Addressing psychosomatic symptom distress with mindfulness-based cognitive therapy in somatic symptom disorder: mediating effects of self-compassion and alexithymia.

Objective: This study explored the association between self-compassion, alexithymia, and psychosomatic symptom distress in a clinical sample of somatic symptom disorder (SSD) patients participating in a mindfulness-based cognitive therapy (MBCT) program. Methods: One hundred sixteen SSD patients who had participated in an MBCT program and completed ≥4 intervention sessions were included in a retrospective study (76.7% women, mean age = 40.0, SD = 9.5). Psychometric measures of psychosomatic symptom distress [Brief Symptom Inventory-18 Global Severity Index (BSI-GSI)], self-compassion [Self-Compassion Scale (SCS)], and alexithymia [Toronto Alexithymia Scale (TAS)] were collected upon admission to the MBCT program and at 6-month follow-up following treatment inclusion. Results: Serial mediation analysis (MBCT→ΔSCS→ΔTAS→ΔBSI-GSI) suggested that changes in both self-compassion and alexithymia had significant indirect effects on improvement in psychosomatic distress [ΔSCS ß = -1.810, 95% bootstrap CI (-2.488, -1.160); ΔTAS ß = -1.615, bootstrap 95% CI (-2.413, -0.896); ΔSCS→ΔTAS ß = -0.621, bootstrap CI (-1.032, -0.315)]. Furthermore, a post-hoc analysis with a reverse sequence (MBCT→ΔTAS→ΔSCS→ΔBSI-GSI) revealed that reduction in alexithymia improved psychosomatic distress and that an increase in self-compassion was a subsequent outcome of alleviation of alexithymia [ΔTAS ß = -2.235, bootstrap 95% CI (-3.305, -1.270); ΔSCS ß = 0.013, 95% bootstrap CI (-0.600, 0.682); ΔTAS→ΔSCS ß = -1.823, bootstrap CI (-2.770, -1.047)]. Conclusion: Both alleviation of alexithymia and improvement in self-compassion play a mediating role in the reduction of psychosomatic distress in SSD patients following an MBCT program. Improvement in self-compassion might be a subsequent outcome of MBCT-related alleviation of alexithymia.

Exploring prognostic markers for patients with acute myeloid leukemia based on cuproptosis related genes.

Background: Acute myeloid leukemia (AML), a common form of acute leukemia, is due to tumor changes and clonal proliferation caused by genetic variants. Cuproptosis is a novel form of regulated cell death. This study aimed to explore the role of cuproptosis-related genes (CRGs) in AML. Methods: Initially, differentially expressed genes (DEGs) between AML samples and normal samples were obtained by differential analysis, which were further intersected with the cuproptosis score-related genes (CSRGs) acquired by weighted gene co-expression network analysis (WGCNA) to obtain cuproptosis score-related differentially expressed genes (CS-DEGs). Then, a risk model was constructed by Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, immune infiltration analysis was performed and the functions and pathways of model genes were explored by single sample gene set enrichment analysis (ssGSEA). Results: Thirty-two CS-DEGs were obtained by overlapping 11,160 DEGs and 132 CSRGs. These 32 CS-DEGs were mainly enriched to cytoplasmic microtubule organization, RNA methylation, mTOR signaling pathway, and notch signaling pathway. Two model genes, PACS2 and NDUFV1, were finally screened for the construction of the risk model. In addition, PACS2 and NDUFV1 were significantly positively correlated with activated B cells, CD56dim natural killer (NK) cells, and negatively correlated with effector memory CD4 T cells and activated CD4 T cells. PACS2 gene was significantly enriched to inositol phosphate metabolism, histone modification, etc. NDUFV1 was mainly enriched to ncRNA metabolic process, 2-oxocarboxylic acid metabolism, and other pathways. Conclusions: A cuproptosis-related risk model consisting of PACS2 and NDUFV1 was built, which provided a new direction for the diagnosis and treatment of AML.

[Clinical Characteristics and Prognostic Influencing Factors of Adult AML Patients with MLL Rearrangement].

OBJECTIVE: To investigate the clinical characteristics and prognostic influencing factors of adult AML patients with MLL rearrangement. METHODS: Clinical data of 184 adult AML patients with MLL rearrangement treated in our hospital from January 2011 to December 2017 were analyzed retrospectively. The clinical features, immunophenotypic characteristics, cytogenetic characteristics, molecular biological characteristics and gene mutation characteristics were recorded, the survival and prognostic influencing factors of patients were analyzed. RESULTS: Among 184 patients, 94 cases were male, 90 cases were female, median age were 36.0 years, median WBC count were 22.0×109/L, 156 cases as 84.78% for FAB typing M5, and 18 cases as 28.13% for MLL/AF9 gene positive. The median total survival time and recurrence-free survival time of 184 patients were 15.7 months and 13.3 months respectively. The cumulative total survival rate and recurrence-free survival rate by followed-up for 2 years were 36.72% and 29.33% respectively. The cumulative overall survival rate and recurrence-free survival rate of transplant recipients were significantly higher than those of non-transplant recipients by follow-up for 2 years (P＜0.05). Univariate analysis showed that age, baseline WBC count, baseline Hb levels, complete remission after one course of treatment and transplantation or no were the influencing factors of overall survival time in adult AML patients with MLL rearrangement (P＜0.05). Cox regression model multivariate analysis showed that baseline WBC count, complete remission after one course of treatment, and transplantation or no were the independent influencing factors for overall survival time in adult AML patients with MLL rearrangement（P＜0.05）. CONCLUSION: Adult AML patients with MLL rearrangement are mostly belong to acute monocytic leukemia, and MLL/AF9 is the most common associated gene. Patients with AML and MLL rearrangement are prone to recurrence after routine chemotherapy. Allo-HSCT treatment is helpful to improve clinical prognosis of patients.

Coagulopathy in cytogenetically and molecularly distinct acute leukemias at diagnosis: Comprehensive study.

We analyzed the characteristics of coagulopathy in cytogenetically and molecularly distinct acute leukemias. We retrospectively analyzed 211 adult patients with de novo non-acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), and 105 newly diagnosed patients with B-cell acute lymphoblastic leukemia (B-ALL). Disseminated intravascular coagulation (DIC) occurrence was assessed according the International Society of Thrombosis and Haemostasis (ISTH) criteria. Further, we analyzed the associations of the cytogenetics and mutations with DIC development and coagulation profile. Significant differences were observed between APL and non-APL AML (P = 0.001), APL and B-ALL (P = 0.002), and non-APL AML and B-ALL (P = 0.009) in the distribution of ISTH DIC scores of the acute leukemia patients that met the criteria for diagnosis of DIC. Except for the elevated leukocyte count, a normal karyotype with NPM1 mutations or/and FLT3-ITD mutations was independently associated with the development of DIC in non-APL AML, characterized by significant PT prolongation and significantly elevated D-Dimers. The P210BCR-ABL1 transcript strongly predicted hypofibrinogenemia in B-ALL in the final multivariate model, but Philadelphia chromosome negatively affected elevated D-dimers. In conclusion, DIC occurrence and the coagulation profile were associated with the cytogenetics and mutations in acute leukemia.

Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.

Acute pro-B-Cell lymphoblastic leukemia transformed from myelodysplastic syndrome with an ASXL1 missense mutation: A case report with literature review.

The development of acute lymphoblastic leukemia (ALL) from myelodysplastic syndrome (MDS) is a very rare event. The current report presents a rare case of a 33-year-old man who was diagnosed with MDS with multiple-lineage dysplasia (MDS-MLD) that transformed into pro-B-ALL. A missense mutation (S1231F) of the additional sex combs like 1, transcriptional regulator gene was identified, which may have a substantial role in the progression, however does not act as an unfavorable prognostic marker. The patient died during induction chemotherapy. The present study further conducted an analysis on 30 patients to determine progression to ALL. Patients were predominantly male (76.7%, 23/30) with a median age of 56 years (3-90 years). The median time to transformation was 5.5 months (2-50 months). The most common type of MDS with ALL transformation comprised of MDS-excess blasts (MDS-EB; 40%, 12/30), MDS with single-lineage dysplasia (MDS-SLD; 30%, 9/30) and MDS with ring sideroblasts (MDS-RS; 16.7%, 5/30). The majority of the patients transformed to B-cell (66.7%, 16/24) followed by T-cell (33.3%, 8/24) ALL. From the 25 cases where data was available, the complete remission rate was 75% (15/20) with ALL-directed chemotherapy and the median remission duration was 15 months (range 4.5 to 51 months). However, the results indicated that ALL following MDS is characterized by a high rate of early death (20%, 5/25).

CIP2A regulates proliferation and apoptosis of multiple myeloma cells.

Multiple myeloma (MM) is one of the most common causes of mortality from hematological malignancy in China. Recent studies have demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) may exhibit a role in promoting the growth of cancer; however, the function of CIP2A in MM remains unknown. In the present study, the expression and molecular mechanism underlying the effects of CIP2A in patients with MM and in MM cell lines were elucidated. Firstly, the expression of CIP2A was detected in patients with MM and in MM cell lines by reverse transcription­quantitative polymerase chain reaction. Furthermore, silencing of CIP2A with short hairpin RNA was performed in MM cells, and the impact on the proliferation and apoptosis of RPMI­8226 cells was analyzed (as endogenous CIP2A is highly expressed in RPMI­8226 cell lines compared with other cells). CIP2A was significantly elevated in patients with MM and in MM cell lines, and silencing of CIP2A could inhibit the proliferation ability of RPMI­8226 cells in vitro. In addition, CIP2A knockdown induced apoptosis and led to substantial reduction of c­Myc protein levels in MM cell lines. This study suggested that CIP2A inhibition may provide a promising therapeutic strategy for patients with MM.

[Effect of Nrf2 and TrxR on proliferation of chronic myeloid leukemia cell and its mechanism].

OBJECTIVE: To explore the effect of nuclear factor erythroid-2 related factor 2 (Nrf2) and thioredoxin reductase (TrxR) gene on proliferation of chronic myeloid leukemia (CML) line cells and its mechanism. METHODS: Four interfering sequences of Nrf2 and one negative control sequence were designed and synthesised based on the principle of target sequence of siRNA, then constructed lentivirus vectors, which were transfected into K562 cell lines. The transfection effect was observed by laser scanning confocal microscope (LSCM) and flow cytometer (FCM); The depressing effect of siRNA was analyzed by real-time PCR. The cell proliferation inhibiting rate was measured with CCK-8 assay, the apoptotic rate by Annexin V-PE/PI with FCM and the apoptotic morphology of cells by LSCM. RESULTS: The transfection efficiency of lentivirus was 65%. One cell line K562-C3 which significantly inhibited Nrf2 mRNA was obtained by real-time PCR, Nrf2 relative quantitation (RQ) expressions were 1.003±0.093 and 0.344±0.032 in the control group and K562-C3 respectively; TrxR expression also decreased with RQ as 1.090±0.549 and 0.395±0.029 respectively. The cellular proliferation inhibition rates of K562-C3 were (4.74±0.39)%, (6.13±1.78)% and (25.36±3.77)%, respectively at 24, 48 and 72 h. The apoptotic rate induced by K562-C3 (29.9%) at 72 hours was obviously higher than in the control group (7.9%). The Annexin V-PE positive K562-C3 cells presented the following apoptotic characteristics, such as karyopyknosis, nuclear fragmentation and apoptotic bodies observed by LSCM. CONCLUSION: Nrf2 specific siRNA could repress its expression at the cellular level and down-regulate the expression of its downstream antioxidant enzyme, such as TrxR, which lead to increased apoptotic rate and decreased cell proliferation.

[Expression of FLT3 internal tandem duplication in pediatric patients with acute myeloid leukemia and its correlation with multidrug resistance].

This study was aimed to investigate the expression of FLT3 internal tandem duplication (FLT3-ITD) in pediatric patients with acute myeloid leukemia (AML) and to analyse the clinical features of patients with mutations and the relation of FLT3-ITD with multidrug resistance gene 1 (mdr1). RT-PCR was used to determine the expressions of FIT3-ITD and mdr1 gene in bone marrow samples from 81 new diagnosed pediatric patients with AML, the cytogenetics and immunophenotypes of bone marrow cells were routinely examined. The results indicated that the FLT3-ITDs were detected in 8 out of 81 pediatric patients (9.88%) and all mutations detected were hybrid, while less frequently this mutation was detected in adult patients. Although they were irrelevant with sex and immunophenotypes, the mutations seemed predominant in older pediatric patients. The leukocyte counts and bone marrow blast cell counts in pediatric patients with FLT3-ITD at diagnosis were higher than those in pediatric patients without FLT3-ITD (p = 0.001 and p = 0.041 respectively), but the normal chromosomes were found in most pediatric patients with FLT-ITD. The patients with FLT3-ITD had lower induction remission rate (only 25%), but the patients without FLT3-ITD had higher remission rate (76.1%). According results detected by RT-PCR, the mdr1 gene was found in 27 pediatric patients, but only 3 out of 8 pediatric patients with FLT3-ITD were detected to express both FLT3-ITD and mdr1, which suggests unrelation between FLT3-ITD occurrence and mdr1 expression. It is concluded that the FLT3-ITD is frequent mutation in pediatric patients with AML, the prognosis is worse and the induction remission rate is lower in these patients, but the FLT3-ITD not relates with the mdr1, which suggests that the common MDR modulators may be un effective for therapy of the patients with FLT3-ITD.

[Double times of autologous peripheral blood stem cell transplantation to treat multiple myeloma].

In order to explore the security and feasibility of double autologous peripheral blood stem cell transplantation (APBSCT) for treatment of multiple myeloma, a 49 years old female patient with multiple myeloma was therapied with double APBSCT. The first peripheral blood stem cell (PBSC) mobilization regimen included CTX 2 g/m(2) x 1d and G-CSF [10 microg/(kgxd)] x 5 d. The conditioning regimen was given melphalan 200 mg/m(2). The transplanted number of mononuclear cells was 6.1 x 10(8)/kg and that of CD34(+) cells was 4.7 x 10(6)/kg. The second APBSCT was performed six months later. PBSC mobilization regimen was G-CSF [10 microg/(kgxd)] x 5 d. The conditioning regimen was melphalan 200 mg/m(2). The transplanted number of mononuclear cells was 10.2 x 10(8)/kg and that of CD34(+) cells was 5.9 x 10(6)/kg. The results showed that the absolute neutrophil count (ANC) rose to above 0.5 x 10(9)/L on day 17 and platelet count exceeded 20 x 10(9)/L on day 15 after first transplantation. After second transplantation ANC rose to above 0.5 x 10(9)/L on day 22 and platelet count exceeded 20 x 10(9)/L on day 13. There were neither obvious adverse reaction nor severe complication during the double transplantations. The patient's ostealgia and anemia were healed through above therapy. In the follow-up of 7 months, the patient's general status was good and she remained in complete remission phase. It is concluded that double APBSCT is safe, effective and feasible for the treatment of multiple myeloma.

Nonmyeloablative allogeneic hematopoietic stem cell transplantation in 26 cases of hematological malignancies.

The purpose of this study was to investigate the efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and its related technologies in hematological malignancies. 26 patients with hematological malignancies (acute leukemia 10, chronic myeloid leukemia 14, multiple myeloma 2) received allo-NST following conditioning regimens with fludarabine/cyclophosphamide/ATG in 14 cases or busulfan or melphalan/cyclophosphamide/ATG in 12 cases prior to infusion of 2 or 3 collections of G-CSF (600 microg/d) or G-CSF (300 microg/d) plus GM-CSF (300 microg/d) mobilized blood stem cell on the fifth day. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients were eligible for donor lymphocyte infusion (DLI) (or donor stem cell infusion (DSI)) given in graded increments according to the chimeric formation and clinical feature. Generally, the dose of the first infusion was 1 x 10(7)/kg in 4th week post-transplantation. The engraftment analyses included the detection of microsatellite short tandem repeats (STRs), bcr/abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that out of 26 patients, 22 (84.62%) were engrafted, 18/22 were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 (11.54%), while chronic GVHD was diagnosed in 6 out of 26 (23.07%) patients. The incidence and degree of infection and hemorrhage were low and slight. It is concluded that NST is a safe and effective therapy for hematological malignancies, whereas related technologies such as adaptation selected, conditioning regimen and transplantation immunotherapy should be studied further.

[Non-myeloablative allogeneic stem cell transplantation in patients with hematologic malignancies].

In order to investigate the clinical efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and related technology in patients with hematologic malignancies, twenty-six cases of hematological malignancies (10 AL, 14 CML, 2 MM patients) received NST following conditioning regimens with fludara + cyclophosphamide + ATG (14 cases) and busulfan or melphalan + cyclophosphamide + ATG (12 cases), G-CSF (600 micro g/d) or G-CSF (300 micro g/d) + GM-CSF (300 micro g/d) were used for mobilizing peripheral blood stem cell. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients will be eligible for donor lymphocyte infusion (DLI) or donor stem cell infusion (DSI) given in graded increments according to the chimeric formation and clinical reaction. Generally the dose of the first infusion was 1 x 10(7)/kg at 4th week post-transplantation. The engraftment analysis included the detection of microsatellite short tandem repeats (STRs), Bcr/Abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that 22 patients (84.62%) were engrafted, among which 18 patients were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 cases (11.54%). Chronic GVHD was diagnosed in 6 of 26 (23.07%) evaluable patients. The incidence of infection and hemorrhage was low and slight. It is concluded that allo-NST is a safe and effective therapeutic method for hematologic malignancies, but the related technology such as selection of indication, conditioning regimen and transplantation immunotherapy should be studied further.

Th1/Th2 cytokine profiles and their relationship to clinical features in patients following nonmyeloablative allogeneic stem cell transplantation.

An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is suggested to play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD). The aim of this study was to investigate the cytokine bias acquired by T cells after transplantation and its possible influence on relapse of original malignancy. Cytokine levels by peripheral CD4 and CD8 T cells were tested at various pre- and post-transplant time points with fluorescein isothiocyanate-based intracellular cytokine assay after short-term in vitro mitogenic stimulation (phorbol myristate acetate + ionomycin). In both CD4+ and CD8+ cells, interferon (IFN)-gamma-producing cell populations increased, indicating a shift to a Th1 cytokine profile with aGVHD. IFN-gamma-producing T cells was significantly lower in patients who experienced relapse of original disease compared to those who showed no signs of relapse and compared to normal controls. Our studies demonstrate that aGVHD correlates with a Th1 bias and that Th1 response may potentiate an effective immune surveillance.