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Background Serum triiodothyronine (T3) concentration was reported to be associated with the prognosis after acute ischemic stroke. The aim of this study was to evaluate the effect of age on the prognostic value of thyroid-related hormones after an acute ischemic stroke. Methods This was a retrospective study involving the review of 1072 ischemic stroke patients who had been consecutively admitted to the hospital within 72 h of symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. Results A total of 768 patients were finally included in the study and divided into two age groups: a younger group (age

Primary pulmonary non-Hodgkin's lymphoma (PP-NHL) is a rare entity with non-specific symptoms and radiographic findings, as well as a difficult preoperative diagnosis. A limited number of studies have described PP-NHL in Chinese patients. The goal of the present study was to improve early diagnosis by examining prognostic factors in patients with PP-NHL. Therefore, a total of 29 patients with PP-NHL were included in the study between January 2001 and June 2017, including 14 with aggressive-type and 15 with indolent-type lymphomas (10 male, 19 female; median age, 50.3 years; range, 19-87 years). Pulmonary nodules and masses (55.2%) were the most common radiographic features. The diagnostic yield was 80% (12/15) by endobronchial biopsy or transbronchial lung biopsy and 100% by computed tomography (CT)-guided percutaneous needle lung biopsy (11/11) or surgery (8/8). Elevated lactate dehydrogenase levels and systemic symptoms were observed considerably more often in patients with aggressive disease than in those with indolent disease. The 1-, 3- and 5-year overall survival (OS) rates were 42, 32, and 21%, respectively, for all patients, 72, 57 and 43%, respectively, for patients with indolent lymphomas, and 13, 6 and 0%, respectively, for patients with aggressive lymphomas. The median OS rate for all patients was 12.0 months; however, the OS rate for patients with aggressive lymphomas was significantly shorter compared with those with indolent lymphomas (7.1 months vs. 16.6 months; P=0.002). Aggressive vs. indolent lymphoma status was indicated to be an independent prognostic factor for poor 5-year OS rate (hazard ratio, 5.98; P=0.014). In conclusion, bronchoscopic and CT-guided percutaneous needle lung biopsies were the most useful and least invasive procedures for diagnosing PP-NHL. Furthermore, aggressive PP-NHL was highly associated with poor 5-year OS rate and a poor prognosis.

Global longitudinal strain (GLS) measured by 2-D speckle-tracking echocardiography (2-D STE) at rest has been recognized as a sensitive parameter in the detection of significant coronary artery disease (CAD). However, the diagnostic power of 2-D STE in the detection of significant CAD in patients with diabetes mellitus is unknown. Two-dimensional STE features were studied in total of 143 consecutive patients who underwent echocardiography and coronary angiography. Left ventricular global and segmental peak systolic longitudinal strains (PSLSs) were quantified by speckle-tracking imaging. In the presence of obstructive CAD (defined as stenosis ≥75%), global PSLS was significantly lower in patients with diabetes mellitus than in patients without (16.65 ± 2.29% vs. 17.32 ± 2.27%, p < 0.05). Receiver operating characteristic analysis revealed that global PSLS could effectively detect obstructive CAD in patients without diabetes mellitus (cutoff value: -18.35%, sensitivity: 78.8%, specificity: 77.5%). However, global PSLS could detect obstructive CAD in diabetic patients at a lower cutoff value with inadequate sensitivity and specificity (cutoff value: -17.15%; sensitivity: 61.1%, specificity: 52.9%). In addition, the results for segmental PSLS were similar to those for global PSLS. In conclusion, global and segmental PSLSs at rest were significantly lower in patients with both obstructive CAD and diabetes mellitus than in patients with obstructive CAD only; thus, PSLSs at rest might not be a useful parameter in the detection of obstructive CAD in patients with diabetes mellitus.

An emerging paradigm in the treatment of stroke in patients with fixed neurologic deficits is stem cell therapy. Mesenchymal stem cells (MSCs) are attractive candidate cells for transplantation because they enhance endogenous repair systems, and the process is highly feasible. In order to further understand the complexity of the biochemical and physiological changes that occur after treatment with human MSCs (hMSC) in a rat model of stroke, we performed proteomic analysis of three groups: sham group, transient middle cerebral artery occlusion (tMCAo) group, and hMSC treated tMCAo group. Using 2-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we identified 14 proteins with altered expression patterns among the treatment groups. Differential protein expression was confirmed by western blotting. Two proteins that were upregulated in both the tMCAo group and the hMSC treated tMCAo group relative to sham were annexin A3 and GRP78, proteins involved in angiogenesis and neuroprotection. Two proteins that were elevated in the tMCAo group relative to the sham group and recovered to normal levels in the hMSC treated tMCAo group were synaptosomal-associated protein-25 (SNAP-25) and transitional endoplasmic reticulum ATPase, proteins involved in neuron loss and apoptosis. Our results revealed differential proteomic profiles that characterize the brain of the hMSC transplanted MCAo rat. These proteomic profiles contribute to the understanding of the mechanisms underlying the efficacy of MSC in stroke therapy.

Objective: To investigate the prevalence of genital high-risk human papillomavirus (HR-HPV) in male sexual partners of HR-HPV infected women and the concordance of viral types in couples in China, and comprehend the role of men play in HPV transmission to women. Methods/Materials: 94 asymptomatic women and their husbands from rural Chaozhou participated in epidemiologic screening for HPV infection. Cervical cells from females were collected for high risk HPV screening by real time-PCR, and they were positive for at least 1 of 13 HR-HPV subtypes, then these samples were genotyped. Approximately one mouth later, penile epithelial cells from 94 asymptomatic husbands were collected for HPV genotyping. At the same time, a cross-sectional study was conducted in 366 male patients from sexually transmitted disease (STD) outpatient clinic in China for the prevalence of genital HR-HPV infection in men having frequent sex behavior. Penial epithelial cells were collected for HPV 6/11 and HPV 16/18 detection by fluorescent real-time quantified PCR. Results: Among 94 couples, the prevalence of genital HR-HPV infection in men whose wife was positive for cervical HR-HPV was 5.32% (5/94). Only 2.63% (2/76) had the same high risk viral type presented by their wife. HPV 16 proved to be the most prevalent viral type in men and in couples. Of 366 male patients from STD outpatient clinic, the prevalence of HPV 16/18 infection in men with or without HPV 6/11 was 6.85% and 8.16%, respectively. The incidence of HPV 16/18 was higher in men aged more than 35 years than the young men (18-35 years). Conclusion: The prevalence of genital HR-HPV infection in male sexual partners of HPV-positive women in China was lower than that expected, and the concordance of high risk viral type between couples was extremely low. These data suggested that infected men consitute an important viral reservoir, contributing to transmission of HR-HPV to women and maintenance of infection, but HR-HPV infection may be less likely to persist in men than in women.

Background Mesenchymal stem cells (MSCs) have the potential to promote brain repair and improve recovery following stroke. We investigated changes in free fatty acids (FFAs) following intravenous human MSC (hMSC) transplantation into rats that had undergone transient middle cerebral artery occlusion (MCAo). Methods Rats were subjected to 2-hours MCAo, followed by intravenous transplantation of hMSC or phosphate-buffered saline (PBS) at one day after MCAo. All rats were sacrificed 5 days after MCAo. Metabolic profiling of free fatty acids (FFAs) level was assessed in plasma and brain from control rats (n = 8), PBS-treated MCAo rats (n = 6), and hMSC-treated MCAo rats (MCAo + hMSC, n = 6). Results The levels of some FFAs in plasma and brain samples of the MCAo and MCAo + hMSC groups were significantly different from those of the control group. The percentage composition of myristic acid in plasma and those of myristic acid, linoleic acid, and eicosenoic acid in brain tissues of the MCAo + hMSC group were significantly reduced compared to those in the untransplanted MCAo group. Conclusion Our metabolic approach has provided insights into understanding the complexity of biochemical and physiological events that occur in ischemic brain injury and the transplantation effects of MSCs in stroke.

This study evaluated the prognostic value of thyroid-related hormones within normal ranges after acute ischemic stroke. This was a retrospective study and we reviewed 1072 ischemic stroke patients consecutively admitted within 72 h after symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. 722 patients were finally included. On univariate analysis, poor functional outcome was associated with presence of atrial fibrillation as the index event. Furthermore, score of National Institutes of Health Stroke Scale (NIHSS), total T4, free T4, and C-reactive protein at admission were significantly higher in patients with poor functional outcome, whereas free T3 and total T3 were significantly lower. On multiple logistic regression analysis, lower total T3 concentrations remained independently associated with poor functional outcome [odds ratio (OR), 0.10; 95% confidence interval (CI), 0.01–0.84;P=0.035]. The only other variables independently associated with poor functional outcome were NIHSS scores. In sum, lower total T3 concentrations that were within the normal ranges were independently associated with poor short-term outcomes.

Background and Purpose— The pathogenesis of internal border-zone (IBZ) and cortical border-zone (CBZ) infarcts is unclear. Both types of infarct have been combined into a single group in most previous reports, which has produced conflicting results. We hypothesized that different pathogenic mechanisms underlie IBZ and CBZ infarcts. Methods— We reviewed 946 consecutive patients with ischemic stroke within the middle cerebral artery territory. IBZ and CBZ infarcts were selected based on diffusion-weighted imaging templates to identify vascular territories. Baseline patient characteristics, clinical courses, and neuroradiological features were compared between patients with IBZ and CBZ infarcts. Results— We identified 45 IBZ and 75 CBZ infarct patients. Compared with the CBZ infarct patients, IBZ infarct patients had a higher degree of stenosis or occlusion in either the middle cerebral or internal carotid artery ( P= 0.008) and exhibited a rosary-like pattern of infarction more frequently ( P P P =0.002 and P =0.003, respectively). Conclusions— IBZ infarcts are caused mainly by hemodynamic compromise, whereas embolic pathogenesis appears to contribute greatly to the genesis of CBZ infarcts. Patients with IBZ infarcts showed poor early and late clinical courses. Our findings suggest that different therapeutic approaches may be required to prevent early clinical deterioration in patients with different types of border-zone infarcts.

Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) serve as a promising source for cell-based therapies in regenerative medicine. However, optimal methods for transforming iPSCs into MSCs and the characteristics of iPSC-MSCs obtained from different methods remain poorly understood. In this study, we developed a one-step method for obtaining iPSC-MSCs (CD146+STRO-1+ MSCs) from human synovial fluid MSC-derived induced iPSCs (SFMSC-iPSCs). CD146-STRO-1-SFMSCs were reprogrammed into iPSCs by transduction with lentivirus-mediated Sox2, Oct-3/4, klf4, and c-Myc. SFMSC-iPSCs were maintained with mTeSR1 medium in Matrigel-coated culture plates. Single dissociated cells were obtained by digesting the SFMSC-iPSCs with trypsin. The dissociated cells were then plated into Matrigel-coated culture plate with alpha minimum essential medium supplemented with 10% fetal bovine serum, 1× Glutamax, and the ROCK inhibitor Y-27632. Cells were then passaged in standard cell culture plates with alpha minimum essential medium supplemented with 10% fetal bovine serum and 1× Glutamax. After passaging in vitro, the cells showed a homogenous spindle-shape similar to their ancestor cells (SFMSCs), but with more robust proliferative activity. Flow cytometric analysis revealed typical MSC surface markers, including expression of CD73, CD90, CD105, and CD44 and lack of CD45, CD34, CD11b, CD19, and HLA-DR. However, these cells were positive for CD146 and stro-1, which the ancestor cells were not. Moreover, the cells could also be induced to differentiate in osteogenic, chondrogenic, and adipogenic lineages in vitro. The differentiation potential was improved compared with the ancestor cells in vitro. The cells were not found to exhibit oncogenicity in vivo. Therefore, the method presented herein facilitated the generation of STRO-1+CD146+ MSCs from SFMSC-iPSCs exhibiting enhanced proliferation and differentiation potential.

The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with survival in several types of tumors. The prognostic value of the PNI in lymphoma remains unclear. The present study aimed to evaluate the prognostic significance of the PNI in patients with extranodal natural killer/T cell lymphoma, nasal type (ENKTL). This retrospective study in two institutions was comprised of 177 patients with newly diagnosed ENKTL. Patients with a combined albumin (g/L) + 5 × total lymphocyte count × 109/l ≥ 45 were allocated a PNI score of 0. Patients in whom this total was

Background Thalassemia is the most common inherited disease in southern China. However, this disorder is usually ignored by Jiangxi provincial health system and government due to lack of epidemiological data. Materials and Methods A total of 9489 samples from Hakka Han and Gan-speaking Han in three geographical areas of Jiangxi Province were analyzed for both complete blood cell (CBC) count and reverse dot blot (RDB) gene chip for thalassemia. Results 1182 cases of suspected thalassemia carriers with microcytosis (MCV

Article history:Received 26 November 2009Received in revised form 18 August 2010Accepted 1 September 2010Available online 22 September 2010Keywords:Stroke, ischemicStem cellsMesenchymal stem cellsBone marrowTrophic factors Background:Several studies have examined the enhanced efcacy of mesenchymal stem cells (MSCs) usingneurotrophic factor transfection in ischemic rat models. However, gene therapy,e.g., the application of MSCstransfected with neurotrophic factors, is not feasible in clinical practice for ethical reasons. Therefore, weevaluated cultivation with speci c trophic factors in an attempt to enhance the ef cacy of human MSCs(hMSCs) in ischemic stroke.Methods:Using quantitative sandwich enzyme-linked immunosorbent assay (ELISA), we analyzed the levelsof trophic factors released from hMSCs after treatment with ischemic brain extract. Trophic factors werepretreated underex vivoculture conditions. The concentrations of each trophic factor produced by the trophicfactor-pretreated and non-pretreated hMSCs were then measured and compared.Results:hMSCs cultured with ischemic rat brain extract showed increased production of BDNF (brain-derivedneurotrophic factor), VEGF (vascular endothelial growth factor) and HGF (hepatocyte growth factor).Ex vivotreatment with trophic factors led to a further increase in the production of the trophic factor by hMSC,suggesting autocrine regulation of hMSCs. The morphology and expression of surface markers of hMSCs werenot changed, but the cell viability and cell proliferation ability increased after treatment with trophic factors.Conclusions:Our data indicate that hMSCs provide trophic support to the ischemic brain, which can beenhanced byex vivotreatment of trophic factors during cultivation of hMSCs.© 2010 Elsevier B.V. All rights reserved.

Although ex vivo culture expansion is necessary to use autologous mesenchymal stem cells (MSCs) in treating stroke patients, and several researchers have utilized culture-expanded cells in their studies, the effects of culture expansion on neurogenesis and trophic support are unknown. Thus, we evaluated the impact of the passage of MSCs on their effects in a rat stroke model. The IV application of ex vivo-cultured human MSCs, earlier (passage 2) or later passage (passage 6), was performed in a rat stroke model. Behavioral tests, immunohistochemical studies, and quantitative analysis using the CAST-grid system were performed to evaluate the degree of neurogenesis. We also evaluated the levels of trophic factors in both control and MSC-treated rat brain extract. Compared to rats that received later-passage human MSCs, behavioral recovery and neurogenesis as revealed by bromodeoxyuridine staining were more pronounced in rats that received earlier-passage human MSCs (p < 0.01 in both cases). Double staining showed that most of the endogenous neuronal progenitor cells, but few human MSCs, expressed neuronal and glial phenotypes. Tissue levels of trophic factors, including glial cell line-derived neurotrophic factor, nerve growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were higher in earlier-passage MSC-treated brains than in control or later-passage MSC-treated brains (p < 0.01 in all cases). Our results indicate that ischemia-induced neurogenesis was enhanced by the IV administration of human MSCs. The effects were more pronounced with earlier-passage than with later-passage human MSCs, which may be related to the differential capacity in trophic support, depending on their passage.

Diffusion-weighted imaging (DWI) infarct patterns can play a useful role in the management of ischemic stroke patients, particularly in identifying index stroke mechanisms. Novel vascular risk factors like high sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome have recently been shown to be of prognostic importance following ischemic stroke. We aimed to determine the relationship between these novel factors and infarct patterns noted on DWI.A total of 886 patients with acute cerebral infarcts within the MCA territory were prospectively studied. Using the DWI data the patients were divided into four groups: cortical, small (1cm) superficial, border-zone, and deep infarcts patterns. The independent associations of various infarct DWI patterns vs. hs-CRP and presence of the metabolic syndrome were evaluated after adjusting for the confounders.hs-CRP was highest among patients with cortical infarcts, while the metabolic syndrome was most frequent in patients with border-zone infarcts. Compared to the lowest quartile of hs-CRP level, those in the highest quartile were more likely to have the cortical pattern (OR, 3.55; 95% CI, 1.92-6.56; P0.001), and less likely to have the deep infarct pattern (OR, 0.49; 95% CI, 0.29-0.81; P=0.006) in logistic regression analyses. There was an independent association between presence of the metabolic syndrome and the border-zone pattern (OR, 1.75; 95% CI, 1.12-2.73; P=0.013).hs-CRP levels and metabolic derangements are independently associated with infarct pattern in acute ischemic stroke, and may be the potential targets for lessening the clinical impact of certain infarct patterns.

This study investigated whether bone marrow mesenchymal stem cell (BMSC) transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 10(6) human BMSCs (hBMSCs) were injected into the tail vein. Fourteen days later, we found that hBMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor (sEPOR) was injected into the lateral ventricle, and on the next 13 consecutive days. sEPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the hBMSCs + sEPOR group than in the hBMSCs + heat-denatured sEPOR group. The adhesive-removal test result and the modified Neurological Severity Scores (mNSS) were lower in the hBMSCs + sEPOR group than in the heat-denatured sEPOR group. The adhesive-removal test result and mNSS were similar between the hBMSCs + heat-denatured sEPOR group and the hBMSCs + sEPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

Background HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011. Methods The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL. Results The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008) and OS (P = 0.008) rates of 52% and 74.1%, respectively. Conclusions This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative de novo DLBCL.