Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and sometimes the only curative therapy for patients with certain hematological diseases. Allo-HSCT has been practiced in China for approximately 30 years, and great improvements have been made within the past decade, particularly in fields such as the haploidentical HSCT system, strategies to overcome relapse and GVHD, and modified HSCT for elderly patients. This review will describe the current situation and provide a prospective of these unique aspects of Allo-HSCT in China

The Search for Higher TcT_c in Houston

It is a great pleasure to be invited to join the chorus on this auspicious occasion to celebrate Professor K. Alex Mueller's 90th birthday by Professors Annette Bussman-Holder, Hugo Keller, and Antonio Bianconi. As a student in high temperature superconductivity, I am forever grateful to Professor Alex Mueller and Dr. Georg Bednorz "for their important breakthrough in the discovery of superconductivity in the ceramic materials" in 1986 as described in the citation of their 1987 Nobel Prize in Physics. It is this breakthrough discovery that has ushered in the explosion of research activities in high temperature superconductivity (HTS) and has provided immense excitement in HTS science and technology in the ensuing decades till now. Alex has not been resting on his laurels and has continued to search for the origin of the unusual high temperature superconductivity in cuprates.Comment: Dedicated to Alex Mueller, whose "important breakthrough in the discovery of superconductivity in ceramic materials" in 1986 has changed the world of superconductivit

Current status of haploidentical stem cell transplantation for leukemia

Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD), graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy

Investigation of therapeutic efficacy and mechanisms of polysaccharide of dendrobium officinale in alleviating cigarette-induced pulmonary inflammation

Posters: no. 13PS36Dendrobium officinale is a medicinal plant from the Orchidaceae family. It has been listed in the latest edition of the Chinese Pharmacopoeia as medicinal material Dendrobii Officinalis Caulis (Tiepishihu) because of its treatment efficacy. According to the Pharmacopoeia it benefits the stomach, promotes the production of body fluid, nourishes yin and eliminates evil-heat. Consequently it com...published_or_final_versio

Shaping bursting by electrical coupling and noise

Gap-junctional coupling is an important way of communication between neurons and other excitable cells. Strong electrical coupling synchronizes activity across cell ensembles. Surprisingly, in the presence of noise synchronous oscillations generated by an electrically coupled network may differ qualitatively from the oscillations produced by uncoupled individual cells forming the network. A prominent example of such behavior is the synchronized bursting in islets of Langerhans formed by pancreatic \beta-cells, which in isolation are known to exhibit irregular spiking. At the heart of this intriguing phenomenon lies denoising, a remarkable ability of electrical coupling to diminish the effects of noise acting on individual cells. In this paper, we derive quantitative estimates characterizing denoising in electrically coupled networks of conductance-based models of square wave bursting cells. Our analysis reveals the interplay of the intrinsic properties of the individual cells and network topology and their respective contributions to this important effect. In particular, we show that networks on graphs with large algebraic connectivity or small total effective resistance are better equipped for implementing denoising. As a by-product of the analysis of denoising, we analytically estimate the rate with which trajectories converge to the synchronization subspace and the stability of the latter to random perturbations. These estimates reveal the role of the network topology in synchronization. The analysis is complemented by numerical simulations of electrically coupled conductance-based networks. Taken together, these results explain the mechanisms underlying synchronization and denoising in an important class of biological models

Structural Basis of Gate-DNA Breakage and Resealing by Type II Topoisomerases

Type II DNA topoisomerases are ubiquitous enzymes with essential functions in DNA replication, recombination and transcription. They change DNA topology by forming a transient covalent cleavage complex with a gate-DNA duplex that allows transport of a second duplex though the gate. Despite its biological importance and targeting by anticancer and antibacterial drugs, cleavage complex formation and reversal is not understood for any type II enzyme. To address the mechanism, we have used X-ray crystallography to study sequential states in the formation and reversal of a DNA cleavage complex by topoisomerase IV from Streptococcus pneumoniae, the bacterial type II enzyme involved in chromosome segregation. A high resolution structure of the complex captured by a novel antibacterial dione reveals two drug molecules intercalated at a cleaved B-form DNA gate and anchored by drug-specific protein contacts. Dione release generated drug-free cleaved and resealed DNA complexes in which the DNA gate instead adopts an unusual A/B-form helical conformation with a Mg2+ ion repositioned to coordinate each scissile phosphodiester group and promote reversible cleavage by active-site tyrosines. These structures, the first for putative reaction intermediates of a type II topoisomerase, suggest how a type II enzyme reseals DNA during its normal reaction cycle and illuminate aspects of drug arrest important for the development of new topoisomerase-targeting therapeutics

Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer

Introduction\ud Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).\ud \ud Methods\ud Tumor samples from 265 ER+LN- tamoxifen-treated patients were identified from a single academic institution's cancer research registry. The BCI assay was performed and scores were assigned based on a pre-determined risk model. Risk was assessed by BCI and AO and correlated to clinical outcomes in the patient cohort.\ud \ud Results\ud BCI was a significant predictor of outcome in a cohort of 265 ER+LN- patients (median age: 56-y; median follow-up: 10.3-y), treated with adjuvant tamoxifen alone or tamoxifen with chemotherapy (32%). BCI categorized 55%, 21%, and 24% of patients as low, intermediate and high-risk, respectively. The 10-year rates of distant recurrence were 6.6%, 12.1% and 31.9% and of breast cancer-specific mortality were 3.8%, 3.6% and 22.1% in low, intermediate, and high-risk groups, respectively. In a multivariate analysis including clinicopathological factors, BCI was a significant predictor of distant recurrence (HR for 5-unit increase = 5.32 [CI 2.18-13.01; P = 0.0002]) and breast cancer-specific mortality (HR for a 5-unit increase = 9.60 [CI 3.20-28.80; P < 0.0001]). AO was significantly associated with risk of recurrence. In a separate multivariate analysis, both BCI and AO were significantly predictive of outcome. In a time-dependent (10-y) ROC curve accuracy analysis of recurrence risk, the addition of BCI+AO increased predictive accuracy in all patients from 66% (AO only) to 76% (AO+BCI) and in tamoxifen-only treated patients from 65% to 81%.\ud \ud Conclusions\ud This study validates the prognostic performance of BCI in ER+LN- patients. In this characteristically low-risk cohort, BCI classified high versus low-risk groups with ~5-fold difference in 10-year risk of distant recurrence and breast cancer-specific death. BCI and AO are independent predictors with BCI having additive utility beyond standard of care parameters that are encompassed in AO

A 20-year multicentre outcome analysis of salvage mechanical circulatory support for refractory cardiogenic shock after cardiac surgery

Abstract Background Refractory post-cardiotomy cardiogenic shock (PCCS) is a relatively rare phenomenon that can lead to rapid multi-organ dysfunction syndrome and is almost invariably fatal without advanced mechanical circulatory support (AMCS), namely extra-corporeal membrane oxygenation (ECMO) or ventricular assist devices (VAD). In this multicentre observational study we retrospectively analyzed the outcomes of salvage venoarterial ECMO (VA ECMO) and VAD for refractory PCCS in the 3 adult cardiothoracic surgery centres in Scotland over a 20-year period. Methods The data was obtained through the Edinburgh, Glasgow and Aberdeen cardiac surgery databases. Our inclusion criteria included any adult patient from April 1995 to April 2015 who had received salvage VA ECMO or VAD for PCCS refractory to intra-aortic balloon pump (IABP) and maximal inotropic support following adult cardiac surgery. Results A total of 27 patients met the inclusion criteria. Age range was 34–83 years (median 51 years). There was a large male predominance (n = 23, 85 %). Overall 23 patients (85 %) received VA ECMO of which 14 (61 %) had central ECMO and 9 (39 %) had peripheral ECMO. Four patients (15 %) were treated with short-term VAD (BiVAD = 1, RVAD = 1 and LVAD = 2). The most common procedure-related complication was major haemorrhage (n = 10). Renal failure requiring renal replacement therapy (n = 7), fatal stroke (n = 5), septic shock (n = 2), and a pseudo-aneurysm at the femoral artery cannulation site (n = 1) were also observed. Overall survival to hospital discharge was 40.7 %. All survivors were NYHA class I-II at 12 months’ follow-up. Conclusion AMCS for refractory PCCS carries a survival benefit and achieves acceptable functional recovery despite a significant complication rate