Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Salvage radiotherapy strategy and its prognostic significance for patients with locoregional recurrent cervical cancer after radical hysterectomy: a multicenter retrospective 10-year analysis.

OBJECTIVE: We aimed to evaluate the clinical efficacy and prognostic significance of intensity-modulated radiotherapy (IMRT)-based salvage concurrent chemoradiotherapy (CCRT) for patients with locoregional recurrence cervical cancer after radical hysterectomy and evaluated two salvage radiotherapy modes-regional RT (involved-field RT combined with regional lymph nodes) and local RT (involved-field RT). METHODS: Patients were enrolled retrospectively from January 2011 to January 2022 in three medical centers. Clinical outcomes were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Propensity score (PS) matching analysis was used to compare the two RT groups. RESULTS: There were 72 patients underwent IMRT-based salvage CCRT. The 5-year overall survival and progression-free survival rates were 65.9% and 57.6%, respectively. Univariate analysis showed that patients with stump recurrence, a lower systemic inflammation response index (SIRI), only one metastatic lesion, and received regional RT had better prognosis than their counterparts. In multivariate analysis, recurrence site was the independent prognostic factor of OS, and SIRI was that of PFS. After PS matching, there were 15 patients each in the regional RT group and local RT group. The 5-year OS rate of regional RT group was better than that of local RT group (90.9 vs. 42.4, p = 0.021). However, there was no significant difference between them in terms of PFS rate (47.1 vs. 38.1, p = 0.195). CONCLUSION: Locoregional recurrent cervical cancer treated with IMRT-based salvage therapy has a good prognosis. Recurrence site and SIRI were independent prognostic factors. Regional RT may be a better option for patients with locoregional recurrent.

Dapagliflozin modulates the faecal microbiota after myocardial infarction in non-diabetic mice.

The gut microbiota seems to be a major modulator of cardiovascular diseases, such as myocardial infarction. Dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2i), is an antidiabetic agent that was recently utilized in patients with cardiovascular diseases. This study aims to investigate the effects of dapagliflozin on the faecal microbiota of postinfarction non-diabetic mice. A total of 19 male mice were randomly divided into three groups, where two groups were enduced with myocardial infarction (MI) by left anterior descending ligation. One day after the surgery, each group was administered normal saline (15 mL/kg/day, 0.9%) or dapagliflozin (1.5 mg/kg/day) for 4 weeks. Echocardiography was obtained on day 28 post MI. Masson's trichrome staining was used to determine the degree of fibrosis. Faecal samples were collected to assess the microbiome by 16S ribosomal RNA gene sequencing. We found that dapagliflozin significantly improved cardiac function in the non-diabetic myocardial infarction mice model after the 28-day treatment, especially in ejection fraction and fractional shortening (p < 0.01). Enterotypes were composed of Muribaculaceae and Lactobacillaceae after dapagliflozin treatment, while Muribaculaceae and Erysipelotrichaceae were the main enterotypes post-MI. Dapagliflozin increased the abundance of beneficial bacteria like Lactobacillaceae, while decreasing the abundance of beneficial bacteria like Bifidobacteriaceae. It was interesting to discover that Proteobacteria (especially Desulfovibrionaceae) were enriched after the dapagliflozin treatment for myocardial infarction. Dapagliflozin increased the abundance of the main beneficial bacteria. In post-myocardial infarction treatments, using dapagliflozin could positively contribute to the improvement of cardiac function and alter the structure of faecal microbiota.

Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma.

BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

Gender differences in brain response to infant emotional faces.

Infant emotional stimuli can preferentially engage adults' attention and provide valuable information essential for successful interaction between adults and infants. Exploring the neural processes of recognizing infant stimuli promotes better understandings of the mother-infant attachment mechanisms. Here, combining task-functional magnetic resonance imaging (Task-fMRI) and resting-state fMRI (rs-fMRI), we investigated the effects of infants' faces on the brain activity of adults. Two groups including 26 women and 25 men were recruited to participate in the current study. During the task-fMRI, subjects were exposed to images of infant emotional faces (including happy, neutral, and sad) randomly. We found that the brains of women and men reacted differently to infants' faces, and these differential areas are in facial processing, attention, and empathetic networks. The rs-fMRI further showed that the connectivity of the default-mode network-related regions increased in women than in men. Additionally, brain activations in regions related to emotional networks were associated with the empathetic abilities of women. These differences in women might facilitate them to more effective and quick adjustments in behaviors and emotions during the nurturing infant period. The findings provide special implications and insights for understanding the neural processing of reacting to infant cues in adults.

Incidence and Prognosis Nomogram of Small Solitary Lung Cancer (≤2 cm) With Extra-Thoracic Metastasis at Initial Diagnosis:A Population-Based Study.

BACKGROUND: Small solitary lung cancer (≤2 cm) with extra-thoracic metastasis and no nodal metastasis or intra-thoracic metastasis is a rare situation in clinic. METHODS: Lung cancer patients with stage T1aN0M0 and T1aN0M1b from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results database. The identified significant parameters were utilized to develop 2 nomogram to predict the extra-thoracic metastasis rates and the overall survival for the group of patients with stage T1aN0M1b. RESULTS: Small solitary lung cancers which occur in the males, younger patients, or locate in the main bronchus or left lung, or with histologic type as small cell lung cancer, or with undifferentiated type, tend to have extra-thoracic metastasis. Application of the nomogram in the intra-group still gave good discrimination and good calibration. Univariable and multivariable analysis identified several clinical data as the prognostic factors for lung cancer patients with stage T1aN0M1b, all the factors above were incorporated into the nomogram. ROC curve analysis showed that the nomogram had good discrimination, with AUC of .779, .786 and .77 for 1-, 3- and 5-year survival in the development group and validation group, respectively. Moreover, decision curve analysis has been implemented to evaluate and compare prediction and prognostic nomogram. CONCLUSIONS: Younger male patients whose lung cancer locates in main bronchus or left lung, or with undifferentiated type, or with histologic type as small cell lung cancer are more likely to have extra-thoracic metastasis. The proposed nomogram reliably predicted OS for lung cancer patients with stage T1aN0M1b, though further validation is needed, it may be a useful tool in clinical practice. These models can be wildly used for easy facilitate the lung cancer individualized prediction of extra-thoracic metastasis and OS.

High fibrinogen-albumin ratio index (FARI) predicts poor survival in head and neck squamous cell carcinoma patients treated with surgical resection.

PURPOSE: The aim of the present study was to investigate the predictive value of the fibrinogen/albumin ratio index (FARI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with operable head and neck squamous cell carcinoma (HNSCC). METHODS: A cohort of 155 operable HNSCC patients were enrolled. Laboratory and clinical data were extracted from the patients' electronic medical record. The optimal cut-off values were determined by receiver operating characteristic (ROC) curves analysis. Clinicopathological characteristics of patients were compared via Chi-square test. Survival curves were analyzed by Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses via the Cox hazards regression analysis. RESULTS: The median follow-up time was 31.7 months. An increased level of NLR was associated with later T stages, later N stages, and more advanced clinical stages(all P < 0.05). On univariate analyses, FARI, NLR, PLR, and N stage were correlated with progression-free survival (PFS) (all P < 0.05) as well as overall survival (OS) (all P < 0.05). And the clinical stage was only relevant to OS (P = 0.007). Multivariate Cox regression analysis revealed that FARI (HR 3.486, 95% CI 2.086-5.825, P < 0.001; HR 4.474, 95% CI 2.442-8.199, P < 0.001), NLR (HR 3.163, 95% CI 1.810-5.528, P < 0.001; HR 3.690, 95% CI 1.955-6.963, P < 0.001), and N stage (HR 1.718, 95% CI 1.058-2.789, P = 0.029; HR 1.777, 95% CI 1.024-3.084, P = 0.041) were independent prognostic factors for PFS and OS. CONCLUSION: Our findings indicate that FARI and NLR are effective and convenient markers for predicting prognosis in operable HNSCC patients.

Micro classes as a primary school-level mathematics education response to COVID-19 pandemic in China: students' degree of approval and perception of digital equity.

The article introduces a mathematics education measure in response to the COVID-19 epidemic in China and explores students' degree of approval and perception of digital equity towards the response. After the outbreak of the COVID-19, the Chinese New Century Primary School Mathematics Textbook (NCPM) committee had developed a series of micro classes (abbreviated as NCPM micro classes), and more than 25 million teachers and students in China watched the NCPM micro classes during the 3 months social isolation. Then, students' degree of approval towards the NCPM micro classes and perception of digital equity were examined after social isolation. A total of 132,740 pieces of data were collected from Chinese primary school students. Quantitative analysis of student's degree of approval towards different parts of NCPM micro classes indicated that the introduction, interaction, summary and consolidation, curriculum characteristics, and goal achievement parts of the NCPM micro classes have received high approval from students, and students with higher former achievement perceived a higher degree of approval towards the NCPM micro classes. Furthermore, we found that gender, socioeconomic status, school location, and learning location had no significant impact on students' degree of approval, indicating a digital equity exists. This study helps researchers or educators understand the mathematics education response to the COVID-19 outbreak in China and extends our understanding of primary students' degree of approval and perception of digital equity with these online classes.

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma.

Lung adenocarcinoma (LUAD), as a form of non-small cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer worldwide. To date, a few biomarkers have been reported to provide valuable information in guiding LUAD treatment. The aim of our study was to explore the functional role of pyrroline-5-carboxylate reductase 1 (PYCR1) in LUAD. Based on Oncomine database, we found that PYCR1 was highly expressed in LUAD tissues. We also confirmed an abnormal increase of PYCR1 expression in LUAD cell lines and patients' tissues. Through Kaplan-Meier plotter database, we further studied the prognostic values of PYCR1. The outcomes indicated that overexpressed PYCR1 associated with poor prognosis among LUAD patients. To further study the function of PYCR1 in LUAD, cell counting kit-8, colony-forming, scratch wound healing, and Transwell assays were conducted. The results suggested that knockdown of PYCR1 curbed cell proliferation, migration, and invasion in LUAD cell lines. Subsequently, we identified 50 top genes positively and negatively correlated with PYCR1 in LUAD, and conducted biological pathway enrichment analysis of these genes. Among those enriched pathways, we selected JAK/STAT signaling pathway for further analysis. The results of Western blot assays revealed that PYCR1 knockdown significantly increased the expression of Bcl-2 and c-Myc, and the phosphorylation level of JAK2 and STAT3. Taken together, this study unearthed that PYCR1 knockdown could inhibit tumor growth and affect the JAK/STAT signaling pathway in LUAD. This study may contribute to a better understanding of PYCR1 in LUAD and provide a potential biomarker for cancer prognosis.

Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway.

OBJECTIVE: The relationship between NF-κB Interacting lncRNA (NKILA) and angiogenesis in breast cancer has never been studied. Our study aimed to investigate effect of NKILA on proliferation, migration, apoptosis, as well as angiogenesis in breast cancer. METHODS: NKILA was over-expressed in MDA-MB-231 cells by transfection of pcDNA3.1-NKILA vector. Cell viability, apoptosis and migration were measured by MTT, flow cytometry and wound healing assays, respectively. Angiogenesis of human umbilical vein endothelial cells (HUVEC) was measured using tube formation assay. The expression levels of NKILA, IL-6, VEGFA, VEGFR, apoptosis and epithelial-mesenchymal transition (EMT) and NF-κB/IL-6 signaling-related markers were determined using qRT-PCR or Western blotting. RESULTS: Cell viability and migration of MDA-MB-231 cells were significantly inhibited, while cell apoptosis was obviously promoted by overexpression of NKILA. Overexpression of NKILA could also inhibit the phosphorylation of IκBα and the nuclear transposition of p65, as well as induce cell apoptosis-related proteins and inhibit epithelial-mesenchymal transition-related proteins. Cell viability and migration of HUVEC were also significantly inhibited when treated with supernatant of cells overexpressed NKILA or treated with BAY11-7028. Exogenous IL-6 significantly increased the cell viability and migration of HUVEC, and overexpression of NKILA could reverse these effects induced by IL-6. Overexpression of NKILA significantly inhibited the protein levels of IL-6 and VEGFA in supernatant, as well as VEGFR in HUVEC, thus inhibited the angiogenesis of HUVEC. NKILA also reversed the above effects on protein levels of IL-6 and VEGFA in supernatant and angiogenesis induced by exogenous IL-6. CONCLUSION: Overexpression of NKILA could inhibit cell proliferation, migration and promote apoptosis of breast cancer cells. It could also inhibit cell proliferation, migration and angiogenesis of HUVEC through inhibiting IL-6 secretion via NF-κB signaling pathway.

The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells along with metastasis in vivo, and to explore the underlying mechanism. METHODS: RT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual-luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-5p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays. RESULTS: miR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interact with STK32A to promote its expression. Following the validation of the supporting role of STK32A in NSCLC cells and NF-κB p65 phosphorylation, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo. CONCLUSIONS: miR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A/NF-κB p65 axis, offering possible targets for the treatment for NSCLC.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.

In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman's R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed.

Clinical and prognostic features of 512 cases of cholangiocarcinoma. / 512例胆管细胞癌的临床及预后特点.

OBJECTIVES: Cholangiocarcinoma (CCA) is an aggressive malignant tumor with a poor overall prognosis. Given that CCA is often diagnosed at the late stage, the current treatments are less effective for most local advanced patients leading to high CCA mortality. This study aims to explore the clinical characteristics and prognostic factors affecting the occurrence and development of CCA and to provide potential methods for early diagnosis and clinical treatment of CCA. METHODS: We retrospectively analyzed the medical records of 512 patients with CCA who had been diagnosed by pathology and had completely clinical data in the Second Xiangya Hospital of Central South University in the past 16 years. The clinical features and prognosis related factors that affect the occurrence and development of CCA were investigated. Survival curves were plotted by the Kaplan-Meier method. P-values were calculated by log-rank for univariate analysis, and multivariate Cox regression was used to analyze multivariate analysis of meaningful variables. RESULTS: The incidence of CCA among ≤60 years old people was higher than of that >60 years old one (61.13% vs 38.87%), and was greater in men than women (52.5% vs 47.5%). Carbohydrate antigen 19-9 (CA19-9) level ≥35 µg/L accounted for 66.21%. The single tumor accounted for 86.91%, and patients in pathological stage III and IV accounted for 49.22% and 17.58%, respectively. Univariate analysis showed that ALB, ALP, CA19-9, and other factors were relevant to the prognosis. The results of multivariate analysis showed that ALP, CA19-9, tmaximum tumor diameter, and other factors were significant prognostic predictors. CONCLUSIONS: The incidence of CCA is higher in ≤60 years old people, and the stage is later at the initial diagnosis. CA19-9 level is a sensitive laboratory indicator. ALP, CA19-9, maximum tumor diameter, merged tumor, cirrhosis, and TNM stage are independent prognostic factors for CCA.

Individualized comprehensive treatment for lung adenocarcinoma with multiple skin and bilateral breast metastasis: A case report. / å¤šæ¬¡çš®è‚¤å’ŒåŒä¾§ä¹³è ºè½¬ç§»çš„è‚ºè ºç™Œä¸ªä½“åŒ–ç»¼åˆæ²»ç–—1例.

Lung adenocarcinoma is a malignant tumor that is prone to distant metastasis. Common metastatic sites are brain, adrenal gland, liver, bone, and so on. Skin soft tissue metastasis is unusual, and breast metastasis is even rarer. This case is a middle-aged female patient who had experienced multi-line treatments for upper limbs, abdominal skin, and bilateral breast tissue metastases.The patient's multiple metastases were susceptible to radiation therapy.Reviewing the entire treatment process of this patient can find that the rational use of individualized comprehensive treatment methods and appropriate timing of genetic testing are very important for patients with lung adenocarcinoma to prolong their survival time and improve their quality of life.

Efficacy and tolerance of GELOXD/P-GEMOXD in newly diagnosed nasal-type extranodal NK/T-cell lymphoma: A multicenter retrospective study.

OBJECTIVES: Nasal-type extranodal natural killer NK/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma with poor prognosis. This research aimed to evaluate the efficacy and safety of the GELOXD or P-GEMOXD regimens in patients with ENKTCL. METHODS: Newly diagnosed ENKTCL patients treated with either the GELOXD or the P-GEMOXD regimen were identified from three cancer centers between January 2010 and December 2016. Kaplan-Meier and Cox regression analyses were used to calculate overall survival (OS) and progression-free survival (PFS) and to investigate prognostic factors. RESULTS: One hundred and eighty-four cases were identified from three cancer centers. After 1-5 treatment cycles of GELOXD or P-GEMOXD chemotherapy, 155 (84%) patients showed a complete response (CR). The 3-year OS (73.0% vs 38.2%, P = .001) and PFS (72.8% vs 32.4%, P = .000) rates were significantly higher in early-stage patients compared with advanced-stage patients. A multivariate analysis revealed that patient CR status was a significant independent factor in disease prognosis. Grade 3/4 leukopenia occurred in 43 (23.4%) patients. Major non-hematological toxicities included nausea (n = 117, 63.6%) and vomiting (n = 66, 35.9%). CONCLUSIONS: The GELOXD and P-GEMOXD chemotherapy regimens are well tolerated and provide favorable survival outcomes in patients with ENKTCL.

Short-Course Versus Long-Course Chemoradiotherapy for Stage IE-IIE Extranodal Natural Killer/T cell Lymphoma, Nasal Type: A Multicenter Retrospective Study.

BACKGROUND This study compared clinical outcomes and adverse events between L-asparaginase/pegaspargase-based short-course and long-course chemoradiotherapy in newly diagnosed stage IE-IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL). MATERIAL AND METHODS Patients were categorized into a short-course (2-4 chemotherapy cycles, median: 4, n=153) and long-course group (5-6 cycles, median: 6, n=83). The chemotherapy regimens included GELOX, SMILE, and VLP. The radiotherapy dose was 40-63 Gy (median: 55 Gy). Adverse events, treatment responses, and survival outcomes between the 2 groups were compared. RESULTS Ann Arbor stage IIE and short-course chemotherapy adversely affected overall survival (OS). Ann Arbor stage IE favorably affected progression-free survival (PFS). Grade 3-4 hematological toxicities were higher in the long-course group (25.3% vs. 14.4%, p=0.038). Ann Arbor stage was the single different clinical feature between the 2 groups, and independently affected survival outcomes. In subgroup analysis of stage IE, there was no difference in response rates and survival outcomes between the 2 groups. In subgroup analysis of stage IIE, the recurrence and death rates were significantly lower in the long-course group (6.1% vs. 23.2%, p=0.015; 12.2% vs. 39.3%, p=0.002; respectively), and the 3-year OS and PFS rates were much longer in the long-course group (87.8% vs. 62.5%, p<0.001; 83.7% vs. 57.1%, p=0.001; respectively). CONCLUSIONS When radiotherapy was combined with L-asparaginase/pegaspargase-based chemotherapy to treat early-stage ENKTL patients, 2-4 cycles of chemotherapy might be sufficient for stage IE patients, while stage IIE patients might require 5+ cycles.

Using Artificial Intelligence (Watson for Oncology) for Treatment Recommendations Amongst Chinese Patients with Lung Cancer: Feasibility Study.

BACKGROUND: Artificial intelligence (AI) is developing quickly in the medical field and can benefit both medical staff and patients. The clinical decision support system Watson for Oncology (WFO) is an outstanding representative AI in the medical field, and it can provide to cancer patients prompt treatment recommendations comparable with ones made by expert oncologists. WFO is increasingly being used in China, but limited reports on whether WFO is suitable for Chinese patients, especially patients with lung cancer, exist. Here, we report a retrospective study based on the consistency between the lung cancer treatment recommendations made for the same patient by WFO and by the multidisciplinary team at our center. OBJECTIVE: The aim of this study was to explore the feasibility of using WFO for lung cancer cases in China and to ascertain ways to make WFO more suitable for Chinese patients with lung cancer. METHODS: We selected all lung cancer patients who were hospitalized and received antitumor treatment for the first time at the Second Xiangya Hospital Cancer Center from September to December 2017 (N=182). WFO made treatment recommendations for all supported cases (n=149). If the actual therapeutic regimen (administered by our multidisciplinary team) was recommended or for consideration according to WFO, we defined the recommendations as consistent; if the actual therapeutic regimen was not recommended by WFO or if WFO did not provide the same treatment option, we defined the recommendations as inconsistent. Blinded second round reviews were performed by our multidisciplinary team to reassess the incongruent cases. RESULTS: WFO did not support 18.1% (33/182) of recommendations among all cases. Of the 149 supported cases, 65.8% (98/149) received recommendations that were consistent with the recommendations of our team. Logistic regression analysis showed that pathological type and staging had significant effects on consistency (P=.004, odds ratio [OR] 0.09, 95% CI 0.02-0.45 and P<.001, OR 9.5, 95% CI 3.4-26.1, respectively). Age, gender, and presence of epidermal growth factor receptor gene mutations had no effect on consistency. In 82% (42/51) of the inconsistent cases, our team administered two China-specific treatments, which were different from the recommendations made by WFO but led to excellent outcomes. CONCLUSIONS: In China, most of the treatment recommendations of WFO are consistent with the recommendations of the expert group, although a relatively high proportion of cases are still not supported by WFO. Therefore, WFO cannot currently replace oncologists. WFO can improve the efficiency of clinical work by providing assistance to doctors, but it needs to learn the regional characteristics of patients to improve its assistive ability.

Serum high-density lipoprotein correlates with serum apolipoprotein M and A5 in obstructive sleep apnea hypopnea syndrome.

PURPOSE: The purpose of this study was to investigate the correlation between serum levels of serum apolipoprotein M (ApoM), A5 (ApoA5), and high-density lipoprotein (HDL) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and study the effects of nasal continuous positive airway pressure treatment on these serum biomarkers. METHODS: Thirty OSAHS patients and 15 non-OSAHS probands as control were selected for the study. Serum HDL, ApoM, and ApoA5 levels in two groups were detected; differences and association among them were analyzed. Patients with moderate and severe OSAHS underwent 3-month auto-continuous positive airway pressure treatment, and a comparative study was conducted to investigate the changes in blood lipids, serum ApoM, and ApoA5. RESULTS: In comparison to the control group, the HDL, ApoM, and ApoA5 serum levels were lower (P < 0.05). HDL was positively correlated to ApoM and ApoA5 (P < 0.001), and ApoM was positively correlated to ApoA5 (r = 0.536, P < 0.001). HDL, ApoM, and ApoA5 were significantly increased in the patients of moderate and severe OSAHS after auto-continuous positive airway pressure treatment for 3 months (P < 0.05). CONCLUSIONS: The HDL level was significantly lower in OSAHS patients. The decrease in serum ApoM and ApoA5 in OSAHS patients was correlated to the severity of OSAHS and HDL levels. Auto-continuous positive airway pressure treatment increased serum levels of ApoM, ApoA5, and HDL in OSAHS patients.

[Mechanisms for inhibitory effect of ALDH2 on doxorubicin-induced cytotoxicity in C2C12 myogenic cell line].

OBJECTIVE: To investigate the mechanisms for inhibitory effect of aldehyde dehydrogenase 2 (ALDH2) on doxorubicin (DOX)-induced cytotoxicity in C2C12 myogenic cell line.
 METHODS: Cell apoptosis was evaluated by flow cytometry and the activity of capase-3/7. The relative content of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) were detected by chemical fluorometric enzyme immunoassay. The protein and mRNA expression of ALDH2, Bcl-2, NADPH oxidase 2 (NOX2) and the cytoplasmic subunit p-p47PHOX were evaluated by Western blot and quantitative PCR, respectively. 
 RESULTS: Overexpression of ALDH2 attenuated DOX-induced cell toxicity (increase in apoptosis and inhibition of proliferation), which were reversed by downregulation of ALDH2. Overexpression of ALDH2 reduced p47PHOX phosphorylation levels, and suppressed activation of NOX2 and ROS production, which were reversed by downregulation of ALDH2. Moreover, apocynin, an inhibitor of NOX, reduced the cytotoxicity of DOX concomitantly with a decrease in phosphorylation of p47PHOX, ROS production and caspase-3/7 activity, and an increase in the activity and expression of ALDH2. 
 CONCLUSION: DOX-induced cytotoxicity is related to increase of intracellular oxidative stress, which is involved in unregulation of NOX2 and downregulation of ALDH2. Activation of ALDH2 could exert cytoprotection via inhibiting NOX2-dependent ROS production.

Association of higher-risk alcohol consumption with injecting paraphernalia sharing behaviours in intravenous drug users.

BACKGROUND: Alcohol use is common among injecting drug users. The coexistence of alcohol consumption and injecting risk behaviour has the potential to increase harms among intravenous drug users (IDUs). OBJECTIVE: This study aimed to determine whether the level of alcohol use is a risk factor for injecting paraphernalia sharing behaviours. METHODS: A total of 637 treatment-seeking IDUs were assessed for injecting paraphernalia sharing behaviours and drinking risk level as defined by the National Institute for Health and Care Excellence (NICE). Multivariate analyses were performed to identify alcohol risk factors associated with injecting paraphernalia sharing behaviours. RESULTS: After adjusting for the effects of ethnicity, employment and drug used, the odds ratio of higher risk drinking for injecting paraphernalia sharing behaviours was 1.92 (95% CI 1.31-2.83). CONCLUSION: Higher-risk drinking in IDUs is associated with higher rates of injecting paraphernalia sharing behaviours. It is important to take alcohol use into account when evaluating these patients for treatment and designing intervention strategies.