Total cholesterol affects the outcome of patients with anterior cerebral artery-occluded acute ischemic stroke treated with thrombolysis.

OBJECTIVE: In this study, we investigated whether certain types of lipid profiles are major contributors of acute ischemic stroke (AIS). PATIENTS AND METHODS: We screened 13,285 hospitalized patients in two stroke medical centers treated with thrombolysis, thrombectomy, or conventional care for anterior cerebral artery-occluded AIS, and found 266 patients. We examined their plasma lipid profiles using the cutoff values from a receiver operating characteristic (ROC) curve. We applied a multivariate logistic regression or Fisher's exact test to compare their outcomes and risk factors. We used the modified Rankin scale (mRS) score to assess the major clinical outcome of the patients 3 months after disease onset. Mortality and symptomatic intracranial hemorrhage (sICH) were both evaluated as risk factors. We analyzed symptoms' improvements at discharge as a disease outcome measure. RESULTS: In the patients with anterior cerebral artery-occluded AIS (NIHSS ≥ 10) treated by intravenous (IV) thrombolysis, a total cholesterol (TC) level greater than 5.07 mmol/L predicted a poor outcome (OR 3.55, 95% CI 1.21,10.46, p=0.021). CONCLUSIONS: In patients with anterior cerebral artery-occluded AIS, the TC level is a promising prognosis marker for the IV thrombolysis outcome.

[High level of hemoglobin during the first trimester of pregnancy associated with the risk of gestational diabetes mellitus].

Objective: To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods: A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People's Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic ß cell function index (HOMA-ß) were used to evaluate insulin resistance and pancreatic ß cell function. Results: (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m(2), (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m(2), (6.7±1.6) mmol/L, (6.1±1.2) mmol/L; (22±3) kg/m(2), (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-ß within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM (OR=2.799, 95%CI: 1.186-6.604; P<0.05). Conclusion: The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.

Microglia M1/M2 polarization contributes to electromagnetic pulse-induced brain injury.

The development of electronic technology has attracted attention on the biological effects of electromagnetic fields (EMFs) and electromagnetic pulse (EMP). It remains controversial whether EMP irradiation is neurotoxic or beneficial for recovery from injuryies such as cerebral ischemia. Microglia is innate immune cells in the brain, exhibiting either neurotoxicity or neuroprotection effect during various central nervous system diseases, depending on their activation into a classical (M1) or alternative (M2) phenotype, respectively. The Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NFκB) pathway is important for microglia activation. In this study, we investigated the effect of EMP on neuronal apoptosis and microglia polarization in vivo and in vitro, using an EMP of 400 kV/m and 1 hertz for 200 pulses. Short EMP irradiation (≤24 h) resulted in microglial conversion from the resting to the M1-type state, activation of the TLR4/MyD88/NFκB pathway, higher levels of inflammatory cytokines including interleukin (IL)-6, IL-1ß and tumor necrosis factor-α, as well as neuronal apoptosis induction. In contrast, long EMP irradiation (3 days) resulted in microglial activation into the M2-type, decreased apoptosis and inflammatory mediator production, and increased levels of the neuroprotective effectors IL-10, transforming growth factor beta, and brain-derived neurotrophic factor. EMP induces both neuronal damage and neuronal recovery by influencing the switch of M1/M2 polarization and the TLR4/MyD88/NFκB pathway.

[Clinical outcomes of peripheral blood stem cell transplantation for aggressive peripheral T-cell lymphoma].

Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion: Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.

[The analysis of systemic concomitant disease in sudden deafness patients].

Objective:To investigate the clinical characteristics of patients with underlying disease in sudden deafness.Method:One hundred and seventy-three inpatients suffered from sudden deafness were included in this study. We analyzed the underlying disease of these patients retrospectively.Result:The underlying disease of sudden deafness patients mainly include atherosclerosis risk factors (hypertension, diabetes, hyperlipemia, hyperhomocystinemia, hyperuricemia) 79.8%, cervical vertebra disease 26.6%, ear disease 19.1%, thyroid disease 13.9%.Conclusion:The characteristics of underlying disease may plays a crucial role in pathogenesis and treatment in sudden deafness patients.

Haploidentical, unmanipulated G-CSF-primed peripheral blood stem cell transplantation for high-risk hematologic malignancies: an update.

Emerging data demonstrate promising results of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) for the treatment of hematologic malignancies. Data about G-CSF primed PBSC as reliable source of graft with myeloablative conditioning are lacking. We updated the outcomes in 130 adult patients with high-risk hematologic malignancies who received haplo-PBSC transplantation consecutively under busulfan-based conditioning. PBSC were freshly isolated and infused without ex vivo T-cell depletion into the recipients. Myeloid recovery was achieved in 99.2% patients with full donor chimerism. The cumulative incidence of acute grade 3-4 GvHD, overall and extensive chronic GvHD was 14.9%, 38.6% and 16.5%, respectively. The 3-year non-relapse mortality rate was 24.1%. Non-remission prior to transplant was associated with higher incidence of relapse (P=0.006), inferior overall survival (P=0.017) and leukemia-free survival (P=0.024). These data suggest that PBSC is a reliable graft source in haploidentical, unmanipulated transplant settings under myeloablative conditioning in patients with high-risk hematologic malignancies.

Membrane microparticles and diseases.

Membrane microparticles (MPs) are plasma membrane-derived vesicles shed by various types of activated or apoptotic cells including platelets, monocytes, endothelial cells, red blood cells, and granulocytes. MPs are being increasingly recognized as important regulators of cell-to-cell interactions. Recent evidences suggest they may play important functions not only in homeostasis but also in the pathogenesis of a number of diseases such as vascular diseases, cancer, infectious diseases and diabetes mellitus. Accordingly, inhibiting the production of MPs may serve as a novel therapeutic strategy for these diseases. Here we review recent advances on the mechanism underlying the generation of MPs and the role of MPs in vascular diseases, cancer, diabetes, inflammation, and pathogen infection.

Hypoxic preconditioning attenuates global cerebral ischemic injury following asphyxial cardiac arrest through regulation of delta opioid receptor system.

This study was designed to investigate whether delta opioid receptor (DOR) is involved in the neuroprotective effect induced by hypoxic preconditioning (HPC) in the asphyxial cardiac arrest (CA) rat model. Twenty-four hours after the end of 7-day HPC, the rats were subjected to 8-min asphyxiation and resuscitated with a standardized method. In the asphyxial CA rat model, HPC improved the neurological deficit score (NDS), inhibited neuronal apoptosis, and increased the number of viable hippocampal CA1 neurons at 24 h, 72 h, or 7 days after restoration of spontaneous circulation (ROSC); however, the above-mentioned neuroprotection of HPC was attenuated by naltrindole (a selective DOR antagonist). The expression of hypoxia-inducible factor-1α (HIF-1α) and DOR, and the content of leucine enkephalin (L-ENK) in the brain were also investigated after the end of 7-day HPC. HPC upregulated the neuronal expression of HIF-1α and DOR, and synchronously elevated the content of L-ENK in the rat brain. HIF-1α siRNA was used to further elucidate the relationship between HIF-1α and DOR in the HPC-treated brain. Knockdown of HIF-1α by siRNA markedly abrogated the HPC induced upregulation of HIF-1α and DOR. The present study demonstrates that the expression of DOR in the rat brain is upregulated by HIF-1α following exposure to 7-day HPC, at the same time, HPC also increases the production of endogenous DOR ligand L-ENK in the brain. DOR activation after HPC results in prolonged neuroprotection against subsequent global cerebral ischemic injury, suggesting a new mechanism of HPC-induced neuroprotection on global cerebral ischemia following CA and resuscitation.

Effects of intracerebroventricular application of the delta opioid receptor agonist [D-Ala2, D-Leu5] enkephalin on neurological recovery following asphyxial cardiac arrest in rats.

The delta opioid receptor (DOR) agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has been implicated as a novel neuroprotective agent in the CNS. The current study was designed to evaluate the effects of intracerebroventricular (ICV) application of DADLE on neurological outcomes following asphyxial cardiac arrest (CA) in rats. Male Sprague-Dawley rats were randomly assigned to four groups: Sham group, CA group, DADLE group (DADLE+CA), and Naltrindole group (Naltrindole and DADLE+CA). All drugs were administered into the left cerebroventricle 30 min before CA. CA was induced by 8-min asphyxiation and the animals were resuscitated with a standardized method. DOR protein expression in the hippocampus was significantly increased in the CA group at 1 h after restoration of spontaneous circulation (ROSC) compared with the Sham group. As time progressed, expression of DOR proteins decreased gradually in the CA group. Treatment with DADLE alone or co-administration with Naltrindole reversed the down-regulation of DOR proteins in the hippocampus induced by CA at 24 h after ROSC. Compared with the CA group, the DADLE group had persistently better neurological functional recovery, as assessed by neurological deficit score (NDS) and Morris water maze trials. The number of surviving hippocampal CA1 neurons in the DADLE group was significantly higher than those in the CA group. However, administration of Naltrindole abolished most of the neuroprotective effects of DADLE. We conclude that ICV administration of DADLE 30 min before asphyxial CA has significant protective effects in attenuating hippocampal CA1 neuronal damage and neurological impairments, and that DADLE executes its effects mainly through DOR.

Prolonged cold preservation promotes the recipient's cell participating in neointima formation but delays the later graft arteriosclerosis in rat model.

Chronic graft dysfunction is the greatest barrier to long-term graft survival, although the immediate outcome in organ transplantation has been greatly improved. Graft arteriosclerosis is a prominent feature of chronic graft dysfunction. Recipient progenitor cells have been shown to participate in neointimal development in graft arteriosclerosis. The present study investigated the role of recipient endothelial cells in the repair and remodeling after a cold preservation injury in an orthotopic cross-sex abdominal aortic allotransplantation model, namely female Wistar to male Sprague-Dawley rats. Grafts were preserved for 48 hours in 4 degrees C University of Wisconsin (UW) solution for a prolonged cold ischemia (PCI) group or preserved for <1 hour in the control group; or for <1 hour in the presence of feeding with cyclosporine (CyA). A direct in situ polymerase chain reaction (ISPCR) for the SRY gene showed SRY-marked endothelial and smooth muscle-like cells in neointima at 2 weeks in the PCI group, at 4 weeks in the control group, and rarely at 3 months in the CyA group. Staining by H&E showed the aortic graft intima to be thicker in the PCI than in the control group at 4 weeks, but thinning thereafter. The SRY-positive cells correlated with intimal thickness in the PCI and the control group (r = .801 and .825; P < .05 and <.05, respectively), but not in the CyA group (r = .247, P > .5). Our data suggest that prolonged cold preservation promotes recipient cell participation in graft arteriosclerosis after endothelium injury. The early neointimal formation via recipient cells incorporated into arteriosclerotic neointima may delay later intimal thickening. In the aortic allotransplantation model, prolonged cold ischemia may be beneficial for long-term graft survival due to early endothelial replacement. We hypothesize that controlled injury to the graft may serve as a new strategy for treatment of intimal thickening.