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Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid macrophage reaction; however, only dectin-1 activation causes macrophage-mediated demyelination and axonal injury. Coactivating TLR2 reduced the injurious effects of dectin-1 activation. When injected into traumatically injured spinal cord, TLR2 agonists enhance the endogenous macrophage reaction while conferring neuroprotection. Indeed, dieback of axons was reduced, leading to smaller lesion volumes at the peak of the macrophage response. Moreover, the density of NG2+ cells expressing vimentin increased in and near lesions that were enriched with TLR2-activated macrophages. In dectin-1-null mutant (knock-out) mice, dieback of corticospinal tract axons also is reduced after SCI. Collectively, these data support the hypothesis that the ability of macrophages to create an axon growth-permissive microenvironment or cause neurotoxicity is receptor dependent and it may be possible to exploit this functional dichotomy to enhance CNS repair. [ABSTRACT FROM AUTHOR]

Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known. Data presented herein indicate that AD causes immune suppression. Using in vivo telemetry, we show that AD develops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency of AD increases, there is a corresponding increase in splenic leucopenia and immune suppression. Experimental activation of spinal sympathetic reflexes in SCI mice (e.g., via colorectal distension) elicits AD and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. Reversal of postinjury immune suppression in SCI mice can be achieved by pharmaco-logical inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function. [ABSTRACT FROM AUTHOR]

Background: The main objective of this meta-analysis was to determine the clinical benefit of concurrent chemoradiotherapy (CCRT) compared with radiation alone (RT) in the treatment of nasopharyngeal carcinoma (NPC) patients in endemic geographic areas. Methods: Using a prospective meta-analysis protocol, two independent investigators reviewed the publications and extracted the data. Published randomized controlled trials (RCTs) in which patients with NPC in endemic areas were randomly assigned to receive CCRT or RT alone were included. Results: Seven trials (totally 1608 patients) were eligible. Risk ratios (RRs) of 0.63 (95% CI, 0.50 to 0.80), 0.76 (95% CI, 0.61 to 0.93) and 0.74 (95% CI, 0.62 to 0.89) were observed for 2, 3 and 5 years OS respectively in favor of the CCRT group. The RRs were larger than that detected in the previously reported meta-analyses (including both endemic and non-endemic), indicating that the relative benefit of survival was smaller than what considered before. Conclusions: This is the first meta-analysis of CCRT vs. RT alone in NPC treatment which included studies only done in endemic area. The results confirmed that CCRT was more beneficial compared with RT alone. However, the relative benefit of CCRT in endemic population might be less than that from previous meta-analyses. [ABSTRACT FROM AUTHOR]

Traumatic injury to the mammalian spinal cord activates B cells, which culminates in the synthesis of autoantibodies. The functional significance of this immune response is unclear. Here, we show that locomotor recovery was improved and lesion pathology was reduced after spinal cord injury (SCI) in mice lacking B cells. After SCI, antibody-secreting B cells and Igs were present in the cerebrospinal fluid and/or injured spinal cord of WT mice but not mice lacking B cells. In mice with normal B cell function, large deposits of antibody and complement component 1q (C1q) accumulated at sites of axon pathology and demyelination. Antibodies produced after SCI caused pathology, in part by activating intraspinal complement and cells bearing Fc receptors. These data indicate that B cells, through the production of antibodies, affect pathology in SCI. One or more components of this pathologic immune response could be considered as novel therapeutic targets for minimizing tissue injury and/or promoting repair after SCI. [ABSTRACT FROM AUTHOR]

Aim: In a previous study, a 130-nm nanoparticle albumin-bound paclitaxel ( nab-paclitaxel) demonstrated improved efficacy and safety profile compared with solvent-based paclitaxel (sb-paclitaxel) in Caucasian patients with metastatic breast cancer (MBC). The aim of the present randomized study was to compare the response rates and safety profile of nab-paclitaxel with sb-paclitaxel in Chinese patients with MBC. Methods: In the present open-label, multicenter study, 210 patients with MBC were randomly assigned to receive nab-paclitaxel 260 mg/m2 intravenously (i.v.) over 30 min every 3 weeks (q3w) with no premedication or sb-paclitaxel 175 mg/m2 i.v. over 3 h q3w with standard premedication. Results: The overall response rate was 54 and 29% in patients treated with nab-paclitaxel and sb-paclitaxel, respectively ( P < 0.001). nab-paclitaxel induced a higher response rate in patients who were <65 years old, patients who were receiving first-line therapy, patients who had no prior anthracycline therapy, patients who had ≤ or >3 metastatic lesions, and patients who had visceral disease. The progression-free survival (PFS) period was 7.6 months for nab-paclitaxel and 6.2 months for sb-paclitaxel ( P = 0.118). Despite the 49% higher paclitaxel dose in patients receiving nab-paclitaxel compared with patients receiving sb-paclitaxel, the safety profile was similar in both treatment groups. The most common grades 3 and 4 adverse event (AE) in both arms was neutropenia. The most common grade 3 nonhematologic AE was peripheral neuropathy, and no grade 4 peripheral neuropathy was observed. Conclusion: Compared with sb-paclitaxel, nab-paclitaxel demonstrated superior efficacy, an acceptable safety profile, and a trend toward increased PFS in patients with MBC. [ABSTRACT FROM AUTHOR]

Activated macrophages can promote regeneration of CNS axons. However, macrophages also release factors that kill neurons. These opposing functions are likely induced simultaneously but are rarely considered together in the same experimental preparation. A goal of this study was to unequivocally document the concurrent neurotoxic and neuroregenerative potential of activated macrophages. To do so, we quantified the length and magnitude of axon growth from enhanced green fluorescent protein-expressing dorsal root ganglion (DRG) neurons transplanted into the spinal cord in relationship to discrete foci of activated macrophages. Macrophages were activated via intraspinal injections of zymosan, a potent inflammatory stimulus known to increase axon growth and cause neurotoxicity. Using this approach, a significant increase in axon growth up to macrophage foci was evident. Within and adjacent to macrophages, DRG and spinal cord axons were destroyed. Macrophage toxicity became more evident when zymosan was injected closer to DRG soma. Under these conditions, DRG neurons were killed or their ability to extend axons was dramatically impaired. The concurrent induction of proregenerative and neurotoxic functions in zymosan-activated macrophages (ZAMs) was confirmed in vitro using DRG and cortical neurons. Importantly, the ability of ZAMs to stimulate axon growth was transient; prolonged exposure to factors produced by ZAMs enhanced cell death and impaired axon growth in surviving neurons. Lipopolysaccharide, another potent macrophage activator, elicited a florid macrophage response, but without enhancing axon growth or notable toxicity. Together, these data show that a single mode of activation endows macrophages with the ability to simultaneously promote axon regeneration and cell killing. [ABSTRACT FROM AUTHOR]

Lymphoblastic lymphoma (LBL) is a highly aggressive lymphoma, for which intensive chemotherapy is necessary. This study was designed to evaluate the efficacy and toxicity of a modified acute lymphoblastic leukemia (ALL)-Berlin-Frankfurt-Münster (BFM)-90-based protocol in Chinese children and adolescents with LBL. From March 1998 to November 2006, 60 untreated patients with LBL (age <18 years) from a single institution were enrolled. All patients were treated with the modified ALL-BFM-90 protocol, and prophylactic cranial radiotherapy was omitted. The median age of the patients was 10 years (range, 2.5–18 years). Forty-eight (80%) patients had T-cell LBL, and 59 (98.3%) of the patients were stage III/IV. At the end of induction remission Ia (day 33), 3 patients had died of treatment-related toxicity. In the remaining 57 patients, complete remission (CR) or CR undetermined (CRu) had occurred in 47 (82.45%), who were designated as the moderate-risk group and partial remission (PR) had occurred in 10 patients (17.54%), who were designated the high-risk group. All patients experienced grade 3–4 hematological toxicity. At a median follow-up of 35 months, event-free survival was 78.81% ± 0.05 for all patients; the figure was 88.34% ± 0.05 for the moderate-risk group (90.91% ± 0.08 for stage III, 87.68% ± 0.06 for stage IV, 100% for those with B-cell LBL, 84.78% ± 0.06 for those with T-cell LBL, and 82.94% ± 0.08 for stage IV patients with more than 25% blast cells in bone marrow [BM]). The event-free survival in the high-risk group was 60% ± 0.15. This modified ALL-BFM-90 protocol is an effective regimen and it greatly improved the survival rate of Chinese children and adolescents with LBL compared with the ALL protocols used previously. [ABSTRACT FROM AUTHOR]

In rituximab-containing regimen for lymphoma, the role of lamivudine therapy has not been well established. Therefore, in this nonrandomized phase II clinical study, hepatitis B virus (HBV) carriers with B-cell lymphoma who received rituximab-containing regimen were treated with oral administration of lamivudine. The incidence and severity of hepatitis along with other adverse clinical outcomes were analyzed. Between January 2003 and March 2006, 29 consecutive patients were enrolled. Four of the 29 patients (13.8%) developed hepatitis during chemotherapy, none of which was attributed to HBV reactivation. According to WHO acute toxicity assessment criteria, the severity of hepatitis was grade I in two patients (6.9%) and grade II in two patients (6.9%). In these four patients, only one (3.5%) had interval delay in chemotherapy. No patient had total abnormal bilirubin. No patient had died as the result of hepatitis during the treatment. Interestingly, one of the 29 patients developed HBV activation 5.1 months after the withdrawal of lamivudine. This patient recovered after reinstallation of lamivudine therapy and is still alive. Consequently, our study confirmed previous reports that prophylactic lamivudine therapy can prevent HBV reactivation in HBV carriers who were receiving rituximab-containing regimen for lymphoma. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and toxicity of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FOLFOX-6) combination therapy in patients with advanced or recurrent gastric cancer. Methods: Patients with previously untreated advanced or recurrent gastric cancer received oxaliplatin 100 mg/m2 and leucovorin 400 mg/m2 (2-hour intravenous infusion) followed by a 5-FU bolus of 400 mg/m2 (10-min infusion) and then 5-FU 2,600–3,000 mg/m2 (46-hour continuous infusion). The chemotherapy was repeated every 14 days. Results: Fifty-one patients were enrolled in this study. Of these, 46 were assessable for efficacy, and all patients were assessable for toxicity. Three of 51 patients achieved a complete response, and 18 had partial responses, giving an overall response rate of 41.2%. Stable disease was observed in 11 (21.6%) patients and progressive disease in 14 (27.5%). The median time to progression was 5.4 months, and the median overall survival was 12.1 months. NCI-CTC grade 3/4 hematological toxicities were neutropenia and anemia in 9.8 and 7.8% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in 3 (5.9%) patients. Other NCI-CTC grade 3 or 4 toxicities included diarrhea in 3 patients (5.9%) and vomiting in 5 (9.8%). There were no treatment-related deaths. Conclusions: This oxaliplatin/5-FU/folinic acid regimen shows good efficacy and an acceptable toxicity profile in advanced or recurrent gastric cancer patients; further clinical trials are warranted. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the anti-tumor activity and toxicity profile of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma (NPC) who had been pretreated with platinum-based chemotherapy. This is an open label, single arm phase II trial. All patients were treated with single agent of gemcitabine. Gemcitabine was given in the dosage of 1.0 g/m2 on days 1, 8, 15, each cycle repeated every 4 weeks. Gemcitabine was added to 100 ml normal saline infused over 30 min. About 32 patients were enrolled in this trial. Thirty patients were assessable for response to treatment. Fourteen patients had a partial response (PR), giving an overall response rate of 43.8% (14/32); 9 patients had stable disease (28.1%) and 7 progressed disease (21.9%). The median time to progression was 5.1 months and median survival time was 16 months, 1 year survival rate was 67%, 2 year overall survival rate was 12%. A total of 11 patients (34.4%) experienced grade 3 and 4 toxicity and the main toxicity was myelosuppression. the non-hematology toxicity was minimal. The effectiveness of gemcitabine was higher and side effects were minimal in advanced NPC patients after platinum-based chemotherapy failed. [ABSTRACT FROM AUTHOR]

The authors investigated the prevalence of hepatitis B virus (HBV) infection by using serologic markers in non‐Hodgkin lymphoma (NHL) compared with other types of cancers in Chinese patients.In this case‐control study, HBV and other hepatitis markers were compared between a study group and a control group. The study group included 587 patients with NHL (age range, 16–86 years), and the control group included 1237 patients (age range, 16–89 years) who were diagnosed with other cancers except liver cancer. An enzyme‐linked immunosorbent assay was used to test serum samples from both groups for HBV markers and other hepatitis markers.Logistic regression analysis showed that there was a higher prevalence of HBV infection in patients with the B‐cell subtype of NHL (30.2%) than in patients with other cancers (14.8%; odds ratio [OR], 2.6; 95% confidence interval [95% CI], 2.0–3.4); however, in patients with the T‐cell subtype of NHL, the HBV infection rate (19.8%) was similar to that among patients with other cancers (OR, 1.2; 95% CI, 0.8–1.8). A significant difference in HBV prevalence was found between B‐cell and T‐cell NHL (OR, 2.3; 95% CI, 1.4–3.6). In the patients with B‐cell NHL, those who were infected with HBV had a significantly earlier disease onset (9.5 years) than those who were not infected with HBV.The current results demonstrated that patients with B‐cell NHL, but not patients with T‐cell NHL, had a higher prevalence of HBV infection. HBV infection was associated with a significantly earlier disease onset (P < .001), a finding that suggested the possibility that HBV may play an etiologic role in the induction of B‐cell NHL. Cancer 2007. © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]

Myelin-reactive T-cells are activated by traumatic spinal cord injury (SCI) in rodents and humans. Despite the historical association of these cells with experimental and clinical neuropathology, recent data suggest a neuroprotective role for myelin-reactive T-cells. Because of the biological and therapeutic implications of these findings, we attempted to reproduce the original neuroprotective vaccine protocols in a model of rat SCI. Specifically, MBP-reactive T-cell function was enhanced in SCI rats via passive or active immunization. Locomotor function was assessed using a standardized locomotor rating scale (Basso-Beattie-Bresnahan scale) and was correlated with myelin and axon sparing. The functional and anatomical integrity of the rubrospinal pathway also was analyzed using the inclined plane test and anatomical tract tracing. MBP-immunized rats exhibited varying degrees of functional impairment, exacerbated lesion pathology, greater rubrospinal neuron loss, increased intraspinal T-cell accumulation, and enhanced macrophage activation relative to SCI control groups. These data are consistent with the conventional view of myelin-reactive T-cells as pathological effector cells. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (SCI) above the major spinal sympathetic outflow (T6 level) disinhibits sympathetic neurons from supraspinal control, causing systems-wide "dysautonomia." We recently showed that remarkable structural remodeling and plasticity occurs within spinal sympathetic circuitry, creating abnormal sympathetic reflexes that exacerbate dysautonomia over time. As an example, thoracic VGluT2+ spinal interneurons (SpINs) become structurally and functionally integrated with neurons that comprise the spinal-splenic sympathetic network and immunological dysfunction becomes progressively worse after SCI. To test whether the onset and progression of SCI-induced sympathetic plasticity is neuron activity dependent, we selectively inhibited (or excited) thoracic VGluT2+ interneurons using chemogenetics. New data show that silencing VGluT2+ interneurons in female and male mice with a T3 SCI, using hM4Di designer receptors exclusively activated by designer drugs (Gi DREADDs), blocks structural plasticity and the development of dysautonomia. Specifically, silencing VGluT2+ interneurons prevents the structural remodeling of spinal sympathetic networks that project to lymphoid and endocrine organs, reduces the frequency of spontaneous autonomic dysreflexia (AD), and reduces the severity of experimentally induced AD. Features of SCI-induced structural plasticity can be recapitulated in the intact spinal cord by activating excitatory hM3Dq-DREADDs in VGluT2+ interneurons. Collectively, these data implicate VGluT2+ excitatory SpINs in the onset and propagation of SCI-induced structural plasticity and dysautonomia, and reveal the potential for neuromodulation to block or reduce dysautonomia after severe high-level SCI. [ABSTRACT FROM AUTHOR]

Abstract Background Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring. Methods Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting. Results There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress’s offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment. Conclusions The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

Abstract Background Felty’s syndrome (FS) is characterized by the triad of rheumatoid arthritis (RA), splenomegaly and neutropenia. The arthritis is typically severe and virtually always associated with high-titer rheumatoid factor. The presence of persistent neutropenia is generally required to make the diagnosis. Most patients diagnosed with FS are aged 50–70 years and have had RA for more than 10 years. It is rarely seen in patients with juvenile idiopathic arthritis (JIA), with only five cases having been reported throughout the world. Case presentation The present study describes the case of a 14-year-old female with a seven-year history of polyarticular JIA, presenting with splenomegaly, hepatomegaly, cholestasis and thrombocytopenia. However, she occasionally developed neutropenia. Titers of rheumatoid factor and anti-CCP were persistently high, and the antinuclear antibody titer was 1:320, while the antibody results for anti-dsDNA and anti-Sm were negative. Serum levels of IgA, IgG, IgM and IgE were all persistently elevated, and the ratio of CD19+ lymphocytes in the subgroups of lymphocytes was persistently high. The level of complements was normal. No STAT3 and STAT5B mutations were found by next-generation sequencing. The patient did not respond to methotrexate, prednisolone, hydroxychloroquine (HCQ), sulfasalazine and etanercept but was responsive to rituximab. Conclusions JIA, thrombocytopenia and splenomegaly are the most common and important features in six children with FS, while persistent neutropenia is not seen in all these patients. No complement deficiency has been found in children with FS so far. Manifestations of FS without neutropenia may be extremely rare. There are differences between adults and children in the clinical and laboratory features of FS.

Abstract Background The association between mutations in the TNFAIP3 gene and a new autoinflammatory disease (called A20 haploinsufficiency, HA20) has recently been recognized. Here, we describe four patients with HA20 from two unrelated Chinese families. Case presentation A total of four patients from two families were included. The average age at onset was 5.9 years. All patients had no signs of eye or skin problems, such as uveitis, rash, folliculitis and dermal abscess. Prior to the recognition of HA20, P1 was diagnosed with SLE, liver fibrosis and hypothyroidism. She also had no oral, genital or perineal ulcers. P2 was diagnosed with Crohn’s disease and inflammatory bowel disease-related arthritis (IBD-RA). He had a perianal abscess but no oral or genital ulcers. P3, the father of P1 and P2, only had mild oral ulcers, arthralgia, and archosyrinx. P4 was diagnosed with polyarticular juvenile idiopathic arthritis (JIA), macrophage activation syndrome (MAS) and interstitial lung disease (ILD). Whole exome sequencing (WES) was performed in two families. WES revealed heterozygous c.559C > T in the TNFAIP3 gene in P1, P2 and P3, while the c.259C > T mutation in the TNFAIP3 gene was identified in P4. The c.259C > T mutations is novel. Conclusion HA20 had a different phenotype between families and even between family members with the same mutation. Liver fibrosis, hypothyroidism, ILD and MAS in the patients with HA20 were first reported in this study. Our results expanded the phenotype and genotype spectrum of A20 haploinsufficiency.

Microglia are dynamic immunosurveillance cells in the CNS. Whether microglia are protective or pathologic is context dependent; the outcome varies as a function of time relative to the stimulus, activation state of neighboring cells in the microenvironment or within progression of a particular disease. Although brain microglia can be "primed" using bacterial lipopolysaccharide (LPS)/endotoxin, it is unknown whether LPS delivered systemically can also induce neuroprotective microglia in the spinal cord. Here, we show that serial systemic injections of LPS (1mg/kg, i.p., daily) for 4 consecutive days (LPSx4) consistently elicit a reactive spinal cord microglia response marked by dramatic morphologic changes, increased production of IL-1, and enhanced proliferation without triggering leukocyte recruitment or overt neuropathology. Following LPSx4, reactive microglia frequently contact spinal cord endothelial cells. Targeted ablation or selective expression of IL-1 and IL-1 receptor (IL-1R) in either microglia or endothelia reveal that IL-1-dependent signaling between these cells mediates microglia activation. Using a mouse model of ischemic spinal cord injury in male and female mice, we show that preoperative LPSx4 provides complete protection from ischemia-induced neuron loss and hindlimb paralysis. Neuroprotection is partly reversed by either pharmacological elimination of microglia or selective removal of IL-1R in microglia or endothelia. These data indicate that spinal cord microglia are amenable to therapeutic reprogramming via systemic manipulation and that this potential can be harnessed to protect the spinal cord from injury. [ABSTRACT FROM AUTHOR]

In the 1980s, recombinant human erythropoietin (rhEPO) began to be used in clinical practice. In this study, the clinical application of rhEPO from single-center in recent ten years was reviewed, and the scope of indications and clinical efficacy were evaluated. The medical records of 35829 in-patients who were treated with rhEPO in the first Medical Center of the Chinese PLA General Hospital from 2009 to 2018 were collected. According to the scope of indications approved by CFDA (China Food and Drug Administration), curative effect and off-label of rhEPO were analyzed. Of the 35829 patients, 19013 (53.1%) were male and 16816 (46.9%) were female, with an average age of (52.1 ± 18.6) years. The usage of rhEPO is increasing year by year. The overall effective rate was 53.1%. The number of patients who met the indications accounted for 67.2%, and the effective rate patients with indications and Off-label were 48.8% and 50.7%. Among the patients with irregular use of rhEPO perioperative imperfect laboratory examination patients accounted for the highest proportion (7.1%). The volume of RBC(s) (red blood cell(s)) transfusion in patients with rhEPO was significantly less than that in patients without rhEPO (p

Rapid global population growth increases the human demand for food. Reliance on the high input of agrochemicals in agricultural production has been shown to be unsustainable and cost ineffective. The combination of planting and breeding can maximize the utilization of agricultural resources. A novel crop–earthworm coculture model has been gradually practiced in urban agriculture in eastern China. We conducted a four-year successive study of taro–earthworm coculture farming to determine the ecological and economic benefits of the model. Our results indicated that earthworm activities in the taro–earthworm coculture system increased taro yield, economic value and net income by depleting the weed seed bank, mitigating weed infestation, and reducing the need for weeding. Compared with those in mono-taro farming, the four-year mean seed bank densities of total weeds, grassy weeds and broadleaf weeds in taro–earthworm farming decreased by 37.1%, 44.4% and 32.2%, respectively; the weed density, biomass, species richness and diversity and need for weeding decreased by 54.1%, 48.3%, 20.8%, 8.2% and 39.7%, respectively; and the taro yield, economic value and net income increased by 19.7%, 19.7% and 50.7%, respectively. Our study suggests that earthworm activities provide ecosystem services in agricultural systems, and the coculture of taro and earthworms enhances crop production by mitigating weed infestation and improving environmental quality. • Earthworms provide multiple ecosystem services. • Earthworm activities accelerate the depletion of soil weed seed bank. • Earthworm activities mitigate weed infestation in crop–earthworm coculture farming. • Earthworm activities enhance crop production and improve environmental quality. • Crop–earthworm coculture farming is a promising and sustainable farm practice. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that is associated with clinical worsening and relapses in multiple sclerosis (MS) patients. The mechanism through which MIF promotes MS progression remains undefined. In this study, we identify a critical role for MIF in regulating CNS effector mechanisms necessary for the development of inflammatory pathology in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Despite the ability to generate pathogenic myelin-specific immune responses peripherally, MIF-deficient mice have reduced EAE severity and exhibit less CNS inflammatory pathology, with a greater percentage of resting microglia and fewer infiltrating inflammatory macrophages. We demonstrate that MIF is essential for promoting microglial activation and production of the innate soluble mediators IL-1β, IL-6, TNF-α, and inducible NO synthase. We propose a novel role for MIF in inducing microglial C/EBP-β, a transcription factor shown to regulate myeloid cell function and play an important role in neuroinflammation. Intraspinal stereotaxic microinjection of MIF resulted in upregulation of inflammatory mediators in microglia, which was sufficient to restore EAE-mediated inflammatory pathology in MIF-deficient mice. To further implicate a role for MIF, we show that MIF is highly expressed in human active MS lesions. Thus, these results illustrate the ability of MIF to influence the CNS cellular and molecular inflammatory milieu during EAE and point to the therapeutic potential of targeting MIF in MS. [ABSTRACT FROM AUTHOR]

Previous studies had researched the relationship between rs9642880 gene polymorphism and bladder cancer risk, but the results remained unclear. The comprehensive meta-analysis was performed to clarify this possible association. Relevant articles were searched from Pubmed, Embase and web of science. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the strength of the association. The assessment of publication bias was conducted by Begg's funnel plots and Egger's regression test. A total of 7 casecontrol studies involving 4072 cases and 4898 controls were included in our study. Overall, an obvious relationship between rs9642880 polymorphism and increased risk of bladder cancer were detected in all models. Besides, the positive results were observed among both Caucasians and Asians when stratified by ethnicity. Moreover, when stratified by genotyping method, the significant results were detected in all genotyping methods except Sequenom. In addition, in the subgroup analysis by source of control, significant results were detected in both population and hospital based controls. This present meta-analysis with accurate and reliable results indicated that the T allele of SNP rs9642880 confers susceptibility to bladder cancer in both Asian and Caucasian populations.

Sperm cryopreservation is a method to preserve sperm samples for a long period. However, the fertility of sperm decreases markedly after freezing and thawing in a certain amount of samples. The aim of the present study was to find useful and reliable predictive biomarkers of the capacity to withstand the freeze-thawing process in human ejaculates. Previous researches have shown that enolase1 (ENO1) and glucose-6-phosphate isomerase (GPI) are closely related to spermatozoa quality. We chose the two proteins as probable markers of sperm freezing capacity. Ejaculate samples were separated into good freezability ejaculates (GFE) and poor freezability ejaculates (PFE) according to progressive motility of the sperm after thawing. Before starting cryopreservation protocols, the two proteins from each group were compared using western blot analysis and immunofluorescence. Results showed that normalized content of ENO1 (P<0.05) and GPI (P<0.01) were both significantly higher in GFE than in PFE. The association of ENO1 and GPI with postthaw sperm viability and motility was confirmed using Pearson's linear correlation. In conclusion, ENO1 and GPI can be used as markers of human sperm freezability before starting the cryopreservation procedure., (Copyright © 2015. Published by Elsevier Inc.)