Predictive model for CAR-T cell therapy success in patients with relapsed/refractory B-cell acute lymphoblastic leukaemia.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute B-cell lymphoblastic leukaemia (R/R B-ALL). However, a subset of patients does not benefit from CAR-T therapy. Our study aims to identify predictive indicators and establish a model to evaluate the feasibility of CAR-T therapy. Fifty-five R/R B-ALL patients and 22 healthy donors were enrolled. Peripheral blood lymphocyte subsets were analysed using flow cytometry. Sensitivity, specificity, accuracy, positive and negative predictive values and receiver operating characteristic (ROC) areas under the curve (AUC) were determined to evaluate the predictive values of the indicators. We identified B lymphocyte, regulatory T cell (Treg) and peripheral blood minimal residual leukaemia cells (B-MRD) as indicators for predicting the success of CAR-T cell preparation with AUC 0.936, 0.857 and 0.914. Furthermore, a model based on CD3+ T count, CD4+ T/CD8+ T ratio, Treg and extramedullary diseases (EMD) was used to predict the response to CAR-T therapy with AUC of 0.938. Notably, a model based on CD4+ T/CD8+ T ratio, B, Treg and EMD were used in predicting the success of CAR-T therapy with AUC 0.966 [0.908-1.000], with specificity (92.59%) and sensitivity (91.67%). In the validated group, the predictive model predicted the success of CAR-T therapy with specificity (90.91%) and sensitivity (100%). We have identified several predictive indicators for CAR-T cell therapy success and a model has demonstrated robust predictive capacity for the success of CAR-T therapy. These results show great potential for guiding informed clinical decisions in the field of CAR-T cell therapy.

Deciphering three predominant biopsy-proven phenotypes of IgG4-associated kidney disease: a retrospective study.

Background: IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. Methods: We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. Results: The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3 g/d, group B 4.0 g/d, group C 0.8 g/d, P < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45 g/l, group B 119.60 g/l, group C 87.94 g/l, P < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. Conclusions: This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.

The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

DNT cells mediate resistance to CAR-T cells therapy in a pediatric patient with relapsed and refractory B-ALL.

Chimeric antigen receptor T (CAR-T) cells therapy is a milestone achievement in the immunotherapy of relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). However, some patients treated with CAR-T cells do not achieve complete remission, the mechanisms of which have not been elucidated. In the present study, we report a 9-year-old pediatric patient with refractory B-ALL received a triple infusion of autologous CD19 CAR-T cells therapy after the second relapse. CAR-T cells expanded in the peripheral blood and bone marrow. However, the patient did not achieve complete remission, indicating a lack of response to CAR-T cells therapy. Analysis of etiological factors revealed that the number of CD4 and CD8 double-negative T (DNT) cells was significantly upregulated in the peripheral blood, bone marrow, and autologous CAR-T cells products. In conclusiont, these findings indicate that DNT cells mediated resistance to CAR-T cells therapy in this pediatric patient with R/R B-ALL.

NET-related gene signature for predicting AML prognosis.

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan-Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs-CFTR, ENO1, PARVB, DDIT4, MPO, LDLR-were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.

Plasticity changes in iron homeostasis in hibernating Daurian ground squirrels (Spermophilus dauricus) may counteract chronically inactive skeletal muscle atrophy.

Disuse-induced muscular atrophy is frequently accompanied by iron overload. Hibernating animals are a natural animal model for resistance to disuse muscle atrophy. In this paper, we explored changes in skeletal muscle iron content of Daurian ground squirrels (Spermophilus dauricus) during different periods of hibernation as well as the regulatory mechanisms involved. The results revealed that compared with the summer active group (SA), iron content in the soleus muscle (SOL) decreased (- 65%) in the torpor group (TOR), but returned to normal levels in the inter-bout arousal (IBA); splenic iron content increased in the TOR group (vs. SA, + 67%), decreased in the IBA group (vs. TOR, - 37%). Expression of serum hepcidin decreased in the TOR group (vs. SA, - 22%) and returned to normal levels in the IBA groups; serum ferritin increased in the TOR group (vs. SA, + 31%), then recovered in the IBA groups. Soleus muscle transferrin receptor 1 (TfR1) expression increased in the TOR group (vs. SA, + 83%), decreased in the IBA group (vs. TOR, - 30%); ferroportin 1 increased in the IBA group (vs. SA, + 55%); ferritin increased in the IBA group (vs. SA, + 42%). No significant differences in extensor digitorum longus in iron content or iron metabolism-related protein expression were observed among the groups. Significantly, all increased or decreased indicators in this study returned to normal levels after the post-hibernation group, showing remarkable plasticity. In summary, avoiding iron overload may be a potential mechanism for hibernating Daurian ground squirrels to avoid disuse induced muscular atrophy. In addition, the different skeletal muscle types exhibited unique strategies for regulating iron homeostasis.

The CDK4/6 Inhibitor Palbociclib Synergizes with ATRA to Induce Differentiation in AML.

Differentiation therapy based on ATRA almost cured acute promyelocytic leukemia (APL). However, it is disappointing that ATRA is not effective against other acute myeloid leukemia (AML) subtypes. Developing new and effective anti-AML therapies that promote leukemia differentiation is necessary. The CDK4/6-cyclin D pathway is a key initiator of the G1-S phase transition, which determines cell fate. Herein, we investigated whether the CDK4/6 inhibitor palbociclib would synergize with ATRA to promote leukemia differentiation in vitro and in vivo. Our findings revealed that CDK4/6-cyclin D pathway genes were aberrantly expressed in AML, and we observed that palbociclib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes indicative of myeloid differentiation. The combination of palbociclib and ATRA attenuated AML cell expansion in vivo. These enhanced differentiation effects may be associated with the regulation of transcription factors, including RARα, E2F1, and STAT1. Overall, our findings demonstrate that CDK4/6 inhibition sensitizes AML cells to ATRA and could guide the development of novel therapeutic strategies for patients with AML.

CD14-CD10-CD45+HLA-DR-SSC+ neutrophils may be granulocytic myeloid-derived suppressor cell-like cells and relate to disease progression in non-Hodgkin's lymphoma patients.

We explored the frequency of CD14-CD10-CD45+HLA-DR-SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10- and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10- or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10+ or CD10- neutrophils were examined. Few CD10- neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10- neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10- neutrophils were shorter than those with low CD10- neutrophils. CD10- neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10- neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.

Postreperfusion Renal Allograft Biopsy Predicts Outcome of Single-Kidney Transplantation: A 10-Year Observational Study in China.

Introduction: Biopsy findings often lead to the discard of many donor kidneys although their clinical value is not fully understood. We investigated the predictive value of postreperfusion biopsy on long-term allograft outcome after single-kidney transplantation. Methods: We retrospectively evaluated the significance of histologic findings, read by experienced renal pathologists, in 461 postreperfusion biopsy specimens collected from 2010 to 2017 after deceased donor renal transplant; and performed time-to-event analyses to determine the association between histology and hazard of death-censored graft failure. Recipients were followed-up with over a median time of 6.8 (range, 0.2-11.9) years. We assessed specimens using the Remuzzi score (scale of 0-12) and categorized them into low-score (≤3) and high-score (>3) groups. Kappa coefficients were calculated to assess agreement in procurement versus reperfusion biopsies. Results: High Remuzzi score kidneys came from older donors with a higher incidence of hypertension, higher final creatinine, death from cerebrovascular disease, expanded criteria donor, and a higher kidney donor risk index (KDRI) (all P < 0.001). In adjusted analyses, Remuzzi score was independently associated with death-censored graft failure (hazard ratio [HR] 1.389 for each 1 score rise in Remuzzi score, 95% confidence interval 1.181-1.633, P < 0.001). Overall histologic agreement (procurement biopsy versus reperfusion biopsy) was kappa = 0.137. Conclusion: Our findings suggest that postreperfusion biopsy is associated with long-time graft outcomes after transplant from a deceased donor. Agreement between procurement and reperfusion biopsy was found to be low. Prospective trials are necessary to optimize procurement biopsy practices.

Increased monocytic myeloid-derived suppressor cells in type 2 diabetes correlate with hyperglycemic and was a risk factor of infection and tumor occurrence.

To investigate the frequency of monocytic myeloid-derived suppressor cells (M-MDSCs) in type 2 diabetes mellitus (T2DM) patients and explore the potential associations between M-MDSCs, glycemic control, and the occurrence of infections and tumor. 102 healthy and 77 T2DM individuals were enrolled. We assessed the M-MDSCs frequency, levels of fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), and other relevant indicators. Each patient underwent a follow-up of at least 6 months after M-MDSCs detection. The M-MDSCs frequency was significantly higher in patients with poor glycemic control (PGC) compared to the healthy population (P < 0.001), whereas there was no significant difference between patients with good glycemic control and the healthy (P > 0.05). There was a positive correlation between the M-MDSCs frequency and FPG, HbA1c (R = 0.517 and 0.315, P < 0.001, respectively). T2DM patients with abnormally increased M-MDSCs have a higher incidence of infection and tumor (48.57% and 11.43% respectively). Our results shed new light on the pathogenesis of T2DM, help to understand why T2DM patients are susceptible to infection and tumor and providing novel insights for future prevention and treatment of T2DM.

SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection.

Serine/arginine repetitive matrix 2 (SRRM2) has been implicated in tumorigenesis, cancer development, and drug resistance through aberrant splicing; however, its correlation with multiple myeloma (MM) has not been reported. We investigated the potential of SRRM2 as a biomarker and immunotherapeutic target in MM by examining its expression in MM cells using flow cytometry. Our study included 95 patients with plasma cell disease, including 80 MM cases, and we detected SRRM2 expression on plasma cells and normal blood cells to analyze its relationship with clinical profiles. We found widespread positive expression of SRRM2 on plasma cells with little expression on normal blood cells, and its expression on abnormal plasma cells was higher than that on normal plasma cells. Comparative analysis with clinical data suggests that SRRM2 expression on plasma cells correlates with MM treatment response. MM patients with high SRRM2 expression had higher levels of serum ß2-mg and LDH, ISS staging, and plasma cell infiltration, as well as high-risk mSMART 3.0 stratification and cytogenetic abnormalities, particularly 1q21 amplification. In patients with previous MM, high SRRM2 expression on plasma cells was associated with higher plasma cell infiltration, high-risk mSMART 3.0 risk stratification, cytogenetic abnormalities, more relapses, and fewer autologous stem cell transplant treatments. In summary, SRRM2 may serve as a novel biomarker and immunotherapeutic target for MM. Its expression level on plasma cells can help in risk stratification of MM and monitoring of treatment response.

The roles and mechanisms of TGFB1 in acute myeloid leukemia chemoresistance.

Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) patients usually have very poor prognoses, and drug-resistance is one of the major limiting factors. In this study, we aimed to explore the functions of Transforming Growth Factor-ß1 (TGFB1) in AML drug-resistance. First, TGFB1 levels in serum and bone marrow are higher in R/R patients compared with newly diagnosed patients, this phenomenon could be due to different sources of secreted TGFB1 according to immunohistochemistry of marrow biopsies. Similarly, TGFB1 expression in AML drug-resistant cell lines is higher than that in their parental cell lines, and blocking the TGFB signaling pathway by specific inhibitors decreased resistance to chemotherapeutic agents. On the other hand, exogenous TGFB1 can also promote AML parental cells senescence and chemotherapy resistance. Next, we found SOX4 level is upregulated in drug-resistant cells, and parental cells treated with exogenous TGFB1 induced upregulation of SOX4 levels. Interference of SOX4 expression by siRNA diminished the TGFB1-induced sensitivity to chemotherapeutic agents. Finally, we conduct metabolomic analysis and find Alanine, aspartate and glutamate metabolism pathway, and Glycerophospholipid metabolism pathway are decreased after inhibiting TGFB signaling pathway or interfering SOX4 expression. This study concludes that TGFB1 level in R/R AML patients and drug-resistant strains is significantly increased. Blocking the TGFB signaling pathway can enhance the chemosensitivity of drug-resistant cells by suppressing SOX4 expression and metabolic reprogramming.

Metabolomic analysis of the serum and urine of rats exposed to diazinon, dimethoate, and cypermethrin alone or in combination.

BACKGROUND: Multiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin. METHODS: Male Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out. RESULTS: The results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys. CONCLUSION: In summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.

Integrated metabolomics and proteomics analysis to understand muscle atrophy resistance in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus experiences minor muscle atrophy, which is an attractive anti-disuse muscle atrophy model. Integrated metabolomics and proteomics analysis was performed on the hibernating S. dauricus during the pre-hibernation (PRE) stage, torpor (TOR) stage, interbout arousal (IBA) stage, and post-hibernation (POST) stage. Time course stage transition-based (TOR vs. PRE, IBA vs. TOR, POST vs. IBA) differential expression analysis was performed based on the R limma package. A total of 14 co-differential metabolites were detected. Among these, l-cystathionine, l-proline, ketoleucine, serine, and 1-Hydroxy-3,6,7-Trimethoxy-2, 8-Diprenylxanthone demonstrated the highest levels in the TOR stage; Beta-Nicotinamide adenine dinucleotide, Dihydrozeatin, Pannaric acid, and Propionylcarnitine demonstrated the highest levels in the IBA stage; Adrenosterone, PS (18:0/14,15-EpETE), S-Carboxymethylcysteine, TxB2, and 3-Phenoxybenzylalcohol demonstrated the highest levels in the POST stage. Kyoto Encyclopedia of Genes and Genomes pathways annotation analysis indicated that biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism were co-differential metabolism pathways during the different stages of hibernation. The stage-specific metabolism processes and integrated enzyme-centered metabolism networks in the different stages were also deciphered. Overall, our findings suggest that (1) the periodic change of proline, ketoleucine, and serine contributes to the hindlimb lean tissue preservation; and (2) key metabolites related to the biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism may be associated with muscle atrophy resistance. In conclusion, our co-differential metabolites, co-differential metabolism pathways, stage-specific metabolism pathways, and integrated enzyme-centered metabolism networks are informative for biologists to generate hypotheses for functional analyses to perturb disuse-induced muscle atrophy.

Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVE: VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004. METHODS: The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests. RESULTS: The maximum plasma concentration (Cmax) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to Cmax (Tmax) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of Cmax, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0-t), and AUC from zero to infinity (AUC0-∞) for VC004 between the two states were 67.18 (58.16-77.60), 103.59 (95.04-112.92) and 103.55 (95.63-112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study. CONCLUSIONS: The intake of high calorie food decreased the absorption rate and increased the Tmax of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT055528120.

Fatty Acid Metabolism-Related lncRNAs are Potential Biomarkers for Predicting Prognoses and Immune Responses in Patients with Skin Cutaneous Melanoma.

Introduction: Skin cutaneous melanoma is becoming more dangerous since it has a poor prognosis and is resistant to treatment. Previous research has shown that lncRNAs and fatty acid metabolism are essential for numerous biological activities. There are no studies on the relationship between fatty acid metabolism-Related lncRNAs and skin cutaneous melanoma. Methods and Results: In order to better understand the prognosis and survival of SKCM patients, we investigated the significance of lncRNAs related to fatty acid metabolism. In this work, we looked at the fatty acid metabolism genes and lncRNAs expression patterns. On the basis of lncRNAs associated with fatty acid metabolism, a nomogram and a prognosis prediction model were created. Based on the profile of lncRNAs associated with fatty acid metabolism, functional and pharmacological sensitivity investigations were also carried out. We also looked at the connection between immunotherapy and the immune response. The findings demonstrated that a risk score model based on 11 essential lncRNAs for fatty acid metabolism may discriminate between the clinical condition of SKCM and more accurately predict prognosis and survival. We conducted quantitative reverse transcription polymerase-chain reaction (RT-PCR) to verify the model. Conclusion: These important lncRNAs further showed a strong association with the tumor immune system, and these important lncRNAs also showed a connection between SKCM and chemotherapeutic treatment sensitivity. Our research strives to provide fresh viewpoints and innovative approaches to the treatment and administration of SKCM.

Immune characteristics and prognostic implications of mucosal-associated invariant T cells in acute myeloid leukemia.

Increasing evidence suggests that mucosal-associated invariant T cells (MAITs) play a crucial role in anti-tumor responses against various cancers. In this study, we investigated the immune characteristics of MAIT cells in patients with acute myeloid leukemia (AML). Using multi-parameter flow cytometry, we performed phenotypic and functional analysis of MAITs in peripheral blood or bone marrow samples collected from 131 patients with AML including 99 newly diagnosed, 18 remission, and 14 relapsed cases, as well as 69 healthy controls. We found that MAITs exhibit signs of aging and exhaustion, particularly in CD8+ MAITs subset, at newly diagnosis. MAITs exhibit an effector memory or terminally differentiated phenotype. Frequency and number of MAITs reflect AML cell genetic features, tumor burden, disease status, and treatment responsiveness. Moreover, MAITs exhibit a highly activated or even exhausted state, as indicated by upregulation of PD-1. Furthermore, impaired production of Th1-type cytokines and increased secretion of Th17-type cytokines, granzyme B, and perforin were observed in MAITs from AML patients. Additionally, MAITs shifted toward producing cytokines that promote tumor progression, such as IL-8. Lower frequency of MAITs was associated with poorer overall survival (OS), and multivariate analysis revealed that MAITs frequency < 2.12% was an independent prognostic factor affecting OS. Collectively, our findings suggest that MAITs may play a role in immune deficiency in AML, emphasizing their potential importance in AML pathogenesis and treatment. These discoveries provide a theoretical basis for the development of novel immunotherapeutic strategies in AML.

Clinical implications of aberrant PD-1 expression for acute leukemia prognosis.

BACKGROUND: Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are the most common types of leukemia in adults with an overall poor prognosis. PD-1 alone or combined with other immune checkpoint blockade is a promising research direction for the treatment of acute leukemia (AL) patients. However, clinical Implications of aberrant PD-1 expression in peripheral CD4+ and CD8+ T lymphocytes of AML and ALL patients in assessing the prognosis of diseases, remains inconclusive. METHODS: In the present study, we used flow cytometry to evaluate PD-1 expression on the surface of CD4+ and CD8+ T lymphocytes in the peripheral circulation of AML and ALL patients and its clinical significance. A total of 53 AML patients, 44 ALL patients and 28 healthy controls were enrolled in this study and peripheral blood specimens were detected by flow cytometry. RESULTS: Our results indicated that percentages of CD4+ PD1+ and CD8+ PD1+ T lymphocytes in newly diagnosed and non-remission groups were significantly higher than healthy control both in AML and ALL patients. The high level of CD4+ PD1+ and CD8+ PD1+ T lymphocytes were respectively poor prognostic indicators of AML patients and ALL patients but had no significant correlation with most common clinical risks. CONCLUSIONS: Our findings show that aberrant PD-1 expression correlates with the prognosis of AL patient and may thus serve as poor prognostic indicators. Immunotherapy using PD-1 inhibitors may be a promising strategy for AML and ALL patients with peripheral circulating CD4+ PD1+ and CD8+ PD1+ T lymphocytes positively expressed, respectively.

Intraoperative application of regional cerebral oxygen saturation monitoring for geriatric patients in China: a survey.

Background: Regional cerebral oxygen saturation (rSO2) monitoring is a real-time and non-invasive technique for estimating the balance of regional cerebral oxygen supply and consumption. Despite the growing popularity of this monitoring technique, data regarding outcome benefits remain sparse and contradictory. This study was conducted to explore the popularity and understanding of cerebral oxygen saturation monitoring during anesthesia in geriatric patients. Methods: An online self-report questionnaire was distributed in March 2021 to various hospitals in China for dissemination to anesthesiologists. Questions surveyed cerebral oximetry equipment and utilization, demographics, and clinical practice of participants. Results: In total, 447 anesthesiologists responded. Of these, 301 (67.3%) respondents reported that their hospitals were equipped with cerebral oximetry, which 274 anesthesiologists use during anesthesia. A high percentage of anesthesiologists chose to monitor rSO2 during cardiac surgery (77.4%, n = 212) and neurosurgery (40.5%, n = 111). Most anesthesiologists agreed that a 30% reduction from the rSO2 baseline requires intervention to avoid cerebral ischemia, mainly via elevating arterial pressure and fraction of inspired oxygen (FiO2). Of those without cerebral oximetry, 138 of 146 (94.5%) anesthesiologists were willing to monitor rSO2. In addition, 291 respondents believed that cerebral oxygen monitoring would help prevent postoperative cognitive dysfunction. Conclusion: Our survey indicated that the prevalence of cerebral oximetry remains relatively low, while almost all anesthesiologists expressed their willingness to use rSO2 monitoring in geriatric anesthesia. Heterogeneity in clinical practice was identified, indicating relevant knowledge gaps that should encourage further clinical research to optimize treatment.