To investigate the role of interferon-induced protein 6 (IFI6) in renal cell carcinoma (RCC) progression and the molecular mechanism in sunitinib resistance.

The differences of IFI6 expression between tumor and normal tissues were analyzed using TCGA data and clinical samples. The human RCC cells (786-O and ACHN) was transfected with either non-targeting siRNA control (scramble) or IFI6 siRNA (siIFI6). Cell proliferation, migration, and invasion were comparatively assessed between control and knockdown groups using CCK-8 and Transwell assays. Apoptosis-related proteins (caspase3、cleaved caspase3、Bcl2、BAX) were detected via Western blot. IFI6 expression was measured in sunitinib-resistant cells (786-O-SuR), and the changes in the half maximal inhibitory concentration (IC₅₀) of sunitinib were evaluated after IFI6 knockdown. Stable OSRC-2 cell lines with IFI6 knockdown (shIFI6) were established, and a subcutaneous tumor xenograft model in nude mice was performed with sunitinib treatment to evaluate its in vivo efficacy. The experiment was divided into four groups: scramble + DMSO, shIFI6 + DMSO, scramble + sunitinib, and shIFI6 + sunitinib. Independent samples t-test was used for comparisons between two groups, and paired samples t-test was used for paired comparisons. For comparisons among three or more groups, one-way ANOVA was employed. Dunnett's t-test was used for pairwise comparison between groups.

IFI6 was significantly upregulated in RCC tissues versus normal tissues (P < 0.05), with high expression correlating with poor prognosis (P < 0.05). IFI6 knockdown markedly suppressed the abilities of proliferation [786-O: (1.33 ± 0.11), (1.24 ± 0.11) vs (2.15 ± 0.15) ; ACHN: (2.03 ± 0.14), (1.59 ± 0.14) vs (3.05 ± 0.18) ; P < 0.05], migration [786-O: (169.67 ± 31.01), (140.67 ± 19.40) vs (371.67 ± 58.05) cells; ACHN: (245.67 ± 33.25), (177.33 ± 18.45) vs (558.00 ± 83.83) cells; P < 0.05], and invasion [786-O: (55.33 ± 9.07), (46.67 ± 7.77) vs (102.00 ± 8.54) cells; ACHN: (43.33 ± 12.66), (37.33 ± 11.93) vs (118.00 ± 12.49) cells; P < 0.05]. Knockdown of IFI6 led to an increased expression of cleaved caspase 3 and BAX, while the expression of total caspase 3 and Bcl2 was decreased. Compared with 786-O, the expression levels of IF16 mRNA and protein were elevated in 786-O-SuR (P < 0.05 for both). The IC₅₀ concentration of sunitinib in the siIFI6-1 and siIFI6-2 groups was significantly lower than that in the Scramble group in 786-O, ACHN and 786-O-SuR cells [ 786-O: (5.02 ± 0.15), (4.40 ± 0.47) vs (7.28 ± 0.28) μmol/L; ACHN: (4.56 ± 0.17), (4.20 ± 0.19) vs (6.68 ± 0.31) μmol/L; 786-O-SuR: (8.02 ± 0.45), (7.50 ± 0.49) vs (16.61 ± 1.16) μmol/L; P < 0.05 for all ]. In vivo tumor formation experiments in nude mice revealed that, the tumor mass and volume in the Scramble + Sunitinib group and shIFI6 + DMSO group were significantly smaller than those in the Scramble + DMSO group [mass: (318.36 ± 40.81), (308.54 ± 36.97) vs (532.76 ± 79.59) mg, volume: (362.68 ± 58.76) and (349.96 ± 59.38) vs (681.20 ± 150.85) mm³; P < 0.05 for all], and the tumor mass and volume in the shIFI6 + Sunitinib group were further reduced compared with the Scramble + Sunitinib group [mass: (109.28 ± 34.43) vs (318.36 ± 40.81) mg, volume: (112.04 ± 40.62) vs (362.68 ± 58.76) mm³; P < 0.05 for all ].

This study reveals that IFI6 promotes RCC progression and confers sunitinib resistance by suppressing apoptosis. Targeting IFI6 sensitizes RCC to therapeutic agents, demonstrating potential clinical significance.

To evaluate the safety and efficacy of umbilical cord blood microtransplantation (UCBM) in the treatment of newly diagnosed acute myeloid leukemia (AML) in the elderly.

Eighteen newly diagnosed elderly AML patients enrolled in Zhongnan Hospital of Wuhan University from January 2022 to June 2024 were randomly divided into two groups. Nine patients in the experimental group achieved remission after 2 courses of induction chemotherapy with azacitidine (AZA) + idarubicin/daunorubicin and cytarabine (IA/DA) or AZA + venetoclax regimens and then received 3 courses of AZA+Ara-C consolidation therapy and UCBM treatment. AZA was used in the maintenance treatment. Nine patients in the control group were not given UCBM treatment, and the other treatments were the same as those in the experimental group. The recovery of hematopoietic function, median survival time, 1- and 2-year overall survival rates, and 1- and 2-year leukemia-free survival rates of the two groups of patients were compared. The independent sample t-test was used for the continuous variables with normal distribution between the two groups, and the difference of non-normally distributed continuous variable between two groups were compared with Mann-Whitney U test. The comparison between groups of unordered categorical variables was conducted using the Fisher's exact probability method, and the Wilcoxon rank sum test was used for comparison between groups of ordered categorical variables.

Within one month after the first consolidation treatment, 7 people in the experimental group achieved hematopoietic recovery, while 3 people in the control group achieved hematopoietic recovery. The median survival time of the experimental group was 25.3 (18.3, 37.8) months, and that of the control group was 15.5 (7.6, 22.9) months (P = 0.022). The overall survival rates of the experimental group at 1 year and 2 years were 100%and 77.8%respectively, which were 33.3%and 55.6%greater than those of the control group. The 1-year and 2-year leukemia-free survival rates were 55.6%and 44.4% respectively, which were 22.3%and 33.3%higher than the control group. The STR-PCR detection in the experimental group was 0%within + 7 days to + 30 days after transplantation. Graft-versus-host disease (GVHD) did not occur in any of the experimental groups.

Based on traditional induction and consolidation chemotherapy, UCBM for the treatment of newly diagnosed AML is safe, and it is conducive to promoting bone marrow recovery, prolongating the median survival time, improving the overall survival rate and the leukemia-free survival rate at 1 year and 2 years.

To systematically explore potential therapeutic targets and molecular subtype characteristics of ulcerative colitis (UC) by integrating single-cell RNA sequencing (scRNA-seq) and microarray data, providing a molecular basis for disease subtyping and personalized treatment.

The scRNA-seq dataset GSE182270, including 3 UC samples and 3 normal samples, was obtained from the GEO database. After quality control, 12 cell subpopulations were identified and annotated. Key genes were screened based on differentially expressed genes (DEGs) from these subpopulations and an inflammation-related gene set. Subsequently, transcriptomic datasets GSE75214 and GSE87473, including 203 UC samples and 32 normal samples, were integrated. Batch effects were corrected using the sva package, and data were normalized using the limma package to construct a unified UC expression matrix. Molecular subtypes were identified via consensus clustering, with differences validated by principal component analysis (PCA). Immunohistochemistry (IHC) was employed to examine the expression of key genes in UC samples. Continuous variables were compared using paired t-tests, non-normally distributed variables were analyzed using Wilcoxon signed-rank tests, and differences among multiple groups were analyzed using one-way analysis of variance.

Seventeen key genes (CCL2, CCL20, CD14, CD48, CD69, CXCL10, F3, GPR183, IL-1β, IL7R, CXCL8, LCK, NAMPT, NFKBIA, PDPN, PLAUR, TIMP1) were significantly upregulated in UC samples (P < 0.05). PCA confirmed that consensus clustering based on these key genes effectively distinguished distinct UC molecular subtypes. Seventeen HLA family genes (including HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DQB1) and 37 immune checkpoint genes was significantly overexpression in subtype 4, while HHLA2 was highly expressed in subtype 3 (P < 0.05), indicating distinct immune microenvironment features across subtypes. Elevated expression of the proteins (IL-1β, TIMP-1, and HLA-F) encoded by three hub genes was observed in the UC group compared to controls by immunohistochemistry.

The integration of scRNA-seq and transcriptomic data reveals that differential expression of HLA family and immune checkpoint genes defines molecular subtypes of UC. Key genes such as IL-1β, TIMP1 and HLA-F play significant pathogenic and regulatory roles and represent potential molecular targets, offering new biological insights for the precise subtyping and personalized treatment of UC.

To evaluate the efficacy and safety of the cladribine, busulfan, and cytarabine (CBA) -based intensified conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) .

Clinical data of AML/MDS patients who underwent CBA-based allo-HSCT at the Department of Hematology, 940th Hospital of the Joint Logistics Support Force from January 2018 to May 2024 were retrospectively analyzed. Engraftment kinetics, incidence of graft-versus-host disease (GVHD), infections, relapse rates, overall survival (OS), and progression-free survival (PFS) were summarized. Survival rates were analyzed using the Kaplan-Meier method, while cumulative incidence of relapse and non-relapse mortality were evaluated by the Fine-Gray competing risk model. Differences between groups were compared using the Log-rank test.

Twenty-four patients were included, with a median age of 35 (range: 6 ~ 52) years including 15 AML cases (including 13 relapsed/refractory AML) and 9 MDS cases. All patients achieved successful neutrophil with median time to engraftment of 18 (13 ~ 22) days. 22 patients achieved successful platelet engraftment with median time to engraftment of 17 (9 ~ 30) days, and 2 patients of poor platelet engraftment function were relieved after treatment. The incidences of acute and chronic GVHD were 45.8 % and 16.7 %, respectively. All 24 patients achieved complete remission (CR) after transplantation, with the flow cytometry-confirmed MRD was negative. After a median follow-up of 44.5 (1.5 ~ 84) months, the estimated 3-year OS and PFS rates were 57.8% (95%CI: 35.7%~74.6%) and 48.9% (95%CI: 27.8% ~ 67.0%), respectively. The 3-year OS rates of AML and MDS patients were 52.5% (95%CI: 25.2%~ 73.9%) and 66.7% (95%CI: 28.2%~ 87.8%), while PFS rates were 45.0% (95%CI: 19.4%~ 67.8%) and 55.6% (95%CI: 20.4%~ 80.4%), showing no statistically significant difference. The 3-year cumulative relapse rate and non-relapse mortality were 21.6% (95%CI: 7.5% ~ 40.4%) and 29.4% (95%CI: 12.6%~ 48.4%), respectively.

For high-risk AML/MDS patients, receiving the CBA conditioning regimen demonstrates low relapse rates, prolonged overall survival, and favorable safety profiles post-allo-HSCT.

Cardiovascular disease (CVD) remains the leading cause of global mortality and disability, and its mechanisms and treatment research rely on effective disease models. However, the clinical translation of research findings has been limited by the inherent constraints of traditional two-dimensional cell cultures and animal models, which often fail to fully recapitulate human pathophysiology due to interspecies differences. In recent years, the convergence of induced pluripotent stem cell (iPSC) technology and organoid systems has established a transformative paradigm for cardiovascular research. By reprogramming patient-derived somatic cells into iPSC and leveraging three-dimentional bioprinting and microfluidic platforms, researchers have successfully engineered cardiac organoids and multi-organ chip systems that exhibit functional electrophysiology, contractility, and vascular networks. These advanced models not only faithfully replicate dynamic disease processes, such as myocardial injury and atherosclerosis, but also enable applications in drug cardiotoxicity assessment, disease modeling, mechanistic investigations and regenerative medicine. Nevertheless, critical challenges persist, including low organoid maturity, batch-to-batch heterogeneity, and the absence of neuro-immune crosstalk in current systems. Future research will focus on bioengineering innovations, constructing multi-disease microenvironments, and combinatorial approaches like CRISPR-Cas9 gene editing coupled with transplantation therapy to accelerate the translation of precision medicine and regenerative therapies for CVD.

Stem cell-derived exosomes, as a cell-free therapeutic approach, circumvent the risks associated with live cell transplantation and offer enhanced biological safety. Through engineering modifications, they can augment tissue targeting and therapeutic efficacy, making them a promising new treatment strategy that could potentially replace stem cells. In response to the clinical translation challenges, such as improving the yield, batch stability, therapeutic efficacy, and activity maintenance of stem cell-derived exosomes, this review proposes coping strategies including the use of 3D culture combined with immortalized cell lines, the development of engineered exosome empowerment systems, and innovative exosome preservation techniques aiming to further advance the clinical translation process of stem cell-derived exosomes in standardized production, therapeutic applications, and long-term storage.

Natural killer (NK) cells, a subset of innate lymphocytes, rapidly activate multiple signaling pathways without prior sensitization to directly eliminate virus-infected cells or tumor cells. Due to the limitations of T lymphocytes and the unique traits of NK cells, NK cell-based immunotherapies reveal multifaceted advantages over T cell-based ones to some extent. However, they still have certain limitations, such as NK cell silence in tumor microenvironment (TME), limited therapeutic effect, and high treatment costs. Nanomaterials are materials with a diameter ranging from 1 nm to 100 nm. By precisely manipulating the physical and chemical properties (e.g, shape, size, hydrophobicity, and surface modifications), nanomaterials can be engineered to achieve targeted delivery of therapeutic agents (e.g., drugs, cytokines, and RNAs). This capability enables precise manipulation of the microenvironment in target tissues or specific modulation of cellular behaviors, thereby enhancing the efficacy of immunotherapy strategies. The state-of-the-art progress in nanoparticles has supplied new applications for NK cell-based immunotherapies. Herein, we outline the immunotherapy of NK cells, nanotechnology that enhances immunotherapy, and recent advances in nanoparticles for facilitating the targeted therapy by NK cells.