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Background: CD8+ T cells are important for protective immunity against intracellular pathogens. Excessive amounts of antigen and/or inflammatory signals often lead to the gradual deterioration of CD8+ T cell function, a state called "exhaustion". However, the association between CD8+ T cell exhaustion and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how CD8+ T cells and inhibitory receptors were related to the clinical prognosis of ARDS.Methods: A prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8+ T cell count, proliferation ratio, cytokine secretion, and the expression of coinhibitory receptors were assayed.Results: Sixty-two patients with ARDS met the inclusion criteria. CD8+ T cell counts and proliferation rates were dramatically decreased in non-surviving ARDS patients. Increasing programmed cell death 1 (PD-1) expression on the CD8+ T cell surface was seen in patients with worse organ function, while an increasing level of T cell immunoglobulin mucin-3 (Tim-3) was associated with a longer duration of the shock. Kaplan-Meier analysis showed that low CD8+ T cell percentages and increased inhibitory molecule expression were significantly associated with a worse survival rate.Conclusions: CD8+ T cells and coinhibitory receptors are promising independent prognostic markers of sepsis-induced ARDS, and increased CD8+ T cell exhaustion is significantly correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Porcine epidemic diarrhea (PED) has increased in severity in China since 2010. To investigate further the infectivity, genetic diversity and molecular epidemiology of its causative agent, the porcine epidemic diarrhea virus (PEDV), we assessed 129 clinical samples, which were the intestinal tissue of piglets with severe diarrhea, from 17 cities in central China. Both the spike (S) glycoprotein (S1, 1-789 amino acids (aa)) and the full-length ORF3 gene of 21 representative field strains from 21 farms in 11 cities were sequenced and analysed., Methods: PEDV was detected by reverse transcription-polymerase chain reaction (RT-PCR), and S1 and ORF3 sequences were processed by the Clustal W method via DNAMAN 8 software, and phylogenetic trees were constructed by the neighbor-joining method using MEGA 6 software., Results: The prevalence of PEDV was 92.25% and was detected in 119 of 129 samples, with 94.03% (63 of 67) of pig farms harbouring the disease. According to the phylogenetic analysis of the S1 genes, our isolates all fell into group G2 (variants) and showed a close relationship to isolates from Chinese (HN1303, CH/ZMDZY/11 and AJ1102), Korean (AD01), American (MN, IA1, IA2 and 13-019349) sources, and these isolates differed genetically from other Chinese (LZC, CH/HNZZ/2011 and SD-M) and Korean (SM98) strains as well Japanese (83-P5 and MK) strains. In addition, our isolates differed from attenuated vaccine strains, CV777 (used in China) and DR13 (used in Korea). According to our derived amino acid sequence analysis, we detected one novel variant PEDV, viz: CH/HNLY, with 4-aa insertion/deletion (RSSS/T) at position 375 and 1-aa (D) deletion at position 430 compared to the CV777 attenuated strain. These mutations were located on the receptor binding domain. Our ORF3 gene analyses showed that the prevalent PEDV isolates were variants, and the isolated strains differed genetically from the vaccine strains., Conclusions: These findings illustrated the existence of genetic diversity among geographically distinct PEDV strains, and our study has provided an impetus to conduct further research on the PEDV receptor binding protein and on the new and efficacious vaccines design.

Background: Recently emerging evidence indicates that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. Due to the commonality of cyclic bleeding as in endometriosis, adenomyotic lesions are also wounds that undergo ReTIAR, and we have recently provided evidence corroborating platelet-induced EMT, FMT and fibrogenesis in adenomyosis. This study sought to evaluate the effect of antiplatelet therapy in a mouse model of adenomyosis., Methods: Adenomyosis was induced in 57 female ICR mice with neonatal dosing of tamoxifen, while another 12 (group C) were dosed with solvent only, serving as a blank control. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups: untreated, low- and high-dose Ozagrel, low- and high-dose anti-mouse GPIbα polyclonal IgG antibody to deplete platelets, and isotype-matched inert IgG non-immune antibody. Group C received no treatment. After 3 weeks of treatment, they were hotplate tested again, their uterine horns and brains were harvested, and a blood sample was taken to measure the plasma corticosterone level by ELISA. The left uterine horn was used for immunohistochemistry analysis. The brainstem nucleus raphe magnus (NRM) sections were subjected to immunofluorescence staining for GAD65. The depth of myometrial infiltration and uterine contractility were evaluated., Results: We found that both Ozagrel treatment and platelet depletion dose-dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels, improved the expression of some proteins known to be involved in adenomyosis and slowed down the process of fibrogenesis. It also elevated the number of GAD65-expressing neurons in the brainstem NRM, possibly boosting the GABAergic inhibition of pain due to adenomyosis., Conclusion: This study further provides evidence that platelets play important roles in the development of adenomyosis. Anti-platelet treatment is efficacious in suppression of myometrial infiltration, improving generalized hyperalgesia, reducing uterine hyperactivity and systemic corticosterone levels. Collectively, these results demonstrate that anti-platelet therapy seems to be promising for treating adenomyosis.

Background: Early treatment responses are important prognostic factors in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. The predictive values of early treatment responses in Chinese childhood T-ALL patients were still unknown., Methods: From January 2003 to December 2012, 74 consecutive patients aged ≤ 15 years with newly diagnosed T-ALL were treated with BCH-2003 protocol or CCLG-2008 protocol in the Department of Pediatric, Institute of Hematology and Blood Diseases Hospital in China. Predictive values of early treatment responses, including prednisone response, bone marrow morphology at day 15 and day 33 during induction chemotherapy, and minimal residual disease (MRD) monitored by flow cytometry after induction therapy (time point 1, TP1) and before consolidation therapy (time point 2, TP2), were analyzed., Results: The 5-year event free survival (EFS) and overall survival (OS) rates for these patients were 62.5% (SE, 6.4) and 62.7% (SE, 6.6), respectively. Prednisone poor responder was strongly associated with increased chance of induction failure (14.8%) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)). Patients with ≥ 25% blast cells in bone marrow at day 15 were more likely to have an inferior outcome. 93.2% of the T-ALL patients achieved complete remission at day 33 while patients with resistant disease all died of disease progression. MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-3) at TP2 was significantly related to dismal prognosis. Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0% of the patients were MRD standard risk (MRD < 10(-4) at both time points) with 3-year EFS rate of 100%, 29.0% were MRD high risk (MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-2) at TP2) with 3-year EFS rate of 55.6% (SE, 16.6) , and the rest of patients were defined as MRD intermediate risk with 3-year EFS rate of 85.7% (SE, 13.2)., Conclusion: Our study demonstrated that MRD was the most powerful predictor of treatment outcome in childhood T-ALL patients and conventional morphological assessments of treatment response still played important roles in predicting treatment outcome and tailoring treatment intensity especially in countries with inadequate skills or financial resources for MRD monitoring.

Background: Vascular cognitive impairment-no dementia (VCIND) refers to the early or mild cognitive impairment induced by cerebral vascular injury. Research shows that serum total homocysteine (tHcy) level is an independent risk factor for cerebral vascular disease and may be closely related to cognitive function.Current studies on the tHcy level in VCIND patients are limited, and the relationship of tHcy with cognitive function remains unclear. This study aims to investigate the tHcy levels in patients with VCIND and to determine their correlation with cognitive function, as well as to provide useful clues for preventing and treating VCIND., Methods: The tHcy, folate, and vitamin B12 levels in 82 patients with VCIND were reviewed retrospectively and compared with those of 80 stroke patients without cognitive impairment and 69 healthy controls by using the Montreal Cognitive Assessment (MoCA) scale and the event-related potential P300 to evaluate cognitive function., Results: The tHcy levels in the VCIND group were higher than those in the other two groups, whereas the folate and Vitamin B12 levels in the VCIND group were lower than those of the other two groups. The tHcy levels in the stroke group were higher than those in the control group, and the folate and vitamin B12 levels in the stroke group were lower than those in the control group. The patients in the VCIND group with high tHcy exhibited lower MoCA scores and prolonged P300 latency than those in with normal tHcy. Correlation analysis showed that tHcy level is positively correlated with P300 latency period and negatively correlated with MoCA score., Conclusion: The tHcy levels were significantly higher and the vitamin B12 and folate levels were significantly lower in the patients with VCIND than those in the other groups. The high tHcy levels in the VCIND patients may be correlated with impaired cognitive function.