Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study.

BACKGROUND: Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously. METHODS: Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse. RESULTS: Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003). CONCLUSION: ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 ).

Impact of myelofibrosis on patients with myelodysplastic syndromes following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. METHODS: We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT. RESULTS: The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%-17.7%), 16.3% (95% CI 10.2%-23.6%), 76.6% (95% CI 69.0%-85.1%), and 72.8% (95% CI 65.0%-81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%-32.9%), 14.7% (95% CI 5.3%-28.7%), 71.8% (95% CI 57.6%-89.6%), and 68.4% (95% CI 53.6%-87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25-5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10-4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type. CONCLUSIONS: In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor.

Outcomes of haploidentical peripheral blood stem cell transplantation following myeloablative conditioning using two types of rabbit ATG: a propensity score-matched analysis.

During hematopoietic stem cell transplantation (HSCT), ATG depletes T cells in-vivo to improve engraftment and prevent graft-versus-host disease (GVHD). Here, we compared the clinical efficacy of two different types of ATGs: thymoglobulin and anti-human T-lymphocyte immunoglobulin (Grafalon). A total of 469 patients who received haploidentical transplantation were enrolled in this retrospective study. We applied a propensity score (PS)-matched analysis and 209 patients were assigned to each group. Clinical outcomes were compared between two groups and primary outcome was overall survival (OS). There was no significant difference in OS between two groups. Within the first 180 days after HSCT, Grafalon was associated with lower incidences of Epstein-Barr virus (EBV) viremia (31.6 vs. 54.5%, P < 0.0001) and cytomegalovirus viremia (CMV) viremia (54.5 vs. 67.9%, P = 0.005) compared to thymoglobulin. Patients receiving Grafalon had a higher rate of moderate/severe chronic GVHD (26.3 vs. 18.2%, P = 0.046). However, the incidences of engraftment failure, grade II-IV acute GVHD, relapse, non-relapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) did not differ greatly between groups. In the subgroup analysis, Grafalon improved the OS of lymphoid malignancies with young ages (< 40 years old) (HR, 0.55; P = 0.04) or with a high/very high disease risk index (HR, 0.36; P = 0.04). In the myeloid cohort, Grafalon reduced NRM in the patients who received non-female for male transplantation grafts (HR, 0.17; P = 0.02). Our results suggest the two types of ATG may differentially influence transplant outcomes and it may optimize ATG selection according to the condition of patients.

Prevalence and factors associated with overweight, obesity and central obesity among adults in Shenmu City, Shaanxi Province, China.

Objectives: This research aimed to explore the prevalence and determinants of overweight, obesity, and central obesity in Shenmu City, Shaanxi Province, China and to offer guidance for preventative health measures. Methods: We conducted a multi-stage, stratified random sampling survey among 4,565 residents of Shenmu City. Data collection included questionnaires and anthropometric assessments to gather socio-demographic data and to identify cases of overweight, obesity, and central obesity. Multivariable logistic regression analysis was utilized to assess the association between various factors and these conditions. Results: The observed prevalence rates for overweight, obesity, central obesity, and the combination of overweight/obesity with central obesity were 39.9%, 18.2%, 48.0%, 32.8%, and 22.8%, respectively. Notably, the incidence of these conditions was significantly higher in men compared to women. The prevalence of overweight and obesity initially increased and then decreased with age, whereas the prevalence of central obesity consistently rose. Furthermore, a higher educational level correlated with lower prevalence rates. Additionally, our analysis indicated that hypertension, dyslipidemia, and hyperuricemia are risk factors for these conditions. Conclusions: The findings of this study offer crucial insights for formulating effective strategies to prevent and manage obesity in Shenmu City.

Characteristics of Coronavirus Disease in Allogeneic Hematopoietic Stem Cell Transplantation During the Omicron Wave: A Single-Center Study.

Objectives: This study aimed to characterize the clinical characteristics, outcomes, and risk factors for coronavirus disease 2019 (COVID-19) in 492 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during the Omicron wave. Methods: Data were retrospectively collected from patient charts and the electronic medical record systems at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2022 and January 2023. Results: The median follow-up period of the entire cohort was 62 days. Myeloid malignancies (58.5%) and acute lymphocytic leukemia (30.5%) constituted the most common underlying disease. Among the 492 patients, 415, 67, and 10 exhibited mild, moderate, and severe COVID-19, respectively. The incidence of moderate-to-severe COVID-19 was 15.7%. The 60-day overall survival and complete resolution rates were 98.1% and 80.6%, respectively. The risk factors for moderate-to-severe COVID-19 included corticosteroid use within 3 months before diagnosis, <6 months interval between allo-HSCT and COVID-19 diagnosis, and antithymocyte globulin use for graft-versus-host disease prophylaxis. Conclusions: During the Omicron wave, patients with allo-HSCT demonstrated a low COVID-19-related mortality rate and high moderate-to-severe and prolonged disease incidence. Prevention in the early posttransplantation period is critical for allo-HSCT recipients receiving corticosteroids.

Elucidating the role of monoacetylphlorogulcinol in the pathogenicity of Pseudomonas 'gingeri' against Agaricus bisporus.

BACKGROUND: Agaricus bisporus is a globally important edible fungus. The occurrence of ginger blotch caused by Pseudomonas 'gingeri' during A. bisporus growth and post-harvest stages results in significant economic losses. The biotoxin monoacetylphloroglucinol (MAPG) produced by P. 'gingeri' is responsible for inducing ginger blotch on A. bisporus. However, the understanding of the toxic mechanisms of MAPG on A. bisporus remains limited, which hinders the precise control of ginger blotch disease in A. bisporus and the breeding of disease-resistant varieties. RESULTS: Integrating transcriptomic, metabolomic, and physiological data revealed that MAPG led to an increase in intracellular superoxide anion (O2 -) levels and lipid peroxidation in A. bisporus. MAPG changed the cellular membrane composition of A. bisporus, causing to damage membrane permeability. MAPG inhibited the expression of genes associated with the 19s subunit of the proteasome, thereby impeding cellular waste degradation in A. bisporus. Unlike melanin, MAPG stimulated the synthesis of flavonoids in A. bisporus, which might explain the manifestation of ginger-colored symptoms rather than browning. Meanwhile, the glutathione metabolism pathway in A. bisporus played a pivotal role in counteracting the cytotoxic effects of MAPG. Additionally, enhanced catalase activity and up-regulation of defense-related genes, including cytochrome P450s, Major Facilitator Superfamily (MFS), and ABC transporters, were observed. CONCLUSION: This study provides comprehensive insights into MAPG toxicity in A. bisporus and uncovers the detoxification strategies of A. bisporus against MAPG. The findings offer valuable evidence for precise control and breeding of resistant varieties against ginger blotch in A. bisporus. © 2024 Society of Chemical Industry.

Investigation on the correlation factors of positive Streptococcus pneumoniae antibody and IgG antibody level of Streptococcus pneumoniae in the elderly over 60 years old in Shenzhen.

BACKGROUND: Pneumococcal Polysaccharide Vaccine (PPV-23), designed to protect against the most common serotype of Streptococcus pneumoniae, is intended to protect the elderly and other high-risk groups. However, the immunogenicity of all 23 pneumococcal polysaccharide vaccines in older adults has not been thoroughly studied. OBJECTIVE: The purpose of this study is to look into the factors that influence the effect of the pneumonia vaccine on the elderly over 60 years old in Shenzhen, as well as their IgG antibody level against Streptococcus pneumoniae. METHODS: To determine the immune effectiveness of pneumococcal vaccination in older adults over 60 years old, we used the 3rd generation enzyme-linked immunosorbent assay to detect the antibody level of older adults to all 23 pneumococcal polysaccharide vaccines following pneumococcal immunization. RESULTS: Vaccination, the number of physical examinations, pneumonia knowledge, and the pneumonia vaccination policy of the elderly in Shenzhen were all positively correlated with Streptococcus pneumoniae antibody positivity. The distribution of subtypes did not differ between elderly adults (over 65) and younger adults (under 65). The GMCs of IgG antibodies to PPS were significantly lower in males than in females for types 7f, 18c and 19a. At the same time, we found that people with chronic respiratory disease have lower type 9n than people without chronic respiratory disease. Other chronic diseases, such as hypertension and diabetes, had no difference in subtype distribution. CONCLUSION: There was a statistically significant difference in antibody positivity rates for older people with more frequent medical check-ups in Shenzhen, indicating that publicity is playing a role. The effects of age, gender, and chronic diseases on naturally acquired anti-PPS IgG differ.

Comparison of long-term outcomes between imatinib and dasatinib prophylaxis after allogeneic stem cell transplantation in patients with Philadelphia-positive acute lymphoblastic leukemia: A multicenter retrospective study.

BACKGROUND: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation. METHODS: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared. RESULTS: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation. CONCLUSIONS: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib.

High serum uric acid is a risk factor for arterial stiffness in a Chinese hypertensive population: a cohort study.

The prospective cohort study was to explore the association between serum uric acid (SUA) and arterial stiffness in a Chinese hypertensive population. A total of 7444 participants with hypertension who completed two or more measurements of brachial-ankle pulse wave velocity (baPWV) and baseline SUA detection were followed-up in the Kailuan Study from 2010 to 2020. A restricted cubic spline curve was used to verify whether there was a linear association between baseline SUA and arterial stiffness. A Cox proportional hazard regression model was used to explore the association of between baseline SUA and the incidence of arterial stiffness. Our results showed that the restricted cubic spline curve revealed a linear relationship between baseline SUA and arterial stiffness in total participants (p < 0.001). After follow-up 4.6 ± 2.8 years, Kaplan-Meier survival curves indicated that the risk of arterial stiffness was increased in the high level of baseline SUA (Log-rank p = 0.0002). After adjusting for potential confounding factors, the HR (95% CI) for risk of stiffness was 1.33 (1.17-1.52, p < 0.001) in the highest SUA group. Hierarchical analysis showed that the HRs (95% CI) for risk of arterial stiffness were 1.45 (1.25-1.69), 1.38 (1.19-1.60), 1.41 (1.21-1.64), and 1.35 (1.15-1.58) in the highest SUA group of males, <65 years old, not taking antihypertensive drugs, and failure to achieve the control targets of blood pressure respectively (p < 0.001). These results reveal that high SUA is a risk factor for arterial stiffness in the Chinese hypertensive population.

MiR-145 Alleviates Sepsis-Induced Inflammatory Responses and Organ Injury by Targeting ADAM17.

BACKGROUND: Current studies have demonstrated that disintegrin and metalloproteinase 17 (ADAM17) plays a critical role in the pathogenesis of sepsis. MicroRNA (miR)-145 is known to control immune responses as an anti-inflammatory modulatory molecule. However, a fundamental understanding of how miR-145 regulates ADAM17 and, more broadly, sepsis-induced inflammatory response remains unknown. METHODS: We used western blotting and quantitative real-time PCR (qRT-PCR) to measure expression levels of ADAM17 and miR-145. Enzyme-linked immunosorbent assays (ELISA) were performed to measure cytokine production. To determine if ADAM17 is a target gene of miR-145, bioinformatics analyses and luciferase reporter assays were conducted. The impacts of ADAM17 and miR-145 on sepsis-induced inflammatory responses were accessed in vitro using human umbilical endothelial cells (HUVECs) treated with lipopolysaccharide (LPS). Sepsis-induced inflammatory response was measured in vivo using a polymicrobial septic mouse model induced by cecal ligation and puncture (CLP) with pre-injection of a miR-145 agomir. RESULTS: In HUVECs treated with LPS, miR-145 expression was downregulated and miR-145 negatively regulated ADAM17 expression through direct binding to the ADAM17 transcript 3'-UTR. MiR-145 overexpression markedly reduced LPS-induced inflammatory cytokine production by targeting ADAM17 in HUVECs. In comparison to CLP-induced septic mice treated with a control agomir, treatment with a miR-145 agomir significantly reduced the expression of ADAM17, numerous downstream cytokines such as IL-6, TNF-α, IL-1ß and MCP-1, and the endothelial injury factors ICAM-1, VCAM-1. The miR-145 agomir also alleviated acute lung and kidney injury and improved the survival rate of septic mice. CONCLUSIONS: This study showed that miR-145, by specifically targeting ADAM17, negatively regulates sepsis-induced inflammatory responses and vascular endothelial injury, and ultimately improved organ injury and survival during sepsis. The underlying mechanism for the regulation of ADAM17 expression by miR-145 and sepsis-induced inflammatory reactions may offer sepsis patients a novel therapeutic option.

Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial.

Background: Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic leukemia (B-ALL), less research about the feasibility and safety of donor-derived CAR T after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported. Methods: This phase 1 clinical trial aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. This trial is registered with ClinicalTrials.gov, NCT04516551. Findings: Between 15 March 2021 and 19 May 2022, fifteen patients were screened, three patients were excluded due to withdraw of consent, donor's reason, and death, respectively. Patients received donor-derived CAR T cells infusions at 6 × 105/kg (n = 3) or 2 × 106/kg (n = 6) dose level. The median time from HSCT to relapse was 185 days (range, 81-2063). The median age of patients was 31 years (range 21-48). Seven patients (77.8%) had BCR-ABL fusion gene. CAR T cells expanded in vivo and the median time to reach Cmax was 9 days (range, 7-11). One patient had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced CRS and hematological adverse events. Three patients had acute graft-versus-host-disease (grade I, n = 1; grade II, n = 1; grade IV, n = 1) and all resolved after treatment. They received CAR T cells from matched sister, haploidentical matched father and sisiter, respectively. At 28 days after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CRi/CR) with undetectable MRD. At a median follow-up of 475 days (range 322-732), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (9/9), 88.9% (8/9), and 75% (6/8) at 3 month, 6 month, and 12 month, respectively. The 1-year progression-free and overall survival were 77.8% and 85.7%, respectively. Interpretation: GC007g expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles. Funding: Gracell Biotechnologies Inc.

Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation.

Objective: This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Methods: Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021. Results: A higher dose of graft CD8+ T cells (≥ 0.85 × 108 kg-1) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P = 0.002) and disease-free survival (DFS; HR, 1.751; P < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P = 0.038) and DFS (HR, 1.532; P = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8+ T-cell risk system based on graft CD8+ T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8+ T-cell dose was negatively correlated with donor age (P < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (P < 0.001). Conclusion: A higher CD8+ T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.

One-dimensional single atom arrays on ferroelectric nanosheets for enhanced CO2 photoreduction.

Single-atom catalysts show excellent catalytic performance because of their coordination environments and electronic configurations. However, controllable regulation of single-atom permutations still faces challenges. Herein, we demonstrate that a polarization electric field regulates single atom permutations and forms periodic one-dimensional Au single-atom arrays on ferroelectric Bi4Ti3O12 nanosheets. The Au single-atom arrays greatly lower the Gibbs free energy for CO2 conversion via Au-O=C=O-Au dual-site adsorption compared to that for Au-O=C=O single-site adsorption on Au isolated single atoms. Additionally, the Au single-atom arrays suppress the depolarization of Bi4Ti3O12, so it maintains a stronger driving force for separation and transfer of photogenerated charges. Thus, Bi4Ti3O12 with Au single-atom arrays exhibit an efficient CO production rate of 34.15 µmol·g-1·h-1, ∼18 times higher than that of pristine Bi4Ti3O12. More importantly, the polarization electric field proves to be a general tactic for the syntheses of one-dimensional Pt, Ag, Fe, Co and Ni single-atom arrays on the Bi4Ti3O12 surface.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors.

KMT2A rearrangement (KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non-KMT2A-r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A-r (n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A-r (n = 42) was lower than that of those without KMT2A-r (n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A-r (n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR (P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9, ELL, and other KMT2A-r subtypes (P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A-r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A-r AML was poor, particularly those harboring AF6-related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.

Donor aKIR genes influence the risk of EBV and CMV reactivation after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) offers the highest curative potential for patients with hematological malignancies. Complications including infection, graft-versus-host disease (GVHD), and relapse reflect delayed or dysregulated immune reconstitution. After transplantation, NK cells rapidly reconstitute and are crucial for immune surveillance and immune tolerance. NK cell function is tightly regulated by killer immunoglobin-like receptors (KIRs). Previous studies have revealed that donor KIRs, especially some activated KIRs (aKIRs) are closely related to transplant outcomes. Here, we performed a retrospective study, including 323 patients who received haploidentical (haplo) HSCT in our center. In univariate analysis, donor KIR2DS1, KIR2DS3 and KIR3DS1 gene protected patients with lymphoid disease from Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation, while donor KIR2DS1, KIR2DS5 and KIR3DS1 gene conferred a higher risk of CMV reactivation for patients with myeloid disease. Multivariate analysis confirmed that donor telomeric (Tel) B/x and KIR2DS3 gene best protected patients with lymphoid disease from EBV (p = 0.017) and CMV reactivation (p = 0.004). In myeloid disease, grafts lacking Tel B/x and KIR2DS5 gene correlated with the lowest risk of CMV reactivation (p = 0.018). Besides, donor aKIR genes did not influence the rates of GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS) in this study. The reactivation of EBV and CMV was associated with poor prognosis of haplo-HSCT. In conclusion, we found that donor aKIR genes might have a synergistic effect on CMV and EBV reactivation after haplo-HSCT. Whether the influence of donor aKIR genes varies with disease types remained to be studied.

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study.

Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We conducted this study to compare the superiority of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 176 patients. In the pre-DLI cohort, 42 patients relapsed without chance for pre-DLI while 95 patients remained CR without detectable minimal residual disease (MRD). Thirty-nine patients in the pre-DLI cohort became minimal MRD positive/mixed chimerism and received pre-DLI. Pro-DLI cohort had higher 3-year progression-free-survival (PFS) (63.4%vs.53.0%, P = 0.026) and overall survival (OS) (65.2% vs. 57.0%, P = 0.14) compared to the pre-DLI cohort. The 3-year cumulative incidence of relapse (CIR) was 25.3% in the pro-DLI cohort which was significantly lower than 36.7% in the pre-DLI cohort (P = 0.02). The cumulative incidence of grade III-IV aGVHD, cGVHD and non-relapse mortality were comparable between cohorts. Multivariable analysis demonstrated strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.63, P = 0.04), PFS (HR = 0.54, P = 0.005) and CIR (HR = 0.50, P = 0.005). In high-risk patients with acute leukemia, early scheduled pro-DLI rather than pre-DLI after detectable MRD would reduce post-transplant relapse and improve long-term survival.

Investigation and prediction of the biotoxicity of Cu2+ to Chlorella vulgaris: modification of the biotic ligand model.

The increased copper ion (Cu2+) concentrations in aquatic ecosystem significantly influence the environmental quality and ecosystem safety, while information on the Cu2+ biotoxicity to aquatic microorganisms and the models for biotoxicity prediction are still unclear. In this study, the toxicities of Cu2+ to Chlorella vulgaris under different environmental conditions (e.g., Na+, K+, Ca2+, Mg2+, pH, and dissolved organic matter) were explored, with the experimental results in comparison with those predicted by the biotic ligand model (BLM). Results showed that increased Cu2+ concentration caused obvious toxicities to C. vulgaris, whereas the commonly occurring cations and dissolved organic matters can protect the metabolism system of C. vulgaris. The presence of extracellular polymeric substances (EPS) matrix can alleviate the biotoxicity via increasing the surface biosorption but decreasing cell internalization of Cu2+ in C. vulgaris. Due to the presence of EPS matrix, the experimental biotoxicity results under each condition were significantly lower than those predicted by the BLM model, which was thus modified via taking the EPS matrix as the supplement of allochthonous organic matters. After that, the modified BLM was characterized with a higher degree of precision and can be used in natural waters for biotoxicity prediction. Results obtained can enhance our insights into the ecological effects and biotoxicity prediction of heavy metals in natural aquatic ecosystems.