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Objective: Toobserve the clinical effect of extracorporeal shock wave combined with hot magner therapy for nonspecific chronic neck pain. Methods: A total of 60 patients with nonspecific chronic neck pain were randomly divided into treatment group and control group. Patients in the treatment group were treated with extracorporeal shock wave combined with hot magner therapy, and patients in the control group were treated with hot magner therapy. Visual analogue scale (VAS) and Neck disability index (NDI) were used before treatment, 2 weeks after treatment, and 3 months after treatment. Results: Two weeks after treatment, the VAS and NDI scores were improved (P<0.05), and the VAS and NDI scores of the treatment group were lower than those of the control group (P<0.05), and the improvement rate of the treatment group was significantly better than that of the control group (P<0.05). 3 months after follow up treatment, VAS and NDI scores in the treatment group showed statistically significant differences with those before treatment(P<0.05),and those at 2 weeks after treatment(P>0.05), while VAS and NDI scores in the control group showed no statistically significant differences with those before treatment(P>0.05),and those at 2 weeks after treatment(P<0.05).The VAS and NDI scores in the treatment group were significantly better than those in the control group(P<0.05).Conclusion: The clinical efficacy of extracorporeal shock wave combined with hot magner treatment for nonspecific chronic neck pain is better than that of hot magner therapy. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are genetic regulators that were earlier considered as “junk”. In contrast to linear RNAs, they have covalently linked ends with no polyadenylated tails. CircRNAs can act as RNA-binding proteins, sequestering agents, transcriptional regulators, as well as microRNA sponges. In addition, it is reported that some selected circRNAs are transformed into functional proteins. These RNA molecules always circularize through covalent bonds, and their presence has been demonstrated across species. They are usually abundant and stable as well as evolutionarily conserved in tissues (liver, lung, stomach), saliva, exosomes, and blood. Therefore, they have been proposed as the “next big thing” in molecular biomarkers for several diseases, particularly in cancer. Recently, circRNAs have been investigated in cardiovascular diseases (CVD) and reported to play important roles in heart failure, coronary artery disease, and myocardial infarction. Here, we review the recent literature and discuss the impact and the diagnostic and prognostic values of circRNAs in CVD. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic sudden sensorineural hearing loss is a clinical emergency with an increased incidence of occurrence in recent years. Hyperbaric oxygen has been widely used in the clinical treatment of sudden hearing loss. However, prognostic factors related to its curative effects are still not clear, which hinders its clinical application. The aim of this study was to investigate the efficacy and prognostic factors of hyperbaric oxygen therapy (HBOT) plus drug therapies in the treatment of sudden hearing loss. Method: Patients with sudden hearing loss who were treated with hyperbaric oxygen from April to October 2017 were retrospectively included. Clinical information was collected, including pure-tone audiometry data before and after hyperbaric oxygen treatment, age, gender, hearing curve classification, concomitant symptoms, history of diseases (diabetes and hypertension), history of hormone therapy, start time of hyperbaric oxygen treatment, and total number of hyperbaric oxygen treatments. The prognostic factors were analyzed with univariate and multivariate analyses. Results: Sixty-four patients with sudden hearing loss were enrolled, including 7 cases of low-frequency loss, 4 cases of high-frequency loss, 32 cases of flat loss, and 21 cases of complete hearing loss. After HBOT, there were 16 cases (25%) of complete recovery, 15 cases (23.43%) of partial recovery, 7 cases (10.93%) of slight improvement, and 26 cases (40.63%) of no improvement. The total effective rate was 59.37%. Twelve of 21 cases (57.14%) of complete hearing loss showed recovery. Multivariate logistic regression analysis showed that the start time of HBOT ≤ 7 days from disease onset was independently associated with hearing recovery (OR = 27.763, 95% CI [4.209, 183.115], p = .001). Conclusion: Combined HBOT can improve the hearing impairment of sudden hearing loss. The early HBOT showed the most promising therapeutic effects, especially among patients with complete hearing loss. [ABSTRACT FROM AUTHOR]

Bladder pain is a prominent symptom of interstitial cystitis/painful bladder syndrome. Hydrogen sulfide (H2S) generated by cystathionine γ-synthase (CBS) or cystathionine β-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H2S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H2S in this model was evaluated by intraperitoneal preadministration of D,L-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H2S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H2S signaling was upregulated in PAR4-induced bladder pain models, and H2S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H2S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H2S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H2S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior. [ABSTRACT FROM AUTHOR]

Background/Aims: Emerging evidence suggests that autophagy plays important roles in the pathophysiological processes of cerebral ischemia and reperfusion injury. Calycosin, an isoflavone phytoestrogen, possesses neuroprotective effects in cerebral ischemia and reperfusion in rats. Here, we investigated the neuroprotective effects of calycosin against ischemia and reperfusion injury, as well as related probable mechanisms behind autophagy pathways. Methods: A cerebral ischemic and reperfusion injury model was established by middle cerebral artery occlusion in male Sprague-Dawley rats. Neurological scores, infarct volumes, and brain water content were assessed after 24 h reperfusion following 2 h ischemia. Additionally, the expression of the autophagy-related protein p62 and NBR1 (neighbor of BRCA1 gene 1), as well as Bcl-2, and TNF-a in rat brain tissues was measured by RT-PCR, western blotting and immunohistochemical analyses. Results: The results showed that calycosin pretreatment for 14 days markedly decreased infarct volume and brain edema, and ameliorated neurological scores in rats with focal cerebral ischemia and reperfusion. It was observed that levels of p62, NBR1 and Bcl-2 were greatly decreased, and levels of TNF-a significantly increased after ischemia and reperfusion injury. However, calycosin administration dramatically upregulated the expression of p62, NBR1 and Bcl-2, and downregulated the level of TNF-a. Conclusions: All data reveal that calycosin exerts a neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms maybe associated with its antiautophagic, anti-apoptotic and anti-inflammatory action. [ABSTRACT FROM AUTHOR]

Background: Vascular dementia (VaD) is the second common form of dementia and Chinese herbal medicine (CHM) has been used for aging-related disorders for thousands of years. However, there is still a lack of scientific evidence using CHM for VaD.Objective: To conduct a systematic review to assess the current evidence available for the effectiveness and safety of CHM for VaD.Methods: Six databases were searched for high-quality randomized-controlled clinical trials that met the requirements of at least 4 of the 7 domains of the Cochrane risk of bias tool from their inception to February 2017. RevMan 5.3 was applied for data analysis.Results: Forty studies with 42 comparisons and 3,572 individuals were included. The studies investigated the CHM versus placebo (n = 4), CHM versus western conventional treatment (WCT) (n = 36), and CHM plus WCT versus WCT (n = 2). Meta-analysis showed that CHM for VaD could improve Mini-Mental State Examination (MMSE), the Activities of Daily Living, Hasegawa's dementia scale, and clinical effective rate but had statistically similar effect based on Blessed Behavior Scale (BBS) outcome when compared with WCTs. When compared with placebo, CHMs were more beneficial in improving MMSE but showed no significant difference in BBS scores. CHM as adjuvant therapy exerted an additive anti-VaD benefit on MMSE scores. The participants of CHM group had fewer adverse events than that of the placebo group or WCT group.Conclusion: The findings of the present study support, at least to an extent, that CHM can be recommended for routine use for treatment of VaD. [ABSTRACT FROM AUTHOR]

Vitamin D (VD) has exhibited immunomodulatory role in the pathogenesis of preeclampsia. We hypothesize VD potentiate nifedipine treatment for preeclampsia by shortened the time to control blood pressure and prolong time before subsequent hypertensive crisis. We conduct a randomized trial of 683 primigravid women with preeclampsia, who were assigned to different treatment groups, either nifedipineCplacebo or nifedipineCVD orally, by random after screening. Primary endpoints include time to control hypertension and time before another hypertensive crisis. Maternal adverse effects including nausea, vomiting, chest pain, mild headache, dizziness, maternal tachycardia, hypotension or shortness of breath, and neonatal parameters including birth weight and Apgar scores, as well as the minimum number of dosages needed to control hypertension were defined as secondary endpoints. Serum levels of cytokines tumor necrosis factor-a (TNF-α) and interleukin-10 (IL-10) were also examined. There was a marked reduction of the time required to control hypertension and a significant lengthening (p = 0.013) of the time before a new hypertensive crisis in participants received nifedipineCVD treatments (41.8 ± 18.3 min), in comparison with the nifedipineCplacebo controls (61.1 ± 15.9 min). In women treated with nifedipineCVD, the minimum number of dosages needed to control hypertension was also lower. With regard to adverse effects, no statistical difference was observed between the two treatment groups. Moreover, treatment with VD increased IL-10 and reduced TNF-α serum levels. VD possesses the potential of serving as a safe and effective adjuvant to oral nifedipine in treating women with preeclampsia against hypertension, possibly through the upregulation of IL-10 and the downregulation of TNF-α. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed, a new and novel agent for primary central nervous system lymphomas (PCNSLs), has shown to be efficient as a savage therapy for recurrent PCNSLs. However, more studies are needed. A prospective study was performed on 17 recurrent PCNSL patients with pemetrexed at Shandong Tumor Hospital in China to assess the efficacy and safety of pemetrexed for recurrent PCNSL patients. Materials and methods: The medical records and imaging data on all the cases of recurrent PCNSL patients with pemetrexed in our study were collected during August 2012 and April 2015. Folic acid, B12, and dexamethasone were used to induce toxicities related to pemetrexed. Patients were treated with pemetrexed at a dose of 900 mg/m2 intravenously every 3 weeks, and one cycle consists of 6 weeks. Results: A total of 17 cases of recurrent PCNSL patients were enrolled in our study, including 10 males and 7 females with a median age of 66.2 years (ranging from 35 to 81). After the treatment, five cases had complete remission, with partial remission in five cases, stable disease in four cases, and progressive disease in three cases. Consequently, the overall response rate was 58.8%, and the disease control rate was 82.4%. The median overall survival was 7.8 months (95% confidence interval: 5.9-9.6 months) in the study of recurrent PCNSL patients. Conclusion: This study has been the first clinical trial that applied pemetrexed to treat recurrent PCNSL patients in China, and results indicated that chemotherapy using large pemetrexed may become an effective treatment for PCNSL recurrence with modest toxicity. [ABSTRACT FROM AUTHOR]

Background: Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a sensitive method for detecting metastatic papillary thyroid carcinoma (PTC). However, the diagnostic threshold is not well established and the influence of the thyroid gland on the cutoff value is also controversial. In this study, patients were classified into two groups according to the presence or absence of thyroid tissue, to determine an appropriate cutoff value for clinical practice.Methods: Patients with a history of thyroid nodules or surgery for PTC and with enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA detection.Results: One hundred ninety-six lymph nodes (189 patients) were included: 100 from preoperative patients, 49 from patients treated with partial thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%). Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in patients without thyroids.Conclusions: The cutoff value for Tg-FNA is influenced by residual thyroid tissue, and a higher cutoff value is recommended for patients with thyroids than for patients without thyroids. [ABSTRACT FROM AUTHOR]

As an anticancer agent, irinotecan (CPT-11) has been widely applied in clinical, especially in the treatment of colorectal cancer. However, its clinical use has long been limited by the side effects and potential tissue toxicity. To discriminate the target toxic tissues and dissect the specific response of target tissues after CPT-11 administration in rats, untargeted metabolomic study was conducted. First, differential metabolites between CPT-11 treated group and control group in each tissue were screened out. Then, based on fold changes of these differential metabolites, principal component analysis and hierarchical cluster analysis were performed to visualize the degree and specificity of the influences of CPT-11 on the metabolic profiles of nine tissues. Using this step-wise method, ileum, jejunum, and liver were finally recognized as target toxic tissues. Furthermore, tissue specific responses of liver, ileum, and jejunum to CPT-11 were dissected and specific differential metabolites were screened out. Perturbations in Krebs cycle, amino acid, purine and bile acid metabolism were observed in target toxic tissues. In conclusion, our study put forward a new approach to dissect target toxic tissues and tissue specific responses of CPT-11 using metabolomics. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-g and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection. [ABSTRACT FROM AUTHOR]

The inflammatory response is an important source of secondary damage to neuronal tissue in the spinal cord following spinal cord injury (SCI). Hyperbaric oxygen (HBO) therapy reduces inflammation and promotes the restoration of locomotor function following SCI, however, the mechanisms underlying this effect remain to be determined. The aim of the current study was to investigate the mechanisms by which HBO therapy promotes recovery in a rat model of SCI by measuring expression levels of receptor for advanced glycation end products (RAGE) and monocyte chemoattractant protein-1 (MCP-1) in spinal cord tissue. Experimental animals (n=90) were divided into three groups: Sham-operated (SH), SCI (T-10 laminectomy) and SCI + HBO. Each group was further divided into five subgroups (n=6) that were examined at 12 h, and at 1, 3, 7 and 14 days post-injury. Recovery of locomotor function was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring system. Neutrophil infiltration was analyzed using myeloperoxidase (MPO) activity assays. The expression of RAGE and MCP-1 was measured by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting. RAGE and MCP-1 expression and MPO activity were higher in the SCI groups than in the SH groups at each time point. HBO therapy reduced RAGE and MCP-1 expression and MPO activity compared with untreated, injured animals at early post-injury stages. In addition, HBO therapy improved BBB scores at post-operative day 7 and 14. HBO therapy was, therefore, demonstrated to relieve secondary inflammatory responses, potentially by inhibiting the expression of RAGE and MCP-1, resulting in significant recovery of locomotor function. The results of the present study may, therefore, be useful in improving the clinical application of HBO therapy for patients with SCI. [ABSTRACT FROM AUTHOR]

Background: Astaxanthin is a carotenoid pigment that possesses potent antioxidative, anti-inflammatory, antitumor, and immunomodulatory activities. Previous studies have demonstrated that astaxanthin displays potential neuroprotective properties for the treatment of central nervous system diseases, such as ischemic brain injury and subarachnoid hemorrhage. This study explored whether astaxanthin is neuroprotective and ameliorates neurological deficits following traumatic brain injury (TBI).Results: Our results showed that, following CCI, treatment with astaxanthin compared to vehicle ameliorated neurologic dysfunctions after day 3 and alleviated cerebral edema and Evans blue extravasation at 24 h (p < 0.05). Astaxanthin treatment decreased AQP4 and NKCC1 mRNA levels in a dose-dependent manner at 24 h. AQP4 and NKCC1 protein expressions in the peri-contusional cortex were significantly reduced by astaxanthin at 24 h (p < 0.05). Furthermore, we also found that bumetanide (BU), an inhibitor of NKCC1, inhibited trauma-induced AQP4 upregulation (p < 0.05).Conclusions: Our data suggest that astaxanthin reduces TBI-related injury in brain tissue by ameliorating AQP4/NKCC1-mediated cerebral edema and that NKCC1 contributes to the upregulation of AQP4 after TBI. [ABSTRACT FROM AUTHOR]

Background: Paraneoplastic neurological syndromes (PNS) are rare disorders associated with malignant tumours, which are triggered by autoimmune reactions. Paraneoplastic cerebellar degeneration (PCD) is the PNS type most commonly associated with ovarian and breast cancer. Two bladder cancers manifesting in PCD were previously reported. However, the cancers in these cases had poor outcomes.Case Presentation: Here, we present a 68-year old man with history of high-grade papillary urothelial carcinoma of the bladder. The patient suffered from persistent cerebellar ataxia accompanied by bladder cancer recurrence five months after transurethral resection of the bladder tumour (TURBt). Laboratory screening for the specific antibodies of paraneoplastic neurological syndromes revealed no positive results. Symptoms were not remitted after a 7-day-course of high-dose glucocorticoid therapy. To our surprise, the patient recovered fully after laparoscopic radical cystectomy. Postoperative pathology revealed that surgical specimens were urothelial carcinoma in situ (CIS) and squamous cell carcinoma of the bladder. The patient remained asymptomatic and there was no evidence of recurrence after the followup period of 11 months.Conclusion: To our knowledge, this is the third report of PCD in a patient with bladder cancer. This case showed that tumour resection cured the PCD. To assist clinical evaluation and management, literature regarding basic PNS characteristics and bladder cancers was reviewed. [ABSTRACT FROM AUTHOR]

Introduction. Luteolin, a falconoid compound in many Chinese herbs and formula, plays important roles in cardiovascular diseases. The underlying mechanism of luteolin remains to be further elaborated. Methods. A model of hydrogen peroxide- (H2O2-) induced H9C2 cells apoptosis was established. Cell viabilities were examined with an MTT assay. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) and flow cytometry were used to detect ROS level and apoptosis rate, respectively. The expressions of signaling proteins related to apoptosis were analyzed by western blot and mRNA levels were detected by real-time polymerase chain reaction (PCR). Quercetin was applied as positive drug. Results. Incubation with various concentrations of H2O2 (0, 50, 100, and 200 μM) for 1 h caused dose-dependent loss of cell viability and 100 μM H2O2 reduced the cell viability to approximately 50%. Treatments with luteolin and quercetin protected cells from H2O2-induced cytotoxicity and reduced cellular ROS level and apoptosis rate. Moreover, luteolin could downregulate the expressions of Bax, caspase-8, cleaved-caspase-3, and p53 in apoptotic signaling pathway. Further study showed that the expressions of Akt, Bcl-2, and Mdm2 were upregulated by luteolin. Conclusion. Luteolin protects H9C2 cells from H2O2-induced apoptosis. The protective and antiapoptotic effects of luteolin could be mediated by regulating the Akt-P53/Mdm2 apoptotic pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adrenomedullin levels in the peripheral blood are associated with prognosis of some cancers. Intermedin is structural similarities to adrenomedullin. OBJECTIVE: The current study aimed to investigate the prognostic value of plasma intermedin levels for progression and distant metastasis in prostate cancers. METHODS: This study included 218 patients undergoing radical prostatectomy for localized prostatic cancer and 218 agematched healthy men. Plasma intermedin levels were measured using radioimmunoassay. The relationships between plasma intermedin levels and 5-year progression and 5-year distant metastasis were evaluated using a multivariate analysis. RESULTS: Plasma intermedin levels were markedly higher in all patients than in healthy men. Patients with Gleason score ≥ 7, tumor node metastasis stage T2, organ unconfined, present extra-prostatic extension, seminal vesicle invasion or positive lymph node had higher intermedin levels. Intermedin was identified as a prognostic predictor for 5-year progression and 5-year metastasis. Under receiver operating characteristic curves, intermedin had high predictive values for 5-year progression and 5-year metastasis. CONCLUSIONS: Elevated plasma intermedin levels are independently associated with long-term recurrence and distant metastasis of prostate cancer and intermedin has potential to be a prognostic predictive biomarker for prostate cancer. [ABSTRACT FROM AUTHOR]

Background With the recent attention to evidence-based medicine in psychiatry, a number of treatment guidelines for bipolar disorders have been published. This survey investigated prescribing patterns and predictors for guideline disconcordance in the acute treatment of a manic and mixed episode across mainland China. Methods The pharmacological treatments of 2828 patients with a recent hypomanic/manic episode or mixed state were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments. Results The most common pattern of pharmacological treatments for an acute manic or mixed episode was a mood stabilizer plus an atypical antipsychotic (n = 1345, 47.6%), and the rate of guideline-disconcordant treatments was 11.1%. The patients who were treated in general hospitals were more likely to receive guideline-disconcordant treatments than those who were treated in psychiatric hospitals, with an OR of 1.84 (95% CI 1.44-2.36). Similarly, the patients with a mixed episode at study entry were more likely to receive guideline-disconcordant treatments than those with a manic episode, with an OR of 1.69 (95% CI 1.22-2.35). In contrast, the patients with a longer duration of disease (>5 years) were less likely to receive guideline-disconcordant treatments than those with a short duration, with an OR of 0.47 (95% CI 0.36-0.60). Conclusions In mainland China, the disconcordance with treatment guidelines for a most recent acute manic or mixed episode was modest under naturalistic conditions. The higher risk for disconcordance in general hospitals than in psychiatric hospitals suggests that special education based on treatment guidelines to practitioners in general hospitals is necessary in order to reduce the risk for disconcordant treatments. [ABSTRACT FROM AUTHOR]

Background: Paroxetine, a selective serotonin reuptake inhibitor for counteracting depression, has been recently suggested as having a role in prevention of dopaminergic neuronal degeneration in substantia nigra, a hallmark of Parkinson's disease (PD). The pathogenesis of this type of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus in this study we aimed to understand the role of paroxetine in microglia activation and to elucidate the underlying mechanism(s). Methods: BV2 and primary microglial cells were pretreated with paroxetine and stimulated with lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory mediator and cytokines, and the related signaling pathways were evaluated and analyzed in BV2 cells. Results: Paroxetine significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α and IL-1β. Further analysis showed inducible nitric oxide synthase (iNOS) and mRNA expression of TNF-α and IL-1β were attenuated by paroxetine pretreatment. Analyses in signaling pathways demonstrated that paroxetine led to suppression of LPS-induced JNK1/2 activation and baseline ERK1/2 activity, but had little effect on the activation of p38 and p65/NF-κB. Interference with specific inhibitors revealed that paroxetine-mediated suppression of NO production was via JNK1/2 pathway while the cytokine suppression was via both JNK1/2 and ERK1/2 pathways. Furthermore, conditioned media culture showed that paroxetine suppressed the microglia-mediated neurotoxicity. Conclusions: Paroxetine inhibits LPS-stimulated microglia activation through collective regulation of JNK1/2 and ERK1/2 signaling. Our results indicate a potential role of paroxetine in neuroprotection via its anti-neuroinflammatory effect besides targeting for depression. [ABSTRACT FROM AUTHOR]

Background Endoscopic transsphenoidal surgery has gradually come to be regarded as a preferred option in the treatment of pituitary adenomas because of its advantages of improved visualization and its minimal invasiveness. The aim of this study was to compare and evaluate the outcomes and complications of endoscopic and microscopic transsphenoidal surgery in the treatment of pituitary adenomas. Methods We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library and the Web of Science between January 1992 and May 2013. Studies with consecutive patients that explicitly and fully compared endoscopic and microscopic approaches in the treatment of pituitary adenomas were included. Results A total of 15 studies (n = 1,014 patients) met the inclusion criteria among 487 studies that involved endoscopic surgery and 527 studies that dealt with microscopic surgery. The rate of gross tumor removal was higher in the endoscopic group than in the microscopic group. The post-operative rates of septal perforation were less frequent in patients who underwent endoscopic surgery. There was no significant difference between the two techniques in the incidence rates of meningitis, diabetes insipidus, cerebrospinal fluid leak, epistaxis or hypopituitarism. The post-operative hospital stay was significantly shorter for the endoscopic surgery group compared with the microscopic surgery group (P < 0.05). There was no significant difference in the length of the operation (P > 0.05). Conclusions The present study indicates that the endoscopic transsphenoidal approach is safer and more effective than microscopic surgery in the treatment of pituitary adenomas. [ABSTRACT FROM AUTHOR]

Intramedullary spinal cord metastases (ISCMs) are rare and account for 4-8.5% of central nervous system metastases. Only one case of biopsy-proven ISCM due to prostate cancer has previously been reported. The current study presents an additional unique case of a 74-year-old male who developed symptoms from an intramedullary conus medullaris metastasis as the first manifestation of prostate adenocarci-noma. To the best of our knowledge, this scenario is even more rare and has not previously been reported. The tumor was radically resected, followed by androgen blockade treatment. The patient's neurological deficit significantly improved, with no tumor recurrence during the follow-up period. In addition, the present study provides an overview of the previous literature concerning ISCMs from prostate cancer, and discusses the treatment options. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have pivotal functions in extracellular matrix turnover and are involved in chronic kidney diseases. However, the exact functions of MMPs in chronic renal failure (CRF) have yet to be demon-strated. The aim of the present study was to examine the effects of MMP-9 on CRF. An adenine-induced model of CRF was generated in rabbits. Following the injection of MMP 9 into the renal arteries of the rabbits, significant improvements in renal morphology and serum levels of creatinine and urea nitrogen were observed. Furthermore, MMP-9 administration was shown to decrease the serum TIMP-1 concentration and upregulate renal MMP-9 expression. These results demonstrate a directly protective role for MMP-9 in CRF. [ABSTRACT FROM AUTHOR]

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin's lymphoma limited to the CNS. Treatment of PCNSL with high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with high rates of relapse and severe treatment-related neurotoxicity . Aim: To report our experience of treating newly diagnosed PCNSL with temozolomide, nedaplatin, and vincristine (TNV), as the replacement of HD-MTX, in combination with concurrent chemoradiotherapy . Materials and Methods: Newly diagnosed PCNSL patients were given concurrent temozolomide (75 mg/m², orally) daily during WBRT. Then, the TNV regimen was given after four weeks. The TNV regimen consisted of temozolomide (200 mg/m² orally: Days 1-5), nedaplatin (80 mg/m intravenous: Day 1), and vincristine (1.4 mg/m² intravenous: Day 1). Each cycle was of a duration of four weeks and a maximum of six cycles were applied. The primary end point was response to treatment obtained by magnetic resonance imaging (MRI). Secondary end points were progression-free survival (PFS) and fewer toxic effects. Results: The study subjects included 14 patients (median age: 53.5, median Karnofsky Performance Scale (KPS): 75). The median number of TNV cycles given was five. Response to treatment: Complete response in 12 (85.7%) patients, partial response in 2 (14.3%) patients, and none with progressive disease. The objective response rate was 100%, and median PFS was 21.4 months. Toxicity was relatively mild, which mainly included nausea in six and fatigue in five, grade 3-4 hematotoxicity in one, and abnormal liver functions in five patients. No neurotoxicity has been observed till date. Conclusion: The efficacy outcomes in this study are comparable to other reported HD-MTX-based regimens plus WBRT, with an added favorable toxicity profile. Prospective, randomized controlled trials are warranted to confirm such results. [ABSTRACT FROM AUTHOR]

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metallo proteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and upregulated levels of apoptotic cells (caspase-3,p53 and tunnel) in my ocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase 3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect. [ABSTRACT FROM AUTHOR]

Background Although sildenafil has been shown to be safe and effective in idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective tissue disease, its effects in Eisenmenger syndrome are less clear. Objective To investigate whether long-term treatment (12 months) with the phosphodiesterase type 5 inhibitor sildenafil improves clinical and haemodynamic parameters in patients with Eisenmenger syndrome. Design Prospective, open-label, multicentre study. Setting Four pulmonary hypertension centres in China. Patients 84 Eisenmenger syndrome functional class II-IV patients. Interventions Oral sildenafil 20 mg orally three times a day. Outcome measures 6-min walk distance (6MWD) test, resting systemic arterial blood oxygen saturation (SaO2) in room air, haemodynamic parameters assessed by right heart catheterisation, safety and tolerability. Results The overall treatment effects at 12 months versus baseline (mean changes with 95% CIs) were 56 m increase (42 to 69, p<0.0001) in 6MWD, and 2.4% increase (1.8% to 2.9%, p<0.0001) in resting room air SaO2. Improvements were also seen in mean pulmonary arterial pressure and pulmonary vascular resistance index (-4.7 mm Hg (-7.5 to -1.9), p=0.001; and -474 dyn×s×cm-5×m2 (-634 to -314), p<0.0001, respectively). Sildenafil was well tolerated. Most adverse events were mild and transient, and occurred in the first 2 weeks of treatment. Conclusions Twelve months of oral sildenafil treatment was well tolerated and appeared to improve exercise capacity, systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome. [ABSTRACT FROM AUTHOR]

Under drug selection pressure, emerging mutations render HIV-1 protease drug resistant, leading to the therapy failure in anti-HIV treatment. It is known that nine substrate cleavage site peptides bind to wild type (WT) HIV-1 protease in a conserved pattern. However, how the multidrug-resistant (MDR) HIV-1 protease binds to the substrate cleavage site peptides is yet to be determined. MDR769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) was selected for present study to understand the binding to its natural substrates. MDR769 HIV-1 protease was co-crystallized with nine substrate cleavage site hepta-peptides. Crystallographic studies show that MDR769 HIV-1 protease has an expanded substrate envelope with wide open flaps. Furthermore, ligand binding energy calculations indicate weaker binding in MDR769 HIV-1 protease-substrate complexes. These results help in designing the next generation of HIV-1 protease inhibitors by targeting the MDR HIV-1 protease. [ABSTRACT FROM AUTHOR]

A new friedelane type triterpene, 3-oxo-11β-hydroxyfriedelane, named as monospermol, was isolated from the roots of Celastrus monospermus Roxb.(Celastraceae) along with seven known compounds friedelin, 3,12-dioxofriedelane, 3-oxo-28-hydroxyfriedelane, 3-oxo-12α-hydroxyfriedelane, β-sitosterol, pristimerin and celastrol. Structural formula and the stereochemistry of the new friedelane type triterpene 1 were established through 1H NMR and 13C NMR spectral data including 2D experiments (HMBC, HSQC, 1H-1H COSY and NOESY) and high resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a serious threat to plants health. Though some genes have been reported to get involved in the regulation of tolerance to Cd, the mechanisms underlying this process are not fully understood. Na+/H+ antiporter (NHX1) plays an important role in Na+/H+ trafficking. The salt and cadmium stress tolerance were found to be enhanced by NHX1 in duckweed according to our previous study, however, its function in Cd2+ flux under Cd stress has not been studied. Here we explored the Cd2+ flux in wild type (WT) and NHX1 transgenic duckweed (NHX1) under Cd stress. We found that the Cd2+ influx in NHX1 duckweed was significantly declined, followed by an increased Cd2+ efflux after 20 min treatment of Cd, which resulted a less accumulation of Cd in NHX1. Reversely, inhibition of NHX1 by amiloride treatment, enhanced Cd2+ influx in NHX1 duckweed, subsequently delayed Cd2+ efflux in both genotypes of duckweed under Cd2+ shock. H+ efflux in NHX1 duckweed was lower compare with that in WT with 20 min Cd2+ shock. NHX1 also increased the pH value with Cd2+ stress in the transgenic rhizoid. These finding suggested a new function of NHX1 in regulation of Cd2+ and H+ flow during short-term Cd2+ shock. • Glycine max Na+/H+ Antiporter (NHX1) firstly declined Cd2+ influx at Cd shock, followed by an increased Cd2+ efflux, which leaded to the decrease of Cd accumulation in NHX1 transgenic duckweed under Cd stress. • NHX1 also increased the pH value with Cd2+ stress in NHX1 duckweed rhizoid, suggesting a new function of NHX1 in regulation of Cd2+ and H+ flow during short-term Cd2+ shock. • Inhibition of NHX1 by amiloride treatment, enhanced Cd2+ influx in NHX1 duckweed, subsequently delayed Cd2+ efflux in both genotypes of duckweed under Cd2+ shock. [ABSTRACT FROM AUTHOR]

The article offers information on a study on a foodborne disease outbreak caused by Clonidine. Materials and methods used in the study along with the findings are presented which include treatments such as nutritional correction of electrolyte imbalance, antioxidants and naloxone treatment. It informs that Clonidine poisoning occurs in children mostly who ate braised eggplant and eggplant with green pepper.

A hallmark of cancer is unbridled proliferation that can result in increased demand for de novo synthesis of purine and pyrimidine bases required for DNA and RNA biosynthesis. These synthetic pathways are frequently upregulated in cancer and involve various folate-dependent enzymes. Antifolates have a proven record as clinically used oncolytic agents. Our recent research efforts have produced LSN 3213128 (compound 28a), a novel, selective, nonclassical, orally bioavailable antifolate with potent and specific inhibitory activity for aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), an enzyme in the purine biosynthetic pathway. Inhibition of AICARFT with compound 28a results in dramatic elevation of 5-aminoimidazole 4-carboxamide ribonucleotide (ZMP) and growth inhibition in NCI-H460 and MDA-MB-231met2 cancer cell lines. Treatment with this inhibitor in a murine based xenograft model of triple negative breast cancer (TNBC) resulted in tumor growth inhibition. [ABSTRACT FROM AUTHOR]

Background: Clinical trials of bone marrow cell-based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific bone marrow cell-derived secreted proteins may provide an alternative biological approach to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in bone marrow cells from patients with acute MI and discovered a poorly characterized secreted protein, EMC10 (endoplasmic reticulum membrane protein complex subunit 10), showing activity in an angiogenic screen.Methods: We investigated the angiogenic potential of EMC10 and its mouse homolog (Emc10) in cultured endothelial cells and infarcted heart explants. We defined the cellular sources and function of Emc10 after MI using wild-type, Emc10-deficient, and Emc10 bone marrow-chimeric mice subjected to transient coronary artery ligation. Furthermore, we explored the therapeutic potential of recombinant Emc10 delivered by osmotic minipumps after MI in heart failure-prone FVB/N mice.Results: Emc10 signaled through small GTPases, p21-activated kinase, and the p38 mitogen-activated protein kinase (MAPK)-MAPK-activated protein kinase 2 (MK2) pathway to promote actin polymerization and endothelial cell migration. Confirming the importance of these signaling events in the context of acute MI, Emc10 stimulated endothelial cell outgrowth from infarcted mouse heart explants via p38 MAPK-MK2. Emc10 protein abundance was increased in the infarcted region of the left ventricle and in the circulation of wild-type mice after MI. Emc10 expression was also increased in left ventricular tissue samples from patients with acute MI. Bone marrow-derived monocytes and macrophages were the predominant sources of Emc10 in the infarcted murine heart. Emc10 KO mice showed no cardiovascular phenotype at baseline. After MI, however, capillarization of the infarct border zone was impaired in KO mice, and the animals developed larger infarct scars and more pronounced left ventricular remodeling compared with wild-type mice. Transplanting KO mice with wild-type bone marrow cells rescued the angiogenic defect and ameliorated left ventricular remodeling. Treating FVB/N mice with recombinant Emc10 enhanced infarct border-zone capillarization and exerted a sustained beneficial effect on left ventricular remodeling.Conclusions: We have identified Emc10 as a previously unknown angiogenic growth factor that is produced by bone marrow-derived monocytes and macrophages as part of an endogenous adaptive response that can be enhanced therapeutically to repair the heart after MI. [ABSTRACT FROM AUTHOR]

Study Design: A prospective cohort study.Objective: In this study, we employed diffusion basis spectrum imaging (DBSI) to quantitatively assess axon/myelin injury, cellular inflammation, and axonal loss of cervical spondylotic myelopathy (CSM) spinal cords.Summary Of Background Data: A major shortcoming in the management of CSM is the lack of an effective diagnostic approach to stratify treatments and to predict outcomes. No current clinical diagnostic imaging approach is capable of accurately reflecting underlying spinal cord pathologies.Methods: Seven patients with mild (mJOA ≥15), five patients with moderate (14≥mJOA ≥11), and two patients with severe (mJOA <11) CSM were prospectively enrolled. Given the low number of severe patients, moderate and severe patients were combined for comparison with seven age-matched controls and statistical analysis. We employed the newly developed DBSI to quantitatively measure axon and myelin injury, cellular inflammation, and axonal loss.Results: Median DBSI-inflammation volume is similar in control (266 μL) and mild CSM (171 μL) subjects, with a significant overlap of the middle 50% of observations (quartile 3 - quartile 1). This was in contrast to moderate CSM subjects that had higher DBSI-inflammation volumes (382 μL; P = 0.033). DBSI-axon volume shows a strong correlation with clinical measures (r = 0.79 and 0.87, P = 1.9 x 10-5 and 2 x 10-4 for mJOA and MDI, respectively). In addition to axon and myelin injury, our findings suggest that both inflammation and axon loss contribute to neurological impairment. Most strikingly, DBSI-derived axon volume declines as severity of impairment increases.Conclusion: DBSI-quantified axonal loss may be an imaging biomarker to predict functional recovery following decompression in CSM. Our results demonstrate an increase of about 60% in the odds of impairment relative to the control for each decrease of 100 μL in axon volume.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Study Design: Experimental animal study of treatment of SCI.Objective: To explore whether HBO treatment protects against secondary SCI by inhibiting the ER stress response.Summary Of Background Data: SCI is a neurological disorder that can severely limit the execution of the simplest day-to-day functions. ER stress plays an important role in the induction of neuronal apoptosis after SCI. HBO treatment can alleviate secondary injury and benefit neurological recovery after SCI, but the effect of HBO on ER stress response after SCI is yet to be characterized.Methods: The spinal cord of rats was injured via T10 laminectomy. Experimental animals were randomly assigned to 1 of 3 groups: sham-operated, SCI, and SCI+HBO. Each group was analyzed 1, 2, 3, 7, and 14 days after injury. Neurological recovery was evaluated using the Basso-Beattie-Bresnahan (BBB) scoring system and the TdT-mediated dUTP nick-end labeling reaction was carried out to visualize apoptotic cells. The expression of ER stress-related factors was evaluated by immunohistochemical, western blot, and real-time reverse transcription-polymerase chain reaction analyses.Results: SCI-induced apoptosis and an increase in the levels of CCAAT-enhancer-binding protein homologous protein (CHOP), and caspase-12 and caspase-3 compared with the sham-operated group. HBO treatment decreased CHOP and caspase-12 and caspase-3 expression as well as apoptosis compared with the SCI group. In addition, BBB scores were improved in the SCI+HBO relative to the SCI group at 7 and 14 days.Conclusion: These results suggest that HBO treatment alleviates secondary injury to the spinal cord by inhibiting ER stress induced apoptosis, thereby promoting the recovery of neurological function.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Background The infrainguinal plug technique for femoral hernia (FH) has gained popularity for its feasibility, simplicity, and encouraging rate of success, but materials and structures of traditional mesh plugs may cause postoperative discomfort, plug migration, and even recurrence. The new hernia repair device ULTRAPRO Plug (UPP) may avoid those problems. Materials and methods In 121 of patients, a total of 125 elective FH repairs with UPP were performed between March 2009 and March 2013. Demographics, surgical information, and outcome were assessed. Results Out of 121 patients, 105 were female. The mean age was 57.6 y. FHs occurred more often on the right (72) than the left (45), and in 4 patients the hernias were bilateral. Mean duration of a hernia surgery was 14.7 min, and 91% patients were discharged within 24 h. Mean time to complete return to daily activities was 7.4 d. No mortality or major complications occurred during the perioperative period. Median follow-up was 26 mo, and the total follow-up rate was 91%. No recurrence or chronic mesh infection was noted. Postoperative chronic pain in two patients, sensory loss in one patient, and foreign body sensation in three patients were found in the follow-up. Conclusions Repair of FHs with UPP through an infrainguinal approach is a simple and effective procedure without major postoperative events. [ABSTRACT FROM AUTHOR]