INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling.

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

The effectiveness of diaphragmatic breathing relaxation training for improving sleep quality among nursing staff during the COVID-19 outbreak: a before and after study.

OBJECTIVES: Recent studies have demonstrated that first-line nurses involved in the coronavirus disease-2019 (COVID-19) crisis may experience sleep disturbances. As breathing relaxation techniques can improve sleep quality, anxiety, and depression, the current study aimed to evaluate the effectiveness of diaphragmatic breathing relaxation training (DBRT) for improving sleep quality among nurses in Wuhan, China during the COVID-19 outbreak. METHODS: This study used a quasi-experimental (before and after) intervention strategy, with 151 first-line nurses from four wards in Leishenshan hospital. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) to evaluate the effectiveness of DBRT before and after the intervention. Data were examined using the Shapiro-Wilk test, Levene's test, and paired t-test. RESULTS: A total of 140 nurses completed the DBRT sessions. First-line nurses achieved significant reductions in global sleep quality (p < 0.01), subjective sleep quality (p < 0.001), sleep latency (p < 0.01), sleep duration (p < 0.001), sleep disturbances (p < 0.001), habitual sleep efficiency (p = 0.015), daytime dysfunction (p = 0.001), and anxiety (p = 0.001). There were no significant reductions in the use of sleeping medication (p = 0.134) and depression (p = 0.359). CONCLUSION: DBRT is a useful non-pharmacological treatment for improving sleep quality and reducing anxiety among first-line nurses involved in the COVID-19 outbreak. The study protocol was clinically registered by the Chinese Clinical Trial Registry. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000032743.

Erratum to "Withdrawal notice to the effectiveness of diaphragmatic breathing relaxation training for improving sleep quality among nursing staff during the COVID-19 outbreak: a before and after study" [Sleep Medicine X (2) (2020) 100026].

[This corrects the article DOI: 10.1016/j.sleepx.2020.100026.].

[Research Progress on the Role of Musashi-2 in the Pathogenesis of Malignant Hematologic Diseases-Review].

Previous studies have found that Musashi-2 (Msi-2) plays an essential role in regulating the gene expression of stem cell populations by inhibiting or activating the translation, and thus regulates stem cell function. Current research shows that Msi-2 involved in the regulation of a variety of malignant hematological diseases through different mechanisms; moreover abnormally expressed in a variety of malignant hematological diseases and involved in the occurrence, development of a variety of malignant hematological diseases. Further study on the role of malignant hematologic diseases will further clarify the pathogenesis of malignant hematologic diseases, and provide a new basis for the diagnosis and treatment of malignant hematological diseases. In this review, the structure and function of Msi-2 and its relationship with malignant hematologic diseases and its latest research progress are summarized.

[Research Progress on miR-125 Family in Malignant Hematologic Diseases-Review].

MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded small noncoding RNAs with the length of 20 to 23 nucleotides. MicroRNA-125 (miR-125) family, which is a highly conserved miRNA family, is consist of miR-125a, miR-125b-1 and miR-125b-2. Accumulating evidence demonstrated that miR-125 can be involved in various physiological and pathological processes in vivo. Importantly, it is closely related with the tumorigenesis and tumor development, including tumor cell proliferation, apoptosis, invasion and metastasis, metabolism and immune response. In malignant hematologic diseases, it is defined either as a oncogene, or as a tumor suppressor gene, even, closely related with the drug resistance in a variety of hematologic malignancies. MiR-125 is expected to become a new therapeutic target. Newly, the research of the relationship between miR-125 family and hematologic malignancies become increasing, including leukemia, lymphoma, multiple myeloma. In this review, the relationship between miR-125 family with malignant hematologic diseases and its latest research progress are summarized.

[Research Progress on Role of Inflammasome in Development of Thrombotic Diseases -Review].

Inflammasome is a group of polyprotein complexes located in the cytoplasm, its activation can induce the maturation and release of proinflammatory cytokines IL-1ß and IL-18, and promote the early atherosclerosis. In the recent years, it is found that the inflammasome is activated in thrombotic deseases, moveover, the activated inflammasome and its activation induced cytokines promote the occurrence and development of thrombolic deseases, and show the unfavaourable effect on prognosis. With further exploration on the mechanisms of thrombotic diseases, the relationship between the inflammasome and thrombotic diseases increasingly become a hot spot of research. This review focuses on the action mechanisms of inflammasome in thrombotic diseases.

[Relationship of TGF-ß and IL-4R gene polymorphisms with risk of classical Hodgkin lymphoma].

OBJECTIVE: This study was aimed to analyze the relationship between single nucleotide polymorphisms of transforming growth factor-ß1 G-800A and C-509T, interleukin-4 receptor V75I and susceptibility of CHL in adults. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to analyze the expressed alleles of the selected SNP loca. The relationship between genomic polymorphisms of TGF-ß1 and IL-4R and susceptibility of CHL were coupled with clinical data. RESULTS: TGF-ß1G-800A and TGF-ß1C-509T had obvious linkage equilibrium (D' = 0.879, r(2) = 0.83, P = 0.020). GT haplotype distribution frequencies in mixed cellularity Hodgkin lymphoma cases and control group were of 53.1% and 34.2%, respectively, with statistically significant (OR = 2.35, P = 0.000); distribution frequencies of mutant gene T/T in disease and control groups were of 38.8% and 15.3%, respectively, also with statistically significant (OR = 3.654, P = 0.000); frequencies of nodular sclerosis CHL patients with IL-4R V75I mutant gene A/A in disease and control groups were of 19.2% and 41.75%, respectively, also with statistically significant (OR = 3.156, P = 0.000). CONCLUSION: Single nucleotide polymorphisms of TGF-ß1 G-800A, C-509T and IL-4R V75I has a significant correlation with Chinese susceptibility to classical Hodgkin lymphoma.

[Special morphological changes of pathologic cells in two cases of Waldenström's macroglobulinemia].

Waldenström's macroglobulinemia (WM) is one of malignant hematological disease on account of abnormal proliferation of B lymphocyte clone and the pathologic cells of WM possess ability to secrete monoclonal immunoglobulin M. In this study, the diagnosis and morphological characteristics of 2 patients with WM were analyzed. The results showed that a special kind of "foam cells" were found by cytochemical staining examinations in both cases, which displayed characteristics of lymphocytes, but neither monocyte-macrophage nor fatty cells. The periodic acid-Shiff's reaction (PAS) demonstrated strong positive, especially on the inclusion bodies in pathologic cell plasma while the acid phosphatase, and alpha-butanoic acetate esterase stainings, resulted both in negative. In conclusion, the cells found in the two cases reported may be described as gemmy ring-like lymphocyte in morphology, a special subtype of ring-like lymphocyte.