male and 1.26 mmol/L in female. During the 15 years, TG levels increased by 0.25 mmol/L and 0.53 mmol/L in male and female, respectively. The prevalence of elevated TG (< 1.70 mmol/L) increased from 23.4% in 1992 to 39.0% in 2007. The 15-year accumulative incidence of diabetes was 13.9% in male and 11.8% in female. The incidence rates were 10.5%, 16.2% and 26.6% for TG levels of < 1.70 mmol/L, 1.70 - 2.25 mmol/L and ≥ 2.26 mmol/L, respectively. Multivariate logistic regression analysis showed that the baseline TG level was significantly associated with the onset risk of diabetes after adjustment for other cardiovascular risk factors. At any given baseline TG level, the onset risk of diabetes increased with the TG levels in the second examination in 2007. After adjusting other risk factors, participants with the highest categories of both baseline and follow-up TG levels had 2.1 folds higher accumulative onset risk of diabetes (RR = 3.39, 95%CI 2.49 - 4.61) than those with the lowest categories of both baseline and follow-up TG levels. CONCLUSION: Baseline TG level is independently associated with diabetes onset risk, and the change of TG level in a 15-year interval predicts the onset risk of diabetes beyond the baseline TG level.

[The epidemiology of out-of-hospital deaths due to acute coronary events in young Beijing adults].

OBJECTIVES: To explore the characteristics of status and different populations of prehospital death associated with acute coronary events among young adults in Beijing. METHODS: Data of acute coronary events of hospitalization or death were obtained from the Hospital Discharge Information System from Beijing Public Health Information Center and Death Register System from Beijing Center for Disease Control in Beijing. The total case fatality rate of acute coronary events and proportion of prehospital coronary heart disease (CHD) death were compared upon gender, area, occupation and marital status among people aged between 25 - 45 years old. RESULTS: A total of 3489 cases were identified during 2007 to 2009 with acute coronary events (male: 3183, female: 306), with a mean age of (40.5 ± 4.3) years old. The 3-years' overall mortality was 26.0%, with female's higher than male's (51.0% vs 23.6%, P < 0.05); and it was higher in rural area than in urban areas (28.9% vs 22.9%, P < 0.05). Ninety-five percent of death due to acute coronary events occurred prehospital, with the proportion of 95.2% in male and 94.2% in female. Among the people with different occupations, self-employed people had the highest rate of prehospital death. Majority of prehospital deaths (64.8%) occurred at home. CONCLUSION: More than 90% of deaths caused by acute coronary events among young adults aged between 25-45 years old occurred before been admitted into hospital, and the site of prehospital deaths was mainly at home.