The antidepressant-like effects of escitalopram in mice require salt-inducible kinase 1 and CREB-regulated transcription co-activator 1 in the paraventricular nucleus of the hypothalamus.

BACKGROUND: The salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) system in the paraventricular nucleus (PVN) of the hypothalamus has been demonstrated to participate in not only depression neurobiology but also the antidepressant mechanisms of fluoxetine, paroxetine, venlafaxine, and duloxetine. Like fluoxetine and paroxetine, escitalopram is also a well-known selective serotonin (5-HT) reuptake inhibitor (SSRI). However, recently it has been found that escitalopram can modulate a lot of targets other than the 5-HT system. Here, we speculate that escitalopram produces effects on the SIK1-CRTC1 system in the PVN. METHODS: Two mice models of depression (chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS)), various behavioral tests, enzyme linked immunosorbent assay (ELISA), western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer were used together in the present study. RESULTS: It was found that escitalopram administration not only significantly prevented the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induced by CSDS and CUMS, but also notably reversed the effects of CSDS and CUMS on SIK1, CRTC1, and CRTC1-CREB binding in the PVN of mice. AAV-based genetic knock-down of SIK1 in PVN neurons evidently abolished the antidepressant-like effects of escitalopram in mice. LIMITATION: A shortage of this study is that only rodent models of depression were used, while human samples were not included. CONCLUSIONS: In summary, regulating the SIK1-CRTC1 system in the PVN participates in the antidepressant mechanism of escitalopram, which extends the knowledge of the pharmacological actions of escitalopram.

Hippocampal MSK1 regulates the behavioral and biological responses of mice to chronic social defeat stress: Involving of the BDNF-CREB signaling and neurogenesis.

Depression is one of the most common psychiatric diseases in the 21st century, while its pathogenesis is not yet fully understood. Currently, besides to the monoaminergic system, the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) signaling is one of the most attractive signaling pathways for treating depression. Mitogen and stress-activated kinase (MSK) 1 and 2 are nuclear proteins activated downstream of the ERK1/2 or p38 MAPK pathways, and it has been demonstrated that MSKs are involved in the BDNF-CREB signaling. Here we assumed that MSKs may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, western blotting, immunofluorescence and virus-mediated gene transfer were used together. It was found that CSDS fully enhanced the expression of both phosphorylated MSK1 and total MSK1 in the hippocampus but not the medial prefrontal cortex (mPFC). CSDS did not influence the expression of phosphorylated MSK2 and total MSK2 in the two brain regions. Genetic over-expression of hippocampal MSK1 fully prevented not only the CSDS-induced depressive-like behaviors but also the CSDS-induced dysfunction in the hippocampal BDNF-CREB signaling and neurogenesis in mice, while genetic knockdown of hippocampal MSK1 aggravated the CSDS-induced depressive-like symptomatology in mice. Our results collectively suggest that although CSDS evidently enhances the activity of hippocampal MSK1, it is not a contributor to the CSDS-induced dysfunction in the brain but a defensive feedback regulator which protects against CSDS. Therefore, hippocampal MSK1 participates in the pathogenesis of depression and is a feasible and potential antidepressant target.

Virus-mediated decrease of LKB1 activity in the mPFC diminishes stress-induced depressive-like behaviors in mice.

As a highly prevalent neuropsychiatric disorder worldwide, the pathophysiology of depression is not yet fully understood and based on multiple factors among which chronic stress is critical. Numerous previous studies have shown the role of central mammalian target of rapamycin complex 1 (mTORC1) signaling in depression. However, so far it remains elusive by which way chronic stress down-regulates the activity of central mTORC1. Liver kinase b1 (LKB1) has been demonstrated to regulate the activity of the mTORC1 signaling cascade by phosphorylating AMP activated protein kinase (AMPK). Here, this study aimed to explore whether LKB1 participates in depression by regulating the downstream AMPK-mTORC1 signaling, and various methods including mouse models of depression, western blotting and immunofluorescence were used together. Our results showed that chronic stress significantly enhanced the expression of both phosphorylated LKB1 and total LKB1 in the medial prefrontal cortex (mPFC) but not the hippocampus. Furthermore, genetic knockdown of LKB1 in the mPFC fully reversed not only the depressive-like behaviors induced by chronic stress in mice but also the effects of chronic stress on the activity of AMPK and the mTORC1 system. Taken together, this study preliminarily suggests that LKB1 in the mPFC could be a feasible target for antidepressants. This study also provides support for the potential use of LKB1 inhibition strategies against the chronic stress-related neuropsychiatric disorders.

Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF.

As a widely-known neuropsychiatric disorder, the exact pathogenesis of depression remains elusive. MiRNA-206 (miR-206) is conventionally known as one of the myomiRs and has two forms: miR-206-3p and miR-206-5p. Recently, miR-206 has been demonstrated to regulate the biosynthesis of brain-derived neurotrophic factor (BDNF), a very popular target involved in depression and antidepressant responses. Here we assumed that miR-206 may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, quantitative real-time reverse transcription PCR, western blotting, immuofluorescence and virus-mediated gene transfer were used together. It was found that CSDS robustly increased the level of miR-206-3p but not miR-206-5p in the hippocampus. Both genetic overexpression of hippocampal miR-206-3p and intranasal administration of AgomiR-206-3p induced not only notable depressive-like behaviors but also significantly decreased hippocampal BDNF signaling cascade and neurogenesis in naïve C57BL/6J mice. In contrast, both genetic knockdown of hippocampal miR-206-3p and intranasal administration of AntagomiR-206-3p produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, it was found that the antidepressant-like effects induced by miR-206-3p inhibition require the hippocampal BDNF-TrkB system. Taken together, hippocampal miR-206-3p participates in the pathogenesis of depression by regulating BDNF biosynthesis and is a feasible antidepressant target.

Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant.

As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor α (PPARα) possesses transcriptional activity and is very important in the brain. Several reports have suggested that hippocampal PPARα is implicated in antidepressant responses. Here we speculate that hippocampal PPARα may participate in the antidepressant mechanism of vortioxetine. In this study, chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated gene knockdown methods were used together. It was found that vortioxetine administration significantly reversed the inhibitory actions of both CUMS and CSDS on the hippocampal PPARα expression. Pharmacological blockade of PPARα notably prevented the antidepressant actions of vortioxetine in the CUMS and CSDS models. Moreover, genetic knockdown of PPARα in the hippocampus also significantly blocked the protecting effects of vortioxetine against both CUMS and CSDS. Therefore, the antidepressant effects of vortioxetine in mice require hippocampal PPARα.

Prone position combined with high-flow nasal oxygen could benefit spontaneously breathing, severe COVID-19 patients: A case report.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, the overall fatality rate of severe and critical patients with COVID-19 is high and the effective therapy is limited. CASE SUMMARY: In this case report, we describe a case of the successful combination of the prone position (PP) and high-flow nasal oxygen (HFNO) therapy in a spontaneously breathing, severe COVID-19 patient who presented with fever, fatigue and hypoxemia and was diagnosed by positive throat swab COVID-19 RNA testing. The therapy significantly improved the patient's clinical symptoms, oxygenation status, and radiological characteristics of lung injury during hospitalization, and the patient showed good tolerance and avoided intubation. Additionally, we did not find that medical staff wearing optimal airborne personal protective equipment (PPE) were infected by the new coronavirus in our institution. CONCLUSION: We conclude that the combination of PP and HFNO could benefit spontaneously breathing, severe COVID-19 patients. The therapy does not increase risk of healthcare workers wearing optimal airborne PPE to become infected with virus particles.

Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. METHODS: Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. RESULTS: We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. CONCLUSION: In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling.

BACKGROUND/AIMS: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. MATERIALS: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. RESULTS: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. CONCLUSION: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

Knockdown of LSD1 ameliorates the severity of rheumatoid arthritis and decreases the function of CD4 T cells in mouse models.

Rheumatoid arthritis (RA) is an immune-mediated disease that causes chronic inflammation of the joints and involves CD4+ T cell activation. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. In the present study, we investigated the role of Lysine-specific histone demethylase 1 (LSD1) in RA. The frequency of LSD1-positive CD4+ T cells in the synovial fluid (SF) of active RA patients was higher than that of inactive RA patients. In CD4+ T cells isolated from SF of active RA patients, LSD1 downregulation significantly increased cell proliferation, as shown by MTT assay. LSD1 knockdown also significantly increased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR aasay. In CD4+ T cells isolated from SF of inactive RA patients, LSD1 was overexpressed by LSD1 plasmid transfection. As expected, LSD1 overexpression resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. LSD1 was downregulated in RA mouse by lenti-vector infection. As expected, LSD1 knockdown in vivo significantly alleviated the disease severity and increased the levels of anti-collagen II antibodies. LSD1 downregulation in the early stage was more effective to ameliorate disease severity. Our data suggested the potential therapeutic role of LSD1 in RA patients.

Expression of TREM-2 and its inhibitory effects on TNF-α induced inflammation in fibroblast-like synoviocytes via inhibiting p38 pathway activation.

OBJECTIVES: It is not clear whether TREM-2 (the "triggering receptor expressed on myeloid cells 2") is expressed in fibroblast-like synovial cells (FLSs). In this study, we aimed to determine the expression of TREM-2 in rheumatoid arthritis (RA)-FLSs and explore whether and how TREM-2 modulates the function of RA-FLSs. METHODS: Western blot and RT-PCR were used to detect the expression of TREM-2 in RA-FLSs, siRNA and lentivirus were used to down-regulate and up-regulate the expression of TREM-2 in RA-FLSs. Then mRNA expression of IL-1ß, IL-6, and MMP-13 was determined by RT-qPCR. Protein secretion of IL-1ß, IL-6, and MMP-13 in the supernatant was determined by ELISA assay; expression of cell signal transduction molecules was determined by western blot. RESULTS: A: Relative to OA-FLSs, mRNA and protein expression levels of TREM-2 in RA-FLSs are significantly elevated. TREM-2 protein is mainly expressed in the cytoplasm of RA-FLSs; B: In RA, the expression of TREM-2 was reduced at first and then up-regulated after stimulation by TNF-α. TREM-2 also inhibited the activation of TNF-α induced of inflammation in RA-FLSs by the p38 pathway, which regulates the production of cytokines and matrix metalloproteinases. CONCLUSIONS: TREM-2 expressed in RA-FLSs and TNF-α mediated reduction of inflammatory reactions. These phenomena indicated that TREM-2 may be a potential target in the treatment of RA.

LncRNA PANDAR as a prognostic marker in Chinese cancer.

BACKGROUND: LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the efficacy of PANDAR as a prognostic marker in malignant tumors. METHODS: The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between PANDAR expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between PANDAR expression and pathological parameters. RESULTS: Eight original studies covering 1,132 cancer patients were included. The pooled HR suggested that high PANDAR expression correlated with poor OS (pooled HR=1.60, 95% CI: 1.09-2.33) in cancer patients. PANDAR expression was also related to lymph node metastasis (OR=3.26, 95% CI: 2.09-5.09), advanced tumor stage (OR=3.60, 95% CI: 2.39-5.44) and histological grade (OR=2.75, 95% CI: 1.73-4.38). Begg's funnel plot showed no evidence of obvious asymmetry for overall survival and lymph node metastasis. CONCLUSIONS: Thus high PANDAR expression appears predictive of poor OS, lymph node metastasis, advanced tumor stage and histological grade in multiple cancers. This suggests PANDAR expression could serve as a biomarker of poor prognosis in Chinese cancer patients.

Ion-Catalyzed Synthesis of Microporous Hard Carbon Embedded with Expanded Nanographite for Enhanced Lithium/Sodium Storage.

Hard carbons attract myriad interest as anode materials for high-energy rechargeable batteries due to their low costs and high theoretical capacities; practically, they deliver unsatisfactory performance due to their intrinsically disordered microarchitecture. Here we report a facile ion-catalyzed synthesis of a phenol-formaldehyde resin-based hard-carbon aerogel that takes advantage of the chelation effect of phenol and Fe3+, which consists of a three-dimensionally interconnected carbon network embedded with hydrogen-rich, ordered microstructures of expanded nanographites and carbon micropores. The chelation effect ensures the homodispersion of Fe in the polymer segments of the precursor, so that an effective catalytic conversion from sp3 to sp2 carbon occurs, enabling free rearrangement of graphene sheets into expanded nanographite and carbon micropores. The structural merits of the carbon offer chances to achieve lithium/sodium storage performance far beyond that possible with the conventional carbon anode materials, including graphite and mesocarbon microbeads, along with fast kinetics and long cycle life. In this way, our hard carbon proves its feasibility to serve as an advanced anode material for high-energy rechargeable Li/Na batteries.

Epigallocatechin-3-gallate protects against tumor necrosis factor alpha induced inhibition of osteogenesis of mesenchymal stem cells.

Anabolic bone accruement through osteogenic differentiation is important for the maintenance of physiological bone mass and often disrupted in various inflammatory diseases. Epigallocatechin-3-gallate, as an antioxidant and anti-inflammatory agent, has been suggested for potential therapeutic use in this context, possibly by the inhibition of bone resorption as well as the enhancement of bone formation through directly activating osteoblast differentiation. However, the reported effects of epigallocatechin-3-gallate modulating osteoblast differentiation are mixed, and the underlying molecular mechanism is still elusive. Moreover, there is limited information regarding the effects of epigallocatechin-3-gallate on osteogenic potential of mesenchymal stem cell in inflammation. Here, we examined the in vitro osteogenic differentiation of human mesenchymal stem cells. We found that the cell viability and osteoblast differentiation of human bone marrow-derived mesenchymal stem cells are significantly inhibited by inflammatory cytokine TNFα treatment. Epigallocatechin-3-gallate is able to enhance the cell viability and osteoblast differentiation of mesenchymal stem cells and is capable of reversing the TNFα-induced inhibition. Notably, only low doses of epigallocatechin-3-gallate have such benefits, which potentially act through the inhibition of NF-κB signaling that is stimulated by TNFα. These data altogether clarify the controversy on epigallocatechin-3-gallate promoting osteoblast differentiation and further provide molecular basis for the putative clinical use of epigallocatechin-3-gallate in stem cell-based bone regeneration for inflammatory bone loss diseases, such as rheumatoid arthritis and prosthetic osteolysis.

Lentiviral Vector-Mediated p27kip1 Expression Facilitates Recovery After Spinal Cord Injury.

Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction attributable to both mechanical damage and secondary biochemical and physiological responses. Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. Increased cell cycle protein is associated with neuronal and oligodendroglial apoptosis, reactive astrogliosis, glial scar formation, and microglial activation. Here, using lentiviral vectors (LV), we induced the expression of the cyclin-dependent kinase (CDK) inhibitor p27kip1 in the lesioned spinal cord of adult rat. Treatment with LV-p27kip1 significantly reduced the expression of cell cycle proteins and improved functional recovery. In addition, p27kip1 overexpression also reduced lesion volume, decreased astrocytic reactivity, attenuated microglial activation, reduced cell death, and improved the local microenvironment. We suggest that these effects reflect the ability of p27kip1 to inhibit cell cycle pathways. Thus, the present study provides further support for the therapeutic potential of cell cycle inhibitors in the treatment of SCI.

EGFR-AKT-mTOR activation mediates epiregulin-induced pleiotropic functions in cultured osteoblasts.

Epidermal growth factor (EGF) receptor (EGFR) emerges as an essential molecule for the regulating of osteoblast cellular functions. In the current study, we explored the effect of epiregulin, a new EGFR ligand, on osteoblast functions in vitro, and studied the underlying mechanisms. We found that epiregulin-induced EGFR activation in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, epiregulin activated AKT-mammalian target of rapamycin (mTOR) and Erk-mitogen-activated protein kinase (MAPK) signalings in cultured osteoblasts, which were blocked by EGFR inhibitor AG1478 or monoclonal antibody against EGFR (anti-EGFR). Further, in primary and MC3T3-E1 osteoblasts, epiregulin promoted cell proliferation and increased alkaline phosphatase activity, while inhibiting dexamethasone (Dex)-induced cell death. Such effects by epiregulin were largely inhibited by AG1478 or anti-EGFR. Notably, AKT-mTOR inhibitors, but not Erk inhibitors, alleviated epiregulin-induced above pleiotropic functions in osteoblasts. Meanwhile, siRNA depletion of Sin1, a key component of mTOR complex 2 (mTORC2), also suppressed epiregulin-exerted effects in MC3T3-E1 cells. Together, these results suggest that epiregulin-induced pleiotropic functions in cultured osteoblasts are mediated through EGFR-AKT-mTOR signalings.

EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in cultured osteoblasts.

Pleiotrophin (Ptn) plays an important role in bone growth through regulating osteoblasts' functions. The underlying signaling mechanisms are not fully understood. In the current study, we found that Ptn induced heparin-binding epidermal growth factor (HB-EGF) release to trans-activate EGF-receptor (EGFR) in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, Ptn activated Akt and Erk signalings in cultured osteoblasts. The EGFR inhibitor AG1478 as well as the monoclonal antibody against HB-EGF (anti-HB-EGF) significantly inhibited Ptn-induced EGFR activation and Akt and Erk phosphorylations in MC3T3-E1 cells and primary osteoblasts. Further, EGFR siRNA depletion or dominant negative mutation suppressed also Akt and Erk activation in MC3T3-E1 cells. Finally, we observed that Ptn increased alkaline phosphatase (ALP) activity and inhibited dexamethasone (Dex)-induced cell death in both MC3T3-E1 cells and primary osteoblasts, such effects were alleviated by AG1478 or anti-HB-EGF. Together, these results suggest that Ptn-induced Akt/Erk activation and some of its pleiotropic functions are mediated by EGFR trans-activation in cultured osteoblasts.

Helicobacter pylori infection contributes to high risk of ischemic stroke: evidence from a meta-analysis.

Chronic infection of Helicobacter pylori (H. pylori) in ischemic stroke (IS) incidence has been previously studied in several publications; however, conflicting results have been reported. A meta-analysis was used to assess whether chronic infection of H. pylori was associated with risk of IS, and which of the following was more effective for predication of IS risk, antibody IgG of H. pylori (anti-H. pylori IgG), antibody IgG of cytotoxin-associated gene-A (anti-Cag A IgG) or the (13)C-urea breath test. We searched the databases of Medline and Embase, and latest update was January 1, 2012. Case-control studies were considered to be eligible. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated using the random-effect model. A total of 13 studies including 4,041 participants were included in this meta-analysis. Of these studies, ten, four and four studies were for anti-H. pylori IgG, anti-Cag A IgG and the (13)C-urea breath test, respectively. Combined analysis indicated that positive anti-H. pylori IgG, anti-Cag A IgG and (13)C-urea breath test were significantly associated with increased risk of IS, respectively, and positive anti-Cag A IgG was more effective for predication of IS risk [OR (95 % CI) = 1.60 (1.21-2.11), P (heterogeneity) = 0.001 for positive versus negative anti-H. pylori IgG; 2.33 (1.76-3.09), P (heterogeneity) = 0.71 for positive versus negative anti-Cag A IgG and 1.65 (1.11-2.47), P (heterogeneity) = 0.17 for positive versus negative (13)C-urea breath test]. In addition, we found that positive anti-H. pylori IgG was closely associated with risk of IS caused by atherosclerosis and small artery disease, but not for cardioembolic IS. This meta-analysis indicated that chronic H. pylori infection was significantly associated with an increased risk of IS, especially for non-cardioembolic IS. Compared with anti-H. pylori IgG and the (13)C-urea breath test, anti-Cag A IgG seemed more effective for prediction of risk of IS.

Ovarian interstitial blood flow changes assessed by transvaginal colour Doppler sonography: predicting ovarian endometrioid cyst-induced injury to ovarian interstitial vessels.

PURPOSE: To evaluate the blood flow changes and their relationships to microvessel density (MVD) and thrombospondin-1 (TSP-1) by transvaginal colour Doppler sonography (TV-CDS) in the ovarian interstitium to predict ovarian interstitial microvascular injury in the pathological process of ovarian endometrial cysts (OEC). METHODS: TV-CDS was preoperatively performed to detect blood flow changes in 60 patients with 76 ovarian endometrioid cysts, and flow classification and resistance indices (RI) values were recorded for analysis. Ovarian interstitial specimens with blood flow signals were collected for postoperative pathologic examination. TSP-1 protein was evaluated by immunohistochemistry and Western blot, TSP-1 mRNA by reverse transcriptase polymerase chain reaction, microvessels by CD34 antibody, and MVD by image analysis. Thirty age-matched patients with benign ovarian tumours served as controls. RESULTS: Blood flow, most of star-shaped, within ovarian interstitial arteries in the OEC group was diminished; however, arterial spectra exhibited a high-resistance flow manifesting a significantly higher RI compared with that of the control group (P < 0.01). In ovarian interstitial specimens, there were significantly (P < 0.01) lower CD34-MVD and higher TSP-1 protein and mRNA in the OEC group than in the controls. CD34-MVD and TSP-1 showed remarkably negative correlation (rs = -0.76, P < 0.01). RI values correlated negatively with MVD values (rs = -0.91, P < 0.01), but positively with TSP-1 (rs = 0.81, P < 0.01), while flow classification correlated positively with MVD values (rs = 0.66, P < 0.01), but negatively with TSP-1 (rs = -0.54, P < 0.01). CONCLUSIONS: Changes in CD34-MVD and TSP-1 reflected ovarian interstitial microvascular injury of OEC, pathologically supported the findings of blood flow changes within ovarian interstitial arteries, and prospectively predicted OEC-induced ovarian interstitial vessel injury. This has important clinical value: early treatment, instead of allowing the cyst to become bigger, is of great importance for OEC patients, because a greater number of functional tissue blood vessels would be destroyed as the disease progresses.

Influence of personal character on quality of life of patients with esophageal cancer in north Henan province and influencing factors.

The aim of this study was to investigate QoL (quality of life) of patients with esophageal cancer in northern Henan province, China, and to accurate evaluate and reflect the relationship between patient characteristics and QoL. In the high risk area of esophageal cancer in the north of Henan province, 735 patients with esophageal cancer were investigated. The Eysenck personality questionnaire (EPQ) and QoL were analyzed by using the questionnaire of general situation, EPQ, QLQ-C30 and QLQ-OES18. The effects of personal character on the QoL of esophageal carcinoma patients were analyzed by SPSS 11.0 software. The QoL of esophageal cancer patients in Northern Henan region was significantly affected by character. The difference between choleric and type of melancholic temperament types was significant (P<0.01), also in OESEAT, OESTA, OESCO and OESSP (P<0.05). Differences in personal character can thus influence the quality of esophageal cancer patient lives.

Expression of ß-1,4-galactosyltransferase I in a surgically-induced rat model of knee osteoarthritic synovitis.

BACKGROUND: There are few reports of a biological role for glycosyltransferases in the infiltration of osteoarthritic synovitis. The aim of this research was to investigate the expression and cellular location of ß-1,4-galactosyltransferase I (ß-1,4-GalT-I) in a surgically-induced rat model of knee osteoarthritis (OA), and explore the role of ß-1,4-GalT-I in the pathogenesis of OA. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: OA group, sham group and normal group. The model of OA was established in the right knees of rats by anterior cruciate ligament transaction (ACLT) with partial medial meniscectomy. Fibroblast-like synoviocytes (FLSs) obtained from normal rat synovial tissue were cultured. The expression of ß-1,4-GalT-I mRNA in the synovial tissue, articular cartilage and FLSs treated with tumor necrosis factor-α (TNF-α) were assayed by real-time PCR. Western-blotting and immunohistochemisty were used to observe the expression of ß-1,4-GalT-I at the protein level. Double immunofluorescent staining was used to define the location of the ß-1,4-GalT-I with macrophage-like synoviocytes, FLSs, neutrophils, and TNF-α in the OA synovium. The alteration of TNF-α in FLSs which were treated with lipopolysaccharide (LPS) and ß-1,4-GalT-I-Ab were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mRNA and protein expression of ß-1,4-GalT-I increased in synovial tissue of the OA group compared with the normal and sham groups at two and four weeks after the surgery, however, no significant difference appeared in the articular cartilage. Immunohistochemistry also indicated that the ß-1,4-GalT-I expression in OA synovium at four weeks after surgery increased sharply compared with the control group. ß-1,4-GalT-I co-localized with macrophage-like synoviocytes, FLSs, neutrophils and TNF-α in rat OA synovitis. Moreover, in vitro ß-1,4-GalT-I mRNA in FLSs was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that the expression of TNF-α was attenuated in FLSs in vitro when treated with anti ß-1,4-GalT-I antibody. CONCLUSION: ß-1,4-GalT-I may play an important role in the inflammation process of rat OA synovial tissue which would provide the foundation for further researching into the concrete mechanism of ß-1,4-GalT-I in OA synovitis.