BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective:To investigate the effect of inflammatory factors(IL-2,INF-γ,IL-10,TNF-α)and CD4+and CD8+T cells in vaginal lavage in high-grade cervical squamous intraepithelial lesions(HSIL)and early cervical cancer(CC).Methods:To collect clinical data of HSIL(n=120)and early CC patients(n=44)after high-risk human papilloma virus(HR-HPV)infection.And healthy middle-aged women not infected with HR-HPV were randomly selected as control.The clinical data of the subjects in three groups were compared,inflammatory factors distribution and ratio of CD4+and CD8+T cells in serum and vaginal lavage fluid were compared.Multivariate Logistic regression performed to analyze the influencing factors of HSIL progression to early CC,ROC and calibration plot were drawn to evaluate the model.Results:The difference was not statistically significant in serum IL-2,INF-γ,IL-10,TNF-α levels,CD4+T cell distribution,CD8+T cell distribution and CD4+/CD8+ratio in sub-jects of control group,HSIL group and early CC group(P>0.05).The difference was statistically significant in the vaginal lavage levels of IL-2,INF-γ,IL-10,TNF-α levels,CD4+T cell distribution,CD8+T cell distribution and CD4+/CD8+ratio(P<0.05),plus the level of HSIL patients was higher than that of control subjects(P<0.05).Logistic regression analysis showed that parity>2(OR=3.119,95%CI:4.353～6.737)and the percentage of CD4+T cells in vaginal lavage fluid(OR=0.327,95%CI:0.188-0.478)in model 2(P<0.001,AUC=0.908),CD4+/CD8+(OR=0.809,95%CI:0.356-1.868)(P<0.001,AUC=0.873)in model 3 has an independent influence on the development of HSIL to early CC;the difference is not significant(Z=1.550 4,P=0.121)in ROC curves of the two models.CD4+/CD8+ratio as only one indictor in Model 3 can be good predic-tion,and the calibration curve of this model is close to the standard curve.Conclusions:After HR-HPV infection,the systemic immune status does not participate in HSIL and HSIL progression to early CC,but the cervical local immune status is involved,in which CD4+/CD8+T cell ratio is an independent protective factor.

Objective To explore the core acupoints and compatibility rules of acupuncture and moxibustion for epilepsy by using complex network method. Methods A prescription database was established through inclusion and exclusion criteria for searching literatures for databases from China National Knowledge Infrastructure, VIP, Wanfang, Web of Science, EMBASE, and Pubmed. SPSS Modeler software was used to analyze the frequency and correlation of acupoints, and Gephi0.10.1 software was used to establish a complex network model to explore the core acupoints and acupoint selection rules of prescriptions for epilepsy. Results Ultimately, 144 valid literatures were included, 199 prescriptions were extracted, involving 102 acupoints. Baihui acupoint had the highest frequency of use, specific acupoints were mainly Five-shu acupoint, the Eight Meridian Intersection acupoint, and the Back-shu acupoint. In selection of meridians, most acupoints were selected from governor meridian. Association rule analysis showed that Baihui-Taichong had the highest level of support and confidence. The analysis of complex network topology showed that 36 acupoints such as Baihui, Dazhui, Yaoqi and Fenglong were the core acupoints in the treatment of epilepsy by acupuncture and moxibustion. The analysis of acupoint communities revealed three major acupoint groups including governor meridian passing through treatment group, far and near matching acupoint group of the four limbs and head, and differentiation group of Zang-fu and body fluid for epilepsy treatment. Conclusion Acupoint compatibility of epilepsy by acupuncture and moxibustion should be mainly based on principle of the governor meridian combined with the differentiation of viscera and body fluid, and attention should be paid to distal-proximal point association.

Long chain non coding RNA (LncRNA) is widely involved in various biological processes such as intracellular chromatin modification, transcriptional regulation, nuclear transport, and protein function regulation, and is closely related to various key physiological functions such as immunity and metabolism in the body. NEAT1 (nuclear parapackle assembly transcript 1) is a newly discovered LncRNA, which is an important component of the nuclear substructural paraplaques. It has been proven to regulate downstream protein expression by binding to various miRNAs, thereby regulating the expression of inflammatory factors, epithelial mesenchymal transition, autophagy, apoptosis, proliferation, migration, and other biological processes, Its abnormal expression plays an important role in the pathogenesis of lung diseases such as asthma, chronic obstructive pulmonary disease, pneumonia, pulmonary fibrosis, and lung cancer, and is closely related to the prognosis of non-small cell lung cancer and the sensitivity of anti-tumor drugs. It is expected to become a new biological marker and therapeutic intervention target. This article mainly reviews the latest research progress on the role of NEAT1 in lung diseases.

Purpose: We aimed to explore whether the prognosis of patients treated with capecitabine and oxaliplatin (XELOX) or S-1 and oxaliplatin (SOX) regimens who received fewer cycles of chemotherapy after D2 radical resection for gastric cancer (GC) would be non-inferior to that of patients who received the standard number of cycles of chemotherapy. Materials and Methods: Data on patients who received XELOX or SOX chemotherapy after undergoing D2 radical resection at Harbin Medical University Cancer Hospital between January 2011 and May 2016 were collected. Results: In patients who received 4, 6, and 8 cycles of chemotherapy, the 5-year overall survival (OS) rates were 59.4%, 64.8%, and 62.7%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (hazard ratio [HR], 0.882; 95% confidence interval [CI], 0.599–1.299; P=0.52) or 8 cycles (HR, 0.882; 95% CI, 0.533–1.458; P=0.62) of chemotherapy did not exhibit significantly prolonged OS. The 3-year disease-free survival (DFS) rate of patients who received 4, 6, and 8 cycles of chemotherapy was 62.1%, 67.2%, and 60.8%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (HR, 0.835; 95% CI, 0.572–1.221; P=0.35) or 8 cycles (HR, 0.972; 95% CI, 0.606–1.558; P=0.91) of chemotherapy did not show significantly prolonged DFS. However, the 3-year DFS and 5-year OS rates of patients who received 6 cycles of chemotherapy appeared to be superior to those of patients who received 4 and 8 cycles of chemotherapy. Conclusions For patients with stage III GC, 4 to 6 cycles of XELOX or SOX chemotherapy may be a favorable option. This study provides a rationale for further randomized clinical trials.

Objective:To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) .Methods:Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) .Results:The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95% CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95% CI 20.0%-35.0%) and 22.4% (95% CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95% CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95% CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95% CI 62.7%-77.8%) and 72.2% (95% CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95% CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% ( P=0.001) , and the 5-year OS rates were 79.9% (95% CI 70.3%-86.7%) , 71.1% (95% CI 50.4%-84.4%) and 52.9% (95% CI 33.0%-69.3%) ( χ2=7.552, P=0.020) , respectively. Conclusions:For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

Objective:To explore the feasibility and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).Methods:From May 2014 to December 2019, clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT. The grades were severe ( n=6) and extremely severe ( n=1). The causes were primary PNH ( n=4) and PNH-aplastic anemia (AA) syndrome ( n=3). There were 5 males and 2 females with a median age of 29 (20-47) years, a median weight of 60(50-71) kg and a median time from diagnosis to transplantation of 62.5(7.7-171) months. All of them were accompanied by transfusion dependence. Myeloablative ( n=6) and reduced-intensity ( n=1) pretreatment was offered. The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG. The median number of input nucleated cells was 2.4(1.71-4.28)×10 7/kg and the median number of CD34+ cells 1.58(0.88-3.02)×10 5/kg. Results:Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21) days and a median erythroid engraftment time of 27. Engraftment time of 37(25-101) days for platelets >20×10 9/L and 62(27-157) days for platelets >50×10 9/L. The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%). The severity of GVHD was grade Ⅱ° acute ( n=2) and mild ( n=1). The median follow-up period was 13.5(3-71.4) months. Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage. The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%). Conclusions:With excellent engraftment and survival in the treatment of PNH, UCBT is indicated for patients without HLA full-match donor. PNH-AA syndrome with iron overload may be one of the important prognostic factors.

Objective To evaluate the effect of pretransplant iron overload on the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). Methods Clinical data of 80 SAA recipients who underwent allo-HSCT for the first time were retrospectively analyzed. According to the incidence of iron overload, all recipients were divided into the iron overload group (n=20) and non-iron overload group (n=60). The engraftment rate, incidence of postoperative complications and clinical prognosis of the recipients afterallo-HSCT were statistically compared between two groups. The influencing factors of 2-year overall survival (OS) and 180 d transplantation related mortality (TRM) were analyzed by Cox proportional hazards regression model. Results The engraftment rate of neutrophils in the non-iron overload group was 98% (59/60), significantly higher than 75% (15/20) in the iron overload group (P < 0.05). The engraftment rate of platelet in the non-iron overload group was 90% (54/60), significantly higher than 65% (13/20) in the iron overload group (P < 0.05). The incidence rate of bloodstream infection in the non-iron overload group was 23% (14/60), remarkably lower than 40% (8/20) in the iron overload group (P < 0.05). The 180 d TRM of the recipients in the non-iron overload group was 17%, significantly lower than 45% in the iron overload group (P < 0.05). The 1- and 2-year OS of the recipients in the non-iron overload group were 82% and 80%, significantly higher than 50% and 44% in the iron overload group (both P < 0.05). Iron overload or not was an independent risk factor of the OS and TRM of the recipients (both P < 0.05). Conclusions Iron overload can affect the OS and TRM of SAA patients after allo-HSCT.

The incidence of non-alcohol fatty liver disease (NAFLD) is increasing year by year, and the relevant cardiovascular events have become a major problem in chronic diseases management. The activation of innate immunity is closely related to the development of NAFLD. The immune cells include Kupffer cells, neutrophils, dendritic cells, and natural killer T cells, which acts through the activation of innate immunity-related signals mediated by pattern recognition receptors.
Humans ; Immunity, Innate ; Kupffer Cells ; Liver ; Non-alcoholic Fatty Liver Disease