Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway.

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS: Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma: A case report.

BACKGROUND: Lung invasive mucinous adenocarcinoma (LIMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare disease that usually presents as bilateral lung infiltration, is unsuitable for surgery and radiotherapy, and shows poor response to conventional chemotherapy. CASE SUMMARY: We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia, but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography -guided percutaneous lung biopsy. Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d. After more than 11 months of treatment, there is no evidence of recurrence or severe adverse events. CONCLUSION: Although the precise mechanism of the antitumor effects of gefitinib are not clear, our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Development of a model for predicting the severity of chronic obstructive pulmonary disease.

Background: Several models have been developed to predict the severity and prognosis of chronic obstructive pulmonary disease (COPD). This study aimed to identify potential predictors and construct a prediction model for COPD severity using biochemical and immunological parameters. Methods: A total of 6,274 patients with COPD were recruited between July 2010 and July 2018. COPD severity was classified into mild, moderate, severe, and very severe based on the Global Initiative for Chronic Obstructive Lung Disease guidelines. A multivariate logistic regression model was constructed to identify predictors of COPD severity. The predictive ability of the model was assessed by measuring sensitivity, specificity, accuracy, and concordance. Results: Of 6,274 COPD patients, 2,644, 2,600, and 1,030 had mild/moderate, severe, and very severe disease, respectively. The factors that could distinguish between mild/moderate and severe cases were vascular disorders (OR: 1.44; P < 0.001), high-density lipoprotein (HDL) (OR: 1.83; P < 0.001), plasma fibrinogen (OR: 1.08; P = 0.002), fructosamine (OR: 1.12; P = 0.002), standard bicarbonate concentration (OR: 1.09; P < 0.001), partial pressure of carbon dioxide (OR: 1.09; P < 0.001), age (OR: 0.97; P < 0.001), eosinophil count (OR: 0.66; P = 0.042), lymphocyte ratio (OR: 0.97; P < 0.001), and apolipoprotein A1 (OR: 0.56; P = 0.003). The factors that could distinguish between mild/moderate and very severe cases were vascular disorders (OR: 1.59; P < 0.001), HDL (OR: 2.54; P < 0.001), plasma fibrinogen (OR: 1.10; P = 0.012), fructosamine (OR: 1.18; P = 0.001), partial pressure of oxygen (OR: 1.00; P = 0.007), plasma carbon dioxide concentration (OR: 1.01; P < 0.001), standard bicarbonate concentration (OR: 1.13; P < 0.001), partial pressure of carbon dioxide (OR: 1.16; P < 0.001), age (OR: 0.91; P < 0.001), sex (OR: 0.71; P = 0.010), allergic diseases (OR: 0.51; P = 0.009), eosinophil count (OR: 0.42; P = 0.014), lymphocyte ratio (OR: 0.93; P < 0.001), and apolipoprotein A1 (OR: 0.45; P = 0.005). The prediction model correctly predicted disease severity in 60.17% of patients, and kappa coefficient was 0.35 (95% CI: 0.33-0.37). Conclusion: This study developed a prediction model for COPD severity based on biochemical and immunological parameters, which should be validated in additional cohorts.

Jidong Restless Legs Syndrome Cohort Study: Objectives, Design, and Baseline Screening.

Background: Restless legs syndrome (RLS) is a common neurological disorder with unpleasant leg sensations and serious negative effects on mental and physical health. Many observational studies showed that people with RLS had a high risk of vascular diseases, including cerebrovascular and cardiovascular diseases (CVD), but the findings were conflicting. The Jidong RLS Cohort Study is a prospective cohort study designed to mainly examine whether or not RLS is associated with an increased risk of CVD. Methods and Design: The study recruited 8,867 healthy participants older than 18 years from October 2014 to December 2015. Participants received a physical examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Restless legs syndrome was assessed using the international RLS diagnostic criteria. All of subjects would be followed up until December 2025. Major cardiovascular/cerebrovascular events including cardiac death, myocardial infarction, ischemic heart disease, heart failure, atrial fibrillation, ischemic, and hemorrhagic stroke will be the primary outcomes. Secondary outcomes include all-cause mortality, the decline in quality of life, cognitive impairment, and depression. Discussion: This study will contribute to the scientific evidence on the association between RLS and cardiovascular risks and also provide an unprecedented opportunity for early detection and prevention of CVD.

Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome.

INTRODUCTION: This study aims at exploring the expression and significance of recombination signal-binding protein for immunoglobulin kappa J region (RBP-Jκ) and C-X-C motif chemokine 11 (CXCL11) in human colon cancer tissues. METHODS: The RBP-Jκ and CXCL11 expression levels were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) in patients with colon cancer, and their prognostic significance was evaluated. RESULTS: Through analyzing 342 samples of colon cancer patients treated at our institution, increased expression of RBP-Jκ and CXCL11 was found in human colon cancer specimens compared with matched paratumorous normal specimens (P<0.001). A positive correlation was found between RBP-Jκ expression and CXCL11 expression (P<0.001). High RBP-Jκ expression was significantly associated with poorly differentiated tumors (P=0.005), invasion beyond propria muscularis (P=0.025), lymph node metastases (P=0.005), distant metastasis (P<0.001), advanced tumor-node-metastasis (TNM) stage (P=0.004), and a shorter overall survival (P<0.001). An increase in CXCL11 protein expression was associated with poorly differentiated tumors (P=0.015), invasion beyond propria muscularis (P=0.029), lymph node metastases (P=0.031), distant metastasis (P=0.045), advanced TNM stage (P=0.026), and a shorter overall survival of patients (P<0.001). In multivariate Cox regression analysis, RBP-Jκ protein expression (P=0.036), CXCL11 protein expression (P=0.001), differentiation (P<0.001), depth of invasion (P=0.009), distant metastasis (P<0.001), and TNM stage (P<0.001) were independent prognostic indicators of colon cancer. CONCLUSION: High expression of RBP-Jκ is closely associated with high CXCL11 expression, which represents a risk factor for the poor overall survival of colon cancer patients.

[The feeding of Zoanthus sp. on two microalgae species.] / 花群珊瑚对两种微藻的摄食.

In this study, we investigated whether Zoanthus sp. feed on two common microalgae, Platymonas subcordiformis and Isochrysis galbana, using the methods of carbon clearance rate, DNA marker, and histological analyses. The results showed that carbon clearance rate of I. galbana by Zoanthus sp. was significantly higher than that of P. subcordiformis, which were 0.44 and 0.11 pg·mL-1·polyp-1·h-1, respectively. 162 bp of 18S rRNA gene from P. subcordiformis and 442 bp of enoyl-ACP reductase gene from I. galbana were used as molecular nutrition markers, both of them were successfully amplified from the Zoanthus sp. fed by both algae species. Results of the histological analyses demonstrated that pholyp from feeding group showed a widen mesentery. Lots of food vacuoles presented in tissues of mesentery and gastrodermis. Undigested cell body of P. subcordiformis and I. galbana could also be found in some food vacuoles around siphonoglyphe as well as the gastrodermis in body wall. Therefore, results from carbon clearance rate, histological and DNA marker results all indicated that Zoanthus sp. could feed on P. subcordiformis and I. galbana.

Differential expression and clinical significance of COX6C in human diseases.

Mitochondria, independent double-membrane organelles, are intracellular power plants that feed most eukaryotic cells with the ATP produced via the oxidative phosphorylation (OXPHOS). Consistently, cytochrome c oxidase (COX) catalyzes the electron transfer chain's final step. Electrons are transferred from reduced cytochrome c to molecular oxygen and play an indispensable role in oxidative phosphorylation of cells. Cytochrome c oxidase subunit 6c (COX6C) is encoded by the nuclear genome in the ribosome after translation and is transported to mitochondria via different pathways, and eventually forms the COX complex. In recent years, many studies have shown the abnormal level of COX6C in familial hypercholesterolemia, chronic kidney disease, diabetes, breast cancer, prostate cancer, uterine leiomyoma, follicular thyroid cancer, melanoma tissues, and other conditions. Its underlying mechanism may be related to the cellular oxidative phosphorylation pathway in tissue injury disease. Here reviews the varied function of COX6C in non-tumor and tumor diseases.

Generation of an induced pluripotent stem cell (iPSC) line (THSJTUi001-A) from a Wilson's disease patient harboring a homozygous Arg778Leu mutation in ATP7B gene.

Induced pluripotent stem cell (iPSC) line, THSJTUi001-A, was generated from a 26-year-old Chinese male patient with Wilson's disease carrying a homozygous Arg778Leu mutation in ATP7B gene, using non-integrated episomal reprogramming vectors. This cell line had normal karyotype, expressed pluripotency markers and could differentiate into the three germ layers in vivo.

Transverse Strips Instead of Wearable Laser Lights Alleviate the Sequence Effect Toward a Destination in Parkinson's Disease Patients With Freezing of Gait.

Background: The sequence effect (SE), referring to step-to-step reduction in amplitude, is considered to lead to freezing of gait (FOG) in Parkinson's disease (PD). Visual cues may alleviate SE and help reduce freezing episodes. FOG patients show significant SE prior to turning or toward a doorway, but the SE toward a destination has not been clearly studied. Objectives: To examine the SE when approaching a destination in PD patients with FOG, and to further explore the effects of different types of visual cues on destination SE. Methods: Thirty-five PD patients were divided into a freezing (PD+FOG, n = 15) group and a non-freezing (PD-FOG, n = 20) group. Walking trials were tested under three conditions, including without cues (no-cue condition), with wearable laser lights (laser condition), and with transverse strips placed on the floor (strip condition). Kinematic data was recorded by a portable Inertial Measurement Unit (IMU) system. The destination SE and some key gait parameters were evaluated. Results: The PD+FOG group showed greater destination SE in the no-cue and laser conditions when compared to the PD-FOG group. There were no significant differences in the strip condition when comparing destination SE of the two groups. The destination SE was alleviated only by using the transverse strips on the floor. In contrast, transverse strips and wearable laser lights could increase the step length. Conclusions: The significant destination SE may explain why FOG patients are prone to freezing when heading toward their destination. Visual cues using transverse strips on the floor may be a more effective strategy for FOG rehabilitation in PD patients.

The function of SEC22B and its role in human diseases.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are a large protein complex that is involved in the membrane fusion in vesicle trafficking, cell growth, cytokinesis, membrane repair, and synaptic transmission. As one of the SNARE proteins, SEC22B functions in membrane fusion of vesicle trafficking between the endoplasmic reticulum and the Golgi apparatus, antigen cross-presentation, secretory autophagy, and other biological processes. However, apart from not being SNARE proteins, there is little knowledge known about its two homologs (SEC22A and SEC22C). SEC22B alterations have been reported in many human diseases, especially, many mutations of SEC22B in human cancers have been detected. In this review, we will introduce the specific functions of SEC22B, and summarize the researches about SEC22B in human cancers and other diseases. These findings have laid the foundation for further studies to clarify the exact mechanism of SEC22B in the pathological process and to seek new therapeutic targets and better treatment strategies.

Risk factors and associations with clinical outcomes of cytomegalovirus reactivation after haploidentical versus matched-sibling unmanipulated PBSCT in patients with hematologic malignancies.

In allogeneic hematopoietic stem cell transplantation recipients, cytomegalovirus (CMV) infection can cause overt CMV-associated disease, which is a main cause of transplantation-associated mortality. CMV infection correlates closely with donor's type. We therefore examined whether risk factors of CMV reactivation and clinical endpoints in patients with hematologic malignancies after allogeneic peripheral blood stem cell transplantation (PBSCT) differed between using matched-sibling donors (MSD-SCT) and haploidentical donors (HID-SCT). In this retrospective cohort study, we enrolled in 200 consecutive patients received an unmanipulated G-CSF-mobilized allogeneic PBSCT. Ninety (45%) patients received MSD-SCT and 110 (55%) received HID-SCT. Quantitative PCR was used for monitoring of CMV reactivation after transplantation. One-year cumulative incidence of CMV DNAemia was 55.0%, ranging from 23.5% in MSD-SCT group to 81.0% in HID-SCT group (p < 0.001). Although univariate analyses showed that non-myeloid malignancies, disease in complete remission status at transplantation, pretreatment with antithymocyte globulin, HLA-haploidentical donors, male donors, previous Epstein-Barr virus DNAemia, and absolute lymphocyte count on day 30 < 0.6 × 109/L were respectively associated with CMV reactivation after transplantation in total cohort of recipients (all p < 0.05), haploidentical donors were found to be the only independent predictor in multivariate analyses (Hazard ratio = 6.4, p < 0.001). Furthermore, univariate analyses revealed that non-myeloid malignancies and previous Epstein-Barr virus DNAemia were respectively associated with CMV reactivation in MSD-SCT recipients, and female was associated with CMV reactivation in HID-SCT recipients (all p < 0.05). In HID-SCT recipients, but not MSD-SCT recipients, previous CMV DNAemia was associated with a lower cumulative incidence of acute graft-versus-host disease (49.2% vs. 72.6%, p < 0.001). CMV DNAemia did not play a role in the relapse rate, but it was strongly associated with an increased risk of non-relapse mortality either in total cohort of recipients (30.5% vs. 13.7%; p = 0.003) or in the HID-SCT subgroup (36.0% vs. 16.7%; p = 0.030). Relapse-free survival and overall survival in total cohort of recipients with CMV DNAemia were both inferior to those without CMV DNAemia (45.3% vs. 57.6% and 54.8% vs. 65.8%, respectively; both p < 0.05). However, in subgroup analysis according to donor's type, neither relapse-free survival nor overall survival was impacted by CMV status (both p > 0.05). This study addressed differences in incidence, risk factors, and associations with clinical outcomes of CMV reactivation after haploidentical versus matched-sibling PBSCT.

Effects of Mindfulness-based Interventions on Dementia Patients: A Meta-analysis.

This study aims to systematically evaluate the efficacy of mindfulness-based intervention (MBI) in improving mental health and quality of life for people with dementia. Comprehensive literature search was performed using the PubMed, EMBASE, Web of Science, Cochrane Library, and CINAHL databases from their inception till June 26, 2019. In total, nine articles met the eligibility criteria and were included. The results of the meta-analysis showed a statistically significant decrease in depressive symptoms (SMD = -0.39, 95% CI: - 0.62 to - 0.15), in people with dementia who were treated with MBI. However, there were no significant improvements in anxiety, stress, or quality of life. These findings suggest that MBI is a promising alternative to conventional interventions in the treatment of depression among dementia patients and warrant further study.

Comparative serum metabolomics between SCID mice and BALB/c mice with or without Schistosoma japonicum infection: Clues to the abnormal growth and development of schistosome in SCID mice.

The small blood flukes of genus Schistosoma, which cause one of the most prevalent and serious parasitic zoonosis schistosomiasis, are dependent on immune-related factors of their mammalian host to facilitate their growth and development, and the formation of granulomatous pathology caused by eggs deposited in host's liver and intestinal wall. Schistosome development is hampered in the mice lacking just T cells, and is even more heavily retarded in the severe combined immunodeficient (SCID) mice lacking both T and B lymphocytes. Nevertheless, it's still not clear about the underlying regulatory molecular mechanisms of schistosome growth and development by host's immune system. This study, therefore, detected and compared the serum metabolic profiles between the immunodeficient mice and immunocompetent mice (SCID mice vs. BALB/c mice) before and after S. japonicum infection (on the thirty-fifth day post infection using liquid chromatography-mass spectrometry (LC-MS). Totally, 705 ion features in electrospray ionization in positive-ion mode (ESI+) and 242 ion features in ESI- mode were identified, respectively. First, distinct serum metabolic profiles were identified between SCID mice and BALB/c mice without S. japonicum worms infection. Second, uniquely perturbed serum metabolites and their enriched pathways were also obtained between SCID mice and BALB/c mice after S. japonicum infection, which included differential metabolites due to both species differences and differential responses to S. japonicum infection. The metabolic pathways analysis revealed that arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and purine metabolism were enriched based on the differential serum metabolites between SCID mice and BALB/c mice after S. japonicum infection, which was addressed to be related to the retarded growth and development of S. japonicum in SCID mice. These findings provide new clues to the underlying molecular events of host's systemic metabolic changes on the growth and development of S. japonicum worms, and also provide quite promising candidates for exploitation of drugs or vaccines against schistosome and schistosomiasis.

Risk factors and clinical outcomes of Epstein-Barr virus DNAemia and post-transplant lymphoproliferative disorders after haploidentical and matched-sibling PBSCT in patients with hematologic malignancies.

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.

How embodied carbon in trade affects labor income in developing countries.

With the growth of international trade, the geographical separation of production and consumption links of goods has become increasingly common. Commodity-consuming countries can transfer carbon emissions generated in the production of commodities to commodity-producing countries through foreign trade while meeting their domestic consumption demands and emission reduction targets. This issue of embodied carbon emissions in international trade has received wide attention in recent years and has exerted significant impact on the labor income share of developing nations. This study determines the relationship between carbon emission and labor income share in the imports and exports of intermediate products from the perspective of the global value chain. Empirical results show that in developing countries, labor income share has a negative relationship with trade and a positive one with embodied carbon emission. Furthermore, to distinguish the heterogeneity between industries and verify the hypothesis, we classified 57 sectors into 7 main industries based on the method of Meng et al. (2018). Specifically, labor-intensive exports and technology-intensive imports increase labor income share while technology-intensive exports and labor-intensive imports reduce it. In addition to the light industry, the upgrading of women's employment structure can promote the increase of labor income share in host countries. The policy relevance of this study rests on its findings that developing countries can increase their labor income share through imports related to technology-intensive industries and exports related to labor-intensive industries; and that countries worldwide can fundamentally reduce embodied carbon emissions in trade by means of innovations in science and technology to realize sustainable development of the environment, economy, and society.

Research progress in scyphozoan polyp strobilation-induced factors and regulation mechanism.

Strobilation is a key stage for polyp-to-jellyfish transition. Knowledge about the strobilation-induced factors and the underlying molecular regulation mechanism could help control jellyfish bloom in nature, improve jellyfish artificial breeding, as well as get insight about the ancestral molecular origin of metamorphosis of amphibians, insect and cnidarians. Natural factors, including temperature, illumination, salinity, and symbiotic zooxanthellae, could induce strobilation. The mode of strobilation and how these natural factors irritate strobilation are distinct in different jellyfish species. Chemicals including indole derivates, 9-cis retinoic acid, elemental iodine, hydrogen peroxide, could also induce strobilation in laboratory. Indole derivates are effective inducers to most scyphozoan species. The molecular mechanism of strobilation is unclear. Results from moon jelly reveal that RxR signaling pathway plays an important role during strobilation. A secreted moon jelly-special protein named CL390 may serve as a strobilation-induced hormone precursor. These results imply that morphological differences in medusa production may mask similarities at the cellular level in different jellyfish species. The molecular mechanism of metamorphosis in jellyfish may share some consistency with amphibians and insects.

Comparison of the safety and efficacy of prophylactic donor lymphocyte infusion after haploidentical versus matched-sibling PBSCT in very high-risk acute myeloid leukemia.

Donor lymphocyte infusion (DLI) might be used prophylactically to reduce relapse after allogeneic hematopoietic stem cell transplantation for very high-risk leukemia/lymphoma without effective targeted therapy. To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective analysis in a cohort of 21 HID-SCT and 13 MSD-SCT recipients, displaying similar baseline characteristics except for donor's gender distribution. Grade 2-4 acute graft-versus-host disease (GVHD) at 100-day post-DLI was higher in HID-SCT group than that in MSD-SCT group (59.5% vs. 30.8%, p = 0.05). The grade 3-4 acute GVHD (17.5% vs. 7.7%), 1-year chronic GVHD (36.6% vs. 33.2%), and severe chronic GVHD (15.3% vs. 27.3%) were not statistically significant different between groups. One-year non-relapse mortality was higher in HID-SCT group than that in MSD-SCT group with marginal significance (27.9% vs. 0.0%, p = 0.061). One-year relapse rate was not statistically significant different between HID-SCT group and MSD-SCT group (21.6% vs. 36.5%, p = 0.543). For HID-SCT recipients, 1-year relapse rate was lower in patients receiving prophylactic DLI than that in a control cohort of eight patients with same very high-risk features but not receiving prophylactic DLI (62.5% vs. 28.3%, p = 0.037). No statistically significant difference was observed in 1-year overall survival (OS, 55.1% vs. 83.9%, p = 0.325) and relapse-free survival (RFS, 50.1% vs. 74.0%, p = 0.419) rates between HID-SCT group and MSD-SCT group. In multivariate analyses, non-remission status prior to transplant, poor-risk gene mutations, and donor's age ≥ 48 years predicted a higher risk of relapse after DLI. Non-remission status prior to transplant predicted inferior OS and RFS. Patient's age ≥ 40 years also predicted an inferior OS. In conclusion, prophylactic DLI was very safe and efficient for reducing relapse in patients with very high-risk AML receiving MSD-SCT. In the recipients of HID-SCT, the application of prophylactic DLI could reduce the risk of relapse, although with a higher incidence of DLI-associated acute GVHD than those of MSD-SCT.

Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies.

Unmanipulated haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2, and DNMT3a. In this study, we aimed to establish the tolerance and efficacy of prophylactic donor lymphocyte infusion (DLI) with G-CSF-primed peripheral blood progenitors for prevention of relapse in these very high-risk patients after haplo-PBSCT. The prophylactic DLI was given at a median of 77 days after transplantation in 31 of 45 consecutive patients with very high-risk leukemia/lymphoma. The median dose of CD3+ cells for infusion was 1.8 × 107/kg. The 100-day incidences of acute graft-versus-host disease (GVHD) grades 2-4 and 3-4 after DLI were 55.3% and 10.2%. The 2-year incidences of chronic GVHD and severe chronic GVHD were 52.0% and 18.2%. The 2-year incidences of non-relapse mortality and relapse were 33.1% and 32.5%. The 2-year probabilities of overall survival and relapse-free survival were 40.1% and 31.9%. Poor-risk gene mutations (p = 0.029), disease in non-remission status prior to transplantation (p = 0.005), and donors older than 40 years of age (p = 0.043) were associated with relapse after DLI. In multivariate analysis, disease in non-remission status prior to transplantation was an independent risk factor of relapse (hazard ratio = 4.079; p = 0.035). These data showed the feasibility of the prophylactic DLI in the haplo-PBSCT setting and the anti-leukemic efficacy in very high-risk leukemia/lymphoma.

Identification and expression of transcription factor sox2 in large yellow croaker Larimichthys crocea.

As an important transcription and pluripotency factor, Sox2 plays its functions essentially in the regulation of self-renewal and pluripotency of embryonic and neural stem cells, as well as embryogenesis, organogenesis, neurogenesis and regeneration. The data is lacking on Sox2 in large yellow croaker (Larimichthys crocea) (Lc-Sox2) which is a limitation on the generation of induced pluripotent stem cells (iPSCs). In this study, Lc-sox2 was cloned by RACE (rapid amplification of cDNA ends) and analyzed by Bioinformatics. The quantitative real-time PCR (qRT-PCR) and whole mount in situ hybridization (WISH) were used to detect the expression of Lc-sox2. The full-length cDNA sequence of Lc-sox2 is 2135 bp and encodes a 322-aa (amino acids). Lc-Sox2 possesses a highly conserved HMG-box as DNA-binding domain, maintains highly conserved with vertebrates, particularly with teleosts. In tissues, Lc-sox2 was expressed with gender difference in brain and eye (female > male), in embryos, Lc-sox2 was expressed with a zygotic type that the high level expression began to appear in the gastrula stage. The spatio-temporal expression patterns of Lc-sox2 suggested the potential involvement in embryogenesis, neurogenesis, gametogenesis and adult physiological processes of large yellow croaker. Our results contributed to better understanding of Sox2 from large yellow croaker.

[Clinical Characteristics, Treatment and Prognosis of PTLD after allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To study the clinical characteristics of patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic peripheral blood hematopoietic stem cell transplantation, and to improve the understanding and diagnosis of PTLD. METHODS: The clinical data of 244 patients underwent allogeneic hematopoietic stem cell transplantation in the General Hospital of PLA from May 2014 to April 2017 were analyzed retrospectively. The follow-up time was up to November 30, 2017. The incidence, risk factors, treatment and survival of patients with PTLD were statistically analyzed. RESULTS: Among the 244 cases the PTLD occurred in 22 cases, the incidence rate was 9.02%, 5 of them were diagnosed by pathology, and 17 were diagnosed clinically. All of them had EB virus infection. They were all ATG user, either underwent related haploidentical hematopoietic stem cell transplantation or unrelated hematopoietic stem cell transplantation, 20 cases were treated with rituximab or rituximab combined with γ-globulin, glucocorticoid, ERV+CTL, chemotherapy and 17 showed the effective response, with a total effective rate of 85%. The median follow-up time was 122 days, the median survival time was 5 months (1-22 months) and the total survival rate was 50%. CONCLUSION: The incidence of PTLD after allogeneic peripheral blood hematopoietic stem cell transplantation closely relates with EB virus infection. The application of ATG in the preconditioning scheme is a high risk factor for the onset of PTLD. In the case of no pathological diagnosis, clinical and laboratory examinations should be actively combined so as to define clinical diagnosis. The riturimab should be used more and more for patients with PTLD.