Xueshuantong injection combined with Salvianolate lyophilized injection improves the synaptic plasticity against focal cerebral ischemia/reperfusion injury in rats through PI3K/AKT/mTOR and RhoA/ROCK pathways.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, ß-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia.

Prevalence and associated factors of lower extremity musculoskeletal disorders among manufacturing workers: a cross-sectional study in China.

OBJECTIVE: To survey the prevalence of lower extremity musculoskeletal disorders (MSDs) among Chinese manufacturing workers, and to identify the associated factors. DESIGN: Observational study with cross-sectional design. SETTING: A self-administered questionnaire survey was conducted in four manufacturing factories in China. PARTICIPANTS: 7908 manufacturing workers were included in this study after excluding non-conforming personnel. OUTCOME MEASURES: Individual and work-related information, and MSDs in the whole leg and knee region were measured by the anonymous self-administered questionnaire. Individual and work-related factors associated with MSDs and their effects were identified through multivariate logistic regression. RESULTS: Of all respondents, 3241 (41.0%) reported having had lower extremity MSDs in the recent 12 months, and for the knees, ankles/feet and hips/thighs were 29.5%, 23.9% and 16.7%, respectively. After confounder-adjusted single-factor analysis, 22 variables (of 24) were significantly related to the disorders. Factors like always kneeling/squatting for long periods, always standing for long periods and often lifting in an uncomfortable position were shown to have higher risks, with ORs of 2.77 (95% CI: 2.33 to 3.30), 2.30 (1.96 to 2.69) and 2.25 (2.04 to 2.47). Comparable results were found on knee disorders. The final model included 15 variables of demography, biomechanics and work organisation. The following factors showed increased risks of lower extremity MSDs: being female, being older, longer working years, higher body mass index (BMI), keeping the same posture for a long time, awkward position, shift work and monotonous work. Whereas having enough breaks reduced the risk. CONCLUSION: The prevalence of lower extremity MSDs among Chinese manufacturing workers is high. The most commonly affected body regions were the knees and ankles/feet. Multiple factors were found associated with lower extremity MSDs including age, BMI, work experience, work organisations, physical ergonomics exposures, etc.

Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study.

PURPOSE: Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties. MATERIALS AND METHODS: This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role. RESULTS: We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1ß-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1ß-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway. CONCLUSION: Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy.

Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity.

Mitochondrial fusion/fission dynamics plays a fundamental role in neuroprotection; however, there is still a severe lack of therapeutic targets for this biological process. Here, we found that the naturally derived small molecule echinacoside (ECH) significantly promotes mitochondrial fusion progression. ECH selectively binds to the previously uncharacterized casein kinase 2 (CK2) α' subunit (CK2α') as a direct cellular target, and genetic knockdown of CK2α' abolishes ECH-mediated mitochondrial fusion. Mechanistically, ECH allosterically regulates CK2α' conformation to recruit basic transcription factor 3 (BTF3) to form a binary protein complex. Then, the CK2α'/BTF3 complex facilitates ß-catenin nuclear translocation to activate TCF/LEF transcription factors and stimulate transcription of the mitochondrial fusion gene Mfn2. Strikingly, in a mouse middle cerebral artery occlusion (MCAO) model, ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2 expression in wild-type but not CK2α'+/- mice. Taken together, our findings reveal, for the first time, that CK2 is essential for promoting mitochondrial fusion in a Wnt/ß-catenin-dependent manner and suggest that pharmacologically targeting CK2 is a promising therapeutic strategy for ischemic stroke.

Study on the Associations of Individual and Work-Related Factors with Low Back Pain among Manufacturing Workers Based on Logistic Regression and Structural Equation Model.

Work-related musculoskeletal injuries are one of the major occupational health issues of the workers, especially low back pain (LBP). The aim of this study was to survey the prevalence of LBP among manufacturing workers and to identify associations of individual and work-related factors with LBP. A cross-sectional questionnaire study was performed with 1173 participating manufacturing workers. The questionnaire included individual factors, psychosocial and physical exposures, and musculoskeletal discomfort. It was analyzed by logistic regression and structural equation modeling (SEM). The 1-year prevalence of LBP among Chinese manufacturing workers was 33.6%. Logistic regression analysis showed that job tenure, awkward postures, vibration and job demand were positively-while social support and job control were negatively associated with LBP (p < 0.05). The SEM results indicated that, as shown in other studies, job types, job tenure, postural load, high job demand, low job control and vibration were directly associated with LBP, but also that job types, high job demand, low social support and vibration may have indirect effects on LBP-mediated by postural load.

Total glycosides and polysaccharides of Cistanche deserticola prevent osteoporosis by activating Wnt/ß-catenin signaling pathway in SAMP6 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Cistanche deserticola Y. C. Ma has effect of "tonifying kidney and strengthening bone". However, the specific active extracts of C. deserticola and mechanisms for treatment of osteoporotic are not clear. AIM OF THE STUDY: We wanted to identify the effective component extracts of C. deserticola for the treatment of osteoporosis and the potential mechanisms. MATERIALS AND METHODS: Our group researched the extracts of C. deserticola with anti-osteoporotic activity, including total glycosides (TGs), polysaccharides (PSs), and oligosaccharides (OSs) in senescence accelerated mouse prone 6 (SAMP6) mice. The Goldner's Trichrome, Van Gieson's (VG), Safranin O-Fast Green staining and Von Kossa staining were performed to investigate the bone structure formation and calcium deposits. Serum was collected for detecting biochemical markers. Bone micro-architecture was detected by micro-CT. Expressions of bone morphogenetic protein-2 (BMP-2), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator of nuclear factor-κ B ligand (RANKL), p-glycogen synthetase kinase-3ß (p-GSK-3ß), and p-ß-catenin were analyzed by western blotting and immunohistochemistry. RESULTS: TGs and PSs ameliorated bone histopathological damages, promoted the formation of new bone, collagenous fiber, and chondrocytes, and accelerated the calcium deposits. Moreover, they remarkable altered the biomarkers of bone turnover and effectively ameliorated bone microarchitecture. The further mechanisms study showed that TGs and PSs significantly decreased the expressions of RANKL, p-ß-catenin, as well as up-regulated the expression of BMP-2, OCN, OPG, and p-GSK-3ß (Ser9). CONCLUSION: The findings of this study suggest that TGs and PSs can promote osteoblastogenic bone formation and improve bone microstructure damage in SAMP6 mice, and their therapeutic effect on osteoporosis is via activating Wnt/ß-catenin signaling pathway.

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats.

BACKGROUND: The traditional Chinese medicine Cistanche deserticola has been reported to be valid for cardiovascular and cerebrovascular diseases. However, its active components for the protection of ischemic stroke are not clear. We aimed to explore the active components of C. deserticola against ischemic stroke as well as its potential mechanisms. METHODS: We investigated the brain protective effects of extracts from C. deserticola, total glycosides (TGs), polysaccharides (PSs), and oligosaccharides (OSs) in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to assess the cerebral infarction volume, and Evans blue assay was adopted to assess the blood-brain barrier (BBB) permeability. Then, the expressions CD31, α-SMA, PDGFRß, SYN, PSD95, MAP-2, ZO-1, claudin-5, occludin, Keap-1, and Nrf-2 were analyzed using western blotting or immunofluorescence, and the activities MDA, SOD, CAT, and GSH-Px were analyzed using kits. RESULTS: TGs treatment remarkably decreased neurological deficit scores and infarction volumes, promoted angiogenesis and neural remodeling, and effectively maintained blood-brain-barrier integrity compared with the model group. Furthermore, TGs significantly decreased MDA levels and increased antioxidant activities (SOD, CAT, and GSH-Px) in brains. Meanwhile, TGs remarkably downregulated Keap-1 expression and facilitated Nrf-2 nuclear translocation. On the contrary, no protective effects were observed for PSs and OSs groups. CONCLUSION: TGs are the main active components of C. deserticola against MCAO/R-induced cerebral injury, and protection is mainly via the Nrf-2/Keap-1 pathway.

Cervical musculoskeletal disorders and their relationships with personal and work-related factors among electronic assembly workers.

INTRODUCTION: Electronics assembly workers are reported to have a high prevalence of musculoskeletal disorders (MSDs). This study investigated the prevalence of cervical MSDs and the complex relationships between cervical MSDs and individual, physical, psychosocial factors among electronics assembly workers. METHODS: In this cross-sectional survey, self-administered questionnaires from 700 workers in electronics manufacturing workshops were analysed. Information concerning musculoskeletal symptoms, personal and work-related factors was collected. Finally, the prevalence of cervical MSDs was computed for different subgroups, and the relationships with different factors were analyzed using logistic regression and structural equation modeling (SEM). RESULTS: The total 12 month prevalence of cervical MSDs among the survey population was 29.4%. Variables of gender, job tenure, twisting head frequently, neck flexion/extension for long time and work required to be done quickly showed significant associations with MSDs in a multivariate logistic regression (P < 0.05). The SEM analysis showed moderate and significant correlations between postural load (γ = 0.279), gender (γ = 0.233) and cervical MSDs, while there were weak but significant correlations between vibration (γ = 0.024), work stress (γ = 0.126), job tenure (γ = 0.024) and cervical MSDs. Both work stress and vibration affected the MSDs indirectly through postural load. CONCLUSIONS: The logistic regression results support previous general epidemiological MSD studies, and indicates that individual, physical, and psychosocial factors are related to cervical MSDs. The SEM provides a better approximation of the complexity of the relationship between risk factors and cervical MSDs. Improving awkward postures may be effective ways to control the influence of occupational stressors or vibration on MSDs. Practical Applications: The study is to improve prevention of MSDs among electronics assembly workers and promote their occupational health.

Ability to Suppress TGF-ß-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions.

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited treatment options. It also leads to progressive respiratory failure, which subsequently affects the heart functionality, a pathological heart-lung interaction increasingly noticed and defined as pulmonary-heart disease (PHD). Traditional Chinese medicine (TCM) theory for treating "phlegm-stasis cementation syndrome" may suggest a possibility of treating PHD complication with Chinese medicine prescriptions previously used for cardiovascular diseases. Methods: Here, we evaluate the efficacies of two compound Chinese medicine prescriptions, Danlou prescription (DLP) and Danhong prescription (DHP), which share a common herbal component, Salvia miltiorrhiza (Danshen), on pulmonary fibrosis. Severity grades of Bleomycin (BLM)-induced pulmonary fibrosis were assessed by micro-Computerized Tomography (µCT) in accordance with the clinical evaluation standard. Lung pathological changes and collagen deposition were investigated by histopathology. Myofibroblast differentiation was assessed by immunohistochemistry of α-SMA and TGF-ß receptor type II expression in situ. Network pharmacology analysis of the drug-target interaction in IPF progression for DLP or DHP was performed using Ingenuity® Pathways Analysis (IPA) system. Results: We show that a non-invasive µCT effectively monitor and quantify BLM-induced pulmonary fibrosis and its treatment efficacy by Chinese medicine prescription in rodents. In addition, although both containing Salvia miltiorrhiza, DLP but not DHP mitigates BLM-induced lung fibrosis by inhibiting the TGF-ß signaling-activated myofibroblast differentiation and α-SMA expression in a mouse model. Core analysis by IPA revealed that DLP ingredients regulated not only pulmonary fibrosis related inflammatory genes but also genes associated with myofibroblast activation and collagen deposition. Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of "removing both phlegm and blood stasis" will better achieve co-protection of heart and lung in PHD.

Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion.

Shuxuetong injection composed of leech (Hirudo nipponica Whitman) and earthworm (Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells (bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N2/5% CO2 for 6 hours, followed by high-glucose medium containing 95% O2 and 5% CO2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations (diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.

Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress.

Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized) (XST) are two herbal standardized preparations that have been widely used in China for the treatment of acute cerebral infarction. In this study, we investigated the neuroprotective effects of SLI combined with XST in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated with SLI or XST alone, or with their combinations via tail vein injection daily for 3 d. Edaravone (EDI, 6 mg·kg-1·d-1) was used as a positive control drug, We showed that administration of a combination of 1X1S (XST 100 mg·kg-1·d-1 plus SLI 21 mg·kg-1·d-1) more effectively protected the ischemic brains than SLI or XST used alone. Administration of 1X1S not only significantly decreased neurological deficit scores and infarct volumes and increased regional cerebral blood flow, but also inhibited the activation of both microglia and astrocytes in the hippocampus. Furthermore, administration of 1X1S significantly decreased the levels of MDA and ROS with concomitant increases in the levels of antioxidant activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST used alone. Moreover, administration of 1X1S remarkably upregulated the expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1 and facilitated the nuclear translocation of Nrf-2 in the brain tissues as compared with XST used alone. Our study demonstrates that a combination of 1X1S effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf-2/Keap1 pathway.

Diosgenin glucoside provides neuroprotection by regulating microglial M1 polarization.

The selective suppression of inflammatory factors in activated microglia, rather than totally inhibiting their activation, might be an effective means of slowing the progression of certain neurodegenerative diseases. Diosgenin glucoside (Dios) is a saponin compound extracted from Tritulus terrestris L. We found that Dios suppressed the synthesis of molecules that promote inflammation (M1 markers, such as NO, IL-6, and TNF-α) in rat microglia and BV-2 cells induced with lipopolysaccharides (LPS). In contrast, Dios had no effects on the cellular production of anti-inflammatory factors (M2 markers, such as IL-10, IL-1Rα and CD206) in LPS and IL-4 treated microglia. Dios repressed IκB-α, ERK MAPK and p38 MAPK phosphorylation, but did not affect JNK in LPS-activated microglia. We also found that conditioned medium obtained from cultures of BV-2 cells incubated with Dios plus LPS was markedly less neurotoxic than conditioned medium obtained from cultures of BV-2 cells incubated with LPS alone. In conclusion, this study demonstrated that Dios can selectively suppress the production/expression of pro-inflammatory M1 markers by activated microglia, without affecting M2 markers, and might provide neuroprotection by regulating microglial M1 polarization. Our results suggest that Dios can be used in treatment of various neuroinflammatory diseases mediated by microglia.

Neuroprotective effect of salvianolate lyophilized injection against cerebral ischemia in type 1 diabetic rats.

BACKGROUND: Salvianolate lyophilized injection (SLI) has been clinically used in China for the treatment of acutely cerebral infarction. Clinical and experimental studies have shown that Diabetes mellitus (DM) not only increases the risk of ischemic stroke recurrence but also leads to poor outcomes and increases fatality rates after stroke. Our previous study has proved that SLI can reduce the infarct volume after stroke in type 1 diabetic rats. The aim of the study is to explore the mechanism of SLI on stroke outcome in type 1 diabetic (T1DM) rats. METHODS: Type 1 diabetes rats model (T1DM) was induced in male Wistar rats by intraperitoneal (i.p) injection of streptozotocin (60 mg/kg) and T1DM rats were subjected to intraluminal middle cerebral artery occlusion (MCAO). The T1DM + MCAO rats were randomly divided into six groups: sham-operated, model-vehicle, positive control group (Edaravone-treating, DE 6 mg/kg) and SLI-treating group (10.5 mg/kg, 21 mg/kg and 42 mg/kg). SLI and DE were administered by tail vein injection at 3 h after MCAO, then daily for 14 days. Micro-CT scans of the brain tissue revealed vessel characteristics and distribution in the ischemia zone. Glucose uptake was analyzed by PET/CT. RAGE, MMP9 and inflammatory factors (COX-2, TNF-α and ICAM-1), HQ-1, HQO-1 and Nrf-2 expression levels in the ischemic brain tissue were analyzed by Immunofluorescence staining and Western blot at 14 days after MCAO. RESULTS: In this study, we have demonstrated that SLI treatment significantly increased the number of brain microvasculature in ipsilateral and glucose uptake in cortex, hippocampus and penumbra in the T1DM + MCAO rats. SLI also significantly decreased the expression of RAGE, MMP9 and inflammatory factors expression, and increased the expression of HQ-1, HQO-1 and Nrf-2 in T1DM + MCAO rats. CONCLUSION: The study showed that SLI could protect against cerebral ischemia injury in T1DM + MCAO rats and the mechanism is related to decrease inflammatory factors and activate of the Nrf2/HO-1 signaling pathway.

Protective effects of total flavonoids in Caragana against hypoxia/reoxygenation-induced injury in human brain microvascular endothelial cells.

This study aimed to explore the protective effect of total flavonoids in Caragana against hypoxia/reoxygenation (H/R)-induced injury in human brain microvascular endothelial cells (BMECs). Human BMECs were selected and assigned into control, H/R, H/R+NMP, H/R+Low dose, H/R+Moderate dose, H/R+High dose groups. MTT and Transwell assays were used to detect cell viability and migration, respectively. Cell adhesion rate and tube formation were also detected. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to test HIF-1α, VEGF and Notch1 mRNA and protein expressions. Compared with the H/R group, the cell viability rates in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were increased. The cell adhesion rates in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were significantly different from those in the H/R group. As compared to the H/R group, the cell migration abilities in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were enhanced. Compared with the H/R group, the number and length of tubes of BMECs in the H/R+NMP, H/R+High dose and H/R+Moderate dose groups were increased. HIF-1α, VEGF and Notch1 mRNA and protein expressions were higher in the H/R+Low dose, H/R+Moderate dose and H/R+High dose groups than in the H/R group. These findings revealed that total flavonoids in Caragana can protect BMECs from H/R-induced injury in a dose-dependent manner and it also may promote angiogenesis in BMECs by activating HIF- 1α-VEGF-Notch 1 signaling pathway.

Characteristics and source appointment of atmospheric particulate mercury over East China Sea: Implication on the deposition of atmospheric particulate mercury in marine environment.

Total Suspended Particulate (TSP) samples were collected at Huaniao Island in northern East China Sea (ECS) from March 2012 to January 2013. Chemical analysis were conducted to measure the concentration of total particulate mercury (TPM) and speciated particulate mercury including HCl-soluble particulate mercury (HPM), elemental particulate mercury (EPM) and residual particulate mercury (RPM). The bromine (Br) and iodine (I) on particles were also detected. The mean concentration of TPM during the study period was 0.23 ± 0.15 ng m-3, while the obviously seasonal variation was found that the concentrations of TPM in spring, summer, fall and winter were 0.34 ± 0.20 ng m-3, 0.15 ± 0.03 ng m-3, 0.15 ± 0.05 ng m-3 and 0.27 ± 0.26 ng m-3, respectively. The statistically strong correlation of bromine and iodine to HPM was only found in spring with r = 0.81 and 0.77 (p < 0.01), respectively. While the strongest correlations between EPM and bromine and iodine were found in winter with r = 0.92 (Br) and 0.96 (I) (p < 0.01), respectively. The clustered 72-h backward trajectories of different seasons and the whole sampling period were categorized into 4 groups. In spring, the clusters passed a long distance across the East China Sea and brought about low concentration of mercury due to the deposition of mercury over the sea. The cluster of air mass across the sea had low concentration of HPM in winter, which suggested that the oxidation of mercury in winter might be related to other oxidants. During the whole sampling period, the air mass from the north of China contributed to the higher concentration of TPM in Huaniao Island.

Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns.

BACKGROUND: Highly active antiretroviral therapy (HAART) is recommended to control the infection of HIV-1. HIV-1 drug resistance becomes an obstacle to HAART due to the accumulation of specific mutations in the RT coding region. The development of resistance mutations may be more complex than previously thought. METHODS: We followed two HIV-1 infectors from a HIV-1 drug resistance surveillance cohort in Henan province and evaluated CD4+ T-cell number and viral load thereafter at ten time-periods and characterized their reverse transcriptase-associated mutation patterns at each time point. Then we constructed the recombinant virus strains with these mutation patterns to mimick the viruses and test the phenotypic resistance caused by the mutation patterns on TZM-b1 cells. RESULTS: CD4+ T-cell number initially increased and then decreased rapidly, while viral load decreased and then dropped sharply during initial antiretroviral treatment. The number of mutations and the combination patterns of mutations increased over time. According to the phenotypic resistance performed by recombinant virus strains, VirusT215Y/V179E/Y181C/H221Y exhibited high levels of resistance to EFV (5.57-fold), and T215Y/V179E-containing virus increased 20.20-fold in AZT resistance (p < 0.01). VirusT215Y/V179E/Y181C increased markedly in EFV resistance (p < 0.01). The IC50 for VirusT215Y/V179E/H221Y was similar to that for VirusT215Y/V179E/Y181C. VirusT215Y/K103N/Y181C/H221Y induced a dramatic IC50 increase of all the four agents (Efavirenz EFV, Zidovudine AZT, Lamivudine 3TC, and Stavudine d4T) (p < 0.01). As for VirusT215Y/K103N/Y181C, only the IC50 of EFV was significantly increased. T215Y/K103N resulted in a 26.36-fold increase in EFV (p < 0.01). T215Y/K103N/H221Y significantly increased the resistance to AZT and 3TC. The IC50 of EFV with T215Y/V179E was lower than with T215Y/K103N (F = 93.10, P < 0.0001). With T215Y/V179E, Y181C significantly increase in EFV resistance, while the interaction between 181 and 221 in EFV was not statistically significant (F = 1.20, P = 0.3052). With T215Y/K103N, neither H221Y nor Y181C showed a significant increase in EFV resistance, but the interaction between 181 and 221 was statistically significant (F = 38.12, P = 0.0003). CONCLUSIONS: Data in this study suggests that pathways of viral evolution toward drug resistance appear to proceed through distinct steps and at different rates. Phenotypic resistance using recombinant virus strains with different combination of mutation patterns reveals that interactions among mutations may provide information on the impact of these mutations on drug resistance. All the result provides reference to optimize clinical treatment schedule.

Multiple mesenteric well-differentiated liposarcoma complicated by purulent inflammation: A case report.

Multiple mesenteric well-differentiated (WD) liposarcoma is an extremely rare entity. The present study describes a case of multiple mesenteric WD liposarcoma, complicated by purulent inflammation, in a 59-year-old male who presented with abdominal pain and pyrexia of unknown origin. A computed tomography scan of the abdomen revealed a large, non-encapsulated mass in the abdomino-pelvic cavity, which was characterized by two components, a main portion of fatty density and a non-adipose solid portion. A re-evaluated CT scan, performed eight days later, revealed an enlargement of the non-adipose mass. A laparotomy was performed, and numerous separated fatty nodules and masses of various sizes were identified within the mesentery of the small intestine. The histological findings were consistent with an adipocytic subtype of multiple mesenteric WD liposarcoma, with the largest of the tumors complicated by purulent inflammation. The multiplicity of these tumors and the concurrent purulent inflammation in the present case make it unique.

Large paravaginal angiomyofibroblastoma: magnetic resonance imaging findings.

Angiomyofibroblastoma (AMFB) is a rare, benign, mesenchymal tumor that occurs mainly in the female lower genital tract. We report on a large posterior paravaginal AMFB that presented as a buttock mass, describing the magnetic resonance imaging (MRI) features of the disease. The tumor displays heterogeneous signal intensity on T2-weighted MRI and fast and persistent inhomogeneous enhancement on dynamic gadolinium-enhanced MRI.