Association between coffee and caffeine intake and risk of COPD: Findings based on NHANES 2007-2012.

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

Abietane diterpenoids from Phlegmariurus carinatus and their biological activities.

Five undescribed abietane diterpenoids, along with eight known analogs, were isolated from Phlegmariurus carinatus. Their structures were unambiguously elucidated by extensive analysis of spectroscopic data and comparison between the literature. The absolute configuration of phlecarinatone C was determined by evaluating ECD spectra. Four undescribed abietane diterpenoids and eight known analogs were tested for their neuroprotective and cytotoxic activities, separately. Teuvincenone C showed potential neuroprotective effect against Hemin-induced HT22 cell damage. Importantly, phlecarinatone C showed pronounced cytotoxic effect against U251 cells in vitro assays. The biological evaluation revealed that phlecarinatone C could inhibit proliferation, migration, and invasion in a concentration-dependent manner of U251 cells. Meanwhile, phlecarinatone C effectively reversed epithelial-to-mesenchymal transition (EMT) and promoted U251 cells apoptosis via a mitochondrial apoptotic pathway. Taken together, phlecarinatone C might be a valuable candidate for anti-metastatic agents against glioblastoma treatment.

Percutaneous Cerclage Wiring Combined with Cephalomedullary Nailing for Irreducible Subtrochanteric Fractures.

OBJECTIVE: To explore the surgical method, operation essentials and the clinical effect of the treatment of irreducible subtrochanteric femoral fractures by percutaneous cerclage wiring and Cephalomedullary nail. METHOD: From February 2016 to October 2019, 17 cases of irreducible subtrochanteric femoral fractures (SFFs) treated via a minimally invasive wire system and intramedullary nail fixation were reviewed retrospectively. Ten male and seven female patients were involved. The average age was 59.88 ± 16.13 years, ranging from 41 to 94 years. Among the patients, seven were injured in traffic accidents, five fell from a standing height, and five injured themselves from falling. The cases were classified based on the Seinsheimer classification. Specifically, five cases were type IIIA, five cases were type IIIB, one case was type IV, and six cases were type V. According to the AO/OTA classification, 10 cases were 32B3, and seven cases were 32C3. During surgery, the patients were placed on a traction bed andattempted closed reduction. For those patients whose closed reduction failed confirmed by fluoroscopy, we performed a small anterolateral incision through which a self-made minimally invasive percutaneous wire introducer (passer; patent Z: 2016 2 1002800.8) was employed for temporary fixation with a wire. A double-stranded steel wire was introduced into a self-made wire traction and lifting device (patent ZL 2020 2 0205658.7), the wire was pulled vertically and firmly fixed. Then an long InterTan nail was used for the fixation. The following information was recorded: (i) length of the invasive incision, (ii) blood loss on the third day after surgery, (iii) operation time; and (iv) maximum displacement and angulation of the fracture ends of the x-rayed front and side fractures before and after surgery and the maximum displacement and formation of the three-dimensional CT-scanned fracture ends in the coronal plane, sagittal plane, and cross section before and after surgery. RESULT: A total of 15 of the 17 patients were followed for 12 to 24 months. The 15 patients recovered, but one died from pulmonary infection 1 year after surgery. In the postoperative X-ray and three-dimensional CT observation reduction treatment, fracture displacement was less than 5 mm, each plane angle was less than 10 degrees, and postoperative fracture healing time was 3 to 14 months, with an average of 4.19 ± 4.04 months. The postoperative Harris hip function score ranged from 66 to 95 points, with an average of 80.81 ± 9.67 points. In terms of clinical outcomes, 11 cases were excellent, four cases were satisfactory, and one case was fair. CONCLUSION: For refractory subtrochanteric fractures, percutaneous wiring combined with Cephalomedullary nail fixation is a minimally invasive, rapid, and effective method, which can achieve satisfactory results in clinical practice and is worth promoting.

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases.

Background: Hepatocellular carcinoma (HCC) is a solid tumor with high recurrence rate and high mortality. It is crucial to discover available biomarkers to achieve early diagnosis and improve the prognosis. The effect of LSM4 in HCC still remains unrevealed. Our study is dedicated to exploring the expression of LSM4 in HCC, demonstrating its clinical significance and potential molecular mechanisms. Methods: Clinical information and LSM4 expression values of HCC were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prognostic and diagnostic significance of LSM4. Calculating pooled standardized mean difference (SMD) and performing summary receiver operating characteristic (sROC) curve analysis to further determine its expression status and diagnostic significance. LSM4-related co-expressed genes (CEGs) were obtained and explored their clinical significance in HCC. LSM4-associated pathways were identified through Gene set enrichment analysis (GSEA). Results: Up-regulated LSM4 was detected in HCC tissues (SMD = 1.56, 95% CI: 1.29-1.84) and overexpressed LSM4 had excellent distinguishing ability (AUC = 0.91, 95% CI: 0.88-0.93). LSM4 was associated with clinical stage, tumor grade, and lymph node metastasis status (p < 0.05). Survival analysis showed that high LSM4 expression was related to poor overall survival (OS) of HCC patients. Cox regression analysis suggested that high LSM4 expression may be an independent risk factor for HCC. We obtained nine up-regulated CEGs of LSM4 in HCC tissues, and six CEGs had good prognostic and diagnostic significance. GSEA analysis showed that up-regulated LSM4 was closely related to the cell cycle, cell replication, focal adhesion, and several metabolism-associated pathways, including fatty acid metabolism. Conclusion: Overexpressed LSM4 may serve as a promising diagnostic and prognostic biomarker of HCC. Besides, LSM4 may play a synergistic effect with CEGs in promoting the growth and metastasis of HCC cells via regulating crucial pathways such as cell cycle, focal adhesion, and metabolism-associated pathways.

[Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens. RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.

RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.

Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.

Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer.

In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.

Expressions of MUC1 and vascular endothelial growth factor mRNA in blood are biomarkers for predicting efficacy of gefitinib treatment in non-small cell lung cancer.

BACKGROUND: Gefitinib, an EGFR-tyrosine kinase inhibitor, significantly improve prognosis in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the usefulness of MUC1 and vascular endothelial growth factor (VEGF) mRNA expression in peripheral blood as means of predicting benefit from gefitinib therapy in NSCLC patients. METHODS: MUC1 and VEGF mRNA expressions were detected in peripheral blood of 66 patients with advanced NSCLC before (B0) and 4 weeks after treatment (B4w) with gefitinib, using real-time quantitative-PCR assay. Correlations between blood MUC1 and VEGF mRNA expression at B0 and B4w and the response to gefitinib treatment and survival were analyzed. RESULTS: Blood levels of MUC1 and VEGF mRNA at B0 and at B4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. Furthermore, blood MUC1 and VEGF mRNA positivity at two time points were strongly associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0.005 and P = 0.008 at B0, and P < 0.001 and P = 0.001 at B4w, respectively, for MUC1; P = 0.004 and P = 0.009 at B0, and P = 0.001 and P < 0.001 at B4w, respectively, for VEGF). Multivariate analyses demonstrated that blood MUC1 and VEGF mRNA positivity at B0 and B4w were independent factors for predicting worse PFS and OS. CONCLUSIONS: MUC1 and VEGF mRNA positivity in blood seem to be indicators of unfavorable response and poor PFS and OS in patients with advanced NSCLC treated with gefitinib and may be promising noninvasive and repeatable markers for predicting efficacy of gefitinib treatment.

Gene mutation analysis in non-small cell lung cancer patients using bronchoalveolar lavage fluid and tumor tissue as diagnostic markers.

Non-small cell lung cancer (NSCLC) is one of the main causes of cancer death in the world. Early detection of NSCLC can improve its outcome. The aim of this study was to identify the mutations of the KRAS and p53 genes in bronchoalveoar lavage (BAL) fluid for the early detection of peripheral NSCLC. We examined the DNA obtained from the tumor, nearby normal lung tissue, and matched BAL fluid for mutations in the KRAS and p53 genes; the material was obtained from 48 patients with peripheral NSCLC, and was analyzed by PCR-single strand conformation polymorphism and DNA sequencing. BAL fluids from 26 patients with benign lung disease were used as controls. Positive rates of KRAS and p53 mutations were distributed as follows: in NSCLC tissue, 52% and 58%; in BAL fluid of NSCLC patients, 38% and 44%; in normal lung tissue, 6% and 4%; and in BAL fluid of patients with benign lung disease, 8% and 4%. The combined detection of both KRAS and p53 mutations yielded a sensitivity of 66% for the diagnosis of peripheral NSCLC, which is markedly higher than that of cytology plus histology by first bronchoscopy (38%, p=0.008). In each patient with the 2 gene mutations in BAL fluid, mutation type and location were the same as those of the primary tumor. Our study indicates that the detection of the KRAS and p53 mutations in BAL fluids could be a helpful addition to cytology and histology examination for the diagnosis of peripheral NSCLC.

Survivin mRNA-circulating tumor cells predict treatment efficacy of chemotherapy and survival for advanced non-small cell lung cancer patients.

The purpose of this prospective study was to evaluate the prognostic and predictive value of survivin mRNA-circulating tumor cells (CTCs) in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) who received first-line chemotherapy. Blood samples were collected from 78 patients with stage IIIB and IV NSCLC before (C0) and after 1 cycle (C1) and 3 cycles (C3) of chemotherapy. Survivin mRNA-CTCs were detected by real-time quantitative-PCR and correlated with treatment response and survival. The results showed that the presence of survivin mRNA-CTCs before and during chemotherapy was associated with histology type, tumor stage, and number of sites of metastasis. Moreover, the detection of survivin mRNA-CTCs after 1 and 3 cycles of chemotherapy was significantly associated with imaging response to treatment. Patients with positivity for survivin mRNA-CTCs at C0, C1, and C3 time points had significantly shorter progressive-free survival (PFS) and overall survival (OS) compared with patients without. Multivariate analysis using a Cox proportional hazards model revealed that the presence of survivin mRNA-CTCs after one and three chemotherapy cycles was a significant independent factor for worse PFS and OS. In conclusion, the detection of survivin mRNA-CTCs before and during chemotherapy is a prognostic and predictive factor correlated with poor PFS and OS in patients with advanced NSCLC.

Prognostic value of EpCAM/MUC1 mRNA-positive cells in non-small cell lung cancer patients.

The aim of this study was to assess the prognostic value of EpCAM/MUC1 mRNA-positive circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). The presence of EpCAM/MUC1 mRNA-positive CTCs was evaluated in 74 NSCLC patients before the initiation of any therapy, from which 61 patients with surgical resection of tumor were also evaluable for EpCAM/MUC1 mRNA-positive CTC analysis after surgery, by quantitative real-time PCR assay. Sixty patients with benign lung disease (BLD) entered this study as controls. The results showed that blood levels of EpCAM and MUC1 mRNA in NSCLC patients before and after surgery were significantly higher than those in BLD patients (P = 0.001 and P = 0.015, respectively, for EpCAM; P = 0.003 and P = 0.026, respectively, for MUC1), and the levels of the two gene mRNA in NSCLC patients significantly decreased after surgery (P = 0.025 and P = 0.033, respectively). Disease recurrence significantly increased in NSCLC patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.004 and P = 0.001, respectively). Disease-free survival and overall survival significantly reduced in patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.012 and P = 0.002, respectively, for preoperation; both P < 0.001 for postoperation). Multivariate analysis demonstrated that the presence of EpCAM/MUC1 mRNA-positive CTCs before and after surgery was an independent factor associated with disease recurrence. In conclusion, the detection of EpCAM/MUC1 mRNA-positive CTCs in the blood before and after surgery is useful for predicting a poor prognosis in NSCLC patients who undergo curative surgery.

CK-19 mRNA-positive cells in peripheral blood predict treatment efficacy and survival in small-cell lung cancer patients.

Small-cell lung caner (SCLC) is the most aggressive form of lung cancer. The aim of this study was to investigate whether the presence of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) predicts treatment response, progression-free survival (PFS), and overall survival (OS) in SCLC patients who received standard therapy. Fifty-five SCLC patients were enrolled in this single-center prospective study. CK-19 mRNA-positive CTCs in blood samples were detected using real-time quantitative-PCR assay before the initiation of chemotherapy (B0) and after one chemotherapy cycle (B1) and three chemotherapy cycles (B3). The association with known prognostic factors and the effect of CK-19 mRNA-positive CTCs on patients' prognosis were analyzed. Patients with positivity for CK-19 mRNA-positive CTCs at B0, B1, and B3 time points had shorter PFS and OS compared with patients without (P = 0.014 and P = 0.01, respectively, at B0; P = 0.008 and P = 0.002, respectively, at B1; P = 0.003 and P = 0.001, respectively, at B3). Conversion of initial positivity for CK-19 mRNA-positive CTCs to negativity at B1 and B3 time points was associated with longer PFS and OS compared with patients with persistent positivity at three time points (P = 0.008 and P = 0.010, respectively). Multivariate analysis demonstrated that the presence of CK-19 mRNA-positive CTCs at B0, B1, and B3 time points remained strong predictors of PFS and OS after adjustment for clinically significant factors. In conclusion, detection of CK-19 mRNA-positive CTCs before and during chemotherapy is an accurate indication of subsequent disease progression and mortality for SCLC patients.

Diagnostic value of the FHIT and p16 mRNA loss and the K-ras gene mutation in pleural fluids for malignant pleural effusion.

Inactivation of the tumor suppressor genes and activation of oncogenes are involved in the development of cancer. The aim of this study was to evaluate the diagnostic value of the fragile histidine triad (FHIT) and p16 mRNA loss and the K-ras gene mutation in distinguishing malignant from benign pleural effusion. A total of 50 patients with malignant pleural effusion and 30 patients with benign pleural effusion were enrolled in this study. All pleural fluid specimens were evaluated in parallel by cytology, reverse transcriptase-PCR for the loss of FHIT and p16 mRNA, and PCR-SSCP (single-stranded conformation polymorphism) for the mutation of K-ras gene. The detection rates of FHIT and p16 mRNA loss were significantly higher in malignant than in benign pleural effusion (P < 0.001 and P = 0.001). The K-ras mutations were more frequent in malignant than benign pleural effusion (P = 0.006). The sensitivity and specificity were 58% and 93% for FHIT loss, 48% and 90% for p16 loss, and 44% and 87% for the K-ras mutation, respectively. In combined evaluation with both FHIT and p16 loss, the sensitivity was 68%, and specificity was 90%. The combination of the three molecular markers reached 74% sensitivity, whereas the combined use of the cytology and the three markers increased the diagnostic yield of the former by 38%. More than one third of cytology negative malignant pleural effusion could be identified by at least one of the three markers. These results suggest that the detection of FHIT and p16 mRNA loss and the k-ras gene mutation in pleural fluid could be helpful adjunct to cytology in the diagnosis of malignant pleural effusion.

Detection of FHIT and p16 mRNA deletion in biopsy specimens obtained by bronchoscopy for the diagnosis of lung cancer.

The purpose of this study was to investigate the diagnostic value of the deletion of fragile histidine triad (FHIT) and p16INK4a (p16) mRNA in biopsies obtained by bronchoscopy. Biopsies were analyzed using RT-PCR in 52 patients with lung cancer and 19 patients with benign lung disease. The results showed that the detection rates of FHIT and p16 gene transcript deletion were significantly higher in lung cancer patients than in patients with benign lung disease (65.4% versus 10.5%, p=0.001 and 59.6% versus 5.3%, p<0.001, respectively). The sensitivities for detecting FHIT and p16 transcript deletion in biopsies were 65.4% and 59.6% (combined 80.8%), respectively, which were markedly better than those of histology and cytology (42.3% and 34.6%, respectively; combined 57.7%). In 22 lung cancer patients with negative histology and cytology at initial bronchoscopy, FHIT and p16 mRNA loss was detected in 40.9% (9/22) and 36.4% (8/22) cases, respectively. FHIT mRNA loss was associated with smoking status in lung cancer patients. In conclusion, deletion of FHIT and p16 mRNA can be identified in biopsies obtained during bronchoscopic procedures. FHIT and p16 mRNA deletion can be used as biomarkers in the clinical diagnosis of lung cancer and may serve as adjuncts to histology and cytology in lung cancer diagnosis.