[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation].

Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Observation of generalized Kibble-Zurek mechanism across a first-order quantum phase transition in a spinor condensate.

The Kibble-Zurek mechanism provides a unified theory to describe the universal scaling laws in the dynamics when a system is driven through a second-order quantum phase transition. However, for first-order quantum phase transitions, the Kibble-Zurek mechanism is usually not applicable. Here, we experimentally demonstrate and theoretically analyze a power-law scaling in the dynamics of a spin-1 condensate across a first-order quantum phase transition when a system is slowly driven from a polar phase to an antiferromagnetic phase. We show that this power-law scaling can be described by a generalized Kibble-Zurek mechanism. Furthermore, by experimentally measuring the spin population, we show the power-law scaling of the temporal onset of spin excitations with respect to the quench rate, which agrees well with our numerical simulation results. Our results open the door for further exploring the generalized Kibble-Zurek mechanism to understand the dynamics across first-order quantum phase transitions.

Observation of Dynamical Quantum Phase Transitions with Correspondence in an Excited State Phase Diagram.

Dynamical quantum phase transitions are closely related to equilibrium quantum phase transitions for ground states. Here, we report an experimental observation of a dynamical quantum phase transition in a spinor condensate with correspondence in an excited state phase diagram, instead of the ground state one. We observe that the quench dynamics exhibits a nonanalytical change with respect to a parameter in the final Hamiltonian in the absence of a corresponding phase transition for the ground state there. We make a connection between this singular point and a phase transition point for the highest energy level in a subspace with zero spin magnetization of a Hamiltonian. We further show the existence of dynamical phase transitions for finite magnetization corresponding to the phase transition of the highest energy level in the subspace with the same magnetization. Our results open a door for using dynamical phase transitions as a tool to probe physics at higher energy eigenlevels of many-body Hamiltonians.

Functional, physical and psychosocial impact of Temporomandibular Disorders in adolescents and young adults.

BACKGROUND: This community-based study investigated the functional, physical and psychosocial impact of Temporomandibular Disorders (TMDs) in adolescents and young adults. It also determined the discriminative capacity of a TMDs-specific oral health related quality of life (OHRQoL) instrument and compared three formats of appraising OHRQoL data. MATERIAL AND METHODS: Subjects were recruited from a local Polytechnic. The presence of TMDs was established with the Fonseca Anamnestic Index (FAI), whilst TMDs-specific OHRQoL was evaluated with the Oral Health Impact Profile-TMDs (OHIP-TMDs). Demographic information, FAI and OHIP-TMDs responses were gathered with an on-line questionnaire. Data was analysed using Mann-Whitney U-test, chi-square test and Spearman's rho correlation with significance level set at 0.05. RESULTS: Data from a total of 244 participants were compiled and examined. The "no TMDs" (NT) group consisted of 140 subjects (119 females; 21 males) with a mean age of 20.41±3.29 years, while the "with TMDs" (WT) group composed of 104 subjects (88 females; 16 males) aged 19.82±3.04 years. Significant differences in median severity scores were observed between subjects with and without TMDs for all OHIP-TMDs domains and total OHIP (p values < 0.001). For appraisal of extent and prevalence, significant differences were again observed (p values < 0.05) with the exception of the functional limitation and handicap domains. CONCLUSIONS: TMDs impacted physical and psychosocial well-being of adolescents and young adults. OHIP-TMDs, preferably appraised by severity, extent and prevalence, was able to discriminate between subjects with and without TMDs. It holds promise as a TMDs-specific OHRQoL instrument for epidemiological studies.

Effect of Epigallo-Catechin-3-Gallate on Lipid Metabolism Related Gene Expression and Yolk Fatty Acid Profiles of Laying Hens Exposed to Vanadium.

As the understanding of the pathways involved in such effect are quite limited, we investigated the gene pathways that modulate lipid metabolism in layers and the fatty acid profiles of the yolk of layers that were challenged with dietary vanadium (V) and supplemented with epigallo-catechin-3-gallate (EGCG). For this purpose, a total of 120 hens were divided into four groups which were fed the following experimental diets for a period of 8 weeks: control (basal diet), V10 (control + 10 mg/kg V), EGCG130 (V10 + 130 mg/kg EGCG), and EGCG217 (V10 + 217 mg/kg EGCG). Blood total cholesterol, triglyceride, glucose, and very low-density lipoprotein-cholesterol concentration were lower in V10, EGCG130, and EGCG217 groups compared to the control group, while total cholesterol and triglyceride content in blood were lower in the EGCG217 group than in V10 group (P < 0.05). Hens consumed V10 diet had the highest triglyceride content in liver among treatments, whereas EGCG130 and EGCG217 groups had lower values when compared to those observed in the control group (P < 0.01). Dietary inclusion of V increased yolk polyunsaturated fatty acid (PUFA) and total unsaturated fatty acid (UFA) content compared to the control group (P < 0.05), whereas the addition of either 130 or 217 mg/kg EGCG in V containing diet resulted in similar yolk PUFA and UFA contents with those observed in the control group. Treatment with V alone upregulated the expression of hepatic fatty acid synthase (FAS) and sterol-regulator element-binding protein 1 (SREBP1), while EGCG downregulated FAS and SREBP1 expressions in contrast to V10 treatments (P < 0.01). Liver gene expression peroxisome proliferator-activated receptor gamma (PPARγ) was lower in the V10 than in the control group while EGCG inclusion groups upregulated their expression (P < 0.05). In conclusion, the data gathered in this study indicate that dietary V and EGCG alter the layers' lipid metabolism and fat deposition pattern in egg yolk, which might be associated with their modulatory effect on lipogenesis-related gene (FAS, SREBP1, and PPARγ) expression.

Functional roles of exosomes in cardiovascular disorders: a systematic review.

Cardiovascular diseases are major causes of people death associated with high mortality and disability. Exosomes are nanosized extracellular vesicles containing protein, lipid, transcription factors, mRNAs, non-coding RNA (ncRNA) and nucleic acid contents, which are critical players of intercellular communication via long-range signals or cell-to-cell contact. The emergence of exosomes provides favorable strategies for the diagnosis and treatment of cardiovascular diseases. Exosomes-based molecular mechanisms are important for developing novel therapeutic approaches for cardiovascular events. In this review, we will (1) provide insights into the detrimental and beneficial effects of exosomes on cardiovascular physiology, (2) summarize the underlying biological mechanisms of the exosome in cardiovascular events, (3) investigate the therapeutic value of exosomes for cardiovascular disorders.

Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells.

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34,+ cells and HSPCs expanded with primary hMSCs.

Design of a core-shelled polymer cylinder for potential programmable drug delivery.

A cylindrical dosage form comprising a laminated composite polymer core and a hydrophobic polycarbonate coating was proposed for programmable drug delivery. In the core, poly[(ethyl glycinate) (benzyl amino acethydroxamate) phosphazene] was synthesized as drug-loaded layers for its strong pH-sensitive degradation (eroded after 1.5 days at pH 7.4 and more than 20 days at pH 5.0 and 6.0). Poly(sebacic anhydride)-b-polyethylene glycol or poly(sebacic anhydride-co-trimellitylimidoglycine)-b-poly(ethylene glycol) was selected as isolating layers for their good processing properties at room temperature and suitable erosion duration. The in vitro drug release studies of these devices were conducted under physiological conditions (pH 7.4). The results revealed that the model drugs (brilliant blue, FITC-dextran, myoglobin) could be released in typical pulsatile manner. Moreover, the duration time of drug release (24-40 h) and the lag time (18-118 h) could be separately regulated by the mass of polyphosphazene and the type or mass of polyanhydride. In this experiment, the cooperative effect of polyanhydrides and pH-sensitive degradable polyphosphazene was specially demonstrated, which offers a new idea to develop a programmable drug delivery system for single dose vaccine and other related applications.

[An analysis of ionic flow of spontaneous slow action potential of guinea pig aortic vestibule].

Spontaneous slow action potentials of aortic vestibule of isolated guinea pig heart were intracellularlly recorded. Electrophysiological parameters examined are: maximal diastolic potential (MDP), amplitude of action potential (APA), maximal rate of depolarization of phase 0 (V(max)), velocity of diastolic depolarization of phase 4 (VDD), duration of 50% and 90% repolarization (APD(50) and APD(90)) and rate of pacemaker firing (RPF). It was found that (1) 0.5 micromol/L nisoldipine (Nis) significantly decreased APA, V(max), VDD and RPF (P<0.01); (2) 1.2 mmol/L tetrodotoxin (TTX) significantly decreased APA and V(max) (P<0.05), but VDD and RPF were significantly slowed down as compared with control (P<0.01); (3) 2 mmol/L 4-aminopyridine (4-AP) elicited a decrease in MDP, APA and V(max) (P<0.01), but an increase in VDD and RPF (P<0.01); (4) when 1.5 mmol/L CsCl was perfused for 5 min, the VDD and RPF were significantly decreased (P<0.05); and (5) under the condition of hypoxia and perfusion with deprived glucose content for 15 min, the VDD and RPF were decreased (P<0.01). The above results suggest that (1) in addition to Ca(2+), Na(+) current contributes to generation of 0 phase of depolarization of slow response activity in aortic vestibule mainly, and (2) in addition to the inward Ca(2+) and Na(+) current and attenuated K(+) current, I(f) current also plays some role in phase 4 of depolarization.