Comparison of prognosis after partial and total surgical resection for parathyroid carcinoma: an inverse probability of treatment weighting analysis of the SEER database.

Background: Complete resection of the tumor and the ipsilateral thyroid lobe at the primary surgery is the "gold standard" for the treatment of parathyroid carcinoma (PC). However, differences in the overall survival (OS) of patients with PC who underwent partial and total surgical resection remain to be determined. Methods: Data on patients with PC who underwent partial and total surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database (2000-2018). The X-tile software (https://medicine.yale.edu/lab/rimm/research/software/) was used to define the optimal cut-off values for continuous variables. The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare the OS of patients with PC in the partial and total surgical resection groups. Results: A total of 334 patients with PC were included in this study (183 and 151 in the partial and total surgical resection groups, respectively). The optimal cut-off values for age at diagnosis were 53 and 73 years, respectively, while that for tumor size was 34 mm. In both the Kaplan-Meier analysis and univariable Cox proportional hazards regression analysis before IPTW, the difference in OS between the partial and total surgical resection groups was not statistically significant (p>0.05). These findings were confirmed in the IPTW-adjusted Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis (p>0.05). Subgroup analysis revealed that total surgical resection was beneficial for OS only in the subgroup with unknown tumor size. Conclusion: There was no significant difference in the prognosis of patients who underwent partial and total surgical resection. This finding may provide a useful reference for the treatment of PC.

A case of diffuse large B-cell lymphoma with interstitial pneumonia.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving "full coverage" treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Inhibition of Rac1 in ventral hippocampal excitatory neurons improves social recognition memory and synaptic plasticity.

Rac1 is critically involved in the regulation of the actin cytoskeleton, neuronal structure, synaptic plasticity, and memory. Rac1 overactivation is reported in human patients and animal models of Alzheimer's disease (AD) and contributes to their spatial memory deficits, but whether Rac1 dysregulation is also important in other forms of memory deficits is unknown. In addition, the cell types and synaptic mechanisms involved remain unclear. In this study, we used local injections of AAV virus containing a dominant-negative (DN) Rac1 under the control of CaMKIIα promoter and found that the reduction of Rac1 hyperactivity in ventral hippocampal excitatory neurons improves social recognition memory in APP/PS1 mice. Expression of DN Rac1 also improves long-term potentiation, a key synaptic mechanism for memory formation. Our results suggest that overactivation of Rac1 in hippocampal excitatory neurons contributes to social memory deficits in APP/PS1 mice and that manipulating Rac1 activity may provide a potential therapeutic strategy to treat social deficits in AD.

Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice.

Accumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer's Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study, we specifically manipulate LIMK1, the key protein kinase that phosphorylates and inactivates cofilin, in the hippocampus of APP/PS1 transgenic mice. Using local injections of the AAV virus containing LIMK1 under the control of the CaMKIIα promoter, we show that expression of LIMK1 in hippocampal excitatory neurons increases cofilin phosphorylation (i.e., decreases cofilin activity), rescues impairments in long-term potentiation, and improves social memory in APP/PS1 mice. Our results suggest that deficits in LIMK1/cofilin signaling in the hippocampal excitatory neurons contribute to AD pathology and that manipulations of LIMK1/cofilin activity provide a potential therapeutic strategy to treat AD.

Combined Antioxidant, Anti-inflammaging and Mesenchymal Stem Cell Treatment: A Possible Therapeutic Direction in Elderly Patients with Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide health problem associated with high morbidity and mortality, especially in elderly patients. Aging functions include mitochondrial dysfunction, cell-to-cell information exchange, protein homeostasis and extracellular matrix dysregulation, which are closely related to chronic inflammatory response and oxidation-antioxidant imbalance in the pathogenesis of COPD. COPD displays distinct inflammaging features, including increased cellular senescence and oxidative stress, stem cell exhaustion, alterations in the extracellular matrix, reduced levels of endogenous anti-inflammaging molecules, and reduced autophagy. Given that COPD and inflammaging share similar general features, it is very important to identify the specific mechanisms of inflammaging, which involve oxidative stress, inflammation and lung mesenchymal stem cell function in the development of COPD, especially in elderly COPD patients. In this review, we highlight the studies relevant to COPD progression, and focus on mechanisms associated with inflammaging.

Evaluation of smoking cessation intervention in patients with chronic diseases in smoking cessation clinics.

This study aimed to evaluate the effects of psychological intervention and psychological plus drug intervention on smoking cessation among male smokers with single chronic diseases.A total of 509 male smokers were divided into psychological group (n = 290) and psychological plus drugs (n = 219) groups according to their will. The physicians provided free individual counseling and follow-up interviews with brief counseling for all the subjects. In addition to mental intervention, patients in psychological plus drug group also received bupropion hydrochloride or varenicline tartrate to quit smoking. Outcomes were self-reported, regarding the 7-day point prevalence on abstinence rate and continuous abstinence rates at 1-, 3-, and 6-month follow-up period. Data analyses were performed using intention-to-treat analysis and per protocol analysis.With regards to the 3 follow-up time points, 7-day point-prevalence abstinence rate in psychological plus drugs group was all higher than that in the psychological intervention group. Additionally, the 3-month continuous abstinence rate (21.4%) of the 6-month follow-up in the psychological group was not significantly higher than that (26.9%) in the psychological plus drugs group (P >.05 for all). Fagerström test score, stage of quitting smoking, perceived confidence or difficulty in quitting, and chronic disease types were independently correlated with 3-month continuous abstinence in the 6-month follow up (P <.05 for all). The results were similar between intentional analysis and protocol analysis.The psychological intervention and psychological plus drugs intervention exerted good effects on smoking cessation in a short time (1 month). Nevertheless, the advantages did not appear during long-time (6 months) follow-up.

Low-expression of miR-7 promotes cell proliferation and exhibits prognostic value in osteosarcoma patients.

AIM: MicroRNAs (miRNAs) play important roles in occurrence and development of osteosarcoma. Previous studies had verified the role of microRNA-7 (miR-7) in various diseases, especially in cancers. Our purpose in this study was to investigate the values of miR-7 in development and prognosis of osteosarcoma. METHODS: QRT-PCR was used to measure the expression of miR-7 in osteosarcoma tissues, adjacent tissues and healthy tissues as well as in osteosarcoma cell lines MG63, U2OS and normal osteoblastic cell line hFOB1.19. CCK-8 and siRNA assays were performed to estimate the effect of miR-7 in the process of cell proliferation. The Kaplan-Meier and Cox regression analysis were performed to detect the prognostic values of the miR-7 in osteosarcoma patients. RESULTS: The results demonstrated that miR-7 expression decreased in osteosarcoma tissues and cell lines compared with the controls. Proliferation assay declared that the cell proliferation was accelerated by down-regulation of miR-7. Kaplan-Meier exhibited that the overall survival time of low-miR-7 expression was shorter than those with high-miR-7 expression (P=0.001). Cox regression analysis revealed that Enneking, distant metastasis and recurrence were all prognostic factors just like low-miR-7. CONCLUSION: The expression of miR-7 was lower in osteosarcoma tissues and cell lines and miR-7 acted as a tumor suppressor. The low-expression of miR-7 was associated with clinicopathologic characteristics (age, tumor site, Enneking, therapies). Moreover, miR-7 might be an independent prognostic marker and promote cell proliferation in osteosarcoma.

Additional follow-up telephone counselling and initial smoking relapse: a longitudinal, controlled study.

OBJECTIVES: Smoking cessation services can help smokers to quit; however, many smoking relapse cases occur over time. Initial relapse prevention should play an important role in achieving the goal of long-term smoking cessation. Several studies have focused on the effect of extended telephone support in relapse prevention, but the conclusions remain conflicting. DESIGN AND SETTING: From October 2008 to August 2013, a longitudinal, controlled study was performed in a large general hospital of Beijing. PARTICIPANTS: The smokers who sought treatment at our smoking cessation clinic were non-randomised and divided into 2 groups: face-to-face individual counselling group (FC group), and face-to-face individual counselling plus telephone follow-up counselling group (FCF group). No pharmacotherapy was offered. OUTCOMES: The timing of initial smoking relapse was compared between FC and FCF groups. Predictors of initial relapse were investigated during the first 180 days, using the Cox proportional hazards model. RESULTS: Of 547 eligible male smokers who volunteered to participate, 457 participants (117 in FC group and 340 in FCF group) achieved at least 24 h abstinence. The majority of the lapse episodes occurred during the first 2 weeks after the quit date. Smokers who did not receive the follow-up telephone counselling (FC group) tended to relapse to smoking earlier than those smokers who received the additional follow-up telephone counselling (FCF group), and the log-rank test was statistically significant (p=0.003). A Cox regression model showed that, in the FCF group, being married, and having a lower Fagerström test score, normal body mass index and doctor-diagnosed tobacco-related chronic diseases, were significantly independent protective predictors of smoking relapse. CONCLUSIONS: Within the limitations of this study, it can be concluded that additional follow-up telephone counselling might be an effective strategy in preventing relapse. Further research is still needed to confirm our findings.

Effectiveness of varenicline and counselling for smoking cessation in an observational cohort study in China.

OBJECTIVES: To evaluate the effectiveness of varenicline for smoking cessation in Chinese smokers in a real world cessation clinic practice. DESIGN: A prospective observational study. SETTING: Beijing, China. PARTICIPANTS: A total of 924 smokers (883 men and 41 women) who attended a smoking cessation clinic of a large general hospital were assessed with data from structured questionnaires at baseline and follow-up at 1, 3 and 6 months. Trained physician counsellors provided free individual counselling for all subjects and follow-up interviews with brief counselling. 332 subjects additionally prescribed varenicline according to their own choice were compared with those without varenicline. MAIN OUTCOME MEASURES: Primary outcomes were self-reported 7-day point prevalence abstinence rate and 3-month continuous abstinence rate at 6-month follow-up. Secondary outcomes were 7-day point prevalence abstinence rates at 1 and 3-month follow-up, and 1-month continuous abstinence rate at 3-month follow-up. RESULTS: By intention-to-treat, the 7-day point prevalence abstinence rate with varenicline and counselling at 6 months was significantly higher than counselling only (37.0% vs 23.1%; OR, 1.75; 95% CI 1.46 to 2.62; p=0.001). The 3-month continuous abstinence rate at 6 months was higher with varenicline (33.1% vs 18.4%; OR, 2.04; 95% CI 1.61 to 2.99; p<0.001). Varenicline also showed better secondary outcomes. CONCLUSIONS: Varenicline prescription in the smoking cessation clinic appeared to be effective with doubling of quit rates in Chinese smokers in a real world cessation clinic practice. CLINICAL TRIAL REGISTRATION: NCT01935505; Results.

Effectiveness of additional follow-up telephone counseling in a smoking cessation clinic in Beijing and predictors of quitting among Chinese male smokers.

BACKGROUND: No previous studies have investigated whether additional telephone follow-up counseling sessions after face-to-face counseling can increase quitting in China, and whether this strategy is feasible and effective for promoting smoking cessation is still unclear. METHODS: A non-randomized controlled study was conducted in Beijing. We compared the quit rates of one group which received face-to-face counseling (FC) alone (one session of 40 min) to another group which received the same face-to-face counseling plus four follow-up sessions of brief telephone counseling (15-20 min each) at 1 week, 1, 3 and 6 month follow-up (FCF). No smoking cessation medication was provided. From October 2008 to August 2013, Chinese male smokers who sought treatment in a part-time regular smoking cessation clinic of a large general hospital in Beijing were invited to participate in the present study. Eligible male smokers (n = 547) were divided into two groups: FC (n = 149) and FCF (n = 398). Main outcomes were self-reported 7-day point prevalence and 6 month continuous quit rates at 12 month follow-up. RESULTS: By intention to treat, at 12 month follow-up, the 7-day point prevalence and 6 month continuous quit rates of FC and FCF were 14.8 % and 26.4 %, and 10.7 % and 19.6 % respectively. The adjusted odds ratios (95 % confidence intervals) of quitting in FCF compared to FC was 2.34 (1.34-4.10) (P = 0.003) and 2.41 (1.28-4.52) (P = 0.006), respectively. Stepwise logistic regression showed that FCF, being married, unemployed and a lower Fagerström score were significant independent predictors of 6 month continuous quitting at 12 month follow-up. CONCLUSIONS: Using systematically collected data from real-world practice, our smoking cessation clinic has shown that the additional telephone follow-up counseling sessions doubled the quit rate.

Relationship between education levels and booster counselling sessions on smoking cessation among Chinese smokers.

OBJECTIVES: Although various effective interventions are available to help individuals quit smoking, the effect of educational levels on cessation rates has rarely been studied, and of the few intervention studies on this topic, the results have been conflicting. DESIGN AND SETTING: From October 2008 to August 2013, a partly retrospective non-randomised study was conducted in a smoking cessation clinic of a large general hospital in Beijing, China. PARTICIPANTS: In total, 547 Chinese smokers who sought treatment were divided into two groups: a face-to-face counselling group (FC, n=149) and an FC group subjected to four telephone follow-up sessions (FCF, n=398). OUTCOMES: We evaluated self-reported cessation rates by day 7 and after 6 and 12 months and stratified the two groups by education levels. RESULTS: The 7-day and 6-month and 12-month continuous cessation rates of smokers of low education levels in the FC group at the time of the 12-month follow-up were 12.5%, 7.1% and 7.1%, respectively, which were lower than those of the highly educated smokers (16.1%, 12.9% and 9.7%, respectively). The results were opposite for the FCF group. The corresponding results for the highly educated smokers of the FCF group were 25.0%, 17.2% and 10.3%, respectively, which were lower than those for the smokers of low education levels (28.3%, 22.9% and 18.1%, respectively). However, significant differences were observed only among the FCF group participants who had experienced 12 months of continuous abstinence, and the crude OR for these individuals was recorded at 0.52 (0.29 to 0.93), p=0.03. A stepwise logistic regression showed that education levels may play a role in various intervention methods. Being married and higher Fagerström test scores were also predictors of cessation tendencies. CONCLUSIONS: Education levels may affect the benefits of booster counselling sessions on smoking cessation among Chinese smokers.

Impaired formation of homotypic cell-in-cell structures in human tumor cells lacking alpha-catenin expression.

Although cell-in-cell structures (CICs) could be detected in a wide range of human tumors, homotypic CICs formed between tumor cells occur at low rate for most of them. We recently reported that tumor cells lacking expression of E- and P-cadherin were incapable of forming homotypic CICs by entosis, and re-expression of E- or P-cadherin was sufficient to induce CICs formation in these tumor cells. In this work, we found that homotypic CICs formation was impaired in some tumor cells expressing high level of E-cadherin due to loss expression of alpha-catenin (α-catenin), a molecular linker between cadherin-mediated adherens junctions and F-actin. Expression of α-catenin in these tumor cells restored cell-cell adhesion and promoted CICs formation in a ROCK kinase-dependent way. Thus, our work identified α-catenin as another molecule in addition to E- and P-cadherin that were targeted to inactivate homotypic CICs formation in human tumor cells.

[Impact of intervention on tobacco related knowledge, attitudes and practice of smokers].

OBJECTIVE: To evaluate the impact of intervention on tobacco related knowledge, attitudes and practice of smokers. METHODS: An observational study was conducted among the smokers seeking counsel at smoking cessation clinic in our hospital from October 2008 to August 2013. First, a face to face counsel and mental intervention for more than 30 minutes was given to smoker, then 4 interventions through telephone call for 15-20 minutes for each time were conducted 1 week later, 1 month later, 3 months later and 6 months later, respectively. The controls were smokers receiving health examination in our hospital. No interventions were conducted among them. The tobacco related knowledge, attitudes and practice at baseline survey and follow up 1 year later were compared between intervention group and control group. RESULTS: The intervention group included 414 smokers and the control group included 213 smokers. Intentional analysis indicated that the awareness/acceptance rates of 5 items about tobacco related knowledge and attitudes at follow up 1 year later was higher than those at baseline survey in intervention group. The smoking cessation rate was 27.3% in intervention group and 4.7% in control group. Multivariate logistic regression analysis indicated that the smoking cessation rate was positively correlated with intervention, female, highly nicotine dependence and positive change of tobacco related knowledge and attitudes (smoking can cause heart disease, all kinds of tobacco advertisements should be prohibited, smoking waste money and restaurant should be smoking free) with OR (95% CI): 2.85 (2.00-4.07), 3.34 (1.23-9.07), 2.78 (1.64-4.72), 2.30 (1.03-5.15), 5.33 (1.47-19.32), 6.32 (1.56-25.62) and 10.47 (2.25-48.84), respectively. CONCLUSION: The awareness rate of tobacco related harm was high among the smokers seeking counsel at smoking cessation clinic. Systematic smoking cessation intervention can improve smokers' tobacco related knowledge and attitudes and increase smoking cessation rate.

Chronotype and a PERIOD3 variable number tandem repeat polymorphism in Han Chinese pilots.

An association has been determined between variable number tandem-repeat (VNTR) polymorphisms in the PERIOD3 gene (PER3, rs57875989) and chronotype. An association has been found in which the longer PER3(5) allele is correlated with diurnal preference and shorter PER3(4) allele is linked with preference for evening, respectively. In this study, we explored the genotype frequency and relationship to the chronotype of a PER3 VNTR polymorphism in Han Chinese pilots compared to other populations to further develop aviation safety research. DNA samples were genotyped with respect to the 4-repeat and 5-repeat alleles of the PER3 VNTR polymorphism. We compared and analyzed PER3 VNTR genotype frequencies of a general Han Chinese population and Han Chinese pilots. The chronotypes of our subjects were evaluated by the morningness-eveningness questionnaire (MEQ). The distribution of PER3 VNTR genotype frequencies from 240 Han Chinese was determined (PER3(4/4), 78.3%; PER3(4/5), 20.0%; PER3(5/5), 1.7%) and compared to the genotype frequencies of 126 Han Chinese pilots (PER3(4/4), 71.4%; PER3(4/5), 26.1%; PER3(5/5), 2.4%). Statistical analysis revealed no significant difference between the general Han Chinese population and Han Chinese pilots regarding the PER3 VNTR genotype and allele frequencies (x(2) = 2.170, p > 0.05). Furthermore, MEQ results showed no association between the PER3 VTNR polymorphism and chronotype. However, PER3 VNTR genotype frequencies differed significantly between Han Chinese and other ethnic groups previously reported, such as Caucasians, African Americans and Italians. These data indicate that the proposed role of the PER3 VNTR needs further clarification and the role of PER3(5) allele in sleep regulation needs to be investigated in more detail. In particular, a study of PER3 polymorphisms with a larger sample size of Han Chinese individuals and Han Chinese pilots may be required.

Influence of Per3 genotypes on circadian rhythmicity in flight cadets after militarized management.

OBJECTIVE: The purpose of this study was to explore the effect of PERIOD3 (PER3) genotypes on circadian rhythmicity in flight cadets after militarized management. METHODS: We performed a preliminary study in 146 newly enrolled male flight cadets. Venous blood samples were collected, and genotyping of PER3 (4/5) was determined by using PCR. The morningness-eveningness questionnaire (MEQ) survey was given to flight cadets upon enrollment and after militarized management for 24 months respectively. Comparison of frequency distribution of PER3 genotypes between cases and controls (120 well-matched civilians) was performed using the X(2) test. We also compared the circadian rhythmicity upon enrollment and 24 months after enrollment in flight cadets, and analyzed the connection of changes in circadian clock with PER3 genotypes. RESULTS: The frequency distribution of PER3 genotypes in flight cadets was not significantly different from that in controls subjects. MEQ survey results showed chronotype within flight cadet group varied widely at the two time-points: the moderately morning type (50%) and the neither type (41.1%) upon enrollment; the neither type (76.7%) and the moderately morning type (21.2%) 24 months after enrollment. The circadian rhythm of individuals with the PER3 (5/5) genotype showed no significant difference before and after 24 months of militarized management, whereas notable changes were found in individuals with the PER3 (4/4) genotype (n=116, X(2) =37.26, P < 0.001). CONCLUSION: In conclusion, we provide some evidence that circadian rhythm of flight cadets with the PER3 (5) allele are less likely to be affected compared to those with the PER3 (4) allele.

[Predictors for 'successful quitting smoking' among males carried out in a smoking cessation clinic].

OBJECTIVE: To investigate the predictors for 'quitting' among male smokers in a smoking cessation clinic. METHODS: The target population consisted of smokers who volunteered to seek treatment for cessation at our clinic in Beijing. Smokers received face-to-face counseling and psychological intervention at the first visit by trained physicians and standardized telephone discussion, was carried out with counselors at 1 week, 1/3/6 months a follow-up study. The main outcomes would involve 'successful quitting' at the 7-day point, continuous quit rates at 3 and 6 months as well as the predictors of 'quitting'. RESULTS: From October 2008 to December 2012, we collected 355 eligible male smokers among whom 255 had completed the 6-month follow-up program. Results from the analysis (n = 255) showed that the quitting rates at the 7-day point and 3 months were 34.9% and 25.5%, while the rates were 25.1% and 18.3% among the 355 smokers who had the intention for treatment. Data from the stepwise logistic regression model analysis showed that lower exhaled CO level at the first visit, higher perceived confidence in quitting, lower expenditure on cigarettes and had diagnosed tobacco-related chronic diseases by physicians, were important predictors for quitting smoking. The main reasons of failure to quit were addiction of tobacco cigarette, craving for cigarettes to relieve pressure from work, peer influence from other smokers, lack of mental preparation and perseverance to quit, etc. CONCLUSION: Smokers who smoked less cigarettes, had higher perceived confidence in quitting and had physician-diagnosed tobacco-related chronic diseases seemed easier to quit. Regular follow-up intervention services for smokers should be established to enhance the motivation for quitting so as to create a favorable environment for the smokers.

A novel long non-coding RNA FOXCUT and mRNA FOXC1 pair promote progression and predict poor prognosis in esophageal squamous cell carcinoma.

Accumulating evidences demonstrated that many long non-coding RNAs (lncRNAs) can cooperate with the adjacent coding genes, forming into "lncRNA-mRNA gene pairs" in multiple biological cellular processes. Here, we showed that a novel long non-coding RNA FOXCUT (FOXC1 promoter upstream transcript) and its neighboring gene FOXC1 played a similar important role in the oncogenesis and progression of esophageal squamous cell carcinoma (ESCC). In this study, the expression of FOXCUT/FOXC1 was measured in 82 ESCC tissues and adjacent noncancerous tissues by real-time quantitative PCR (qPCR). The prognostic significance of the lncRNA-mRNA gene pair was evaluated using Kaplan-Meier survival analysis and log-rank test. Cell biological experiments were performed in ESCC cell lines to explore their functions in tumor progression. Notably elevated FOXCUT and FOXC1 expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (86.6% and 84.1%, respectively; P < 0.01), showing strong correlations with poor differentiation, advanced lymph node classification and metastasis (P < 0.05). Moreover, patients with upregulated FOXCUT or FOXC1 experienced a significantly worse prognosis than those with downregulated FOXCUT or FOXC1 (P < 0.001 and P = 0.014, respectively). In addition, the expression of FOXCUT was positively correlated with expression of FOXC1 in ESCC specimens. And the expression of FOXC1 was also decreased as the FOXCUT expression was silenced by siRNA. Assays in vitro demonstrated that knockdown of either FOXCUT or FOXC1 remarkably inhibited cell proliferation, colony formation, migration, invasion in ESCC cells. In conclusion, FOXCUT may be functionally involved in the tumor progression and survival of ESCC patients, at least in part, by modulating FOXC1. FOXCUT and FOXC1 may function as a lncRNA-mRNA gene pair, which may represent a potential prognostic biomarker and therapeutic target for ESCC patients.

Combination of BIBW2992 and ARQ 197 is effective against erlotinib-resistant human lung cancer cells with the EGFR T790M mutation.

Although the EGFR tyrosine kinase inhibitors (EGFR-TKI) erlotinib and gefitinib have shown marked effects against EGFR-mutated lung cancer, patients acquire resistance by various mechanisms, including the EGFR T790M mutation and Met induction, consequently suffering relapse. Thus, novel agents to overcome EGFR-TKI resistance are urgently needed. We aimed to investigate the inhibitory effects of a combination of BIBW2992 (irreversible EGFR inhibitor)/ARQ 197 (MET inhibitor) on the human lung adenocarcinoma cell line H1975. H1975 cells (harboring a T790M mutation in EGFR) were treated with erlotinib, BIBW2992 or ARQ 197 separately or with combinations of erlotinib/ARQ 197 or BIBW2992/ARQ 197. Cell growth, apoptosis and cell cycle distribution were evaluated by MTT assay, Annexin V/propidium iodide (PI) double staining and flow cytometry, respectively. EGFR, MET, AKT, ERK and the respective phosphorylated counterparts were detected by western blot analysis. Pathway-specific knockdown of MET and/or EGFR kinase signaling was achieved by siRNA interference. H1975 cells displayed EGFR and MET activation, and were resistant to erlotinib. The BIBW2992/ARQ 197 combination significantly inhibited growth, induced cell cycle arrest and apoptosis, and altered the phosphorylation of EGFR, MET, AKT and ERK1/2 in the H1975 cells. Phosphorylation of AKT and ERK1/2, downstream effectors of the EGFR and MET pathways, was not affected by the other tested treatments. Finally, knockdown of MET and/or EGFR in the H1975 cells confirmed the enhanced downstream inhibition of both MET and EGFR pathways. Combination of an irreversible EGFR inhibitor and MET inhibitor is effective in controlling H1975 cells with acquired resistance to erlotinib, by a mechanism involving the downregulation of PI3K/AKT and MEK/ERK signaling pathways.

[Effectiveness of Varenicline with counseling programs on smoking cessation in a targeted clinical setting in China].

OBJECTIVE: To evaluate the effectiveness of Varenicline for smoking cessation in a community-based smoking-cessation-clinic (SCC) in Chinese smokers. METHODS: A prospective observational study was conducted in Beijing, China. 799 smokers (762 men and 37 women) were assessed on data gathered from structured questionnaires at baseline and follow up programs at 1, 3 and 6 months. Trained physician counselors provided free individual counseling and follow-up interviews with brief counseling for all the subjects. 272 subjects were additionally prescribed Varenicline according to their own choice and reported data were compared to those without Varenicline. Outcomes were self-reported, regarding the 7-day point prevalence on abstinence rate and continuous abstinence rates at 1, 3 and 6 month follow-up periods. RESULTS: At 6-month and by intention-to-treat, the 7-day point prevalence on abstinence rate with Varenicline and counseling, was significantly higher than the group with counseling only (34.6% versus 23.1%; OR = 1.75, 95% CI: 1.27-2.42;P < 0.001). The 3-month continuous abstinence rate at 6 month was higher in the group with Varenicline(31.3% versus 18.2% ;OR = 2.04, 95% CI:1.46-2.86;P < 0.001). Varenicline also showed better outcomes at 1 and 3 month follow-up. CONCLUSION: Varenicline prescription in the smoking cessation clinic appeared to be effective that doubled the rates of quitting among Chinese smokers in the practice at a community-based SCC.