Sequential haplo-identical conditioning transplant regimen for pediatric patients with relapsed or refractory hemophagocytic lymphohistiocytosis.

Allogeneic hematopoietic stem cell transplantation (HSCT) currently stands as the sole remedy for individuals afflicted with hemophagocytic lymphohistiocytosis (HLH). In this study, we retrospectively evaluated how pediatric patients with relapsed or refractory (R/R) HLH responded to our institution's cocktail conditioning regimen. The disease was diagnosed according to criteria applicable to patients with familial/genetic, relapsing, or severe/persistent HLH. All donors were HLA haplo-identical family donors. In our cohort, sixty-five patients (P-HLH), including 28 with familial/genetic HLH, 36 with secondary HLH, and 1 with an unknown cause, underwent haplo-identical family donor HSCT. The conditioning regimen consisted of intravenous administration of etoposide (VP-16), busulfan, fludarabine, rabbit anti-human thymocyte globulin (r-ATG), and cyclophosphamide (Cy). Tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GvHD) prevention. We observed that the median time for neutrophil recovery was 11 days (range, 8-24), and for platelet counts to exceed 20 × 109/L, it was 14 days (range, 7-130). There were 5 patients (7.7%) who experienced grades III to IV acute GvHD, and 6 patients (9.2%) developed extensive chronic GvHD. The estimated 3- and 5-year overall survival rates were 78.1% (95% CI, 65.8-84.6%) and 74.9% (95% CI, 61.2-84.4%), respectively. The estimated 3- and 5-year event-free survival rates were 73.5% (95% CI, 60.8-82.6%) and 70.3% (95% CI, 56.4-80.5%), respectively. Our findings demonstrate that our innovative conditioning regimen is both effective and safe, offering valuable insights for healthcare professionals evaluating the merits of existing therapies.

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Blockade of CCR5 suppresses paclitaxel-induced peripheral neuropathic pain caused by increased deoxycholic acid.

Paclitaxel leads to peripheral neuropathy (paclitaxel-induced peripheral neuropathy [PIPN]) in approximately 50% of cancer patients. At present, there are no effective treatment strategies for PIPN, the mechanisms of which also remain unclear. In this study, we performed microbiome and metabolome analysis of feces and serum from breast cancer patients with different PIPN grades due to paclitaxel treatment. Our analysis reveals that levels of deoxycholic acid (DCA) are highly increased because of ingrowth of Clostridium species, which is associated with severe neuropathy. DCA, in turn, elevates serum level of C-C motif ligand 5 (CCL5) and induces CCL5 receptor 5 (CCR5) overexpression in dorsal root ganglion (DRG) through the bile acid receptor Takeda G-protein-coupled receptor 5 (TGR5), contributing to neuronal hyperexcitability. Consistent with this, administration of CCR5 antagonist maraviroc suppresses the development of neuropathic nociception. These results implicate gut microbiota/bile acids/CCR5 signaling in the induction of PIPN, thus suggesting a target for PIPN treatment.

Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study.

Purpose: To investigate the association between sleep duration and age-related macular degeneration (AMD). Design: Cross-sectional study, bidirectional two-sample Mendelian randomization (MR). For cross-sectional analysis, we used survey data of 5,481 participants aged ≥40 years from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES). For MR analysis, we used sleep- and AMD-associated genome-wide association studies (GWAS) data involving large populations. Methods: The association between sleep duration and AMD was assessed using logistic regression models. For MR analysis, the primary approach for MR analysis was the inverse-variance weighted (IVW) method. Results: In cross-sectional analysis, after adjusting for multiple covariates, short sleep duration (SSD) was found to be associated with increased risk of early AMD [odds ratio (OR) = 1.364, P = 0.036). MR analysis supported the results of cross-sectional analysis: SSD increases the risk of early AMD (ß = 0.102, IVW-P = 0.003). Conclusion: Our findings provide the evidence supporting the association between sleep deficiency and higher risk of AMD. Further studies are required to confirm our findings and elucidate the mechanisms underlying this association.

Second Allogeneic Hematopoietic Stem Cell Transplantation for Hemophagocytic Syndrome with Engraftment Failure.

This study aims to assess the efficacy of second allogeneic hemopoietic stem cell transplantation (allo-HSCT) for treating hemophagocytic syndrome with first engraftment failure. Among a total of 35 patients who underwent allo-HSCT between June 2015 and July 2021 for HLH, 10 patients who underwent a second HSCT following graft rejection were retrospectively analyzed. Various factors, such as the treatment course and outcome, the remission status, donor selection, and the conditioning regimen of patients before second allo-HSCT, were scrutinized for transplant-related complications and transplant-related mortality, as well as transplant outcomes. All the subjects have achieved complete donor engraftment, in which the neutrophils and platelets engraftment occurred in a median time of 12 d (range 10-19 d) and 24 d (range 11-97 d), respectively. Among the selected subjects, 20% of patients are diseased due to transplant-related thrombotic microangiopathy. Further, 90% of patients are diagnosed with aGVHD, in which 3 of them with grade I aGVHD, one patient with grade II aGVHD, two patients with grade III GVHD, and three patients with localized chronic GVHD. Moreover, 70% of patients showed signs of combined viral infections. Despite the complex symptoms, the overall survival rate is around 80%, with transplant-related mortality and the incidence of post-transplant GVHD of 20% and 60%, respectively. Together, our findings indicated that the second allo-HSCT showed great potential in treating hemophagocytic syndrome with engraftment failure.

Characterization of RNA modifications in gastric cancer to identify prognosis-relevant gene signatures.

BACKGROUND: Most human genes have diverse transcript isoforms, which mainly arise from alternative cleavage and polyadenylation (APA) at 3' ends. N7-methylguanosine (m7 G) is also an essential epigenetic modification at the 5' end. However, the contribution of these two RNA modifications to the development, prognosis, regulation mechanisms, and drug sensitivity of gastric cancer (GC) is unclear. METHODS: The expression data of 2412 patients were extracted from 12 cohorts and the RNA modification patterns of 20 marker genes were systematically identified into phenotypic clusters using the unsupervised clustering approach. Following that, we developed an RNA modification model (RMscore) to quantify each GC patient's RNA modification index. Finally, we examined the correlation between RMscore and clinical features such as survival outcomes, molecular subtypes identified by the Asian Cancer Research Group (ACRG), posttranscriptional regulation, and chemotherapeutic sensitivity in GC. RESULTS: The samples were categorized into two groups on the basis of their RMscore: high and low. The group with a low RMscore had a bad prognosis. Moreover, the low RMscore was associated with KRAS, Hedgehog, EMT, and TGF-ß signaling, whereas a high RMscore was related to abnormal cell cycle signaling pathway activation. The findings also revealed that the RMscore contributes to the regulation of the miRNA-mRNA network. Drug sensitivity analysis revealed that RMscore is associated with the response to some anticancer drugs. CONCLUSIONS: The RMscore model has the potential to be a useful tool for prognosis prediction in patients with GC. A comprehensive investigation of APA-RNA and m7 G-RNA modifications may reveal novel insights into the epigenetics of GC and aid in the development of more effective treatment strategies.

A report on second neo-plasms in seven children with solid tumors.

OBJECTIVE: This study aims to investigate the characteristics and related high risk factors of second neoplasms after chemotherapy and radiotherapy in children with solid tumors. METHODS: The detailed clinical data of seven children with malignant solid tumors, who were treated in our department, were retrospectively analyzed, in order to summarize the clinical characteristics of the secondary onset of second neoplasms, and determined the risk factors related to the occurrence of second neoplasms. RESULTS: (1) Clinical characteristics: Among the seven children with malignant solid tumors, three children had rhabdomyosarcoma (3/132, 2.27%), two children had hepatoblastoma (2/313, 0.64%), one child had neuroblastoma (1/305, 0.33%), and one child had inflammatory myofibroblastoma (1/3, 33.33%). Furthermore, among these children, four children were boys and three children were girls, and their onset age ranged within 5-34 months, with a median onset age of 27 months. Moreover, among these children, three children were ≤1 year old. All second neoplasms exhibited symptoms, and the diagnosis was made after the complete remission of the first primary tumor. The time interval between these two tumors was within 17-78 months, and the median time was 38 months. Three of seven children with rhabdomyosarcoma were treated with chemotherapy in combination with radiotherapy, while four children only received the chemotherapy. The chemotherapy cycles were 6-39 times, and the median chemotherapy cycles were 10 times. Among these children, one child with relapsed stage IV rhabdomyosarcoma and one child with stage IV retroperitoneal neuroblastoma had 39 cycles and 33 cycles of chemotherapy respectively. (2) Characteristics of the accumulated doses of high-risk chemotherapy drugs: The accumulated dose of cyclophosphamide in six patients was within 2.47-44.45 g/m2, with a median of 6.14 g/m2. The accumulated dose of ifosfamide in five patients was within 13.63-96.41 mg/m2, with a median of 31.23g/m2. The accumulated dose of etoposide in six patients was within 1,237.35-3,754.95 mg/m2, with a median of 1,548.67 mg/m2. The accumulated dose of anthracyclines in seven patients was within 150.68-843.78 mg/m2, with a median of 329.73 mg/m2. The accumulated dose of vincristine in seven patients was within 3.11-18.89 mg/m2, with a median of 15.92 mg/m2. The accumulated dose of cisplatin in seven patients was within 271.23-1,681.59 mg/m2, with a median of 733.07 mg/m2. Children with abdominal inflammatory myofibroblastic tumors did not apply cyclophosphamide, ifosfamide and etoposide regimens. The main chemotherapy drugs consisted of methotrexate, pirarubicin, cisplatin and vincristine. (3) Radiotherapy doses. (4) Characteristics of second neoplasms: Among the seven children with second neoplasms, five children had leukemia, 3 patients with rhabdomyosarcoma were combined with radiotherapy. The doses of radiation were 40 and 45GY" after "(3) Radiotherapy doses (four children had acute myeloid leukemia and one children had acute B-lymphoblastic leukemia), one child had myelodysplastic syndrome, and one child had myeloid sarcoma. Furthermore, among these seven children, four children (4/7) had abnormal chromosomes, two children were normal, and one child gave up the treatment and underwent the chromosome test after the diagnosis of second neoplasms. CONCLUSION: The incidence of secondary onset of second neoplasms in children with malignant solid tumors is not high, considering that this is correlated to the use of alkylating agents, topoisomerase II inhibitors, platinum-based chemotherapy drugs and radiotherapy, and associated with the chromosomal abnormalities of children. KEY WORDS: Chemotherapy, Children, Radiotherapy, Second malignant neoplasm, Solid tumor.

Long-term modification of gut microbiota by broad-spectrum antibiotics improves stroke outcome in rats.

BACKGROUND: The brain-gut axis is a major regulator of the central nervous system. We investigated the effects of treatment with broad-spectrum antibiotics on gut and brain inflammation, infarct size and long-term behavioral outcome after cerebral ischemia in rats. METHODS: Rats were treated with broad-spectrum antibiotics (ampicillin, vancomycin, ciprofloxacin, meropenem and metronidazole) for 4 weeks before the endothelin-1 induced ischemia. Treatment continued for 2 weeks until the end of behavioral testing, which included tapered ledged beam-walking, adhesive label test and cylinder test. Gut microbiome, short-chain fatty acids and cytokine levels were measured together with an assessment of infarct size, neuroinflammation and neurogenesis. RESULTS: The results revealed that the antibiotics exerted a clear impact on the gut microbiota. This was associated with a decrease in systemic and brain cytokine levels, infarct size and apoptosis in the perilesional cortex and improved behavioral outcome. CONCLUSION: Our results highlighted the significant relationship between intestinal microbiota and beneficial neuro-recovery after ischemic stroke.

Exploring the potential biomarkers for prognosis of glioblastoma via weighted gene co-expression network analysis.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor in the central system with a poor prognosis. Due to the complexity of its molecular mechanism, the recurrence rate and mortality rate of GBM patients are still high. Therefore, there is an urgent need to screen GBM biomarkers to prove the therapeutic effect and improve the prognosis. RESULTS: We extracted data from GBM patients from the Gene Expression Integration Database (GEO), analyzed differentially expressed genes in GEO and identified key modules by weighted gene co-expression network analysis (WGCNA). GSE145128 data was obtained from the GEO database, and the darkturquoise module was determined to be the most relevant to the GBM prognosis by WGCNA (r =  - 0.62, p = 0.01). We performed enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the interaction activity in the selected modules. Then Kaplan-Meier survival curve analysis was used to extract genes closely related to GBM prognosis. We used Kaplan-Meier survival curves to analyze the 139 genes in the darkturquoise module, identified four genes (DARS/GDI2/P4HA2/TRUB1) associated with prognostic GBM. Low expression of DARS/GDI2/TRUB1 and high expression of P4HA2 had a poor prognosis. Finally, we used tumor genome map (TCGA) data, verified the characteristics of hub genes through Co-expression analysis, Drug sensitivity analysis, TIMER database analysis and GSVA analysis. We downloaded the data of GBM from the TCGA database, the results of co-expression analysis showed that DARS/GDI2/P4HA2/TRUB1 could regulate the development of GBM by affecting genes such as CDC73/CDC123/B4GALT1/CUL2. Drug sensitivity analysis showed that genes are involved in many classic Cancer-related pathways including TSC/mTOR, RAS/MAPK.TIMER database analysis showed DARS expression is positively correlated with tumor purity (cor = 0.125, p = 1.07e-02)), P4HA2 expression is negatively correlated with tumor purity (cor =-0.279, p = 6.06e-09). Finally, GSVA analysis found that DARS/GDI2/P4HA2/TRUB1 gene sets are closely related to the occurrence of cancer. CONCLUSION: We used two public databases to identify four valuable biomarkers for GBM prognosis, namely DARS/GDI2/P4HA2/TRUB1, which have potential clinical application value and can be used as prognostic markers for GBM.

Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation with Cocktail Conditioning Regimen for the Treatment of Pediatric Patients with Chronic Active Epstein-Barr Virus: A Retrospective Observational Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was considered as an only therapeutic strategy for chronic active Epstein-Barr virus (CAEBV) infection with few exceptions, while efficacy of various allo-HSCT conditioning regimens for CAEBV has not been fully investigated yet. This study aimed to compare the effectiveness of cocktail conditioning regimen (CCR)-allo-HSCT with reduced-intensity conditioning regimen (RICR)-allo-HSCT for pediatric patients with CAEBV. Data of a total of 54 children with CAEBV from July 2015 to December 2020 were retrospectively analyzed. Among them, 32 patients received VP16, total body irradiation (TBI), busulfan, fludarabine, cyclophosphamide, and antithymocyte globulin (ATG) (CCR1 group), 10 patients received VP16, ara-C, TBI, busulfan, fludarabine, cyclophosphamide, and ATG (CCR2 group), and the remaining 12 patients received VP16, busulfan or melphalan, fludarabine, and ATG with or without ara-C (RICR group). The overall survival (OS), hematopoietic engraftment, the incidence of severe graft-versus-host disease, and other parameters were analyzed. After adjusting for potential confounders, CCR1 (hazard ratio [HR]: 0.023; 95% confidence interval [CI]: 0.001-0.448; P < 0.02) and CCR2 (HR: 0.028; 95% CI: 0.002-0.457; P < 0.02) were associated with a longer OS than RICR. The use of CCR could markedly improve the engraftment success rate and OS rate compared with RICR for pediatric patients with CAEBV.

Ketogenic diet prevents paclitaxel-induced neuropathic nociception through activation of PPARγ signalling pathway and inhibition of neuroinflammation in rat dorsal root ganglion.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect during the course of cancer treatment, which is mainly manifested as a series of sensory abnormalities. At present, there are no recommended prevention or treatment strategies, and the underlying mechanisms are unclear. The ketogenic diet (KD), a special diet that is high in fat and low in carbohydrate intake, shows good therapeutic potential in children with epilepsy. In this study, it was found that KD significantly prevented paclitaxel-induced neuropathic nociception. Using the GSE113941 database, 281 differentially expressed genes (DEGs) were found in an animal model of CIPN and controls. The DEGs were mainly enriched in peroxisome proliferator activated receptor (PPAR) and oxidative phosphorylation signalling pathways. As a main regulatory pathway of lipid metabolism, the PPARγ signalling pathway was significantly upregulated in the KD model. In addition, KD also inhibited the expression of pro-inflammatory cytokines and the TLR4/NF-κB signalling pathway in the dorsal root ganglion (DRG) in paclitaxel-treated rats. In vitro, rat primary DRG neurons were used to investigate the role of PPARγ in paclitaxel-induced neurotoxicity. It was found that PPARγ agonist rosiglitazone significantly protected DRG neurons against cell apoptosis and reactive oxygen species generation induced by paclitaxel administration. Therefore, KD is a prospective treatment option when applied as a dietary intervention in the prevention and treatment of paclitaxel-induced neuropathic nociception, possibly through the activation of PPARγ and its neuroprotective functions.

Communications Between Peripheral and the Brain-Resident Immune System in Neuronal Regeneration After Stroke.

Cerebral ischemia may cause irreversible neural network damage and result in functional deficits. Targeting neuronal repair after stroke potentiates the formation of new connections, which can be translated into a better functional outcome. Innate and adaptive immune responses in the brain and the periphery triggered by ischemic damage participate in regulating neural repair after a stroke. Immune cells in the blood circulation and gut lymphatic tissues that have been shaped by immune components including gut microbiota and metabolites can infiltrate the ischemic brain and, once there, influence neuronal regeneration either directly or by modulating the properties of brain-resident immune cells. Immune-related signalings and metabolites from the gut microbiota can also directly alter the phenotypes of resident immune cells to promote neuronal regeneration. In this review, we discuss several potential mechanisms through which peripheral and brain-resident immune components can cooperate to promote first the resolution of neuroinflammation and subsequently to improved neural regeneration and a better functional recovery. We propose that new insights into discovery of regulators targeting pro-regenerative process in this complex neuro-immune network may lead to novel strategies for neuronal regeneration.

Peripheral and Central Nervous System Immune Response Crosstalk in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by muscle weakness due to the degeneration of the upper and lower motor neurons. Neuroinflammation is known as a prominent pathological feature of ALS. Although neuroinflammation cannot trigger ALS, activated central nervous system (CNS) microglia and astrocytes, proinflammatory periphery monocytes/macrophages and T lymphocytes, and infiltrated monocytes/macrophages and T lymphocytes, as well as the immunoreactive molecules they release, are closely related to disease progression. The crosstalk between the peripheral and CNS immune components mentioned above significantly correlates with survival in patients with ALS. This review provides an update on the role of this crosstalk between the CNS and peripheral immune responses in ALS. Additionally, we discuss changes in the composition of gut microbiota because these can directly or indirectly influence this crosstalk. These recent advances may well provide innovative ways for targeting the molecules associated with this crosstalk and breaking the current treatment impasse in ALS.

[Clinical Biological Characteristics and Prognostic Factors of Children with Ph+ALL].

OBJECTIVE: To investigate the clinical biological characteristics of children with Ph+ ALL and the factors that affecting its prognostic. METHODS: 34 children with Ph+ ALL were selected retrospectively in the period from January 2006 to December 2017; the clinical biological characteristics, clinical efficacy for short-term and survival time for long-term were recorded and the related factors that affecting the clinical efficacy for short-term and survival time for long-term were evaluated. RESULTS: The median overall survival time was 16.5 months and the cumulative OS rates for 2 years and 5 years with followed-up were separately (61.57±7.09)%, (50.75±8.22)%. The median progression-free survival time was 13.5 months and the cumulative progression-free survival rates for 2 years and 5 years with followed-up were separately (54.49±6.77)%, (48.77±7.42)%. The early treatment response of patients with myeloid antigen expression were significantly lower than the patients without myeloid antigen expression (P＜0.05). The CR rate in one treatment course of patients with good response for early treatment response group were significantly higher than the patients with poor response for early treatment response (P＜0.05). The CR rate in one treatment course of the patients with TKI addition in induction therapy period group were significantly higher than the patients with chemotherapy used alone（P＜0.05）. The OS rate and PFS rate of patients in chemotherapy + TKI + allo-HSCT and chemotherapy + TKI group were significantly higher than the patients with chemotherapy used alone group（P＜0.05）. Univariate analysis showed that the factors affecting OS rate of children with Ph+ ALL for 2 years with followed-up included baseline WBC count level, LDH level, distances between lower hepatic margin and costal margin, distances between lower splenic margin and costal margin, combined myeloid antigen (+), early treatment response, FCM-MRD status after one treatment course, BCR-ABL status after one treatment course and TKI application (P＜0.05) and the factors that the affecting PFS rate of children with Ph+ ALL for 2 years with followed-up included LDH level, distances between lower hepatic margin and costal margin, distances between lower splenic margin and costal margin, combined myeloid antigen (+), early treatment response, FCM-MRD status after one treatment course, BCR-ABL status after one treatment course and TKI application (P＜0.05). Multivariate analysis showed that the distances between lower splenic margin and costal margin 3 cm were independent risk factors on OS rate and PFS rate of children with Ph+ ALL (P＜0.05). CONCLUSION: Children with Ph+ ALL possess unique clinical and biological features. The prognosis of patients with chemotherapy used alone is more poor, and the combination of chemotherapy and TKI can effectively increase the survival benefit; patients with Ph+ ALL combined with myeloid antigen (+) shows a poor early treatment response. while the distances between lower splenic margin and costal margin 3 cm are independent risk factors on clinical prognosis of children with Ph (+) ALL.

Autologous cord blood transplantation in children with acquired severe aplastic anemia.

OBJECTIVE: To investigate the efficacy of ACBT for acquired SAA in children. METHODS: Four patients including three girls and one boy were diagnosed with acquired SAA. Their ages were 5, 3, 1, and 3 years, respectively. Patients received an immunoablative preparative regimen using low-dose antithymocyte globulin, cyclophosphamide, and fludarabine. The unrelated human umbilical cord MSC were infused before the autologous cord blood was transfused on day 0. The first and second patients were not treated with immunosuppressive agents after transplantation. The third and the fourth patients received cyclosporine A for half a year after transplantation followed by a 6-month taper. RESULTS: Initial hematopoietic reconstitution was seen in all the four patients. There was no association between engraftment time and the number of total cells and CD34+ cells. Relapse was seen in the first case about half a year after the transplantation. The other three patients with durable hematopoietic reconstitution are with good quality of life. No GVHD was observed. CONCLUSIONS: Three of four patients maintained prolonged hematopoiesis following an immunosuppressive-based preparative regimen and infusion of autologous cord blood cells. It is recommended that cyclosporine be maintained for 6 months after transplantation. ACBT could be considered for acquired SAA if available.

Clinical evaluation of haploidentical hematopoietic combined with human umbilical cord-derived mesenchymal stem cells in severe aplastic anemia.

BACKGROUND: This study not only evaluated the clinical effects of treatment using haploidentical hematopoietic stem cells (haplo-HSCs) combined with human umbilical cord mesenchymal stem cells (UC-MSCs) in patients with severe aplastic anemia (SAA), but also investigated the factors related to graft versus host disease (GVHD). METHODS: Cotransplantation of haplo-HSCs and UC-MSCs was performed in 24 SAA patients. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide, and fludarabine with or without busulfan. GVHD was prevented using cyclosporine A, ATG, anti-CD25 monoclonal antibody, and mycophenolate material. RESULTS: The incidence of acute GVHD was 50%. The incidence of severe acute GVHD was not related to gender, age, donor-recipient relations, and patient/donor pair, while patient/donor pair (r = 0.541, P = 0.022) was significantly correlated with incidence of chronic GVHD. Upon follow-up for a median of 13 months, 5 of the 24 patients (20.8%) were dead. The survival rates at 3 and 6 months in all patients were 87.5% (21/24) and 83.3% (20/24), respectively. CONCLUSION: Cotransplantation of haplo-HSCs combined with UC-MSCs was an effective and safe approach for the treatment of patients with SAA. The appropriate conditioning regimen and early treatment for infection also played a critical role in the success of HSCT.

[Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation Using Tumor-ablative Conditioning Regimen for Patients with Refractory/Relapsed Non-Hodgkin's Lymphoma].

OBJECTIVE: To investigate the safety and effectiveness of autologous hematopoietic stem cell transplantation (auto-HSCT) using tumor-ablative conditioning regiment for patients with refractory/relapsed non-Hodgkin's lymphoma. METHODS: The clinical data of 16 patients with refractory/relapsed non-Hodgkin's lymphoma received above-mentioned therapeutic regimen from January 2013 to July 2015 was analyzed retrospectively, and conditioning-related toxicity, engraftment, infection, relapse and survival rate were evaluated. RESULTS: No conditioning-related organs' failure and mortality were found. Only 1 patient had not been engrafted, and the engraftment rate was 93.7%. The incidence of serious infection was 31.2%. The median follow-up was 20.5(1-30) months, and 3 patients died, out of them 2 patients died of relapse. Two year overall survival (OS) , disease-free survival (DFS) and relapse rates were 80.2%, 74.5% and 20.6% respectively. CONCLUSION: Auto-HSCT using tumor-ablative conditioning regimen is safe and effective for patients with refractory/relapsed non-Hodgkin's lymphoma, and it possess a certain effect for reducing disease relapse after transplantation.

Admissibility analysis for linear singular systems with time-varying delays via neutral system approach.

This paper studies the admissibility problem for a class of linear singular systems with time-varying delays. In order to highlight the relations between the delay and the state, the singular system is transformed into a neutral form. Then, an appropriate type of Lyapunov-Krasovskii functionals is proposed to develop a delay-derivative-dependent admissibility condition in terms of linear matrix inequalities. The derivation combines the Wirtinger-based inequality and reciprocally convex combination method. The present criterion is also for the stability test of retarded and neutral systems with time-varying delays. Some examples are provided to illustrate the effectiveness and the benefits of the proposed method.