Lanzhou Army General Hospital

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for severe aplastic anemia (SAA), with donor sources including matched sibling donors (MSDs), haploidentical donors (HIDs), and unrelated donors (URDs). However, the optimal criteria for donor selection remain undefined. We performed a multicenter retrospective study of 795 consecutive SAA patients who underwent allo-HSCT between 2012 and 2020 across 11 transplant centers in China. The overall survival (OS), failure-free survival (FFS), and GVHD-free/FFS (GFFS) rates were 85.2%, 83.6%, and 76.1%, respectively. Donor-related variables including relationship, age, sex match, blood type, and HLA mismatches were evaluated. Multivariable Cox regression identified donor age ≥50years as an independent risk factor for inferior GFFS (HR=2.13), OS (HR=2.09), and FFS (HR=2.18) (all P<0.001). To directly compare the prognostic weight of donor age versus HLA compatibility, we stratified patients into four subgroups according to donor type (HID vs. MSD) and donor age (<50 vs. ≥50years). Kaplan-Meier analysis with log-rank testing revealed that recipients of haploidentical grafts from younger donors achieved superior OS and FFS compared with those transplanted from older HLA-matched sibling donors. These findings demonstrate that donor age has a greater influence on transplant outcomes than HLA matching. With continuous improvements in haploidentical transplantation techniques, selecting younger haploidentical donors may represent a more favorable strategy than choosing older matched sibling donors.

Current therapeutic strategies for hepatic fibrosis remain limited, primarily due to lack of effectively targeting activated hepatic stellate cells (aHSCs) without compromising treatment safety. Although human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exhibit promising therapeutic potential, their clinical application is constrained by rapid clearance via the mononuclear phagocyte system (MPS) and inadequate target specificity. This study aimed to develop engineered exosomes with enhanced targeting capabilities toward aHSCs through surface modification, thereby improving their anti-fibrotic efficacy. We developed an exosomal delivery system modified with a pPB cyclic peptide (hUCMSC-Exos@pPB) using DSPE-PEG-NH2-based nanoengineering to enable specific targeting of aHSCs. The targeting efficiency of hUCMSC-Exos@pPB was assessed via in vivo imaging and immunofluorescence co-localization analysis with α-smooth muscle actin (α-SMA). Biosafety of the hUCMSC-Exos@pPB delivery system was comprehensively evaluated through CCK-8 assays in vitro, hematoxylin and eosin (HE) staining of major organs in experimental animals, and the analysis of liver and kidney function indicators. The anti-liver fibrosis efficacy of hUCMSC-Exos@pPB was evaluated through multiple approaches, including histopathological assessments (HE, Masson, and Sirius red staining), oxidative stress markers (malondialdehyde and NADPH oxidase 4), measurement of liver function parameters (aspartate aminotransferase and alanine aminotransferase), and analysis of fibrogenic protein expression (α-SMA and COL1a1) in vivo and in HSC-T6 cells. Transcriptome RNA sequencing of liver tissue revealed the PI3K-Akt signaling pathway as a pivotal mechanism through which hUCMSC-Exos@pPB exerts its anti-fibrotic effects. Through rational surface engineering with pPB peptide ligands, we developed a novel exosomal nanoplatform that effectively evades clearance by the MPS and achieves targeted delivery to aHSCs. This strategy significantly enhanced the therapeutic efficacy of hUCMSC-Exos against hepatic fibrosis, therey providing a promising translational approach for the precision treatment of chronic liver diseases.

Background: Esophageal squamous cell carcinoma (ESCC) is a strongly metastatic and fatal cancer. Currently, the mechanisms underlying the pathogenesis of ESCC are poorly understood. Lysine-specific demethylase 6B (KDM6B) plays a key role in the occurrence and development of various human diseases, such as cancers, immune diseases and developmental diseases. Studies have confirmed that KDM6B may exhibit both tumour-suppressive and oncogenic activities in different cancer types. However, the expression and role of KDM6B in ESCC remain unclear. Methods: KDM6B expression was analysed using The Cancer Genome Atlas (TCGA) database, and the correlation between KDM6B mRNA expression and prognosis was analysed. The expression of KDM6B in Eca109 and TE11 ESCC cells and ESCC tissues was evaluated using immunohistochemical (IHC) and Quantitative Real-time PCR (RT‒qPCR) analyses. In vitro assays were further performed to reveal the functions and characterize the upstream and downstream regulation of KDM6B expression. Results: KDM6B was overexpressed in stage T3/T4 as well as N2/N3 ESCC tissues relative to stage T1/T2 and N1/N2 ESCC tissues, respectively, and this overexpression was linked to worse prognosis of ESCC. Inhibiting KDM6B expression significantly impaired the proliferation and metastasis of ESCC cells. Lactate dehydrogenase isoform A (LDHA) plays a critical role in tumour aerobic glycolysis. The expression of LDHA was inhibited in ESCC cells to assess its role in ESCC proliferation. In this study, KDM6B knockdown suppressed not only LDHA expression but also ESCC cell proliferation. Conclusions: Based on these results, we speculate that KDM6B might be a novel therapeutic target for ESCC.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-associated acute kidney injury (SA-AKI) is a common organ dysfunction of sepsis, and its incidence and mortality are increasing,which brings heavy economic burden to patients and society. Early diagnosis and effective intervention can block the occurrence and progression of SA-AKI effectively, improve prognosis, and reduce medical costs. Diagnosis on SA-AKI relies on urine volume and serum creatinine, which has the disadvantages of being easily disturbed and delaying. The identification of biomarkers in blood and urine can facilitate diagnosis and provide targeted therapy to enhance the management of SA-AKI. This article reviews the characteristics of a variety of SA-AKI biomarkers that have been found and validated, including pre-damage biomarkers, damage biomarkers and functional biomarkers, and explore the clinical value of newly discovered biomarkers related to the diagnosis and treatment of SA-AKI, such as blood uncoupling protein 2 (UCP2), Sestrin 2 protein and pannexin 1 (PANX1), to provide reference for the early diagnosis and effective treatment of SA-AKI.

Chronic graft-versus-host disease (cGVHD) is one of the leading causes of mortality following allogeneic hematopoietic stem cell transplantation (HSCT), with only 50 % of patients responding to conventional corticosteroids with or without calcineurin inhibitors. Monoclonal antibodies (mAbs), such as CD20 mAbs, are the first drugs to demonstrate greater efficacy than corticosteroids in first-line treatment of cGVHD. This review provides a comprehensive overview of recent developments in the clinical utilization of mAbs to prevent and treat cGVHD. We also describe the application of drugs with target sites that are identical to or linked to those of cGVHD in autoimmune diseases as potential future treatments for cGVHD. In summary, we collected known evidence concerning the clinical research progress on the use of mAbs in the prevention and treatment of cGVHD and identified drugs with the same target sites in autoimmune diseases for potential future applications in cGVHD, with the goal of providing suggestions and inspiration for optimizing cGVHD treatment strategies and research directions.

Despite the continuous developments and advancements in the treatment of gastric cancer (GC), which is one of the most prevalent types of cancer in China, the overall survival is still poor for most patients with advanced GC. In recent years, with the progress in tumor immunology research, attention has shifted toward immunotherapy as a therapeutic approach for GC. Programmed cell death protein 1 (PD-1) inhibitors, as novel immunosuppressive medications, have been widely utilized in the treatment of GC. However, many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy. To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy, to maximize the clinical activity of immunosuppressive drugs, and to elicit a lasting immune response, it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients. This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment, aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Monthly precipitation is a typical non-linear time series data. According to the poor fitting ability of the traditional ARIMA time series model to the nonlinear sequence, the nonlinear fitting characteristics of the LSTM model in the deep neural network are used to establish the nonlinear combined prediction model of ARIMA-LSTM monthly precipitation. Taking the 60-year precipitation observation data of an observatory for example, the ARIMA-LSTM combination model was applied to the monthly precipitation prediction. In order to test the feasibility of the model, the BP neural network model was introduced for comparative verification. The experimental results showed that the ARIMA-LSTM model has higher prediction accuracy than the ARIMA model and the BP model, which can provide reference and utilize for short-term climate prediction business.