BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To explore the application of standardized teaching mode in clinical teaching for B-type ultrasound-guided peripherally inserted central catheters(PICC),and to discuss its influence on the teaching quality,comprehensive skills and student satisfaction.Methods A total of 74 nurses,who learned B-type ultrasound-guided PICC operation at the Department of Emergency of a certain grade Ⅲ-A hospital in Guangzhou City of China from September 2021 to September 2023,were randomly divided into the study group and the control group with 37 nurses in each group.The teaching content of both groups was B-type ultrasound-guided PICC operation.The conventional teaching method was adopted for the control group,while on the basis of the conventional teaching method,additional standardized teaching mode was carried out for the study group.Teaching and training lasted for 3 months.The management indicators,teaching quality,comprehensive skills and student satisfaction with teaching were compared between the two groups.Results Compared with the control group,in the study group the catheterization time was shorter,the pain score was lower,and the success rate of single puncturing was higher(all P＜0.05).The results of final theory examination,case analysis ability,and clinical actual operation score(including the indications,puncturing method,and puncturing technique of B-type ultrasound-guided PICC)in the study group were significantly better than those in the control group(all P＜0.05).The comprehensive skills were remarkably improved in both groups.The scores of doctor-patient communication,physical examination,medical ethics,operation process in the study group were obviously higher than those in the control group(all P＜0.05).Moreover,the expression ability,the sense of team cooperation,the ability to search and read literature,the ability of clinical practice,the degree of knowledge mastery,the ability to analyze and solve problems,and the learning initiative in the study group were prominently better than those in the control group(all P＜0.05).Conclusion In clinical teaching for B-type ultrasound-guided PICC operation,the implement of standardized teaching mode can help to improve the quality of teaching and improve the nurse s comprehensive skills of PICC operation with higher degree of satisfaction with teaching,therefore,this kind of teaching mode is worth popularizing and applying.

Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area. Methods A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10). Results The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer（χ²=16.032，P=0.014) , liver cancer（χ²=8.099，P=0.030) , bladder cancer（χ²=11.274 , P=0.018) , and gastric cancer（χ²=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05). Conclusion Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.

Liver macrophages are important immune cells in the liver,and they express proinflammatory factors and anti-inflammatory factors through polarization into M1 type and M2 type,respectively,thereby playing a role in regulating inflammatory damage response.The malignant transformation of hepatic progenitor cells is the core mechanism of the malignant progression of hepatic precancerous lesions,and its key factor is the continuous stimulation of inflammatory microenvironment,which is closely associated with M1/M2 macrophage polarization.This review mainly focuses on the association between macrophage polarization,chronic inflammation,and malignant transformation of hepatic progenitor cells,so as to provide a theoretical basis for the prevention and treatment of hepatic precancerous lesions.

Brain organoids are self-organized 3D aggregates generated by human embryonic stem cells or human induced pluripotent stem cells. Their cell type and structure are similar to embryonic human brain, which are good in vitro models for the study of neurogenetic diseases and have been widely used in the study of neurogenetic diseases. This paper will discuss the advantages and challenges of brain organoids in the modeling of genetic diseases of the nervous system.

Objective:This study aimed to observe the dynamic changes of NUP98::NSD1 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Moreover, the clinical value of measurable residual disease (MRD) was analyzed.Methods:Sixteen AML patients who were diagnosed with the NUP98::NSD1 fusion gene and received allo-HSCT at Peking University People’s Hospital were included. The NUP98::NSD1 fusion gene and leukemia-associated immunophenotype (LAIP) were monitored before and after transplantation to evaluate their MRD status.Results:The median follow-up time for all patients was 526 days (139-1136 days) , with four patients (25.0%) experiencing hematological recurrence at a median of 474 days (283-607 days) after transplantation. Three patients (18.8%) died, two of whom (12.5%) died of leukemia recurrence. The median expression level of NUP98::NSD1 in newly diagnosed patients with complete data was 78.5% (18.9%-184.4%) at the time of initial diagnosis. The recurrence rate was higher in NUP98::NSD1-positive patients after transplantation, with 44.4% of patients experiencing recurrence, whereas no recurrence occurred in NUP98::NSD1-negative patients after transplantation. The area under the receiver operating characteristic curve predicted by the NUP98::NSD1 level after transplantation was 1.000 (95% confidence interval: 1.000-1.000, P=0.003) . Among the four patients with recurrence, NUP98::NSD1 was more sensitive than flow cytometry residual (FCM) and Wilms’ tumor gene 1 (WT1) . Conclusions:The NUP98::NSD1 fusion gene can be used to evaluate the MRD status of allo-HSCT. NUP98::NSD1-positive patients after transplantation have a high relapse rate and poor prognosis. NUP98::NSD1 was more sensitive than FCM and WT1 in predicting posttransplant relapse.

BACKGROUND: Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial. METHODS: We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China. RESULTS: With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs . 67.0%, P < 0.001) and overall survival (89.2% vs . 78.5%, P  = 0.007), and better cumulative incidences of relapse (10.5% vs . 19.6%, P  = 0.020) and non-relapse mortality (4.2% vs . 14.9%, P  = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs . 67.7%, P  = 0.003) and a lower cumulative incidence of relapse (9.6% vs . 23.3%, P  = 0.013) than those with ≤ 2 courses. CONCLUSION Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.
Humans ; Retrospective Studies ; Consolidation Chemotherapy/methods* ; Siblings ; Hematopoietic Stem Cell Transplantation/methods* ; Leukemia, Myeloid, Acute/etiology* ; HLA Antigens ; Allografts