Clinical characteristics, genetic alterations, and prognosis of adult T-cell leukemia/lymphoma: an 11-year multicenter retrospective study in China.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis, and there is little data available from the Chinese population. This retrospective study included 115 patients diagnosed with ATLL who were treated across five hospitals in China from June 2011 to December 2022. The median age at diagnosis was 53 years. Several genes involved in T-cell receptor-induced nuclear factor κB (TCR-NF-κB) signaling were commonly mutated, including PLCG1, CIC, PRKCB, CARD11, and IRF4. Eighty-seven patients received chemotherapy. Of these, 13 received a hematopoietic stem cell transplant (HSCT) (allogeneic-HSCT, n=9; autologous-HSCT, n=4) after chemotherapy. Following initial multiagent chemotherapy using EPOCH/CHOEP and other regimens, the overall response rates were 80.6% (complete response [CR], 44.4%) and 42.8% (CR, 14.2%), respectively. The 4-year survival rates (median survival time in days) for EPOCH/CHOEP (n=43), HSCT (n=13), and CHOP-based regimens (n=31) were 12.7% (138), 30.8% (333), and 0% (66), respectively. Lymphadenopathy, EPOCH/CHOEP, and hematopoietic stem cell transplantation were independent prognostic protective factors in patients with aggressive ATLL. Chinese patients exhibit a higher incidence of aggressive-type ATLL, sharing similar genetic alterations with Japanese patients. Etoposide-based chemotherapy (EPOCH or CHOEP) remains the preferred choice for aggressive ATLL, and upfront allogeneic HSCT should be considered in all eligible patients.

Insights into the Semiconductor SERS Activity: The Impact of the Defect-Induced Energy Band Offset and Electron Lifetime Change.

The significant boost in surface-enhanced Raman scattering (SERS) by the chemical enhancement of semiconducting oxides is a pivotal finding. It offers a prospective path toward high uniformity and low-cost SERS substrates. However, a detailed understanding of factors that influence the charge transfer process is still insufficient. Herein, we reveal the important role of defect-induced band offset and electron lifetime change in SERS evolution observed in a MoO3 oxide semiconductor. By modulating the density of oxygen vacancy defects using ultraviolet (UV) light irradiation, SERS is found to be improved with irradiation time in the first place, but such improvement later deteriorates for prolonged irradiation even if more defects are generated. Insights into the observed SERS evolution are provided by ultraviolet photoelectron spectroscopy and femtosecond time-resolved transient absorption spectroscopy measurements. Results reveal that (1) a suitable offset between the energy band of the substrate and the orbitals of molecules is facilitated by a certain defect density and (2) defect states with relatively long electron lifetime are essential to achieve optimal SERS performance.

[Effect of Eltrombopag on Response to Immunosuppressive Therapy in Patients with Transfusion-Dependent Non-Severe Aplastic Anemia].

OBJECTIVE: To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA). METHODS: The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed. RESULTS: There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated. CONCLUSION: Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.

Inflammatory mediators and immune function in different stages of systemic lupus erythematosus.

This study aimed to study the relationship between the expression levels of inflammatory mediators IL-36ß and IL-36R and disease symptoms, laboratory indices and somatic immune function in Systemic Lupus Erythematosus (SLE) of different stages. In this research 70 patients with SLE who were treated in public hospitals from February 2020 to December 2021 were randomly divided into the stable group (n=35) and active group (n=35), and serum IL-36 was measured in the two groups ß and IL-36R concentration with the standard curve of Enzyme-Linked Immunosorbent Assay (ELISA) to analyze IL-36ß and IL-36R concentrations. 36ß and IL-36R concentrations were analyzed in relation to the Disease activity score of systemic lupus erythematosus (SLEDAI), disease duration, typical symptoms of SLE and experimental characteristics. Results showed that the differences in IL-36ß and IL-36R concentrations between the stable and active groups overall and for each disease duration group were tiny. There was no significant correlation between serum IL-36ß and IL-36R concentrations and SLEDAI scores in stable and active patients, and a negative correlation between them and disease duration. Serum inflammatory mediator IL-36R concentrations were significantly higher in patients with mucosal ulcers and the difference was statistically significant. differences in IL-36ß concentrations were statistically significant only for indicators of decreased erythrocyte count and IL-36R concentrations were statistically significant for indicators of decreased erythrocyte count, decreased haemoglobin and decreased lymphocytes The differences were huge and tiny in C4 decline, anti-dsDNA, and urinary routine protein. There was a significant positive correlation between IL-36ß and IL-36R concentrations in patients with stable and active SLE, with correlation coefficients of 0.448 and 0.452 respectively. The differences in IL-36ß and IL-36R concentrations between the stable and active groups were tiny for patients in the stable and active groups as a whole and for all disease groups. The differences in the number of each inflammatory mediator positive cells in the epidermal stratum corneum and superficial dermis between patients in the stable and active groups were tiny. In conclusion, IL-36ß and IL-36R proteins in SLE patients are expressed in immune cells as well as epithelial cells of patients, indicating that these two inflammatory mediators may be one of the early signals that activate the immune system of SLE patients and trigger the immune response of patients; the onset of SLE may be associated with the inflammatory response induced by IL-36ß and IL-36R.

Intermolecular singlet fission in a radical dianion system in solution phase.

Singlet fission (SF) is a spin-allowed exciton multiplication process, in which a photogenerated singlet separates efficiently into two free triplets. Herein, we report an experimental study on the solution-phase intermolecular SF (xSF) in a prototype radical dianion system of PTCDA2-, which is produced from its neutral precursor PTCDA (i.e., perylenetetracarboxylic dianhydride) via a two-step consecutive photoinduced electron transfer mechanism. Our ultrafast spectroscopic results enable a comprehensive mapping of the elementary steps involved in the solution-phase xSF process of photoexcited PTCDA2-. Along the cascading xSF pathways, the three intermediates including excimer 1(S1S0), spin-correlated triplet pair 1(T1T1), and spatially separated triplet pair 1(T1·S0·T1) have been identified, with their formation/relaxation time constants being determined. This work demonstrates that the solution-phase xSF materials can be extended to charged radical systems and that the three-step model usually adopted to describe the crystalline-phase xSF can also be valid in describing solution-phase xSF.

Adoptive immune transfer from donors offers Anti-HBV protection to HBsAb-negative patients after Allo-HSCT.

Adoptive transfer of hepatitis B virus (HBV) immunity may occur following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we investigated the adoptive transfer of HBV immunity in 112 patients without HBV surface antibody (HBsAb) (HBsAb-) at the time of their first allo-HSCT. After allo-HSCT, HBV-DNA（87.5%） and HBsAg（11.1%%）cleared in HBsAg+ patients. All HBsAg- patients acquired HBsAb immediately. Nevertheless, HBsAb titers subsequently declined, and 39/67 (58.2%) patients lost HBsAb during follow-up. The 5-year overall survival (OS) was better in patients who lost HBsAb. Multivariate analysis showed that the independent risk factors for OS were lack of cytomegalovirus (CMV) clearance, acute graft-versus-host disease (aGVHD), and no HBsAb loss. Overall, adoptive immune transfer offers anti-HBV protection to patients without HBsAb, as they acquire HBsAb and clear HBV-DNA and HBsAg, while HBsAb loss after allo-HSCT predicts better survival.

[Clinical Study of Chemotherapy Combined with Antivirals for Adult T-cell Leukemia/Lymphoma].

OBJECTIVE: To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors. METHODS: Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, ß2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed. RESULTS: The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower ß2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)％ and (40.9±2.1)％ (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)％ and (13.6±2.8)％ (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy ï¼»HR=5.617 (95%CI 1.803-11.293), P=0.027ï¼½ were independent prognostic factors for the long-term efficacy. CONCLUSION: Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.

Intermediate Complex-Mediated Interfacial Electron Transfer in a Radical Dianion/TiO2 Dye-Sensitized Photocatalytic System.

We present a mechanistic study of a PTCDA2-/TiO2 dye-sensitized photocatalytic system, in which the stable radical dianion PTCDA2- is formed via a two-step consecutive photoinduced electron transfer from its neutral precursor PTCDA (i.e., perylenetetracarboxylic dianhydride). Photoexcitation of PTCDA2- brings forth an interesting behavior known as vibrationally excited-state-selective, visible-light photocatalytic hydrogen evolution reaction (HER). In conjunction with the information gleaned from optical spectroscopy and ultrafast dynamics, we reveal that an intermediate complex (IC) state with a lifetime of ∼12 ps exists in the vicinity of a certain vibrationally excited state of PTCDA2-. Such a unique IC state mediates the interfacial electron transfer (IET) channel from the specific excited state of PTCDA2- to the conduction band continuum of TiO2. As an outcome, the effective IC-mediated IET process in this photocatalytic system leads to a remarkable HER rate that reaches ∼4660 µmol g-1 h-1.

Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis.

Multiple myeloma (MM) is a malignant cancer with an increasing in incidence that can be alleviated through bortezomib (BTZ) treatment. Activating transcription factor 3 (ATF3) plays a major role in cancer development. Moreover, microRNAs (miRNAs) regulate carcinogenic pathways, apoptosis, and programmed necrotic cell death. However, the detailed mechanism by which ATF3 modulates BTZ drug sensitivity/resistance remains elusive. In the current study, expression of ATF3 was significantly increased under BTZ treatment in a dose-dependent manner in MM cell lines. In addition, ATF3 could regulate cell apoptosis under BTZ treatment. The effect of ATF3 was negatively regulated by its binding miRNA, miR-135a-5p. When either ATF3 was silenced or miR-135a-5p mimics were added to MM cells, they partially lost sensitivity to BTZ treatment. This was accompanied by low levels of Noxa, CHOP, and DR5, and a decrease in mitochondrial membrane potential. These results revealed the combinatorial regulatory patterns of ATF3 and miR-135a-5p in the regulatory protein interactome, which indicated a clinical significance of the miR-135a-5p-ATF3 protein interaction network in BTZ therapy. This study provides potential evidence for further investigation into BTZ resistance.

Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer related mortality worldwide. The 5-year survival rate is rather low owing to advanced unresectable and distant metastasis. The EMT has been widely implicated in the stemness, metastatic dormancy, and chemoresistance of different solid tumors. Given the fact that activating transcription factor-3 (ATF3) is a member of the ATF/CREB family of transcription factors and its role in regulation of GC recurrence and metastasis remain poorly understood, the aim of the present study was to investigate its potential impact in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties and GC aggression. METHODS: To elucidate the potential role of ATF3 in gastric cancer, we utilized SGC-7901 and MGC-803 gastric cancer cell lines as research models and constructed stable cell lines overexpressing ATF3. We conducted a series of assays including cell proliferation, colony formation, cell migration, tumorsphere formation, and invasion to investigate the functional roles of ATF3 in stemness of gastric cancer. The possible effect of ATF3 on epithelial-mesenchymal transition (EMT) was assessed through flow cytometry and qRT-PCR. In vivo functional effect of upregulation of ATF3 on tumor growth was examined in a mouse xenograft model. RESULTS: We found that overexpression of ATF3 inhibited cell proliferation, colony formation, cell migration and invasion. In addition, up-regulation of ATF3 attenuated tumorsphere formation, cell stemness, and potentially decreased expression of EMT markers. Moreover, ATF3 overexpression inhibited tumorigenesis in mouse xenograft model. CONCLUSION: Our data suggest a suppressive role of ATF3 in gastric cancer development. Our findings will provide a potential therapeutic strategy and novel drug target for gastric cancer.

Predictors and Mortality of Rapidly Progressive Interstitial Lung Disease in Patients With Idiopathic Inflammatory Myopathy: A Series of 474 Patients.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM. Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan-Meier estimator and univariate and multivariate analyses were used for data analysis. Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes <30% in BALF might also be associated with poor survival of myositis-associated RP-ILD (P < 0.05). Conclusion: Our study shows that RP-ILD results in increased mortality in IIM. Anti-MDA5 positivity and a lower lymphocyte ratio in BALF might be the predictive factor of mortality due to RP-ILD.

[Efficacy of Low Dose Combined Chemotherapy for Patients with Relapsed and Refractory Aplastic Anemia-Paroxysmal Nocturnal Hemoglobinuria Syndrome].

OBJECTIVE: To evaluate the clinical efficacy of low dose combined chemotherapy（LDCC） for patients with relapsed and refractory aplastic anemia-paroxysmal nocturnal hemoglobinuria（AA-PNH） syndrome, and to analyze the advantages of LDCC in the treatment of AA-PNH syndrome. METHODS: The clinical characteristics and the curative effect of LDCC in 9 patients with relapsed and refractory AA-PNH syndrome were retrospectively analyzed. Five patients were treated with MP therapyï¼»melphalan 2 mg/(m2·d); prednisone 0.5 mg/(kg·d)ï¼½, and the other 4 patients were treated with HA therapy(HHT 2 mg/d iv drip, for 5 days; Ara-C 100 mg/d iv drip, for 5 days). The changes of PNH clone, dosage of corticosteroid, hemolysis and the relapse of disease, hematological parameters and adverse reactions were compared before and after therapy. All patients were treated for 1-2 courses. RESULTS: Seven out of 9 patients responded well, the dosage of corticosteroid and the bilirubin concentration decreased significantly and anemia was relieved in 7 patients (P<0.05). One patient relapsed in one year. PNH clone of 3 patients turned negative. Five patients did not rely on blood transfusion in 1 year. There was no bone marrow failure to be found in all patients. CONCLUSION: The LDCC has better efficacy and safety in the treatment of patients with AA-PNH syndrome, moreover, the patients is more tolerant to LDCC, thus the LDCC may be a selection for treatment of patients with relapsed and refractory AA-PNH syndrome.

Complete plastome sequence of Jacaranda mimosifolia D. Don (Bignoniaceae): a beautiful landscaping tree species.

Jacaranda mimosifolia is a deciduous arbor with blue flowers native to Brazil, Bolivia, and Argentina in South America. After introduction from South America, it was widely cultivated as a garden ornamental plant in South China. The complete chloroplast (cp) genome sequence of this ornamental species is reported in this study, based on high-throughput sequencing (Illumina). The complete cp genome is 153,514 bp in length, containing a pair of inverted repeat regions (IRs) of 25,408 bp, a large single-copy (LSC) region of 84,755 bp, and a small single-copy (SSC) region of 17,943 bp. The cp genome contains 130 genes, consisting of 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall A/T content in the cp genome of J. mimosifolia is 61.70%. The phylogenetic analyses indicate that there is a close relationship between J. mimosifolia and Tecomaria capensis. The complete cp sequence of J. mimosifolia will provide a useful resource for the development and utilization of this species as well as for the phylogenetic studies in Bignoniaceae.