Role of Radiation-related Lung Function Genes in Prognosis and Immune Infiltration of Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common malignant tumor with no obvious clinical symptoms in its early stages. Patients can be divided into radiotherapysensitive groups (RS) and radiotherapy-resistant groups (RR) due to their varying conditions. The therapeutic effect of radiotherapy is quite different between the two groups. Therefore, this paper explores the role of radiation-related lung function genes in LUAD and its immune landscape. METHODS: Firstly, we divided LUAD samples from the TCGA cohort into RS and RR groups and analyzed differential expression to obtain differentially expressed genes (DEGs). Then, DEGs and patients' grouping information were input into the weighted co-expression network, and the genes in the radiotherapy-related modules were identified. Furthermore, after the intersection of DEGs and lung function-related genes, the prognosis-related genes were obtained through univariate Cox and Lasso-Cox analyses, respectively, and the risk model was constructed. Finally, the differences in prognosis and immunity of the samples in the risk model were explored. Additionally, we also performed a qPCR experiment on lung function-related genes. RESULTS: In this paper, radiation-related genes of LUAD were identified through a series of bioinformatics analyses. By conducting enrichment analysis on these genes, several pathways related to LUAD radiation were identified, and DEGs associated with significant prognosis were determined. Furthermore, a radiation-related risk model of LUAD was developed. All samples were divided into high-risk and low-risk groups based on the risk score, and the differences in immune cell infiltration abundance and immune function between these groups were evaluated. The qPCR experimental results demonstrated a significant difference in the expression of genes related to lung function. CONCLUSION: The prognosis-related genes identified in this paper and the risk model created can serve as a reference for diagnosing and treating LUAD.

Autophagy flux in bladder cancer: Cell death crosstalk, drug and nanotherapeutics.

Autophagy, a self-digestion mechanism, has emerged as a promising target in the realm of cancer therapy, particularly in bladder cancer (BCa), a urological malignancy characterized by dysregulated biological processes contributing to its progression. This highly conserved catabolic mechanism exhibits aberrant activation in pathological events, prominently featured in human cancers. The nuanced role of autophagy in cancer has been unveiled as a double-edged sword, capable of functioning as both a pro-survival and pro-death mechanism in a context-dependent manner. In BCa, dysregulation of autophagy intertwines with cell death mechanisms, wherein pro-survival autophagy impedes apoptosis and ferroptosis, while pro-death autophagy diminishes tumor cell survival. The impact of autophagy on BCa progression is multifaceted, influencing metastasis rates and engaging with the epithelial-mesenchymal transition (EMT) mechanism. Pharmacological modulation of autophagy emerges as a viable strategy to impede BCa progression and augment cell death. Notably, the introduction of nanoparticles for targeted autophagy regulation holds promise as an innovative approach in BCa suppression. This review underscores the intricate interplay of autophagy with cell death pathways and its therapeutic implications in the nuanced landscape of bladder cancer.

Immune modulatory roles of radioimmunotherapy: biological principles and clinical prospects.

Radiation therapy (RT) not only can directly kill tumor cells by causing DNA double-strand break, but also exerts anti-tumor effects through modulating local and systemic immune responses. The immunomodulatory effects of RT are generally considered as a double-edged sword. On the one hand, RT effectively enhances the immunogenicity of tumor cells, triggers type I interferon response, induces immunogenic cell death to activate immune cell function, increases the release of proinflammatory factors, and reshapes the tumor immune microenvironment, thereby positively promoting anti-tumor immune responses. On the other hand, RT stimulates tumor cells to express immunosuppressive cytokines, upregulates the function of inhibitory immune cells, leads to lymphocytopenia and depletion of immune effector cells, and thus negatively suppresses immune responses. Nonetheless, it is notable that RT has promising abscopal effects and may achieve potent synergistic effects, especially when combined with immunotherapy in the daily clinical practice. This systematic review will provide a comprehensive profile of the latest research progress with respect to the immunomodulatory effects of RT, as well as the abscopal effect of radioimmunotherapy combinations, from the perspective of biological basis and clinical practice.

LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation.

Hepatitis B virus (HBV) infection results in liver cirrhosis and hepatocellular carcinoma (HCC). HBx/nuclear factor (NF)-κB pathway plays a role in HBV replication. However, whether NF-κB-interacting long noncoding RNA (NKILA), a suppressor of NF-κB activation, regulates HBV replication remains largely unknown. In this study, gain-and-loss experiments showed that NKILA inhibited HBV replication by inhibiting NF-κB activity. In turn, HBV infection down-regulated NKILA expression. In addition, expression levels of NKILA were lower in the peripheral blood-derived monocytes (PBMCs) of HBV-positive patients than in healthy individuals, which were correlated with HBV viral loads. And a negative correlation between NKILA expression level and HBV viral loads was observed in blood serum from HBV-positive patients. Lower levels of endogenous NKILA were also observed in HepG2 cells expressing a 1.3-fold HBV genome, HBV-infected HepG2-NTCP cells, stable HBV-producing HepG2.2.15 and HepAD38 â€‹cells, compared to those HBV-negative cells. Furthermore, HBx was required for NKILA-mediated inhibition on HBV replication. NKILA decreased HBx-induced NF-κB activation by interrupting the interaction between HBx and p65, whereas NKILA mutants lack of essential domains for NF-ĸB inhibition, lost the ability to inhibit HBV replication. Together, our data demonstrate that NKILA may serve as a suppressor of HBV replication via NF-ĸB signalling.

Feasibility of flattening filter free beams for hippocampal avoidance whole-brain radiotherapy: a dosimetric and radiobiological analysis.

Objectives: The purpose of this study is to evaluate the potential of the flattening filter free (FFF) mode of a linear accelerator for patients with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) by comparison with flattened beams (FF) technique in the application of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) using dosimetric and radiobiological indexes based on the volume of hippocampus and target. Methods: 2 VMAT- and 2 IMRT- plans were optimized in Eclipse planning system with 2 different delivery modes (6 MV standard vs. 6 MV FFF) for each of 25 patients. Dose distributions of the target and organs at risk (OARs), normal tissue complication probability (NTCP) of the hippocampus, monitor units, treatment time and quality assurance results were evaluated to compare the normal and FFF beam characteristics by Wilcoxon matched-pair signed-rank test with a significance level of 0.05. Results: VMAT-FFF provided the significantly best homogeneity and conformity of the target, delivered the lowest dose to hippocampus and the other OARs, and led to the lowest NTCP of the hippocampus among all modalities, which has the potential to alleviate neurocognitive decline after WBRT. IMRT-FFF reduced the dose to the lens with similar dose distributions of the target compared with IMRT-FF, whereas the lower dose to the hippocampus was achieved using the conventional beams. The monitor units were obviously increased by 19.2% for VMAT and 33.8% for IMRT, when FFF beams w ere used. The removal of flattening filter for IMRT resulted in a 26% reduction in treatment time, but VMAT had the similar treatment time for the two modes owing to the limitation of gantry rotation speed. Gamma analysis showed an excellent agreement for all plans at 3%/2 mm, and no statistical differences were found between FF and FFF. Conclusion: In conclusion, this study suggests that FFF mode is feasible and advantageous in HA-WBRT and VMAT-FFF is the optimal solution in terms of dose distribution of the target, OARs sparing, NTCP of the hippocampus and delivery efficiency compared to the other three techniques. Additionally, the advantages of the FFF technique for VMAT are more prominent in cases with small hippocampal volumes.

Current and future research on the association between gut microbiota and breast cancer.

Breast cancer (BC) is a prevalent malignancy. There exists a strong association between gut microbiota (GM) and the development of BC. The GM composition in individuals with BC significantly differs from that in their healthy counterparts. Furthermore, the distribution of GM varies significantly among individuals with different types of BC. The GM can impact BC through metabolite secretion, the gut-mammary axis, and other pathways. Modulating the GM can serve as a very promising potential therapeutic strategy in the treatment of BC. This article will summarize existing research, focusing on the relationship between intestinal microbiota and BC. At the same time, the project will also analyze the application value of intestinal microorganisms in BC intervention work, so as to provide a reference for the further development of BC prevention and treatment work.

Effectiveness of S-1-Based Chemoradiotherapy in Patients 70 Years and Older With Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial.

Importance: Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for patients with inoperable esophageal cancer. However, patients tend to tolerate intravenous chemotherapy less well with age and comorbidities. It is essential to find a better treatment modality that improves survival outcomes without reducing the quality of life. Objective: To evaluate the effectiveness of simultaneous integrated boost radiotherapy (SIB-RT) with concurrent and consolidated oral S-1 chemotherapy for patients aged 70 years and older with inoperable esophageal squamous cell carcinoma (ESCC). Design, Setting, and Participants: This multicenter, phase III randomized clinical trial was conducted between March 2017 and April 2020 in 10 centers in China. Patients with inoperable, locally advanced, clinical stage II to IV ESCC were enrolled and randomized to receive SIB-RT concurrent with and followed by oral S-1 chemotherapy (CRTCT group) or SIB-RT alone (RT group). Data analysis was completed on March 22, 2022. Interventions: In both groups, the planning gross tumor volume was administered with radiation dose of 59.92 Gy and the planning target volume was administered with radiation dose of 50.4 Gy, in 28 fractions each. In the CRTCT group, concurrent S-1 was administered on radiotherapy days, and consolidated S-1 was administered at 4 to 8 weeks after SIB-RT. Main Outcomes and Measures: The primary end point was overall survival (OS) of the intent-to-treat population. Secondary end points were progression-free survival (PFS) and toxicity profile. Results: A total of 330 patients (median [IQR] age, 75.5 [72-79] years; 220 [66.7%] male patients) were included, with 146 patients randomized to the RT group and 184 randomized to the CRTCT group. A total of 107 patients (73.3%) in the RT group and 121 patients (67.9%) in the CRTCT group were clinically diagnosed with stage III to IV disease. At the time of analysis of the 330 patients in the intent-to treat-population (March 22, 2022), OS was improved in the CRTCT group compared with the RT group at 1 year (72.2% vs 62.3%) and 3 years (46.2% vs 33.9%; log-rank P = .02). PFS was similarly improved in the CRTCT group compared with the RT group at 1 year (60.8% vs 49.3%) and 3 years (37.3% vs 27.9%; log-rank P = .04). There was no significant difference in the incidence of treatment-related toxic effects higher than grade 3 between the 2 groups. Grade 5 toxic effects occurred in each group, including 1 patient who experienced myelosuppression and 4 patients with pneumonitis in the RT group and 3 patients with pneumonitis and 2 patients with fever in the CRTCT group. Conclusions and Relevance: These findings suggest that oral S-1 chemotherapy administered with SIB-RT should be considered as an alternative treatment option for patients aged 70 years and older with inoperable ESCC, since it improved survival outcomes without additional treatment-related toxic effects compared with SIB-RT alone. Trial Registration: ClinicalTrials.gov Identifier: NCT02979691.

Bone marrow-derived mesenchymal stem cells accelerate angiogenesis in pregnant experimentally induced deep venous thrombosis rat model via up-regulation of pro-angiogenic secretogranin II.

The present study investigated whether bone marrow-derived mesenchymal stem cells (BMMSCs) facilitate angiogenesis and improve outcomes of pregnancy with obstetric deep venous thrombosis (DVT) and explored the underlying mechanism. A pregnant DVT rat model was established using a "stenosis" method on the lower segment of the inferior vena cava (IVC). The extent of vascularization in thrombosed IVC was examined by immunohistochemistry. In addition, the effect of BMMSCs on DVT pregnancy outcomes was evaluated. We also characterized the effect of BMMSC-derived conditioned medium (BM-CM) on the impaired human umbilical vein endothelial cells (HUVECs). Thereafter, transcriptome sequencing was employed to identify the differentially expressed genes in thrombosed IVC tissues of DVT and DVT plus BMMSCs (thrice) groups. Lastly, the candidate gene's role in the promotion of angiogenesis was demonstrated in vitro and in vivo. The DVT model was successfully established using IVC stenosis. The injection of three consecutive BMMSC doses into pregnant SD rats with DVT was demonstrated to be the most effective treatment, which significantly reduced the length and weight of the thrombus, induced the highest level of angiogenesis, and ameliorated the embryo absorption rate. In vitro, BM-CM efficiently increased the abilities of impaired endothelial cells to proliferate, migrate, invade, and form vessel-like tubes, while inhibiting their apoptosis. Transcriptome sequencing revealed that BMMSCs induced a prominent upregulation of a variety of pro-angiogenic genes, including secretogranin II (SCG2). When SCG2 expression was knocked down by lentivirus, the BMMSCs' and BM-CM-induced pro-angiogenic effects on pregnant DVT rats and HUVECs were markedly attenuated. In conclusion, the study results suggest that BMMSCs enhance angiogenesis via up-regulation of SCG2, providing an effective alternative regenerative agent and novel target for the therapy of obstetric DVT.

Application of Clavien-Dindo classfication-grade in evaluating overall efficacy of laparoscopic pancreaticoduodenectomy.

Background: The Clavien-Dindo classification (CDC) has been widely accepted and applied in clinical practice. We investigated its effectiveness in prediction of major complications (LPPC) after laparoscopic pancreaticoduodenectomy (LPD) and associated risk factors. Methods: A retrospective analysis was conducted covering clinical data of 793 patients undergoing LPD from April 2015 to November 2021. CDC was utilized to grade postoperative complications and analyze the differences. Risk factors of LPPC were identified according to univariate and multivariate analyses. Resluts: For the 793 patients undergoing laparoscopic pancreaticoduodenectomy in the northeast of China, LPPC was reported in 260 (32.8%) patients, pancreatic fistula in 169 (21.3%), biliary fistula in 44 (5.5%), delayed gastric emptying in 17(2.1%), post pancreatectomy hemorrhage in 55 (6.9%), intestinal fistula in 7 (0.8%), abdominal infections in 59 (7.4%) and pulmonary complication in 28 (3.5%). All complications were classified into five levels with the C-D classification (Grade I-V), with 83 (31.9%) patients as grade I, 91 (35.0%) as grade II, 38 (14.6%) as grade IIIa, 24 (9.2%) as grade IIIb, 9 (3.5%) as grade IV and 15 (5.8%) as grade V. 86 (10.8%) patients experienced major complications (grade III-V).The results of univariate and multivariate analysis revealed the independent risk factors for laparoscopic pancreaticoduodenectomy complications to be preoperative total bilirubin (P = 0.029, OR = 1.523), soft pancreas texture (P < 0.001, OR = 1.399), male (P = 0.038, OR = 1.396) and intraoperative transfusion (P = 0.033, OR = 1.517). Preoperative total bilirubin (P = 0.036, OR = 1.906) and intraoperative transfusions (P = 0.004, OR = 2.123) were independently associated with major postoperative complications. The influence of different bilirubin levels on C-D grade of complications was statistically significant (P = 0.036, OR = 1.906). Conclusions: The Clavien-Dindo classification (CDC) may serve as a valid tool to predict major postoperative complications and contribute to perioperative management and comparison of surgical techniques in different medical centers.

Construction of survival prediction model for elderly esophageal cancer.

Background: The purpose of this study was to analyze the clinical characteristics and prognosis of EPEC and to construct a prediction model based on the SEER database. Methods: All EPECs from the SEER database were retrospectively analyzed. A comprehensive and practical nomogram that predicts the overall survival (OS) of EPEC was constructed. Univariate and multivariate Cox regression analysis was performed to explore the clinical factors influencing the prognosis of EPEC, and finally, the 1 -, 3 - and 5-year OS were predicted by establishing the nomogram. The discriminant and predictive ability of the nomogram was evaluated by consistency index (C-index), calibration plot, area under the curve (AUC), and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to evaluate the clinical value of the nomogram. Results: A total of 3478 patients diagnosed with EPEC were extracted from the SEER database, and the data were randomly divided into the training group (n=2436) and the validation group (n=1402). T stage, N stage, M stage, surgery, chemotherapy, radiotherapy, age, grade, and tumor size were independent risk factors for 1 -, 3 - and 5-year OS of EPEC (P< 0.05), and these factors were used to construct the nomogram prediction mode. The C-index of the validation and training cohorts was 0.718 and 0.739, respectively, which were higher than those of the TNM stage system. The AUC values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, and 3-year OS showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, and 3-year DCA compared with the AJCC stage system. Conclusions: This study shows that the nomogram prediction model for EPEC based on the SEER database has high accuracy and its prediction performance is significantly better than the TNM staging system, which can accurately and individually predict the OS of patients and help clinicians to formulate more accurate and personalized treatment plans.

The prognostic risk stratification model for metastatic small-cell lung cancer: An analysis of the SEER database.

Distant metastases of small-cell lung cancer (DM-SCLC) is an important factor in the selection of treatment strategies. In this study, we established a nomogram to predict DM-SCLC and determine the benefit of radiotherapy (RT) for DM-SCLC. We analyzed DM-SCLC prognosis based on surveillance, epidemiology, and end result database (SEER) data. A comprehensive and practical nomogram that predicts the overall survival (OS) of DM-SCLC was constructed and the results were compared with the 7th edition of the American Joint Committee on Cancer (AJCC) TNM stage system. A concordance index (C-index) and receiver operating characteristic plot were generated to evaluate the nomogram discrimination. The calibration was evaluated with a calibration plot, and its effectiveness was evaluated by a decision curve analysis (DCA). A score was assigned to each variable, and a total score was established for the risk stratification model. A total of 13,403 DM-SCLC patients were included. Eight characteristic variables were identified as independent prognostic variables. The C-index of the validation and training cohorts was 0.716 and 0.734, respectively. The area under the receiver operating characteristic curve (AUC) values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, 3-year survival rates showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, 3-year DCA compared with the AJCC stage system. A predictive nomogram and risk stratification model have been constructed to evaluate the prognosis of DM-SCLC effectively and accurately. This nomogram may provide a reference for prognosis stratification and treatment decisions.

Incidence and risk of severe adverse events associated with trastuzumab emtansine (T-DM1) in the treatment of breast cancer: an up-to-date systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVES: We performed an up-to-date meta-analysis to quantify the overall incidence and risk of severe adverse events (AEs) associated with T-DM1 in patients with breast cancer. METHODS: Pubmed, Embase, and oncology conference proceedings were searched for relevant studies. Data were extracted to calculate the summary incidence rate and relative risk (RR) of grade ≥3 AEs. RESULTS: A total of 5,045 patients from 7 RCTs were included in the meta-analysis. The use of T-DM1 was associated with an increased risk of severe thrombocytopenia (RR 10.66, 95% CI 3.23-35.18, P < 0.001), anemia (RR 1.68, 95% CI 1.15-2.44, P = 0.007), elevated ALT (RR 2.67, 95% CI 1.60-4.47, P < 0.001), and AST (RR 3.76, 95% CI 1.45-9.78, P = 0.007). In addition, the use of T-DM1 can increase the risk of severe hypertension (RR 1.59, 95% CI 1.03-2.45, P = 0.037) and peripheral sensory neuropathy (RR 8.13, 95% CI 1.89-35.03, P = 0.005). CONCLUSIONS: Treatment with T-DM1 increases the risk of severe hematologic toxicities, hepatotoxicity, hypertension, and peripheral sensory neuropathy in patients with breast cancer, while the overall incidence of these AEs is low.

The benefit of radiotherapy in distant metastatic small-cell lung cancer: A retrospective study based on propensity score matching (PSM).

Due to extensive tumor spread, systemic chemotherapy is the main treatment for distant metastatic small-cell lung cancer (DM-SCLC). It is still unclear whether adding local radiotherapy (RT) on the basis of chemotherapy can improve the long-term survival of patients with DM-SCLC. This study aims to explore the population with DM-SCLC who can benefit from RT. Patients with metastatic SCLC with complete data were collected from the Surveillance, Epidemiology, and End Results database and divided into 2 groups according to whether RT was given or not. The propensity score matching method was used to balance the covariate differences between the RT group and the non-RT group. Lasso Cox regression model and Cox proportional hazards regression analyses were used to identifying independent risk factors affecting survival. Kaplan-Meier method was used to calculate the survival rate. P < .05 was considered statistically significant. After matching, there were 3150 patients in both groups. Sex, tumor size, N stage, RT, chemotherapy, brain metastasis, liver metastasis, age, and site metastasis were independent factors of survival in DM-SCLC. The 1- and 2-year survival rates were 24.5% and 5.8% in the RT group and 14.8% and 2.3% in the non-RT group (P < .001). The median survival time of the RT group was 9 months, and that of the non-RT group was 7 months, and the difference was statistically significant (P < .001). RT improved survival in all sex subgroups, any N stage subgroup, any tumor size subgroup, no brain metastases subgroup, no liver metastases subgroup, any age subgroup, and 1-2 organ metastases subgroup. RT improves 1- and 2-year survival in DM-SCLC.

Association of Adjuvant Radiation Therapy With Long-Term Overall and Recurrence-Free Survival After Hepatectomy for Hepatocellular Carcinoma: A Multicenter Propensity-Matched Study.

PURPOSE: R0 resection with a wide surgical margin is the gold standard for hepatocellular carcinoma (HCC), yet R0 resection with narrow margins and even R1 resection is not uncommon in real-world clinical practice. We sought to use a propensity-matched analysis to characterize the efficacy of adjuvant radiation therapy on long-term oncological survival after hepatectomy for HCC with narrow or positive margins. METHODS AND MATERIALS: Using a multi-institutional database, patients with HCC who underwent hepatectomy with negative margins of 0.1 to 1.0 cm or pathologically positive margins were analyzed. Using propensity score matching (PSM) and multivariate Cox-regression analysis, the effect of adjuvant radiation therapy on long-term overall survival (OS) and recurrence-free survival (RFS) was evaluated. RESULTS: Among 683 patients who met inclusion criteria, 82 patients received adjuvant radiation therapy within 10 weeks after surgery. Radiation therapy-related major toxic effects were minimal among patients receiving adjuvant radiation therapy. PSM analysis created 78 matched pairs of patients. In the PSM cohort, median OS and RFS among patients treated with adjuvant radiation therapy were more favorable than individuals who were not treated (72.5 and 37.3 months versus 52.5 and 24.0 months, both P < .05). After adjustment for other confounding factors on multivariate analyses, adjuvant radiation therapy remained independently associated with favorable OS and RFS after hepatectomy with close/positive surgical margins for HCC (hazard ratios, 0.821 and 0.827, respectively). CONCLUSIONS: Despite the lack of consensus on the role of adjuvant radiation therapy after HCC resection, this PSM analysis suggested improved OS and RFS with adjuvant radiation therapy after hepatectomy with close/positive surgical margins for HCC. Future randomized controlled trials are needed to further define the survival benefit of adjuvant radiation therapy for patients with HCC.

Construction and Verification of Nomogram Model for Lung Adenocarcinoma With ≤ 5 Bone-Only Metastases Basing on Hematology Markers.

Objectives: This retrospective study investigated prognostic factors in advanced lung adenocarcinoma (LUAD) with one to five bone-only metastasis (BOM) and developed a nomogram model to estimate patient survival. Methods: We investigated patients with advanced LUAD with one to five bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in two hospitals. A formula named Risk-H was constructed using hematological variables screened by LASSO-Cox regression analysis in the internal set and verified by the external set. Two nomogram models were developed by clinical variables selected by LASSO-Cox regression analysis with or without Risk-H in the internal set. The concordance index (C-index), calibration curves, time-dependent receiver operating characteristic (ROC) analysis, area under the curve (AUC), and decision curve analysis (DCA) were formulated to verify nomogram models. The primary endpoint was overall survival. Results: We finally included 125 and 69 patients, respectively, in the internal and external sets for analysis. The following were significant hematology prognostic factors and were included in the Risk-H formula: alkaline phosphatase and albumin, leukocyte. Four clinical factors, including loss of weight, sensitive mutation status, T and N stage, with or without Risk-H were used to establish nomogram models. C-index, calibration curves, ROC analysis, AUC, and DCA showed the addition of hematological data improved the predictive accuracy of survival. Conclusions: Pretreatment peripheral blood indexes may be a meaningful serum biomarker for prognosis in LUAD. The addition of Risk-H to the nomogram model could serve as a more economical, powerful, and practical method to predict survival for LUAD patients with one to five BOM.

Association of the fat-free mass index with mortality in patients with cancer: A multicenter observational study.

OBJECTIVES: Low fat-free mass index (FFMI) has been related to a higher mortality in community populations. However, information on the relationship between FFMI and mortality is lacking for patients with cancer. The objective of this study was to examine the association between FFMI and all-cause mortality in Chinese cancer patients. METHODS: This retrospective analysis included data on 1744 patients with cancer from a multicenter cohort study. The restricted cubic splines were used to flexibly model the association of FFMI with all-cause mortality. The association between low FFMI and overall survival was analyzed with the Kaplan-Meier method and a Cox model. RESULTS: Among all patients, there were 702 men (40.3%) and 1042 women (59.7%). The optimal cutoff point of low FFMI was 16.31 for men and 14.14 for women. The FFMI showed an inverse association with all-cause mortality for men (per standard deviation [SD] increment; hazard ratio [HR]: 0.72; 95% confidence interval [CI], 0.60-0.87; P < 0.001) and a nonlinear relation for women (per SD increment; HR: 0.88; 95% CI, 0.78-0.99; P = 0.048). After adjustment, a low FFMI score was independently associated with an increased risk of mortality for both men and women. In addition, FFMI showed a strong L-shape (per SD increment; HR: 0.59; 95% CI, 0.46-0.76; P < 0.001) relation with all-cause mortality in elderly patients with cancer. For specific tumor type, a low FFMI score was independently associated with worse prognosis in patients with lung and upper gastrointestinal cancer. CONCLUSIONS: A low FFMI score was associated with all-cause mortality in patients with cancer, especially for elder adults with cancer. These results highlight the usefulness of the FFMI for routine clinical assessment and prognostic estimation in patients with cancer.

Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.

BACKGROUND: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure. RESULTS: The protein and mRNA expression levels of PI3K、p-AKt、p-mTOR、NF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency. CONCLUSIONS: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.

Nomogram for predicting the survival of patients with small cell carcinoma of the esophagus: A population study based on the surveillance, epidemiology, and end results database.

ABSTRACT: This study aims to establish an effective prognostic nomogram for small cell carcinoma of the esophagus (SCCE).A total of 552 patients with SCCE from 1975 to 2016 were extracted from the surveillance, epidemiology, and end results (SEER) database. A Cox proportional hazard regression model was used to analyze the prognostic factors of patients, and a nomogram was constructed. The nomogram was then validated internally by using a consistency index (C-index) and a correction curve to evaluate its predictive value.The Cox proportional hazard regression model showed that age, stage, surgery, primary site, radiotherapy, and chemotherapy were the prognostic factors of SCCE (P < .1), and they were used to construct the nomogram. The C-index of the nomogram for predicting survival was 0.749 (95% confidence interval [CI] = 0.722-0.776). The data were randomly divided into a modeling group and a validation group based on 7:3 for internal validation. The C-indices of the modeling and validation groups were 0.753 and 0.725, respectively, and they were close to 0.749. The calibration curves exhibited good consistency between the predicted and actual survival rates.The nomogram of the survival and prognosis of patients with SCCE in this study had a good predictive value and could provide clinicians with accurate and practical predictive tools. It could also be used to facilitate a rapid and accurate assessment of patients' survival and prognosis on an individual basis.

BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma.

The current treatment for natural killer/T-cell lymphoma (NKTL) among advanced/relapsed patients is unsatisfying, thereby highlighting the need for novel therapeutic targets. B-cell chronic lymphocytic leukemia/lymphoma 11 A (BCL11A), as a transcription factor, is oncogenic in several neoplasms. However, its function in NKTL remains unclear. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure the BCL11A expression levels among NKTL patients and in NKTL cell lines. Natural killer (NK) cells from healthy subjects were used as negative control. Transient transfection with small interfering RNA was used to knockdown the expression in NKTL cell lines. Samples and clinical histories were collected from 343 NKTL patients (divided into test and validation groups) to evaluate the clinical value of BCL11A expression level. The BCL11A expression was upregu\lated among NKTL patients and in NKTL cell lines. Reduced cell proliferation and increased apoptosis were observed after silencing BCL11A in NKTL cell lines. BCL11A expression level was correlated with RUNX3, c-MYC, and P53 in NKTL. Notably, a high BCL11A expression was correlated with unfavorable clinical characteristics and predicted poor outcomes in NKTL. In conclusion, BCL11A was overexpressed in NKTL, while its upregulation promoted tumor development. Therefore, BCL11A expression level may be a promising prognostic biomarker for NKTL.

LncRNA LOXL1-AS1 regulates the tumorigenesis and development of lung adenocarcinoma through sponging miR-423-5p and targeting MYBL2.

Lung adenocarcinoma (LUAD) is the most common form of malignant tumor and closely correlated with high risk of death worldwide. Accumulating researches have manifested that long noncoding RNAs (lncRNAs) are deeply involved in the progression of multiple cancers. LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) was identified as an oncogene in several cancers, nonetheless, its biological effect and regulatory mechanism have not been explained in LUAD. Our present study suggested that LOXL1-AS1 expression was considerably increased in LUAD tissues and cells. Moreover, LOXL1-AS1 deficiency notably hampered cell proliferation and migration as well as dramatically facilitated cell apoptosis. Through molecular mechanism assays, LOXL1-AS1 was identified as a cytoplasmic RNA and acted as a sponge of miR-423-5p. Furthermore, MYBL2 was targeted and negatively modified by miR-423-5p. Rescue experiments revealed that MYBL2 knockdown could counteract miR-423-5p repression-mediated enhancement on the progression of LOXL1-AS1 downregulated LUAD cells. More importantly, MYBL2 was discovered to interact with LOXL1-AS1 promoter, indicating a positive feedback loop of LOXL1-AS1/miR-423-5p/MYBL2 in LUAD. These findings manifested the carcinogenic role of LOXL1-AS1 and LOXL1-AS1/miR-423-5p/MYBL2 feedback loop in LUAD, which could be helpful to explore effective therapeutic strategy for LUAD patients.