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Abstract The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the “responders”, n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.

IntroductionCurrently, no study has determined whether platelet transfusion refractoriness (PTR) post-hematopoietic stem cell transplantation (HSCT) before engraftment in patients with myelodysplastic syndrome (MDS) would impacts clinical outcomes.MethodsWe performed a MDS-specific retrospective analysis to determine whether PTR in one-month post-HSCT in patients with MDS could influence outcomes.Results and discussionAmong the 315 patients enrolled, 110 (34.9 %) had PTR from stem cell infusion to one-month post-HSCT. Baseline characteristics of the PTR and non-PTR groups were similar. We found that patients with PTR had a slower and lower rate of platelet engraftment by day 28, as well as a slower recovery of neutrophils. The median days of neutrophil and platelet engraftment were 14 days (9-23) and 17 days (8-28) in the PTR groups versus 13 days (9-23) and 15 days (7-28) in the non-PTR group (P1041ng/ml (median level) were independent adverse factors of platelet engraftment.

Abstract This study aimed to assess haematopoietic stem cell transplantation (HSCT) safety and efficacy while exploring strategies for optimising outcomes in patients with hepatitis-associated aplastic anaemia (HAAA). We retrospectively reviewed 35 HAAA patients who underwent HSCT at a large Chinese blood disease hospital between 2008 and 2022. HAAA patients receiving HSCT typically presented with severe (28.6%) and very severe (65.7%) AA. Male patients predominated (68.6%), with a median onset age of 23 years (range, 9–44). Haploidentical donor-HSCT and matched sibling donor-HSCT were in comparable proportions. The 5-year overall survival (OS) rate was 74.0%, with cumulative incidences of grade II–IV acute and chronic graft-versus-host disease (GVHD) at 37.1% and 22.4%, respectively. A diagnosis-to-HSCT interval ≥ 75 days, acute GVHD, and post-HSCT liver events (e.g., hepatic GVHD and a three-fold increase in aminotransferase or bilirubin) significantly worsened 5-year OS. In the multivariate models, recipients with sex-matched grafts had better OS, and those with younger male donors had a lower incidence of II–IV aGVHD. Higher HLA matching degree (HLA > = 7/10) was an independent prognostic factor associated with better OS and GFFS. A diagnosis-to-HSCT interval ≥ 75 days was predictive of post-transplant liver events in HAAA patients. In conclusion, HSCT was a safe and effective treatment for HAAA. Early transplantation, careful donor selection and improving post-transplant liver events were crucial to optimise outcomes.

Abstract The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P

IntroductionRetrospective studies have suggested that Ursodeoxycholic Acid (UDCA) provide a protective effect against SARS-CoV-2 infection, particularly in patients with liver disease. However, it is uncertain whether this finding can be extended to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Therefore, we aim to examine the protective potential of UDCA against SARS-CoV-2 infection in recently received allo-HSCT patients.MethodsDuring the initial Omicron variant wave in China (December 2022 to February 2023), we conducted a prospective observational study involving 91 hospitalized patients who had undergone allo-HSCT within the previous 6 months as part of the National Longitudinal Cohort of Hematological Diseases (NICHE). Throughout hospitalization, we continuously monitored the status of COVID-19 using SARS-CoV-2 PCR kits or SARS-CoV-2 Antigen Rapid Tests.ResultsAmong these patients, 67.0% (n = 61) were confirmed to have contracted SARS-CoV-2 infection. For the 52 patients evaluated, 23.1% experienced a severe or critical clinical course. There was no difference in the infection rate or severity of COVID-19 between the UDCA group and the non-UDCA group. We found that only patients transplanted between 3 and 6 months ago demonstrated a higher risk of SARS-CoV-2 infection compared to those who received allo-HSCT within 3 months (Odds Ratio [OR]: 3.241, 95% Confidence Interval [CI]: 1.287-8.814, P = 0.016). But other clinical factors, such as administration of UDCA, showed no difference. Notably, only age ≥38 years old remained as an independent risk factor for a severe clinical course of SARS-CoV-2 infection (OR: 3.664, 95% CI: 1.129-13.007, P = 0.035).ConclusionThe effectiveness of UDCA in protecting newly allo-HSCT recipients against SARS-CoV-2 infection remains unconfirmed. Presently, the most effective strategy appears to be minimizing exposure to SARS-CoV-2.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04645199, identifier NCT04645199.

ABSTRACTObjective To investigate the preventive effect of low-dose porcine anti-thymocyte globulin (P-ATG) on graft versus host disease (GVHD) in patients' donors over 40 years old or female donors undergoing HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT).Methods The clinical data of 30 patients received Low-dose Porcine antithymocyte globulin (P-ATG) as a part of the conditioning regimen (the P-ATG group), while the other 30 patients didn’t receive ATG (the Non-ATG group).Results There was a significant difference in the incidence of aGVHD ([23.3 (10.1–39.7) %] vs [50.0 (30.8–66.5) %], P = 0.028), grade II–IV aGVHD ([16.7 (5.94–32.1) %] vs [40.0 (22.4–57.0) %], P = 0.049) and chronic GVHD (cGVHD) ([22.4 (6.03–45.1) %] vs [69.0 (43.4–84.8) %], P = 0.001) between two groups. But there was no significant difference in terms of moderate-severe cGVHD (P = 0.129), 1-year relapse rate (P = 0.742), non-relapse mortality (P = 0.237), or overall survival (P = 0.441).Conclusion The application of low-dose P-ATG in patients/donors over 40 years old or female donors undergoing MSD-HSCT for hematological malignancy can significantly reduce the incidence of aGVHD, grade II–IV aGVHD and cGVHD, doesn’t increase the risk of relapse.

ABSTRACTObjectives To determine the impact of pretransplant measurable residual disease (pre-MRD) and the efficacy of maintenance therapy in t(8;21) acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (allo-HCT).Methods We retrospectively analyzed 100 t(8;21) AML patients who underwent allo-HCT between 2013 and 2022. 40 patients received pre-emptive therapy including immunosuppressant adjustment, azacitidine, and donor lymphocyte infusion (DLI) combined with chemotherapy. 23 patients received prophylactic therapy, including azacitidine or chidamide.Results Patients with a positive pre-MRD (pre-MRDpos) had a higher 3-year cumulative incidence of relapse (CIR) (25.90% [95% CI, 13.87%–39.70%] vs 5.00% [95% CI, 0.88%–15.01%]; P = 0.008). Pre-MRDpos patients were less likely to have a superior 3-year disease-free survival (DFS) (40.83% [95% CI, 20.80%–80.16%]) if their MRD was still positive at 28 days after transplantation (post-MRD28pos). The 3-year DFS and CIR were 53.17% (95% CI, 38.31% – 73.80%) and 34.87% (95% CI, 18.84% – 51.44%), respectively, for patients receiving pre-emptive interventions after molecular relapse. The 3-year DFS and CIR were 90.00% (95%CI, 77.77% – 100%) and 5.00% (95%CI, 0.31% – 21.10%), respectively, for high-risk patients receiving prophylactic therapy. In most patients, epigenetic-drug-induced adverse events were reversible with dose adjustment or temporary discontinuation.Conclusion Patients with pre-MRDpos and post-MRD28pos were more likely to have higher rates of relapse and inferior DFS, even after receiving pre-emptive interventions. Prophylactic therapy may be a better option for high-risk t(8;21) AML patients; however, this warrants further investigation.

Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy. Prophylaxis with intravenous and oral suspended itraconazole (200 mg Q12h intravenously × 2 days followed by 5 mg/kg·d orally in twice) or oral suspension of posaconazole (200 mg Q8h) was administered for preventing IFDs. The only 2 episodes of proven IFDs were not included after propensity-score matching (PSM), while the incidence of possible IFDs was 8.2% (9/110) in itraconazole group and 1.8% (2/110) in posaconazole group, respectively (P = .030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, P = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.

SET-NUP214 fusion gene, also known as TAF-1-CAN and SET-CAN, is observed in acute myeloid leukemia (AML) and T-cell lymphoblastic leukemia (T-ALL). SET-NUP214 fusion in T-cell lymphoblastic leukemia is associated with chemotherapy resistance, but the prognosis of patients with AML with SET-NUP214 has rarely been reported. In the present study, we retrospectively analyzed all patients with acute leukemia including AML and T-ALL patients with SET-NUP214 fusion who underwent allogeneic stem cell transplantation (alloHSCT) in our center from July 2017 to November 2022. Of the total 11 patients, 5 patients were diagnosed with AML and 6 patients were diagnosed with T-ALL de novo. All patients received myeloablative regimens in CR1, and there were three (60%) AML patients who relapsed post-alloHSCT and three T-ALL (50%) patients who relapsed post-alloHSCT. Only one patient with AML who relapsed post-alloHSCT responded to subsequent chemotherapy plus donor lymphocyte infusion and survived the last follow-up. The estimated 1-year overall survival and 3-year overall survival for all these 11 patients were 69.3% and 38.5%, respectively. The estimated 1-year leukemia-free survival and 3-year leukemia-free survival for all patients were 69.3% and 38.5%, respectively. The research shows a high incidence of relapse for patients with acute leukemia with the SET-NUP214 fusion gene, even after alloHSCT. More clinical trials or research with larger samples are urgently needed for this group of patients.

Abstract Background Necrotizing fasciitis is a rapid and severe soft tissue infection that targets subcutaneous fat tissue, muscle, and fascia. This study compares the clinical outcomes of vacuum-assisted closure (VAC) versus conventional dressing on necrotizing fasciitis. Methods We systematically searched Embase, Cochrane, and PubMed for clinical trials (published between January 1, 1995 and September 30, 2021), which compared VAC with conventional dressing for necrotizing fasciitis. The mortality rate of necrotizing fasciitis was the primary outcome of this study. The number of debridements, the total length of hospital stay, and the complication rate were secondary outcomes. A random effects model assessed all pooled data. Results A total of 230 identified studies and seven controlled clinical trials met the inclusion criteria and were included in this analysis (n = 249 participants). Compared to the conventional dressing, patients treated with VAC had a significantly lower mortality rate [OR = 0.27, 95% CI (0.09, 0.87)] (P = 0.03). Total length of hospital stays [MD = 8.46, 95% CI (− 0.53, 17.45)] (P = 0.07), number of debridements [MD = 0.86, 95% CI (− 0.58, 2.30)] (P = 0.24), and complication rate [OR = 0.64, 95% CI (0.07, 5.94)] (P = 0.69) were not significant. These results did not show significant differences between both groups treated with VAC or conventional treatment. Conclusion VAC could significantly decrease the death rate compared to conventional dressing. No significant impacts were found on the number of debridements, the total length of hospital stay, and the complication rate in this study. Level of evidence Level-III. Registration Research Registry (reviewregistry1246).

Objectives Graft failure (GF) is an intractable complication of transplantation, which can severely affect the efficacy of the graft; however, the characteristics, incidence, and risk factors of primary GF have not been well described. This study aimed to analyze the risk factors and outcomes of primary GF to swiftly identify high-risk patients for GF. Methods We performed a case-control study with a case-control ratio of 1:4 with 869 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2015 and December 2019 at our center. Results Nineteen (2.19%) patients experienced primary poor graft function (PGF), while eleven (1.27%) patients developed primary graft rejection (GR). Univariate and multivariate logistic analyses identified two independent risk factors for primary PGF: splenomegaly [P = 0.030; odds ratio (OR), 3.486; 95% confidence interval (CI), 1.139 to 13.109], and donor type [non-matched sibling donor (non-MSD)] (P = 0.018; OR, 4.475; 95% CI, 1.289 to 15.537). However, only donor type (non-MSD) was statistically significant (P = 0.020; OR, 19.432; 95% CI, 1.595 to 236.691) for primary GR. The overall survival was significantly lower in the primary PGF (P = 0.001) and GR group (P = 0.000), respectively, compared to the control group. Conclusion GF can significantly affect the overall survival of patients who underwent allo-HSCT, despite its considerably low incidence. A human leukocyte antigen-matched sibling donor should be the first choice for patients undergoing allo-HSCT for the prevention of GF. Moreover, splenomegaly is an independent risk factor for PGF, and caution must be exercised while treating such patients.

Background: Hyperchloremia is associated with increased mortality in critically ill patients. The objective of this study was to investigate the association between increased chloride levels and mortality outcomes in intracerebral hemorrhage (ICH) patients admitted to the intensive care unit (ICU). Methods: We performed a retrospective study of all patients diagnosed with ICH and included in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ) from 2001 to 2012. Inclusion criteria were the first diagnosis of ICH, ICU length of stay (LOS) over 72 h, and not receiving hypertonic saline treatment. Serum chloride perturbation within 72 h of admission was evaluated as a predictor of outcomes. The increase in chloride from baseline was dichotomized based on an increase in chloride in 72 h (≤5 mmol/L or >5 mmol/L). The primary outcome was 90-day mortality. Results: A total of 376 patients (54.5% male, median age 70 years, interquartile range:58–79 years) were included. The overall 90-day mortality was 32.2% (n=121), in-hospital mortality was 25.8% (n=97), and Day 2 acute kidney injury (AKI) occurred in 29.0% (n=109) of patients. The prevalence of hyperchloremia on admission, during the first 72 h, and an increase in chloride (>5 mmol/L) were 8.8%, 39.4%, and 42.8%, respectively. After adjusting for confounders, the hazard ratio of increase in chloride (>5 mmol/L) was 1.66 (95% confidence interval:1.05–2.64, P=0.031). An increase in chloride (>5 mmol/L) was associated with a higher odds ratio for 90-day mortality in both the AKI and non-AKI groups. Conclusions: An increase in chloride from baseline is common in adult patients with ICH admitted to ICU. The increase is significantly associated with elevated mortality. These results support the significance of diligently monitoring chloride levels in these patients.

Abstract Objective To evaluate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with favorable-risk acute myeloid leukemia in first remission. Method Twenty patients who received auto-HSCT at our center between January 2014 and January 2021 were retrospectively reviewed. Results Until last follow-up, three patients in the cohort were dead due to relapse. The estimated 1-year and 5-year overall survival were 95.00% ± 4.87% and 83.82% ± 8.58%, respectively. The estimated 5-year RFS and CIR (cumulative incidence of relapse) were 85.00% ± 7.98% and 15.00% ±7.98%, respectively. Conclusion The outcome of auto-HSCT in patients with favorable-risk acute myeloid leukemia in first remission was excellent and auto-HSCT could be an effective treatment for these patients.

Abstract Background To estimate the incidence, risk factors, and impact on mortality and functional outcomes for early coagulopathy after the return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) patients. Methods A post hoc analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial was conducted. Early coagulopathy was defined as presence of at least one of the following coagulation abnormalities upon admission: international standard ratio (INR), platelets, and age-adjusted activated partial thromboplastin time (APTT) within 6 h after OHCA and before therapeutic hypothermia initiation. The outcomes included 28-day mortality and functional prognosis. Multivariable logistic regression models were used to explore risk factors and association between early coagulopathy and outcomes. Results Of the 227 patients included, 152 (67%) were male and the median age was 2.3 years [interquartile range (IQR), 0.7–8.6 years]. The overall 28-day mortality was 63%. The incidence of early coagulopathy was 46%. Lower age, longer duration of chest compression, lower temperature, and higher white blood cell (WBC) upon admission increased the risk of early coagulopathy. Early coagulopathy [OR, 2.20 (95% CI, 1.12–4.39), P = 0.023] was independently associated with 28-day mortality after adjusting for confounders. Conclusions Early coagulopathy occurred in almost half of pediatric patients with OHCA. Lower age, longer duration of chest compression, lower temperature, and higher WBC increased the risk. The development of early coagulopathy was independently associated with increased mortality.

Abstract Background Mucosal-associated invariant T (MAIT) cells are innate-like T cells, some studies have reported that the number of circulating MAIT cells reduced in patients with acute graft-versus-host-disease (aGVHD) development. However, the role of donor MAIT cells on aGVHD development and subsequent functional change still remain unclear. Methods The study recruited 86 patients with hematological malignancies who underwent allogeneic hematopoietic cell transplantation (HCT) from May 1, 2018 to June 30, 2019. MAIT cells, their subset, and cytokine levels were measured by flow cytometry. Gray’s test was used to assess the impact of graft MAIT cell proportion and number on aGVHD incidence. The Cox proportional hazard model was used in the multivariate analysis. The comparison for continuous variables was assessed using Mann–Whitney analysis. RNA-sequencing was performed to investigate the possible molecular pathway changes. Results Our study showed that the proportion of MAIT cells in grafts was not different from normal controls, but the CD4/8 subsets were altered. Taking the median of the proportion and number of MAIT cells in the graft as the threshold, the results showed that the incidence of grade B-D aGVHD in patients with MAIT cell proportion ≥ 3.03% was significantly higher than that in patients with MAIT cell proportion

ObjectiveTo summarize and evaluate the experiences and expectations of newly qualified midwives (NQMs) during their transition from school to clinical practice. One of the main objectives was to provide references for the development of midwifery professional teaching and provide a basis for hospital administrators and instructors of midwifery to develop guidelines and strategies.MethodsA systemic review of qualitative research using meta-aggregation was conducted. We collected studies from 12 databases between inception and February 2023. All qualitative studies published in English and Chinese that reported on the experiences of NQMs during their transition to practice were included. Two independent reviewers assessed the study quality and the credibility of study findings by using the JBI Qualitative Assessment and Review Instrument. The process of searching followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.ResultsA total of 14 studies were included, and 84 findings were extracted. The results were grouped into 8 new categories and synthesized into 3 main themes: multi-dimensional challenges, physical and emotional responses, and demands and expectations. The included studies were identified to be of good quality and the results of the methodological quality appraisal were all B grade or higher.ConclusionThe transition period is a critical career development for NQMs. However, they faced various stress during the period, which had a negative impact on their physical and mental health. Therefore, it’s important to deeply understand their challenges and needs. And effective management strategies should be implemented, such as in-depth cooperation between hospitals and schools, improvement of the clinical transition support system, enhancement of continuing education, and standardization of the management system. This may be beneficial to improve the quality of clinical midwifery and maintain the stability and sustainable development of the midwifery team.

Objective:. To investigate the risk factors for cytomegalovirus (CMV) infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods:. Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed. Results:. Of 359 patients, 48.19% (173) patients experienced CMV infection within 100 days posttransplantation. In univariate and multivariate logistic analysis, haploidentical-related donor (HRD) (P < 0.001; odds ratio [OR], 5.542; 95% confidence interval [CI], 3.186–9.639), and ratio of CD3+CD8+ cells in lymphocytes

IntroductionSince allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients’ survival. MethodsWe retrospectively compared patients who received venetoclax plus hypomethylating agents (VEN+HMA, n=23) or intensive chemotherapy (IC, n=42) for hematological relapse of myeloid malignancies after allo-HSCT. HMA selection included decitabine (n=2) and azacitidine (n=21), and combined donor lymphocyte infusion was administered to 21 and 42 patients in VEN+HMA and IC groups, respectively. ResultsMedian age of all patients was 39 (16-64) years old. Overall response rates, including complete response (CR), CR with incomplete recovery of normal neutrophil or platelet counts (CRi) and partial response (PR), were not significantly different between VEN+HMA and IC groups (60.1% versus 64.3%, P=0.785). CR/CRi rate was 52.2% in VEN+HMA and 59.5% in IC group (P=0.567). The rate of relapse after response was 66.7% in VEN+HMA group and 40.7% in IC group (P=0.176). Median overall survival was 209.0 (95%CI 130.9-287.1) days for VEN+HMA group versus 211.0 (95%CI 28.7-393.3) days for IC group (P=0.491). The incidence of lung infection (17.4% versus 50.0%, P=0.010), thrombocytopenia (73.9% versus 95.2%, P=0.035) and acute graft-versus-host disease (aGvHD) (50.0% versus 13.0%, P=0.003) was significantly higher in IC group. DiscussionIn conclusion, VEN+HMA is not inferior to IC regimen in terms of improving response and survival, and is associated with a lower incidence of adverse events and aGvHD. However, further research is required to enhance long-term survival.

Maintaining the efficacy of anti-CD19 chimeric antigen receptor modified (CAR) T-cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) is an urgent problem. In this study, we aimed to compare the efficacy of donor hematopoietic stem cell infusion (DSI) therapy and donor lymphocyte infusion (DLI) therapy as a maintenance therapy after R/R B-ALL patients achieved CR in anti-CD19-CAR T-cell therapy but relapsed after allo-HSCT. In total, 22 B-ALL patients who relapsed after allo-HSCT received anti-CD19-CAR T-cell therapy. Patients who responded to CAR T-cell therapy received DSI or DLI as maintenance therapy. We compared the clinical responses, acute graft versus host disease (aGVHD), expansion of CAR-T-cells, and adverse events between the two groups. In our study, 19 patients received DSI/DLI as maintenance therapy. After DSI/DLI therapy, progression-free survival and overall survival were higher in the DSI group than in the DLI group at 365 days. The grades I and II of aGVHD was observed in four patients (36.4%) in the DSI group. Only one patient developed grade II aGVHD in the DLI group. The peaks of CAR T-cells in the DSI group were higher than those in the DLI group. IL-6 and TNF-α levels increased again in nine of 11 patients after DSI but not in the DLI group. Our findings indicate that for B-ALL patients who relapse after allo-HSCT, DSI is a feasible maintenance therapy if CR is obtained with CAR-T-cell therapy.

Abstract. Hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). The incidence is about 7% to 68%, and some patients have to suffer a long period of frequent, urgent, and painful urination, which brings great pain. This study aimed to analyze risk factors of HC and its effect on patient survival. We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020. Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex, age, and diagnosis, and logistic regression analyses were used to identify factors associated with HC. We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups. We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve (ROC) analysis. After propensity score matching, there were 131 patients each in the HC and non-HC groups. In the HC group, 89 patients (67.9%) had mild HC (stage II°) and 43 (32.1%) had severe HC (stage III–IV). The median interval between stem cell transplantation and HC development was 31 (3–244) days. Univariate analysis indicated that donor age, hematopoietic stem cell source, HLA, acute graft-versus-host disease, busulfan, anti-thymocyte globulin (ATG), total body irradiation, cytomegalovirus (CMV) (urine), and BK polyomavirus (BKV) (urine) were significantly associated with HC. ATG, CMV (urine), and BKV (urine) were independent risk factors for HC based on the multivariate analysis. The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups (P = .14). The 1- and 2-year survival rates in the HC group were 78.4% and 69.6%, respectively, and the corresponding rates in the non-HC group were 84.4% and 80.7%, respectively. ROC analysis indicated that a urine BKV load of 1 × 107 copies/mL was able to stratify the risk of HC. In conclusion, when the BKV load is >1 × 107, we need to be aware of the potential for the development of HC.

Abstract A simple, practical, and high chemo-selective method for the synthesis of propargyl alcohol and allenyl alcohols via Cu-catalyzed, Mn-mediated propargylation and allenylation of aldehydes with propargyl bromides has been established. When 3-bromo-1-propyne was conducted under the standard condition, the aldehydes were transformed to the corresponding propargylation products completely, while when 1-bromo-2-pentyne was used, allenic alcohol was the only product. Variety of homopropargyl alcohols and allenyl alcohols were obtained in high yields and the reaction is compatible with broad substrate scopes. In addition, the large-scale reaction could also be proceeded smoothly indicating the potential synthetic applications of this transformation. Graphical Abstract

Abstract Objective To evaluate the efficacy and safety of P-ALG (porcine anti-lymphocyte globulin) and R-ATG (rabbit anti-thymocyte globulin) in the conditioning regime for patients with acquired aplastic anemia who underwent HLA-haploidentical hematopoietic stem cell transplantation (halpo-HSCT). Methods A total of 91 patients with acquired aplastic anemia who received haplo-HSCT at our center between January 2014 and December 2020 were retrospectively reviewed. Twenty-eight patients were in the P-ALG group while sixty-three patients were in the R-ATG group. Results The median time was 11 versus 13 days (P = 0.294) for myeloid engraftment and 12.5 versus 15 days (P = 0.465) for platelet engraftment in the P-ALG and R-ATG groups, respectively. There were no significant difference in 5-year overall survival (74.83% ± 8.24% vs 72.29% ± 6.26%, P = 0.830), GVHD-free, failure-free survival (71.05% ± 8.65% vs 62.71% ± 6.22%, P = 0.662), failure-free survival (74.83% ± 8.24% vs 66.09% ± 5.84%, P = 0.647) and transplantation-related mortality (25.17% ± 8.24% vs 26.29% ± 6.22%, P = 0.708) between the two groups. The incidence of aGVHD (acute graft versus host disease) (65.39% ± 9.33% vs 62.71% ± 6.30%, P = 0.653), II–IV aGVHD (38.46% ± 9.54% vs 35.64% ± 6.24%, P = 0.695), III–IV aGVHD (19.23% ± 7.73% vs 10.53% ± 4.07%, P = 0.291), cGVHD (chronic graft versus host disease) (22.22% ± 12.25% vs 22.31% ± 6.30%, P = 0.915), and moderate to severe cGVHD (5.56% ± 5.40% vs 9.28% ± 4.46%, P = 0.993) were not significantly different. Similar outcomes were observed between the P-ALG and R-ATG groups for severe bacterial infection (17.9% vs 25.4%, P = 0.431), invasive fungal diseases (3.6% vs 9.5%, P = 0.577) and graft rejection (0% vs 9.5%, P = 0.218). However, the incidence of cytomegalovirus infection and Epstein-Barr virus infection was significantly lower in the P-ALG group (46.4% vs 71.4%, P = 0.022; 3.6% vs 25.4%, P = 0.014). Conclusion The efficacy and safety of P-ALG were similar with R-ATG in the setting of haplo-HSCT for patients with acquired aplastic anemia patients. P-ALG could be an alternative for R-ATG.

Cardiac involvement in hematological malignancies is uncommon, with only a few cases reported to date, and it often leads to a poor prognosis. Here, we report a case of a 42-year-old woman with a history of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for B-cell lymphoblastic lymphoma/acute lymphoblastic leukemia in whom cardiac mass and myocardial infiltration were detected. Prior to this presentation, massive pericardial effusion had occurred 6 months after CAR T-cell therapy, which was improved via ultrasound-guided pericardiocentesis. We observed elevated cytokine levels and increased copy number of CAR DNA in both pericardial effusion and serum. Upon detecting cardiac mass and myocardial infiltration, the patient was administered tocilizumab (a humanized monoclonal antibody against IL-6 receptor), which controlled the serum cytokine levels, and reduced intensity chemotherapy, including vindesine, cyclophosphamide, and prednisolone. However, the patient finally died of multiple organ failure. To the best of our knowledge, this is the first report on the development of a cardiac mass and occurrence of myocardial infiltration after allo-HSCT and CAR T-cell therapy. This report may provide supporting data for the early diagnosis and immediate treatment of patients with cardiac involvement.

ObjectiveThis study aims to compare the characteristics of early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) and non-ETP ALL patients and the outcomes of these patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodA total of 57 patients with T-cell acute lymphoblastic leukemia/lymphoma receiving allo-HSCT at our center between January 2016 and March 2022 were enrolled in the study. Twenty-eight patients were diagnosed as ETP-ALL/LBL (28/57, 49.12%) in the cohort.ResultsThe baseline characteristic was not significantly different between the two groups. The median time for myeloid engraftment was 14 days (ranged from 11 to 21) versus 14 days (ranged from 10 to 20) (P = 0.067) and 18 days (ranged from 12 to 27) versus 15.5 days (ranged from 12 to 72) (P = 0.183) for platelet engraftment in the ETP-ALL/LBL and non-ETP ALL groups, respectively. There was no significant difference in 5-year overall survival (54.74% ± 10.33% vs. 64.20% ± 10.30%, P = 0.786), relapse-free survival (56.22% ± 10.11% vs. 57.17% ± 12.71%, P = 0.841), cumulative incidence of relapse (30.14% ± 9.85% vs. 22.79% ± 8.24%, P = 0.774), and non-relapse mortality (19.52% ± 8.99% vs. 25.95% ± 14.44%, P = 0.967) between the two groups. The incidence of acute graft versus host disease (aGVHD) (P = 0.922), II–IV aGVHD (P = 0.940), III–IV aGVHD (P = 0.664), cytomegalovirus infection (P = 0.862), Epstein–Barr virus infection (P = 0.610), and severe bacterial infection (P = 0.145) was also similar.ConclusionThe prognosis of patients with ETP-ALL/LBL was similar to non-ETP ALL patients when they received allo-HSCT.

Whether infections before transplantation impair the survival of patients with severe aplastic anemia (SAA) remains unclear. The aim of this retrospective cohort analysis was to compare survival between patients with SAA who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with infection (n=66) and patients without infection (n=189) from one medical center. There were no differences in baseline characteristics, except that more patients in the infection group were diagnosed with VSAA (59.09% vs. 30.69%, P

Bronchiolitis obliterans syndrome (BOS) is a life-threatening pulmonary complication of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we retrospectively identified seven patients newly diagnosed with BOS post HSCT and analyzed the outcomes in those patients treated with ruxolitinib as a first-line treatment. All seven patients achieved symptom responses within 2 weeks after ruxolitinib administration. Three months after treatment, five patients (71.43%) achieved a CR, and two (28.57%) achieved a PR. The overall response rate (ORR) was 100%. In addition, the steroid therapy was determined within 2 months after ruxolitinib treatment, indicating ruxolitinib as a steroid-sparing agent. We also found that ruxolitinib was well-tolerated and safe in treating newly diagnosed BOS. According to our results, ruxolitinib would be a promising and safe option in newly diagnosed BOS post HSCT.

We compared the efficacy and safety of porcine anti-lymphocyte globulin (pALG) (n=140) and rabbit anti-thymocyte globulin (rATG) (n=86) in patients with acquired aplastic anemia (AA) receiving hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSD) in two transplantation centers in China ranging from 2005 to 2020. The groups had similar baseline characteristics except for a higher number of infused mononuclear cells (P

BackgroundThe main aim of this study was to evaluate the effect of oxygen saturation on mortality in critically ill patients with mechanical ventilation according to obesity status.MethodsWe conducted an observational study in mechanically ventilated patients admitted to the ICU retrospectively. Demographic, arterial blood gas, ventilator setting, interventions, and peripheral oxygen saturation (Spo2) during the first 24 h were recorded and analyzed between non-obese and obese patients. The main exposure included Spo2, time-weighted mean Spo2 (TWM-Spo2), and proportion of time spent in different Spo2 (PTS-Spo2) levels. The primary outcome was hospital mortality. We used multivariable logistic regression models to assess the relationship between Spo2 and mortality, as well as the interaction between PTS-Spo2 and obesity status.ResultsA total of 25,100 patients were included, of which 10,564 (42%) were obese patients. After adjusting for confounders, compared with TWM-Spo2 of 94–98%, TWM-Spo2 of < =88% (OR 3.572; CI [2.343, 5.455]; p < 0.001) and of 89–93% (OR 1.514; CI [1.343, 1.706]; p < 0.001) were both associated with higher risk of mortality. PTS-Spo2 of 99–100% was associated with increased risk of mortality for obese patients (OR 1.028; 95% CI 1.010–1.046; p = 0.002; Pinteraction = 0.001), while PTS-Spo2 of 89–93% was associated with increased risk of mortality (OR 1.089; 95% CI 1.051–1.128; p < 0.001; Pinteraction = 0.001) for non-obese patients.ConclusionsFor obese and non-obese critically ill patients with mechanical ventilation, the impact of oxygen saturation on hospital mortality is different.

Systemic hypoxia is characterized by peripheral vasodilation and pulmonary vasoconstriction. However, the system-wide mechanism for signaling hypoxia remains unknown. Accumulating evidence suggests that hemoglobin (Hb) in RBCs may serve as an O2 sensor and O2-responsive NO signal transducer to regulate systemic and pulmonary vascular tone, but this remains unexamined at the integrated system level. One residue invariant in mammalian Hbs, β-globin cysteine93 (βCys93), carries NO as vasorelaxant S-nitrosothiol (SNO) to autoregulate blood flow during O2 delivery. βCys93Ala mutant mice thus exhibit systemic hypoxia despite transporting O2 normally. Here, we show that βCys93Ala mutant mice had reduced S-nitrosohemoglobin (SNO-Hb) at baseline and upon targeted SNO repletion and that hypoxic vasodilation by RBCs was impaired in vitro and in vivo, recapitulating hypoxic pathophysiology. Notably, βCys93Ala mutant mice showed marked impairment of hypoxic peripheral vasodilation and developed signs of pulmonary hypertension with age. Mutant mice also died prematurely with cor pulmonale (pulmonary hypertension with right ventricular dysfunction) when living under low O2. Altogether, we identify a major role for RBC SNO in clinically relevant vasodilatory responses attributed previously to endothelial NO. We conclude that SNO-Hb transduces the integrated, system-wide response to hypoxia in the mammalian respiratory cycle, expanding a core physiological principle.

Takotsubo syndrome (TTS) is an acute, stress-induced cardiomyopathy that occurs predominantly in women after extreme physical and/or emotional stress. To date, our understanding of the molecular basis for TTS remains unknown and, consequently, specific therapies are lacking. Myocardial infiltration of monocytes and macrophages in TTS has been documented in clinical studies. However, the functional importance of these findings remains poorly understood. Here, we show that a single high dose of isoproterenol (ISO) in mice induced a TTS-like cardiomyopathy phenotype characterized by female predominance, severe cardiac dysfunction, and robust myocardial infiltration of macrophages. Single-cell RNA-Seq studies of myocardial immune cells revealed that TTS-like cardiomyopathy is associated with complex activation of innate and adaptive immune cells in the heart, and macrophages were identified as the dominant immune cells. Global macrophage depletion (via clodronate liposome administration) or blockade of macrophage infiltration (via a CCR2 antagonist or in CCR2-KO mice) resulted in recovery of cardiac dysfunction in ISO-challenged mice. In addition, damping myeloid cell activation by HIF1α deficiency or exposure to the immunomodulatory agent bortezomib ameliorated ISO-induced cardiac dysfunction. Collectively, our findings identify macrophages as a critical regulator of TTS pathogenesis that can be targeted for therapeutic gain.

It is widely recognized that inflammation plays a critical role in cardiac hypertrophy and heart failure. However, clinical trials targeting cytokines have shown equivocal effects, indicating the need for a deeper understanding of the precise role of inflammation and inflammatory cells in heart failure. Leukocytes from human subjects and a rodent model of heart failure were characterized by a marked reduction in expression of Klf2 mRNA. Using a mouse model of angiotensin II–induced nonischemic cardiac dysfunction, we showed that neutrophils played an essential role in the pathogenesis and progression of heart failure. Mechanistically, chronic angiotensin II infusion activated a neutrophil KLF2/NETosis pathway that triggered sporadic thrombosis in small myocardial vessels, leading to myocardial hypoxia, cell death, and hypertrophy. Conversely, targeting neutrophils, neutrophil extracellular traps (NETs), or thrombosis ameliorated these pathological changes and preserved cardiac dysfunction. KLF2 regulated neutrophil activation in response to angiotensin II at the molecular level, partly through crosstalk with HIF1 signaling. Taken together, our data implicate neutrophil-mediated immunothrombotic dysregulation as a critical pathogenic mechanism leading to cardiac hypertrophy and heart failure. This neutrophil KLF2-NETosis-thrombosis mechanism underlying chronic heart failure can be exploited for therapeutic gain by therapies targeting neutrophils, NETosis, or thrombosis.

We retrospectively compared the outcomes of 387 consecutive patients with acquired aplastic anemia (AA) who underwent hematopoietic stem cell transplantation (HSCT) with a fludarabine-based conditioning regimen from matched sibling donors (MSD) (n = 108) or haploidentical donors (HID) (n = 91) and immunosuppressive therapy (IST) (n = 188) from 2014 to 2020 at our hospital. Compared with HID-HSCT, MSD-HSCT had a lower incidence of graft failure (1% vs. 7%, p = 0.062), grade II–IV acute graft versus host disease (aGvHD) (16% vs. 35%, p = 0.001), and mild to severe chronic GvHD (cGvHD) (8% vs. 23%, p = 0.007), but an equivalent incidence of grade III–IV aGvHD (8% vs. 12%, p = 0.237) and moderate to severe cGvHD (3% vs. 9%, p = 0.076). HSCT had superior blood count recovery at 3, 6, and 12 months compared with IST (p < 0.001). The estimated 5-year overall survival (OS) of the MSD, HID, and IST groups were 86%, 72%, and 79% (p = 0.02), respectively; accordingly, the failure-free survival (FFS) rates were 85%, 68%, and 56%, respectively (p < 0.001). For patients aged ≤40 years, the OS rate was still significantly superior for MSD-HSCT receipients compared to HID-HSCT receipients (89% vs. 76%, p = 0.024) while the HID-HSCT recipients showed similar OS (76% vs. 78%, p = 0.166) but superior FFS (p = 0.047) when follow-up was longer than 14.5 months in contrast to IST. In a multivariate analysis, HID-HSCT and a conditioning regimen that included busulfan were adversely related to OS among patients who received allografts. In conclusion, MSD-HSCT was the frontline choice for patients with severe AA aged ≤40 years, while HID-HSCT was as effective as IST for patients without an MSD.

Secondary failure of platelet recovery (SFPR) is a life-threatening complication that may affect up to 20% of patients after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, to evaluate the efficacy of recombinant human thrombopoietin (rhTPO), we retrospectively analyzed 29 patients who received continuous rhTPO for the treatment of SFPR. Overall response and complete response were observed in 24 (82.8%) patients and 10 (34.5%) patients, at a median time of 21.5 days (range, 3-41 days) and 39.5 days (range, 7-53 days) after initiation of rhTPO treatment, respectively. Among the responders, the probability of keeping overall response and complete response at 1 year after response was 77.3% and 80.0%, respectively. In multivariate analysis, higher CD34 + cells (≥3 × 10 6 /kg) infused during HSCT (HR: 7.22, 95% CI: 1.53-34.04, P = 0.01) and decreased ferritin after rhTPO treatment (HR: 6.16, 95% CI: 1.18-32.15, P = 0.03) were indicated to associate with complete response to rhTPO. Importantly, rhTPO was well tolerated in all patients without side effects urging withdrawal and clinical intervention. The results of this study suggest that rhTPO may be a safe and effective treatment for SFPR.

Accurate and automatic segmentation of medical images is in increasing demand for assisting disease diagnosis and surgical planning. Although Convolutional Neural Networks (CNNs) have shown great promise in medical image segmentation, they prefer to learn texture features over shape information. Moreover, recent studies have shown the promise that learning the data in a meaningful order can make the network perform better. Inspired by these points, we aimed to propose a two-stage medical image segmentation framework based on contour-aware CNN and voting strategy, which could consider the contour information and a meaningful learning order. In the first stage, we introduced a plug-and-play contour enhancement module that could be integrated into the encoder–decoder architecture to assist the model in learning boundary representations. In the second stage, we employed a voting strategy to update the model using easy samples in order to further increase the performance of our model. We conducted studies of the two publicly available CHAOS (MR) and hippocampus MRI datasets. The experimental results show that, when compared to the recent and popular existing models, the proposed framework can boost overall segmentation accuracy and achieve compelling performance, with dice coefficients of 91.2 ± 2.6% for the CHAOS dataset and 88.2 ± 0.4% for the hippocampus dataset.

Hearing loss is a serious illness affecting people’s normal life enormously. The acoustic properties of a tympanic membrane play an important role in hearing, and highly depend on its geometry, composition, microstructure and connection to the surrounding annulus. While the conical geometry of the tympanic membrane is critical to the sound propagation in the auditory system, it presents significant challenges to the study of the 3D microstructure of the tympanic membrane using traditional 2D imaging techniques. To date, most of our knowledge about the 3D microstructure and composition of tympanic membranes is built from 2D microscopic studies, which precludes an accurate understanding of the 3D microstructure, acoustic behaviors and biology of the tissue. Although the tympanic membrane has been reported to contain elastic fibers, the morphological characteristic of the elastic fibers and the spatial arrangement of the elastic fibers with the predominant collagen fibers have not been shown in images. We have developed a 3D imaging technique for the three-dimensional examination of the microstructure of the full thickness of the tympanic membranes in mice without requiring tissue dehydration and stain. We have also used this imaging technique to study the 3D arrangement of the collagen and elastic fibrillar network with the capillaries and cells in the pars tensa-annulus unit at a status close to the native. The most striking findings in the study are the discovery of the 3D form of the elastic and collagen network, and the close spatial relationships between the elastic fibers and the elongated fibroblasts in the tympanic membranes. The 3D imaging technique has enabled to show the 3D waveform contour of the collagen and elastic scaffold in the conical tympanic membrane. Given the close relationship among the acoustic properties, composition, 3D microstructure and geometry of tympanic membranes, the findings may advance the understanding of the structure—acoustic functionality of the tympanic membrane. The knowledge will also be very helpful in the development of advanced cellular therapeutic technologies and 3D printing techniques to restore damaged tympanic membranes to a status close to the native.

Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts.Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF.Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF.

Adipose tissue stores energy in the form of triglycerides. The ability to regulate triglyceride synthesis and breakdown based on nutrient status (e.g., fed versus fasted) is critical for physiological homeostasis and dysregulation of this process can contribute to metabolic disease. Whereas much is known about hormonal control of this cycle, transcriptional regulation is not well understood. Here, we show that the transcription factor Kruppel-like factor 15 (KLF15) is critical for the control of adipocyte lipid turnover. Mice lacking Klf15 in adipose tissue (AK15KO) display decreased adiposity and are protected from diet-induced obesity. Mechanistic studies suggest that adipose KLF15 regulates key genes of triglyceride synthesis and inhibits lipolytic action, thereby promoting lipid storage in an insulin-dependent manner. Finally, AK15KO mice demonstrate accelerated lipolysis and altered systemic energetics (e.g., locomotion, ketogenesis) during fasting conditions. Our study identifies adipose KLF15 as an essential regulator of adipocyte lipid metabolism and systemic energy balance.

KLF family transcription factors (KLFs) regulate many cellular processes, including proliferation, survival and stress responses. Here, the authors position KLFs as important regulators of autophagy and lifespan in C. elegans, a role that may extend to the modulation of age-associated vascular phenotypes in mammals.

Digestive tract tumors account for 15% and 19.3% of the cancer incidence and deaths, respectively. Early detection of digestive tract tumors is crucial to the reduction of global cancer burden. Two-photon excitation fluorescence lifetime imaging microscopy (TP-FLIM) allows non-invasive, label-free, three-dimensional, high-resolution imaging of living tissues with not only histological but also biochemical characterization ability in both qualitative and quantitative way. Benefiting from these advantages, this technology is promising for clinical diagnosis of digestive tract tumors. In recent years, many efforts have been made in this field and some remarkable progress has been achieved. In this paper, we overview the recent progress of TP-FLIM-based researches on digestive tract tumor detection. Among them, our latest results on the gastric cancer and esophageal cancer are elaborately depicted. Finally, we outlook and discuss the potential advantages and challenges of TP-FLIM in future clinical applications.

Circadian rhythms offer temporal control of anticipatory physiologic adaptations in animals. In the mammalian cardiovascular system, the importance of these rhythms is underscored by increased cardiovascular disease in shift workers, findings recapitulated in experimental animal models. However, a nodal regulator that allows integration of central and peripheral information and coordinates cardiac rhythmic output has been elusive. Here, we show that kruppel-like factor 15 (KLF15) governs a biphasic transcriptomic oscillation in the heart with a maximum ATP production phase and a remodeling and repair phase corresponding to the active and resting phase of a rodent. Depletion of KLF15 in cardiomyocytes leads to a disorganized oscillatory behavior without phasic partition despite an intact core clock. Thus, KLF15 is a nodal connection between the clock and meaningful rhythmicity in the heart.

Objectives: Febrile neutropenia (FN) is a common but lethal complication of chemotherapy in hematological malignance. The aim of this study was to identify the prognostic risk factors for antibiotic treatment outcome in PN patients, and provide the optimal choice for the initial empirical antibiotic treatment. Methods: 227 consecutive FN hematologic malignancies from four hospitals in Northeast China were enrolled. The outcome of antibiotic therapy was investigated until 14 days after the onset of FN. The factors affecting antibiotic therapy outcome were evaluated using Univariate analysis and Multivariate logistic regression analysis. Results: Among all patients, 27 patients did not achieve favorable outcome either clinically or bacteriologically. It was shown that the risk factors for poor FN therapy outcome were associated with prolonged duration of neutropenia over 9 days during FN (P=0.019), slow neutrophil recovery (P=0.039), respiratory infection (P=0.005), and that initial monotherapy with drugs recommended by the guidelines indicated better outcome (P=0.009). Additionally, patients with multi-bacterial infection, as well as further ANC decrease after fever, had a poor prognosis. Conclusions: Our results indicate that early application of antibiotics and prevention of respiratory infection as well as good clinical care are able to improve clinical outcomes from empirical antibiotic treatment in FN patients with hematological malignances.

In this study, we firstly reported the complete mitochondrial genome of Copadichromis trimaculatus. The whole mitochondrial genome is 16,581 bp in length, including 2 ribosomal RNA genes, 22 transfer RNA genes and 13 protein-coding genes. Its GC content is 46.00%, similar to Copadichromis virginalis (45.74%). We also analyzed its phylogenic relationship with other 14 related species, which would facilitate our understanding of the phylogenic relationship of Cichlidae mitochondrial genome.

The metabolic myocardium is an omnivore and utilizes various carbon substrates to meet its energetic demand. While the adult heart preferentially consumes fatty acids (FAs) over carbohydrates, myocardial fuel plasticity is essential for organismal survival. This metabolic plasticity governing fuel utilization is under robust transcriptional control and studies over the past decade have illuminated members of the nuclear receptor family of factors (e.g., PPARα) as important regulators of myocardial lipid metabolism. However, given the complexity of myocardial metabolism in health and disease, it is likely that other molecular pathways are likely operative and elucidation of such pathways may provide the foundation for novel therapeutic approaches. We previously demonstrated that Kruppel-like factor 15 (KLF15) is an independent regulator of cardiac lipid metabolism thus raising the possibility that KLF15 and PPARα operate in a coordinated fashion to regulate myocardial gene expression requisite for lipid oxidation. In the current study, we show that KLF15 binds to, cooperates with, and is required for the induction of canonical PPARα-mediated gene expression and lipid oxidation in cardiomyocytes. As such, this study establishes a molecular module involving KLF15 and PPARα and provides fundamental insights into the molecular regulation of cardiac lipid metabolism.

Understanding of the RNA editing process has been broadened considerably by the next generation sequencing technology; however, several issues regarding this regulatory step remain unresolved--the strategies to accurately delineate the editome, the mechanism by which its profile is maintained, and its evolutionary and functional relevance. Here we report an accurate and quantitative profile of the RNA editome for rhesus macaque, a close relative of human. By combining genome and transcriptome sequencing of multiple tissues from the same animal, we identified 31,250 editing sites, of which 99.8% are A-to-G transitions. We verified 96.6% of editing sites in coding regions and 97.5% of randomly selected sites in non-coding regions, as well as the corresponding levels of editing by multiple independent means, demonstrating the feasibility of our experimental paradigm. Several lines of evidence supported the notion that the adenosine deamination is associated with the macaque editome--A-to-G editing sites were flanked by sequences with the attributes of ADAR substrates, and both the sequence context and the expression profile of ADARs are relevant factors in determining the quantitative variance of RNA editing across different sites and tissue types. In support of the functional relevance of some of these editing sites, substitution valley of decreased divergence was detected around the editing site, suggesting the evolutionary constraint in maintaining some of these editing substrates with their double-stranded structure. These findings thus complement the "continuous probing" model that postulates tinkering-based origination of a small proportion of functional editing sites. In conclusion, the macaque editome reported here highlights RNA editing as a widespread functional regulation in primate evolution, and provides an informative framework for further understanding RNA editing in human.