Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

Infections associated with CAR-T cell therapy in patients with relapsed refractory multiple myeloma: Risks and prevention strategies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety. METHODS: This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome. RESULTS: The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome. CONCLUSION: To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment.

Physical Activity Levels and Factors Affecting Them in Hospitalized Children With Leukemia.

BACKGROUND: Physical activity promotes healthy physical and mental development in children with leukemia. However, the level of physical activity in hospitalized children with leukemia and the factors that influence it are unknown. OBJECTIVES: The aims of this study were to understand the physical activity level of hospitalized children with leukemia and to explore the factors influencing it to provide a reference for physical activity assessment and intervention in such children. METHODS: A total of 133 hospitalized children with leukemia completed a general information questionnaire, the Chinese University of Hong Kong Physical Activity Rating for Children and Youth, and the Children's Social Anxiety Scale. A cross-sectional study was used to explore the effects of different variables on the children's activity levels. RESULTS: Among the study participants, 44.4% had a low-intensity activity level, 35.3% had a moderate-intensity activity level, and 20.3% had a high-intensity activity level, with a total physical activity rating of 3 (1, 6). Chemotherapy phase (P = .007), screen time (P = .001), and social anxiety (P = .012) were identified as influential factors. CONCLUSIONS: Our results showed that children with hospitalized leukemia had lower-intensity physical activity levels, especially in the chemotherapy phase of induction remission. Furthermore, screen time and social anxiety had negative effects on the children's activity levels. IMPLICATIONS FOR PRACTICE: According to the physical activity level of the children and the influencing factors, healthcare professionals should gradually improve children's mobility and promote their physical and mental health development through guidance and encouragement, and the development of personalized activity intervention programs.

A Smart Pesticide-Controlled Release Platform with Dual Stimuli-Responsive Functions for Enhanced Treatment of Plant Black Shank.

Realizing controllable input of botanical pesticides is conducive to improving pesticide utilization, reducing pesticide residues, and avoiding environmental pollution but is extremely challenging. Herein, we constructed a smart pesticide-controlled release platform (namely, SCRP) for enhanced treatment of tobacco black shank based on encapsulating honokiol (HON) with mesoporous hollow structured silica nanospheres covered with pectin and chitosan oligosaccharide (COS). The SCRP has a loading capacity of 12.64% for HON and could effectively protect HON from photolysis. Owing to the pH- and pectinase-sensitive property of the pectin, the SCRP could smartly release HON in response to a low pH or a rich pectinase environment in the black shank-affected area. Consequently, the SCRP effectively inhibits the infection of P. nicotianae on tobacco with a controlled rate for tobacco black shank of up to 87.50%, which is mainly due to the SCRP's capability in accumulating ROS, changing cell membrane permeability, and affecting energy metabolism. In addition, SCRP is biocompatible, and the COS layer enables SCRP to show a significant growth-promoting effect on tobacco. These results indicate that the development of a stimuli-responsive controlled pesticide release system for plant disease control is of great potential and value for practical agriculture production.

Pinobanksin from peony seed husk: A flavonoid with the potential to inhibit the proliferation of SH-SY5Y.

Pinobanksin, as one of the flavonoids, has powerful biological activities but has been under-recognized. In this study, we optimized the extraction method of phragmites from peony seed shells by using organic solvent extraction. The yield of PSMS was 10.54 ± 0.13% under the conditions of ethanol volume fraction 70%, extraction temperature 70°C, material-liquid ratio 1:25 g/mL, and extraction time 60 min; the optimized PSMS could be effectively separated in S-8 macroporous resin coupled with C18. The relative content of PSMS was increased from 0.42% in PSMS to 92.53% after C18 purification; the antioxidant activity test revealed that pinobanksin could exert antioxidant ability by binding catalase (CAT) enzyme. Second, it was found that pinobanksin could effectively inhibit the proliferation of SH-SY5Y cells, mainly by binding to BCL2-associated X (BAX), B-cell lymphoma-2 (BCL-2), and cyclin-dependent Kinase 4/6 (CDK4/6) to produce more hydrogen bonds to inhibit their activities. This study confirms the medicinal potential of pinobanksin and provides the basis for the proper understanding of pinobanksin and the development of related products.

Improving the safety of CAR-T-cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B-cell lymphoma undergoing CAR-T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy, an innovative immunotherapeutic against relapsed/refractory B-cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR-T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post-pandemic era, marked by the Omicron variant, new and severe threats to CAR-T therapy emerge, necessitating exploration of preventive and treatment measures for COVID-19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR-T product safety and recipient survival.

Synthesis and biological activity assay of novel camptothecin-peptidic conjugates based on PEPT1.

Camptothecin (CPT) and its derivatives are potent candidates for cancer treatment. However, the clinical applications are largely restricted by non-selectivity and severe toxicities. The peptide transporter 1 (PEPT1), which is highly expressed in human intestines, has been found to be overexpressed in several cancer cells. This discovery suggests that PEPT1 has the potential to serve as a therapeutic target for both improving bioavailability and cancer-targeting treatment. Therefore, a prodrug approach for CPT targeting at PEPT1 highly expressed cancer cells was adopted in the present study. Eighteen CPT prodrugs, its peptidic conjugates, were synthesized and the structures were confirmed by NMR and HRMS. The protein expression profiles of PEPT1 in different cell lines were performed using immunofluorescence assay and western blotting analysis. The cytotoxicity of CPT prodrugs and their uptake via competition with Gly-Sar, a typical substrate of PEPT1, were evaluated in both PEPT1-overexpressed and under expressed cells. The results demonstrated that most CPT prodrugs significantly impaired Gly-Sar uptake, suggesting a higher affinity of CPT-peptidic conjugates for PEPT1 and PEPT1 overexpression cells. In addition, these prodrugs demonstrated a higher capability for inhibiting cell growth in PEPT1 highly-expressed cancer cells compared to PEPT1 under expressed cells. These results indicated that this peptidic prodrug strategy might offer great potential for improved tumor selectivity and chemotherapeutic efficacy of CPT.

Co-application of chitooligosaccharides and arbuscular mycorrhiza fungi reduced greenhouse gas fluxes in saline soil by improving the rhizosphere microecology of soybean.

Soil salinization can affect the ecological environment of soil and alter greenhouse gas (GHG) emissions. Chitooligosaccharides and Arbuscular mycorrhizal fungi (AMF) reduced the GHG fluxes of salinized soil, and this reduction was attributed to an alteration in the rhizosphere microecology, including changes in the activities of ß-glucosidase, acid phosphatase, N-acetyl-ß-D-glucosidase, and Leucine aminopeptidase. Additionally, certain bacteria species such as paracoccus, ensifer, microvirga, and paracyclodium were highly correlated with GHG emissions. Another interesting finding is that foliar spraying of chitooligosaccharides could transport to the soybean root system, and improve soybean tolerance to salt stress. This is achieved by enhancing the activities of antioxidant enzymes, and the changes in amino acid metabolism, lipid metabolism, and membrane transport. Importantly, the Co-application of chitooligosaccharides and Arbuscular mycorrhiza fungi was found to have a greater effect compared to their application alone.

The Characteristics and Treatment Outcomes of 71 Duodenal Brunner's Gland Adenomas with Endoscopic Submucosal Dissection.

INTRODUCTION: The aim of this study was to investigate outcomes of patients with duodenal Brunner's gland adenomas (BGAs) that were treated endoscopically. METHODS: We identified 71 consecutive patients treated at our center with endoscopic submucosal dissection (ESD) for their duodenal tumors diagnosed pathologically as BGAs over the period between January 1, 2011 and December 31, 2021. We retrospectively analyzed our experience and short- and long-term outcomes of ESD therapy on patients with BGAs. RESULTS: Among 71 BGA patients with an average age of 57 ± 11.7 years (range: 30-82), 48 (67.6%) were male and 23 (32.4%) were female. The accuracy of preoperative diagnosis with endoscopic ultrasonography was 44.0% (22/50). The H. pylori infection was found in 29 patients (29/71, 40.8%). The median size of BGAs was 1.5 cm (interquartile range [IQR] 0.8-2.7 cm). The most common location was the duodenum bulb (50/71, 64.8%). For the ESD procedure, the median operation time was 15.0 min (IQR 9.5-25.5 min). The en bloc and the complete resection rates were 97.2% and 92.3%, respectively. ESD-related mild acute obstructive pancreatitis was present in 2 patients (2/4, 50%) with BGAs located in the ampulla region. During the follow-up period, 1 patient with a positive peripheral margin experienced tumor recurrence 2 years after the initial ESD. There was no disease-related death for the cohort. CONCLUSION: ESD was an effective and safe therapeutic option for BGA patients with excellent outcomes. Long-term follow-up is needed.

Microstructure evolution of medium carbon steel during heat-assisted 3D ultrasonic vibration-assisted turning.

Medium carbon steel is an excellent carbon structural steel, and is one of the most common materials for metal cutting. Little research has been done on the microstructural changes induced by thermal-force coupling. In this paper, a finite element simulation method based on the improved J-C model is used to predict the grain size, microstructure change depth and surface hardness of medium carbon steel surface induced by heat-assisted 3D-UVAT are studied. The numerical simulation results are compared with the experimental results, and the significant influence of turning conditions on them is analyzed. The results show that heat-assisted 3D-UVAT lowered the grain size of machined induced deformation zone. Numerical model foresees this case with a mean error of 9.4%. Microstructure and hardness measurements under different turning conditions show that the turning speed and feed rate contribute significantly to grain size and grain refinement layer depth in the area being machined.

Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era.

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

CD26 CAR-T cells have attenuated mitochondrial and glycolytic metabolic profiling.

BACKGROUND: Multiple targets of chimeric antigen receptor T cells (CAR-T cells) are shared expressed by tumor cells and T cells, these self-antigens may stimulate CAR-T cells continuously during the expansion. Persistent exposure to antigens is considered to cause metabolic reprogramming of T cells and the metabolic profiling is critical in determining the cell fate and effector function of CAR-T cells. However, whether the stimulation of self-antigens during CAR-T cell generation could remodel the metabolic profiling is unclear. In this study, we aim to investigate the metabolic characteristics of CD26 CAR-T cells, which expressed CD26 antigens themselves. METHODS: The mitochondrial biogenesis of CD26 and CD19 CAR-T cells during expansion was evaluated by the mitochondrial content, mitochondrial DNA copy numbers and genes involved in mitochondrial regulation. The metabolic profiling was investigated by the ATP production, mitochondrial quality and the expression of metabolism-related genes. Furthermore, we assessed the phenotypes of CAR-T cells through memory-related markers. RESULTS: We reported that CD26 CAR-T cells had elevated mitochondrial biogenesis, ATP production and oxidative phosphorylation at early expansion stage. However, the mitochondrial biogenesis, mitochondrial quality, oxidative phosphorylation and glycolytic activity were all weakened at later expansion stage. On the contrary, CD19 CAR-T cells did not exhibit such characteristics. CONCLUSION: CD26 CAR-T cells showed distinctive metabolic profiling during expansion that was extremely unfavorable to cell persistence and function. These findings may provide new insights for the optimization of CD26 CAR-T cells in terms of metabolism.

Demethylating therapy increases cytotoxicity of CD44v6 CAR-T cells against acute myeloid leukemia.

Background: CD44v6 chimeric antigen receptor T (CD44v6 CAR-T) cells demonstrate strong anti-tumor ability and safety in acute myeloid leukemia (AML). However, the expression of CD44v6 on T cells leads to transient fratricide and exhaustion of CD44v6 CAR-T cells, which affect the application of CD44v6 CAR-T. The exhaustion and function of T cells and CD44v6 expression of AML cells are associated with DNA methylation. Hypomethylating agents (HAMs) decitabine (Dec) and azacitidine (Aza) have been widely used to treat AML. Therefore, there may be synergy between CD44v6 CAR-T cells and HAMs in the treatment of AML. Methods: CD44v6 CAR-T cells pretreated with Dec or Aza were co-cultured with CD44v6+ AML cells. Dec or aza pretreated AML cells were co-cultured with CD44v6 CAR-T cells. The cytotoxicity, exhaustion, differentiation and transduction efficiency of CAR-T cells, and CD44v6 expression and apoptosis in AML cells were detected by flow cytometry. The subcutaneous tumor models were used to evaluate the anti-tumor effect of CD44v6 CAR-T cells combined with Dec in vivo. The effects of Dec or Aza on gene expression profile of CD44v6 CAR-T cells were analyzed by RNA-seq. Results: Our results revealed that Dec and Aza improved the function of CD44v6 CAR-T cells through increasing the absolute output of CAR+ cells and persistence, promoting activation and memory phenotype of CD44v6 CAR-T cells, and Dec had a more pronounced effect. Dec and Aza promoted the apoptosis of AML cells, particularly with DNA methyltransferase 3A (DNMT3A) mutation. Dec and Aza also enhanced the CD44v6 CAR-T response to AML by upregulating CD44v6 expression of AML cells regardless of FMS-like tyrosine kinase 3 (FLT3) or DNMT3A mutations. The combination of Dec or Aza pretreated CD44v6 CAR-T with pretreated AML cells demonstrated the most potent anti-tumor ability against AML. Conclusion: Dec or Aza in combination with CD44v6 CAR-T cells is a promising combination therapy for AML patients.

Effects of using WeChat/WhatsApp on physical and psychosocial health outcomes among oncology patients: A systematic review.

The purpose of this systematic review is to summarize the potential effects of the WeChat and WhatsApp mobile applications in cancer management. This systematic review was written in accordance with PRISMA guidelines. CINAHL, PubMed, ProQuest Nursing and Allied Health Database, PsycINFO, PsycARTICLES, and ERIC were utilized for the literature search. Articles were included if they evaluated the outcomes of using WeChat/WhatsApp for cancer management, and excluded if they were qualitative studies, not published in peer-reviewed journals, protocols for a future study, or conference abstracts. 20 studies were included in this systematic review, with a total sample of 3110 participants. Interventions were utilized to share educational information with participants, follow-up after surgical operations, and in clinical communication. Outcomes, including pain, medication adherence, self-efficacy, quality of life, and depression, were statistically significantly improved in the WeChat/WhatsApp intervention groups in comparison to the control groups or to baseline measurements of the study participants. Outcomes of sleep and rehospitalization rate were improved without reaching statistical significance. Outcomes of anxiety, fatigue, and adverse drug reactions were found to be conflictive among included studies. This systematic review suggested that use of WeChat/WhatsApp on cancer management might improve various physical and psychosocial health outcomes among oncological patients. Limitations of the study include solely reviewing English language articles published in academic journals and most of the studies being from one country. Future research should be conducted in various countries among diverse communities, including rural areas, to ascertain the effects of WeChat/WhatsApp in different populations.

Fastigial nuclei surgical damage and focal midbrain disruption implicate PAG survival circuits in cerebellar mutism syndrome.

BACKGROUND: Pediatric postoperative cerebellar mutism syndrome (CMS) is a rare but well-known complication of medulloblastoma (Mb) resection with devastating effects on expressive language, mobility, cognition, and emotional regulation that diminishes quality of life for many Mb survivors. The specific anatomical and neuronal basis of CMS remains obscure. We address this issue by identifying patterns of surgical damage and secondary axonal degeneration in Mb survivors with CMS. METHODS: Children with Mb deemed high risk for CMS based on intraventricular location of the tumor had T1 images analyzed for location(s) of surgical damage using a specially developed algorithm. We used three complementary methods of spatial analysis to identify surgical damage linked to CMS diagnosis. Magnetization transfer ratio (MTR) images were analyzed for evidence of demyelination in anatomic regions downstream of the cerebellum, indicating neuronal dysfunction. RESULTS: Spatial analyses highlighted damage to the fastigial nuclei and their associated cerebellar cortices as the strongest predictors of CMS. CMS-related MTR decrease was greatest in the ventral periaqueductal gray (PAG) area and highly consistent in the left red nucleus. CONCLUSION: Our evidence points to disruption of output from the fastigial nuclei as a likely causal trigger for CMS. We propose that core CMS symptoms result from a disruption in the triggering of survival behaviors regulated by the PAG, including the gating of vocalization and volitional movement. The fastigial nuclei provide the densest output to the PAG from the cerebellum, thus sparing these structures may provide a greater likelihood of CMS prevention.

Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China.

Background: To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. Objective: To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. Methods: We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. Results: A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. Conclusion: The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown; the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway.

Although tyrosine kinase inhibitors (TKIs) improve the prognosis of chronic myeloid leukemia (CML) patients, resistance to TKIs and residual leukemia stem cells (LSCs) inevitably become the bottleneck of cure. Therefore, we need to explore novel treatment strategies based on conventional treatment strategies. Our previous study found that CML cell senescence may be one of the main factors to achieve clinical cure of CML. Studies have shown that lipid metabolism plays a key role in cellular senescence. Here, we found that long-chain acyl-CoA synthetase 1 (ACSL1) was significantly up-regulated in senescent CML cells. Furthermore, we demonstrated that overexpression of ACSL1 induces senescence and inhibits cell growth in K562 cells by altering cell cycle progression, and enhances the proliferation-inhibiting effect of imatinib. Overexpression of ACSL1 enhances imatinib-induced tumorigenic decline in K562 cells in vivo. Knockdown of ACSL1 reverses imatinib-induced senescence in K562 cells. Mechanistically, overexpression of ACSL1 induced senescence in K562 cells via the SIRT1/p53/p21 axis. Collectively, our study showed that ACSL1 promotes imatinib-induced K562 cells senescence and tumor growth by regulating SIRT1/p53/p21 pathway. The ACSL1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in CML and a new potential target for eradication of CML LSCs.

CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy for acute myeloid leukaemia (AML) has thus far been elusive, in part due to target restriction and phenotypic heterogeneity of AML cells. Mutations of the FMS-like tyrosine kinase 3 (FLT3) and DNA methyltransferase 3A (DNMT3A) genes are common driver mutations that present with a poor prognosis in AML patients. We found that AML patients with FLT3 or DNMT3A mutations had higher expression of CD44 isoform 6 (CD44v6) compared to normal specimens. Therefore, we intended to demonstrate CD44v6 could be a specific option for AML with FLT3 or DNMT3A mutations. METHODS: Internal tandem duplication (ITD) mutations of FLT3 (FLT3/ITD) knock-in clone and DNMT3A-R882H mutant clones of SKM-1 cells were generated using CRISPR/Cas9 and lentiviral transfection, respectively. CD44v6 CAR-T cells were constructed by transfecting T cells with lentivirus containing CD44v6 CAR. CD44v6 expression in AML cell lines, AML patients and healthy donors was evaluated by flow cytometry. DNA methylation assays were used to analyse the mechanisms of FLT3 and DNMT3A mutations affecting CD44v6 expression. RESULTS: Aberrant overexpression of CD44v6 was observed in AML cell lines with FLT3 or DNMT3A mutations compared to the wild-type SKM-1 or K562 cells. AML patients with FLT3 or DNMT3A mutations had higher expression of CD44v6 compared to normal specimens. Then we constructed CD44v6 CAR-T cells and found that CD44v6 CAR-T specifically lysed CD44v6+ cells, accompanied by cytokines release. No significant killing effect was observed from CD44v6- AML cells and normal cells after co-culture with CD44v6 CAR-T. These results were also observed in vivo. Furthermore, we found that FLT3 or DNMT3A mutations induced CD44v6 overexpression by downregulating the CpG methylation of CD44 promoter. CONCLUSIONS: Collectively, CD44v6 is a promising target of CAR-T for AML patients with FLT3 or DNMT3A mutations.

Risk factors for the in-hospital mortality of CRRT-therapy patients with cardiac surgery-associated AKI: a single-center clinical study in China.

OBJECTIVE: We retrospectively analyzed risk factors on in-hospital mortality in CRRT-therapy patients with open cardiac surgery (CS)-induced acute kidney injury (AKI), to provide the clinical basis for predicting and lowering the in-hospital mortality after CS. METHODS: 84 CS-AKI patients with CRRT were divided into survival and death groups according to discharge status, and the perioperative data were analyzed with R version 4.0.2. RESULTS: There were significant differences between the two groups, including: urea nitrogen, Sequential Organ Failure Assessment (SOFA) score and vasoactive-inotropic score (VIS) on the first day after operation; VIS just before CRRT; SOFA score and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, severe infection and MODS after operation; and the interval between AKI and CRRT. Univariate logistic regression analysis showed that SOFA score and VIS on the first day after operation; VIS just before CRRT; VIS and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, infection and multiple organ dysfunction syndrome (MODS) after operation; bootstrap resampling analysis showed that SOFA score and VIS 24 h after CRRT, as well as the incidence of bleeding after operation were the independent risk factors. CONCLUSION: Maintaining stable hemodynamics and active prevention of bleeding are expected to decrease the in-hospital mortality.