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Background Lung cancer is the leading cause of cancer-related death in China. Results from a randomized controlled trial using annual low-dose computed tomography ( LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. Methods A China national lung cancer screening guideline was developed by lung cancer early detection and treatment expert group appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. Results Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. Conclusions A lung cancer screening guideline is provided for the high-risk population in China. [ABSTRACT FROM AUTHOR]

Summary: In this paper, an event‐triggered adaptive tracking control strategy is proposed for strict‐feedback stochastic nonlinear systems with predetermined finite‐time performance. Firstly, a finite‐time performance function (FTPF) is introduced to describe the predetermined tracking performance. With the help of the error transformation technique, the original constrained tracking error is transformed into an equivalent unconstrained variable. Then, the unknown nonlinear functions are approximated by using the multi‐dimensional Taylor networks (MTNs) in the backstepping design process. Meanwhile, an event‐triggered mechanism with a relative threshold is introduced to reduce the communication burden between actuators and controllers. Furthermore, the proposed control strategy can ensure that all signals of the closed‐loop system are bounded in probability and the tracking error is within a predefined range in a finite time. In the end, the effectiveness of the proposed control strategy is verified by two simulation examples. [ABSTRACT FROM AUTHOR]

Abstract: Amyloid β-peptide (Aβ) is a very important pathogenic factor for Alzheimer''s disease (AD). It is a constitutive product of cellular metabolism and occurs in normal biological fluids, such as CSF and plasma. As the steady state levels of all peptides in vivo are a direct consequence of the balance between their anabolism and catabolism, peptide accumulation can arise not only from increased production but also from decreased breakdown. Although increasing evidence indicates that cholesterol is a risk factor for AD development, the exact mechanisms of cholesterol on Aβ metabolism or deposition have remained unclear. Here, we focus our attention on the effect of cholesterol depletion on the degradation of Aβ1–40. Cholesterol depletion of cultured rat pheochromocytoma (PC12) cells was achieved by methyl-β-cyclodextrin (MβCD) extraction. It was found that cholesterol depletion by MβCD extraction can suppress Aβ degradation in PC12 cells. [Copyright &y& Elsevier]

The relationship between arsenic exposure and all-cause of death and the combined effects of arsenic exposure and smoking have been poorly evaluated in the available studies. Workers exposed to arsenic had significantly higher mortality rates for all causes (HR = 1.457, 95% CI = 1.242 to 1.708), cancer (HR = 1.517, 95% CI = 1.139 to 2.022), and cerebrovascular disease (HR = 1.796, 95% CI = 1.225 to 2.634). More effective measures should be taken to control arsenic among miners with arsenic exposure. Background: The relationship between arsenic exposure and all-cause mortality and the joint effects of arsenic exposure and smoking have been poorly described in previous studies. Methods: After 27 years of follow-up, a total of 1738 miners were included in the analysis. Different statistical methods were used to explore the relationship between arsenic exposure and smoking and the risk of all-cause mortality and various causes of death. Results: A total of 694 deaths occurred during the 36,199.79 person-years of follow-up. Cancer was the leading cause of death, and arsenic-exposed workers had significantly higher mortality rates for all-cause, cancer, and cerebrovascular disease. All-cause, cancer, cerebrovascular disease, and respiratory disease increased with cumulative arsenic exposure. Conclusions: We demonstrated the negative effects of smoking and arsenic exposure on all-cause mortality. More effective actions should be taken to reduce arsenic exposure in miners. [ABSTRACT FROM AUTHOR]

Most tumor cells show different metabolic pathways than normal cells. Even under the conditions of sufficient oxygen, they produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, which is known as aerobic glycolysis or the Warburg effect. Lung cancer is a malignant tumor with one of the highest incidence and mortality rates in the world at present. However, the exact mechanisms underlying lung cancer development remain unclear. The three key enzymes of glycolysis are hexokinase, phosphofructokinase, and pyruvate kinase. Lactate dehydrogenase catalyzes the transfer of pyruvate to lactate. All four enzymes have been reported to be overexpressed in tumors, including lung cancer, and can be regulated by many oncoproteins to promote tumor proliferation, migration, and metastasis with dependence or independence of glycolysis. The discovery of aerobic glycolysis in the 1920s has provided new means and potential therapeutic targets for lung cancer. [ABSTRACT FROM AUTHOR]

Background: The performance of lung cancer screening with low‐dose computed tomography (CT) (LDCT) in China is uncertain. This study aimed to evaluate the performance of LDCT lung cancer screening in the Chinese setting. Methods: In 2014, a screening cohort of lung cancer with LDCT was established in Gejiu, Yunnan Province, a screening center of the Lung Cancer Screening Program in Rural China (LungSPRC). Participants received a baseline screening and four rounds of annual screening with LDCT in two local hospitals until June 2019. We analyzed the rates of participation, detection, early detection, and the clinical characteristics of lung cancer. Results: A total of 2006 participants had complete baseline screening results with a compliance rate of 98.4%. Of these, 1411 were high‐risk and 558 were nonhigh‐risk participants. During this period, 40 lung cancer cases were confirmed, of these, 35 were screen‐detected, four were post‐screening and one was an interval case. The positive rate of baseline and annual screening was 9.7% and 9.0%, while the lung cancer detection rate was 0.4% and 0.6%, respectively. The proportion of early lung cancer increased from 37.5% in T0 to 75.0% in T4. Adenocarcinoma was the most common histological subtype. Lung cancer incidence according to the criteria of LungSPRC and National Lung Cancer Screening Trial (NLST) was 513.31 and 877.41 per 100 000 person‐years, respectively. Conclusions: The program of lung cancer screening with LDCT showed a successful performance in Gejiu, Yunnan. However, further studies are warranted to refine a high‐risk population who will benefit most from LDCT screening and reduce the high false positive results. Key points: This study reports the results of lung cancer screening with LDCT in Gejiu, Yunnan, a high‐risk area of lung cancer, and it demonstrates that lung cancer screening with LDCT is effective in detecting early‐stage lung cancer. Our program provides an opportunity to explore the performance of LDCT lung cancer screening in the Chinese context. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to assess the efficacy of molecularly targeted agents (MTAs) in the treatment of elderly patients with metastatic oesophago-gastric cancer (mOGC).Material and Methods: We systematically searched electronic databases and abstracts presented at American Society of Clinical Oncology (ASCO) meetings up to January 31, 2017. Hazard ratios (HRs) were used to estimate overall survival (OS) and progression-free survival (PFS). Subgroup analysis and publication bias were also evaluated. All statistical analysis was conducted using Comprehensive Meta Analysis software (Version 2.0).Results: A total of 2,149 elderly patients with mOGC from thirteen trials were included. Compared to non-MTA-containing regimens, OS was significantly improved in the MTA-containing regimens (HR = 0.86, 95% CI: 0.75-0.99, p = 0.037), but not for PFS (HR = 1.05, 95% CI: 0.85-1.30, p = 0.67). In addition, subgroup analysis indicated that MTA-containing regimens as second-line therapy in elderly mOGC patients significantly improved PFS (HR = 0.58; 95% CI: 0.39-0.85, p = 0.005) and OS (HR = 0.82, 95% CI: 0.70-0.96, p = 0.016), but did not significantly improve PFS (HR = 1.36; 95% CI: 1.06-1.76, p = 0.017) and OS (HR = 0.98, 95% CI: 0.77-1.27, p = 0.90) for MTA-containing regimens as first-line therapy in these patients. No publication bias was detected by Begg's and Egger's tests for OS and PFS.Conclusions: Our results indicate that the MTA-containing therapies significantly improve OS but not for PFS in elderly mOGC patients. Sub-group analysis shows that improved efficacy is only observed in the second-line setting and not in the first-line setting. Our findings support the use of angiogenesis as second-line treatment for elderly mOGC patients. [ABSTRACT FROM AUTHOR]

Abstract The human SLC25A13 gene encodes the liver type aspartate/glutamate carrier isoform 2 (AGC2, commonly named as citrin), which plays a key role in the main NADH-shuttle of human hepatocyte. Biallelic SLC25A13 mutations result in Citrin deficiency (CD). In order to identify the important regulatory region of SLC25A13 gene and elucidate the way how potential promoter mutations affect the citrin expression, we performed promoter deletion analysis and established the reporter constructs of luciferase gene-carrying SLC25A13 promoter containing several mutations located in putative transcription factor-binding sites. The luciferase activities of all promoter constructs were measured using a Dual-Luciferase Reporter Assay System. Bioinformatic analysis showed that the promoter of SLC25A13 gene lacks TATA box and obviously typical initiator element, but contains a CCAAT box and two GC box. Promoter deletion analysis confirmed the region from −221 to −1 upstream ATG was essential for SLC25A13 to maintain the promoter activity. We utilized dual-luciferase reporter system as function analytical model to tentatively assess the effect of artificially constructed promoter mutations on citrin expression, and our analysis revealed that mutated putative CCAAT box and GC box could significantly affect the citrin expression. Our study confirmed the important SLC25A13 promoter regions that influenced citrin expression in HL7702 cells, and constructed a function analytical model. This work may be useful to further identify the pathogenic mutations leading to CD in the promoter region. Highlights • Human SLC25A13 gene promoter is GC-rich and TATA-less with a dispersed transcription pattern. • A GC box and a CCAAT box were predicted in the region upstream of the translational start site. • The region from −221 to −1 upstream of translation initiation codon was essential for SLC25A13 transcription. • A function analytical model of SLC25A13 gene promoter was established. [ABSTRACT FROM AUTHOR]

Patients with non-small-cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations generally react well to tyrosine kinase inhibitors (TKIs). However acquired resistance eventually occurs. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification and PIK3CA mutation. In recent years, cancer stem cells (CSCs) have been suggested to be involved in TKI resistance. MAP17 is aberrantly overexpressed in a number of malignancies. However, the expression pattern and function of MAP17 in CSCs are still unclear. The aim the present study was to illustrate the effect of CSC-like cells on the resistance to TKIs in EGFR mutant NSCLC cells and explore the possible role of MAP17 in CSCs. The EGFR mutant cell line PC9 was cultured under serum-deprived undifferentiated conditions. The CSC properties including expression of stem cell markers CD133, CD44, Oct-4 and ABCG2, ability of self-renewal, invasion, proliferation and tumorigenesis were examined. The expression of MAP17 was compared in sphere and parent cells. Sphere cells displayed stem cells phenotypes and were resistant to erlotinib. Sphere cells expressed higher levels of MAP17, and MAP17 was associated with self-renewal and TKI resistance. The function of MAP17 demonstrated to be partially dependent on Na-dependent glucose transporter 1. Collectively these findings suggest that MAP17 serves a role in TKI resistance through regulation of CSCs in lung cancer. [ABSTRACT FROM AUTHOR]

Angiogenesis is an indispensible process for tumor growth and metastasis. Anti-angiogenesis based therapy is one of the most promising treatments for inhibiting cancer progression. Through the exploration of inhibitors of vascular endothelial growth factor receptor ( VEGFR)-2, deemed as the major angiogenesis pathway, pazopanib was found as a small molecular pan- VEGFR and pan-platelet-derived growth factor receptor (PDGFR) inhibitor, with suitable pharmacodynamic and pharmacokinetic parameters to be an oral drug. In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf- MAPK/ERK ( MEK)-extracellular signal-regulated kinase (ERK) pathway, and directly targeted on v-raf murine sarcoma viral oncogene homolog B ( B-raf) as well. It inhibited the proliferation of cell lines, such as DU-145 and HRC-45 in hepatocellular carcinoma, through mechanisms like 'cell cycle arrest.' In vivo xenograft studies and phase I/ II clinical trials revealed a series of plasma cytokine and angiogenic factors, such as interleukin ( IL)-6, IL-12, hepatocyte growth factor ( HGF), and soluble VEGFR2, which have significant association with clinical curative effect. Pazopanib has been shown to be effective in solid tumors and some hematological malignancies. Future studies should focus on the exploration of biomarkers to screen sensitive patients and concomitant or metronomic dosage with other kinds of medicines. [ABSTRACT FROM AUTHOR]

Background: Nature killer (NK) cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment. Materials and methods: Our study analyzed the change about NK cells surface markers (NK cells receptors) through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse. Results: We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently. Conclusions: The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy. [ABSTRACT FROM AUTHOR]

We explored the shape of the exposure-response relationship of arsenic-related lung cancer and the interaction between arsenic and tobacco use. A total of 3278 tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. After excluding radon-exposed miners and former smokers, 1620 miners were included into the sub-cohort. Lung cancer risks were estimated by modeling total exposure and intensity of arsenic exposure. The cohort experienced 73,866 person-years and 414 lung cancer cases. Firstly, the ERR/mg/m3-year was 0.0033 (95% CI: 0.0014–0.0045) in arsenic concentration <3 mg/m3 and 0.0056 (95% CI: 0.0035–0.0073) in arsenic concentration ≥3 mg/m3. After adjusting for cumulative arsenic exposure, and the ERR/mg/m3 increased with increasing intensity (0.129 (95% CI: 0.039, 0.189)). Secondly, an unique aspect of this population was the early age at first arsenic exposure for workers. Results showed that lung cancer incidence risk from exposed in childhood (<13 years) was non-significantly greater than those in other age groups (13–17 and ≥ 18 years). Finally, the most likely joint effects of inhaled arsenic and tobacco use was sub-multiplicative. This study enlightened us that for fixed cumulative arsenic exposure, higher concentration over shorter duration might be more deleterious than lower concentration over longer duration. Substantial reductions in the lung cancer burden of smokers exposed to arsenic could be achieved by reductions in either exposure. • For a fixed cumulative exposure, short duration at high rate may be more deleterious. • No modification of the arsenic-related lung cancer with age at first exposure. • The most likely interaction of arsenic and tobacco use is sub-multiplicative. [ABSTRACT FROM AUTHOR]

Background: Phase II-III trials in patients with untreated and previously treated locally advanced or non-small cell lung cancer ( NSCLC) suggested that Endostar was able to enhance the effect of platinum-based chemotherapy ( NP regimen) with tolerable adverse effects. Methods Four hundred and eighty six patients were randomized into two arms: study arm A: NP plus Endostar (n = 322; vinorelbine, cisplatin, Endostar), and study arm B: NP plus placebo (n = 164; vinorelbine, cisplatin, 0.9% sodium chloride). Patients were treated every third week for two to six cycles. Results: Overall response rates were 35.4% in arm A and 19.5% in arm B (P = 0.0003). The median time to progression was 6.3 months for arm A and 3.6 months for B, respectively (P < 0.001). The clinical benefit rates were 73.3% in arm A and 64.0% in arm B (P = 0.035). Grade 3/4 neutropenia, anemia, and nausea/vomiting were 28.5%, 3.4%, and 8.0%, respectively, in Arm A compared with 28.2%, 3.0%, and 6.6%, respectively, in Arm B (P > 0.05). There were two treatment related deaths in arm A and one in arm B (P > 0.05). The median overall survival was longer in arm A than in arm B (P < 0.0001). Conclusion: Long-term follow-up revealed that the addition of Endostar to an NP regimen can result in a significant clinical and survival benefit in advanced NSCLC patients, compared with NP alone. [ABSTRACT FROM AUTHOR]

Abstract: We used the data from a prospective cohort study among tin miners in Yunnan, China to investigate whether prior lung disease is a risk factor for lung cancer. Information on prior lung disease was obtained from baseline questionnaires. The Cox proportional hazards model was used to examine the relationship between prior lung disease and lung cancer risk. From 1992 to 2001, a total of 502 lung cancer cases were confirmed among 9295 cohort participants. Prior chronic bronchitis was associated with an increase in lung cancer risk with an adjusted HR of 1.50 (95% CI: 1.24–1.81). There was an increased risk of developing squamous cell carcinoma in the setting of prior chronic bronchitis and small cell carcinoma in association with asthma with an adjusted HRs of 1.57 (95% CI: 1.19–2.09) and 2.56 (95% CI: 1.38–4.75), respectively. This prospective study provides further evidence that prior chronic bronchitis correlates with increased lung cancer risk, especially for squamous cell carcinoma. Asthma is associated with increased risk of small cell lung carcinoma. [Copyright &y& Elsevier]

Summary: CpG island methylator phenotype (CIMP) involving methylation abnormalities of tumor suppressor gene (TSG) on short arm of chromosome 3 (chromosome 3p) has not been so far epigenetically elucidated in non-small cell lung cancer (NSCLC). Using methylation-specific PCR (MSP) method, we examined methylation profiles for eight TSGs harbored in chromosome 3p in 60 NSCLC tissues and 60 paired normal tissues as well as 11 normal blood samples. CIMP positive is referred to having four or more than four synchronously methylated genes per sample. Consequently, 59 of 60 (98.3%) NSCLC presented promoter methylation of at least one gene while only one malignant tumor showed no methylation of any of eight genes. The frequency of promoter methylation for eight genes explored ranged from 12% for hMLH1 to 67% for RASSF1A given that of VHL (none) was not considered. Interestingly, CIMP+ was found in 56.7% (34/60) of NSCLC, and in 6.7% (4/60) of paired normal tissues and 0% (0/11) of normal blood samples, respectively; CIMP− was present in 43.3% (26/60) of NSCLC, 93.3% (56/60) of paired normal tissues, and 100% (11/11) of normal blood samples, respectively. The data suggest that CIMP status was significantly associated with NSCLC, paired normal tissues and normal blood samples (P <0.001). In addition, there appeared to be a significant association between CIMP status and survival prognosis of NSCLC (P =0.0166). In the present study, for the first time, we shed light on the presence of chromosome 3p-specific CIMP, which might play an important role in tumorigenesis of NSCLC. [Copyright &y& Elsevier]

Identification of rapid, inexpensive, and reliable prognostic factors can improve survival estimation and guide healthcare in patients with acute heart failure (AHF). In this study, we aimed to determine the prognostic value of the platelet-to-lymphocyte ratio (PLR) in patients with AHF. A total of 443 patients from two hospitals met the inclusion criteria from January 2010 to December 2017. Univariate and multivariate Cox analyses were performed to determine the association of PLR with survival. All-cause mortality was analysed using the Kaplan-Meier method. The 6-month survival rate for patients according to PLR quartiles (<110.63, 110.63–139.23, 139.23–177.17, and >177.17) were 90.09%, 76.79%, 50.07%, and 37.27%, respectively (p < 0.001). Univariate analysis identified high PLR (>110.63), old age (≥73 years), smoking habit, low estimated glomerular filtration rate (<57), and high platelet count (≥198 × 109/l) as poor prognostic factors for survival. In the multivariate analysis, after adjusting for confounding factors, the third (hazard ratio [HR] = 3.118, 95% confidence interval [CI] = 1.668–5.386, p < 0.001) and fourth (HR = 2.437, 95% CI = 1.302–3.653, p < 0.001) quartiles of PLR were identified as independent prognostic factors in patients with AHF. A higher PLR was associated with poor clinical outcomes in patients with AHF and might be a novel marker in AHF management. [ABSTRACT FROM AUTHOR]