Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.

Good endometrial receptivity is an essential factor for embryo implantation,and gene expression in endometrial tissue during the window of implantation(WOI)is closely related to receptivity.Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases,as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression.Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism.Moreover,gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure,thereby guiding individualized embryo transfer strategies.This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions.This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level,in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Ventricular assist devices(VADs)have emerged as a pivotal therapeutic option for end-stage heart failure,undergoing significant technological advancements from pneumatic membrane pumps to continuous-flow centrifugal pumps.This review provides a detailed overview of several VAD models,including HeartMate Ⅲ,EVAHEART 2,and Heart Con.The initial generation of VADs established a foundation for subsequent developments,despite the occurrence of frequent complications.The second generation of VADs demonstrated a notable improvement in patient prognosis but carried the risk of ventricular collapse.The third generation of VADs represents a further reduction in size,incorporating magnetic levitation technology to enhance durability and blood compatibility.In the future,the development of VADs will focus on better emulating the physiological function of the native heart,improving pulsatility,and extending device longevity.As technology advances,VADs are expected to offer heart failure patients with a greater range of treatment options and a higher quality of life.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.

Ventricular assist devices(VADs)have emerged as a pivotal therapeutic option for end-stage heart failure,undergoing significant technological advancements from pneumatic membrane pumps to continuous-flow centrifugal pumps.This review provides a detailed overview of several VAD models,including HeartMate Ⅲ,EVAHEART 2,and Heart Con.The initial generation of VADs established a foundation for subsequent developments,despite the occurrence of frequent complications.The second generation of VADs demonstrated a notable improvement in patient prognosis but carried the risk of ventricular collapse.The third generation of VADs represents a further reduction in size,incorporating magnetic levitation technology to enhance durability and blood compatibility.In the future,the development of VADs will focus on better emulating the physiological function of the native heart,improving pulsatility,and extending device longevity.As technology advances,VADs are expected to offer heart failure patients with a greater range of treatment options and a higher quality of life.

Objective:To summarize and analyze the characteristics of delayed hemolytic transfusion reaction in children,in order to provide a scientific basis for clinical prevention,and ensure the safety of children's blood transfusion.Methods:The basic situation,clinical symptoms and signs,diagnosis time and disappearance time of alloantibody of delayed hemolytic transfusion reaction in children were retrospectively analyzed.The serological test,routine blood test,biochemical detection and urine analysis results were compared pre-and post-transfusion.Results:Among 15 164 children with repeated blood transfusion,23 cases occurred delayed hemolytic transfusion reactions,with an incidence rate of 0.15％,and mainly children with thalassemia and acute leukemia.39.13％of delayed hemolytic reactions occurred in children with more than 20 times of blood transfusions.Anemia was the main clinical symptom in 86.96％of children.4.35％of children had hypotension and dyspnea.Serological test results showed that the positive rate of direct antiglobulin test was 91.30％,and that of erythrocyte homologous antibody test was 100％.Erythrocyte alloantibodies were common in Rh and Kidd blood group systems,accounting for 73.91％and 13.04％,respectively.Laboratory test results showed that hemoglobin,reticulocyte,spherocyte,total bilirubin,indirect bilirubin,lactate dehydrogenase,serum ferritin and urine color were significantly different after transfusion compared with those before transfusion(all P＜0.05).The average diagnosis time of delayed hemolytic transfusion reactions was 18.56 days,and the average disappearance time of erythrocyte alloantibodies was 118.43 days.Conclusion:The incidence of delayed hemolytic transfusion reaction is high in children with repeated blood transfusion,and the disappearance time of erythrocyte homologous antibody is long.Blood matched ABO,Rh and Kidd blood group antigens should be transfused prophylactically.Once diagnosed,erythrocyte alloantibody corresponding to antigen-negative blood should be used throughout the whole process.