Significance of tumor mutation burden and immune infiltration in thymic epithelial tumors

Background: Thymic epithelial tumors (TETs) are relatively rare malignant thoracic tumors. Tumor mutation burden (TMB) and immune infiltration play important roles in tumorigenesis. Methods: Research data was obtained using the Cancer Genome Atlas (TCGA) database to evaluate the landscape of tumor mutations, related factors, and relationship of prognosis. The CIBERSORT algorithm was used to evaluate immune cell infiltration in TETs and its relationship with TMB. Immune-related differentially expressed genes (irDEGs) were identified. Hub irDEGs independently related to prognosis were analyzed using univariate and multivariate Cox proportional hazard models. A survival signature was constructed from hub irDEGs. Results A total of 122 patients were included in this study. GTF2I was the most common gene mutation. Higher TMB was significantly associated with the later stage, more advanced pathological type, and older age. The overall survival (OS) of patients in the low-TMB group was significantly better. There was no significant correlation between TMB levels and PD-L1 expression. Enrichment analysis showed that DEGs were mainly involved in the P13K-Akt signaling pathway. There were significant differences in macrophage and other types of immune cell infiltration between the high- and low-TMB groups. CCR5, FASLG, and CD79A independently relating to prognosis were screened from 391 irDEGs. The low-risk group had a significantly better prognosis than the high-risk group based on the signature, which has a good predictive effect on OS. Conclusions: In this study, TETs patients with high TMB had a significantly poor prognosis and an immune-related gene signature was found to effectively evaluate the long-term prognosis

A new nursing pattern based on ERAS concept for patients with lumbar degenerative diseases treated with OLIF surgery: A retrospective study

ObjectiveThe purpose of this study was to introduce enhanced recovery after surgery (ERAS) concept into patients with lumbar degenerative diseases who were treated with oblique lumbar interbody fusion (OLIF), and to assess whether it could increase clinical efficacy, reduce perioperative complications, shorten length of hospital stay (LHS), decrease readmission rate, and improve patient satisfaction.MethodsThe study included patients with lumbar degenerative diseases (LDDs) who underwent OLIF between July 2017 and October 2018 (non-ERAS group), and between November 2018 and July 2020 (ERAS group). The two groups were compared according to the demographic and clinical characteristics.ResultsThere was no significant difference in descriptive characteristics and concomitant diseases between the two groups. The preoperative Oswestry disability index (ODI) score (P = 0.191), lumbar visual analogue scale (VAS) score (P = 0.470), and leg VAS score (P = 0.657) did not significantly different. Most of the ERAS measures were also well implemented after surgery, except for early delivery (74.2%), early catheter removal (63.9%), and multimodal analgesia (80.6%). The LHS in the ERAS group was significantly shorter than that in the non-ERAS group (P = 0.004). Besides, Hamilton Anxiety Rating Scale (HAMA) score at 3 days after surgery showed a significant difference between the two groups (P = 0.019). The patient satisfaction in ERAS group was significantly higher than that in the non-ERAS group (P = 0.001).ConclusionThe new nursing pattern combined with ERAS in patients with LDDs who underwent OLIF did not improve the short-term prognosis of surgery, while it could effectively reduce postoperative complications, shorten the LHS, and improve patient satisfaction, and did not lead to additional adverse events

The Positive Effect of Moderate-Intensity Exercise on the Mirror Neuron System: An fNIRS Study

A growing number of studies have reported the beneficial effect of exercise on human social behavior. The mirror neuron system (MNS) plays a critical role in a variety of social behaviors from imitation to empathy. However, neuroimaging investigations into the effects of exercise on the MNS remain unexplored. To address this question, our study determined the effect of moderate-intensity exercise on the MNS using functional near-infrared spectroscopy (fNIRS). Specifically, 23 right-handed young individuals were asked to perform a table-setting task that included action execution and action observation before and after a 25-min exercise session on a cycle ergometer at moderate intensity (65% VO2peak). The control condition was the same task performed without exercise. Cortical hemodynamic changes in the four primary brain regions of the MNS were monitored with fNIRS, using a modified probe configuration that covered all four MNS regions in the left hemisphere. We used a region of interest (ROI)-based group analysis to determine which regions were activated during action execution and action observation. Following a session of moderate-intensity exercise, we found a significant increase in activation in all four MNS regions, namely the inferior frontal gyrus (IFG), premotor cortex (PMC), superior parietal lobule (SPL), and rostral inferior parietal lobule (IPL). This result indicated a positive effect of exercise on the MNS, specifically that moderate-intensity exercise could activate the MNS

Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34+ acute myeloid leukemia cell lines and primary sorted CD34+ acute myeloid leukemia cells

<p>Abstract</p> <p>Background</p> <p>Acute myeloid leukemia (AML) is an immunophenotypically heterogenous malignant disease, in which CD34 positivity is associated with poor prognosis. CD34⁺AML cells are 10-15-fold more resistant to daunorubicin (DNR) than CD34^-AML cells. Curcumin is a major component of turmeric that has shown cytotoxic activity in multiple cancers; however, its anti-cancer activity has not been well studied in DNR-insensitive CD34⁺AML cells. The aim of this study was to therefore to explore curcumin-induced cytotoxicity in DNR-insensitive CD34⁺AML cell lines (KG1a, Kasumi-1), DNR-sensitive U937 AML cells, and primary CD34⁺AML bone-marrow-derived cells.</p> <p>Methods</p> <p>Primary human CD34⁺cells were isolated from peripheral blood mononuclear cells or bone marrow mononuclear cells using a CD34 MicroBead kit. The growth inhibitory effects of curcumin were evaluated by MTT and colony-formation assays. Cell cycle distribution was examined by propidium iodide (PI) assay. Apoptosis was analyzed by Wright-Giemsa, Hoechst 33342 and Annexin-V/PI staining assays. The change in mitochondrial membrane potential (MMP) was examined by JC-1 staining and flow cytometry. Expression of apoptosis-related proteins was determined by reverse transcription-polymerase chain reaction and Western blotting. Short interfering RNA (siRNA) against <it>Bcl-2 </it>was used in CD34⁺KG1a and Kasumi-1 cells incubated with/without DNR.</p> <p>Results</p> <p>Curcumin inhibited proliferation and induced apoptosis and G1/S arrest in both DNR-insensitive KG1a, Kasumi-1 and DNR-sensitive U937 cells. Curcumin-induced apoptosis was associated with reduced expression of both Bcl-2 mRNA and protein, subsequent loss of MMP, and activation of caspase-3 followed by PARP degradation. Curcumin synergistically enhanced the cytotoxic effect of DNR in DNR-insensitive KG1a and Kasumi-1 cells, consistent with decreased Bcl-2 expression. Accordingly, siRNA against <it>Bcl-2 </it>increased the susceptibility of KG1a and Kasumi-1 cells to DNR-induced apoptosis. More importantly, curcumin suppressed Bcl-2 expression, selectively inhibited proliferation and synergistically enhanced the cytotoxicity of DNR in primary CD34⁺AML cells, while showing limited lethality in normal CD34⁺hematopoietic progenitors.</p> <p>Conclusion</p> <p>Curcumin down-regulates Bcl-2 and induces apoptosis in DNR-insensitive CD34⁺AML cell lines and primary CD34⁺AML cells.</p

Construction and validation of a prognosis signature based on the immune microenvironment in gastric cancer

BackgroundGastric cancer (GC) is an aggressive malignant tumor with a high degree of heterogeneity, and its immune microenvironment is closely associated with tumor growth, development and drug resistance. Therefore, a classification system of gastric cancer based explicitly on the immune microenvironment context might enrich the strategy for gastric cancer prognosis and therapy.MethodsA total of 668 GC patients were collected from TCGA-STAD (n = 350), GSE15459 (n = 192), GSE57303 (n = 70) and GSE34942 (n = 56) datasets. Three immune-related subtypes (immunity-H, -M, and -L) were identified by hierarchical cluster analysis based on the ssGSEA score of 29 immune microenvironment-related gene sets. The immune microenvironment-related prognosis signature (IMPS) was constructed via univariate Cox regression, Lasso-Cox regression and multivariate Cox regression, and nomogram model combining IMPS and clinical variables was further constructed by the “rms” package. RT-PCR was applied to validate the expression of 7 IMPS genes between two human GC cell lines (AGS and MKN45) and one normal gastric epithelial cell line (GES-1).ResultsThe patients classified as immunity-H subtype exhibited highly expressed immune checkpoint and HLA-related genes, with enriched naïve B cells, M1 macrophages and CD8 T cells. We further constructed and validated a 7-gene (CTLA4, CLDN6, EMB, GPR15, ENTPD2, VWF and AKR1B1) prognosis signature, termed as IMPS. The patients with higher IMPS expression were more likely to be associated with higher pathology grade, more advanced TNM stages, higher T and N stage, and higher ratio of death. In addition, the prediction values of the combined nomogram in predicting 1-year (AUC = 0.750), 3-year (AUC = 0.764) and 5-year (AUC = 0.802) OS was higher than IMPS and individual clinical characteristics.ConclusionsThe IMPS is a novel prognosis signature associated with the immune microenvironment and clinical characteristics. The IMPS and the combined nomogram model provide a relatively reliable predictive index for predicting the survival outcomes of gastric cancer

On-chip black hole: Hawking radiation and curved spacetime in a superconducting quantum circuit with tunable couplers

Hawking radiation is one of quantum features of a black hole, which can be understood as a quantum tunneling across the event horizon of the black hole, but it is quite difficult to directly observe the Hawking radiation of an astrophysical black hole. Remarkable experiments of analogue black holes on various platforms have been performed. However, Hawking radiation and its quantum nature such as entanglement have not been well tested due to the experimental challenges in accurately constructing curved spacetime and precisely measuring the thermal spectrum. Based on the recent architecture breakthrough of tunable couplers for superconducting processor, we realize experimentally an analogue black hole using our new developed chip with a chain of 10 superconducting transmon qubits with interactions mediated by 9 transmon-type tunable couplers. By developing efficient techniques to engineer the couplings between qubits via tuning couplers, we realize both the flat and curved spacetime backgrounds. The quantum walks of quasi-particle in the curved spacetime reflect the gravitational effect around the black hole, resulting in the behavior of Hawking radiation. By virtue of the state tomography measurement of all 7 qubits outside the analogue event horizon, we show that Hawking radiation can be verified. In addition, an entangled pair is prepared inside the horizon and the dynamics of entanglement in the curved spacetime is directly measured. Our results would stimulate more interests to explore information paradox, entropy and other related features of black holes using programmable superconducting processor with tunable couplers.Comment: modified manuscripts, 7 pages, 4 figures (main text) + 12 pages (supplementary information

Clinical Characteristics and Prognostic Factors of Primary Splenic Angiosarcoma: A Retrospective Clinical Analysis from China

Background/Aims: Primary splenic angiosarcoma is an aggressive malignancy originating from endothelial cells with a particularly poor outcome despite radical therapy. Owing to its extremely low incidence, available data for splenic angiosarcoma are limited. The present study aimed to address this limitation by presenting a thorough retrospective analysis of Chinese primary splenic angiosarcoma patients over a 53-year period (1963-2016). Methods: To determine the characteristics of Chinese primary splenic angiosarcoma and identify factors that impact the outcomes of this histology, we retrospectively retrieved reports of 110 Chinese primary splenic angiosarcoma cases published between 1963-2012. Results: In total, 61 males and 49 females diagnosed with primary splenic angiosarcoma were included in the present study. The median age at diagnosis was 50 years (range 2.5–76 years). Of these patients, 25.5% had received prior radiotherapy. The rate of splenic rupture was 59.11%. The 1-year overall survival rate was 19.1% with a median overall survival time of 8.1 months. Age, gender, and radiation history showed no correlation with survival rate. However, by univariate analysis, we found that significant adverse predictors of survival were splenic rupture before surgery and large tumor size (&#x3e; 5 cm), while adjuvant chemotherapy was a favorable predictor. Furthermore, multivariate analysis revealed that splenic rupture and adjuvant chemotherapy were independent adverse and favorable predictors, respectively. Conclusion: Our large series describes and confirms the characteristics and poor prognosis of Chinese primary splenic angiosarcoma, thus indicating a critical role for early diagnosis and surgical intervention (prior to rupture) in management, and highlights the promising potential of adjuvant chemotherapy for improving the outcome in these cases