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Right ventricular (RV) dysfunction has been linked to a poor response to cardiac resynchronization therapy (CRT). We sought to determine whether cardiovascular magnetic resonance (CMR)-derived measures of RV function influence clinical outcomes after CRT.In this retrospective study, we used CMR to assess pre-implant RV volumes and RV ejection fraction (RVEF) in relation to clinical outcomes after CRT implantation.Among 243 patients (age: 70.3 ± 10.8 years [mean ± SD]; 68.7% male; 121 [49.8%]) with ischemic cardiomyopathy and 122 (50.2%) with nonischemic cardiomyopathy, 141 (58%) after CRT-defibrillation (CRT-D) and 102 (42%) after CRT-pacing (CRT-P), 101 (41.6.0%) patients died, 61 (25.1%) from cardiac causes and 24 (9.88%) from noncardiac causes, over 5.87 years (median; interquartile range: 4.35-7.73). Two (0.82%) patients underwent cardiac transplantation and four (1.64%) had a left ventricular assist device (LVAD). A total of 41 (16.9%) met the composite endpoint of sudden cardiac death (SCD), ventricular tachycardia, or ventricular fibrillation. In univariate analyses, no measure of RV function was associated with total mortality or the arrhythmic endpoint. RVEF was associated with cardiac mortality on univariate analyses (HR per 10%: 0.82, 95% CI 0.70-0.96), but not on multivariate analyses that included left ventricular ejection fraction.There is no relationship between measures of RV function, such as RV volumes and RVEF, and the long-term clinical outcome of CRT. These findings indicate that such measures should not be considered in patient selection.

Breast cancer is the most common cancer among women worldwide. Researches show that Aurora kinase A (AURKA) is highly expressed in approximately 73% of breast cancer patients, which induces drug resistance in breast cancer patients and decreases the median survival time. AURKA regulates spindle assembly, centrosome maturation, and chromosome alignment. AURKA overexpression affects the occurrence and development of breast cancer. Besides AURKA overexpression, heat shock protein 90 (HSP90) maintains the survival and proliferation of tumor cells by stabilizing the structure of oncoproteins, including P53 mutants (mtP53). TP53 mutations accounted for approximately 13%, 40%, 80%, 33%, 71%, and 82% of luminal A, Luminal B, Luminal C, normal basal-like, HER2-amplified, and basal-like breast cancers, respectively. TP53 mutation can aggravate cell genome instability and enhance the invasion, migration, and resistance of cancer cell. This review describes the research status of AURKA and HSP90 in breast cancer, summarizes the structure, function, and the chaperone cycle of HSP90, elaborates the interrelation between HSP90, mtP53, P53, and AURKA, and proposes the combination of HSP90 inhibitor and AURKA inhibitor to treat breast cancer. Targeting AURKA and HSP90 to treat cancer with AURKA overexpression and TP53 mutations will help improve the specificity and efficiency of breast cancer treatment and solve the problem of drug resistance.

Background Depression and sarcopenia are common diseases in the elderly population. However, the association between them is controversial. Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, a cross-sectional study was conducted to explore the relationship of calf circumference and physical performance with depression. Methods From the 8th wave of CLHLS conducted in 2018, data on calf circumference, physical performance, depressive symptoms, and demographic, socioeconomic, and health-related characteristics were collected. Multiple logistic regression was conducted to explore the impact of calf circumference, physical performance and their combination on depressive symptoms. Results We enrolled a total of 12,227 participants aged 83.4 ± 11.0 years, including 5689 (46.5%) men and 6538 (53.5%) women. Patients with depression were more likely to have low calf circumference (2274 [68.2%] vs. 5406 [60.8%], pppp Conclusions Physical performance was significantly associated with depression in the elderly Chinese population. Attention should be paid to assess depressive symptoms in patients with poor physical performance.

Background With the prevalence of infertility increasing every year around the world, it has seriously impacted the individual quality of family and social life. Anxiety is one of the most prevalent anxiety disorders among infertile patients. After the two-child policy, whether it affected the prevalence of anxiety is controversial. This study aimed to determine the prevalence of anxiety and its potential risk factors among Chinese infertile women after the enforcement of ‘two-child policy’. Methods This cross-sectional study included 693 infertile patients in a reproductive medical center in Chongqing, China, between February 2016 and December 2018. Data was collected by Self-filling questionnaires including basic demographic information and the Generalized Anxiety Disorder-7 (GAD-7). SPSS statistical software (IBM SPSS version 25) was used to analyse the obtained data. Descriptive analysis was used to describe basic information and anxiety scores, the chi-square test and binary logistic regression were used to analyse the relationship between anxiety and other variables. Results The prevalence of anxiety among total infertile patients was 21.8%, and its 23.5% among first-child infertile patients (FI), and 18.4% among second-child infertile patients (SI) respectively (P > 0.05). Binary logistic regression showed that patients with lower education levels were more likely to have anxiety (P, Plain language summary With the formulation of China's two-child policy and the increase in the incidence of infertility, anxiety is one of the most common anxiety disorders among infertility patients. This study mainly discussed the prevalence of anxiety among infertile women in China and its potential risk factors after the implementation of the "two-child" policy. First-child infertile patients (FI) or Second-child infertile patients (SI) were asked to self-fulfilled the 7-item Generalized Anxiety Disorder scale questionnaires to understand their anxiety. Of the 693 respondents: the prevalence of anxiety among total infertile patients was 21.8%, and its 23.5% among first-child infertile patients, and 18.4% among second-child infertile patients. The group of infertile patients with middle salary incomes, a history of oral contraceptive use, and a history of allergy were more likely to be anxious. In conclusion: under the current situation, low education levels, middle incomes, OC taking and allergy history can be the related risk factors of anxiety. It is of guiding significance for the mental health of special populations of infertility.

BACKGROUND Patients with lung cancer often experience reduced functional capacity and quality of life after surgery. The current study investigated the impact of a short-term, home-based, multimodal prehabilitation program on perioperative functional capacity in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for nonsmall cell lung cancer (NSCLC). METHODS A randomized controlled trial was conducted with 73 patients. Patients in the prehabilitation group (n = 37) received a 2-week multimodal intervention program before surgery, including aerobic and resistance exercises, respiratory training, nutrition counseling with whey protein supplementation, and psychological guidance. Patients in the control group (n = 36) received the usual clinical care. The assessors were blinded to the patient allocation. The primary outcome was perioperative functional capacity measured as the 6-minute walk distance (6MWD), which was assessed at 1 day before and 30 days after surgery. A linear mixed-effects model was built to analyze the perioperative 6MWD. Other outcomes included lung function, disability and psychometric evaluations, length of stay (LOS), short-term recovery quality, postoperative complications, and mortality. RESULTS The median duration of prehabilitation was 15 days. The average 6MWD was 60.9 m higher perioperatively in the prehabilitation group compared to the control group (95% confidence interval [CI], 32.4-89.5; P < .001). There were no differences in lung function, disability and psychological assessment, LOS, short-term recovery quality, postoperative complications, and mortality, except for forced vital capacity (FVC; 0.35 L higher in the prehabilitation group, 95% CI, 0.05-0.66; P = .021). CONCLUSIONS A 2-week, home-based, multimodal prehabilitation program could produce clinically relevant improvements in perioperative functional capacity in patients undergoing VATS lobectomy for lung cancer.

BACKGROUND AND AIMS Patients with moderate-to-severe chronic kidney disease (CKD) are underepresented in clinical trials of cardiac resynchronization therapy (CRT)-defibrillation or CRT-pacing (CRT-P). We sought to determine whether outcomes after CRT-D are better than after CRT-P over a wide spectrum of CKD. METHODS AND RESULTS Clinical events were quantified in relation to pre-implant estimated glomerular filtration rate (eGFR) after CRT-D (n = 410 [39.2%]) or CRT-P (n = 636 [60.8%]) implantation. Over a follow-up period of 3.7 years (median, interquartile range: 2.1-5.7), the eGFR

Background and Aims Randomized, controlled trials of cardiac resynchronization therapy (CRT) excluded patients with adult congenital heart disease (ACHD). We sought to explore long‐term clinical outcomes. Methods and Results In this single‐center, observational study, events were collected from hospital records on patients with structural ACHD (sACHD) and adults with ischemic (ICM) or nonischemic (NICM) cardiomyopathy undergoing CRT. Patients with sACHD (n = 23, age: 41.6 ± 13.5 years [mean ± standard deviation]) and adults with ICM (n = 533) or NICM (n = 458) were followed‐up for 4.1 years (median; interquartile range: 2.2‐6.1). Total mortality was 5/23 (21.7%; 4.4 per 100 person‐years) in sACHD, 221/533 (41.5%; 11.8 per 100 person‐years) in ICM, and 154/458 (33.6%; 9.7 per 100 person‐years) in NICM. In univariate analyses, total mortality in sACHD was lower than in ICM (hazard ratio [HR]: 0.38; 95% confidence interval [CI] 0.15‐0.91), but similar to NICM (HR: 0.48, 95% CI 0.20‐1.16). Cardiac mortality in sACHD was similar to ICM (HR: 0.78, 95% CI 0.32‐1.92) and NICM (HR: 1.12, 95% CI 0.45‐2.78). Heart failure (HF) hospitalization rates were similar to ICM (HR: 0.44, 95% CI 0.11‐1.77) and NICM (HR: 0.75, 95% CI 0.18‐3.08). In multivariate analyses, no differences emerged in total mortality, cardiac mortality, or HF hospitalization between sACHD and NICM or ICM, after adjustment for age, sex, New York Heart Association class, diabetes, atrial rhythm, QRS duration, QRS morphology, systemic ventricular ejection fraction, and medical therapy. Conclusion Total mortality, cardiac mortality, and HF hospitalization after CRT in patients with sACHD was similar to adults with ICM or NICM.

Accurate grading of liver fibrosis can effectively assess the severity of liver disease and help doctors make an appropriate diagnosis. This study aimed to perform the automatic staging of hepatic fibrosis on patients with hepatitis B, who underwent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging with dynamic radiomics analysis. The proposed dynamic radiomics model combined imaging features from multi-phase dynamic contrast-enhanced (DCE) images and time-domain information. Imaging features were extracted from the deep learning-based segmented liver volume, and time-domain features were further explored to analyze the variation in features during contrast enhancement. Model construction and evaluation were based on a 132-case data set. The proposed model achieved remarkable performance in significant fibrosis (fibrosis stage S1 vs. S2–S4, accuracy (ACC) = 0.875, area under the curve (AUC) = 0.867), advanced fibrosis (S1–S2 vs. S3–S4, ACC = 0.825, AUC = 0.874), and cirrhosis (S1–S3 vs. S4, ACC = 0.850, AUC = 0.900) classifications in the test set. It was more dominant compared with the conventional single-phase or multi-phase DCE-based radiomics models, normalized liver enhancement, and some serological indicators. Time-domain features were found to play an important role in the classification models. The dynamic radiomics model can be applied for highly accurate automatic hepatic fibrosis staging.

Developmental and epileptic encephalopathy Type 31 (DEE31) is a severe early infantile epileptic encephalopathy with intellectual and movement disability caused by heterozygous mutations in the Dynamin 1 gene, which encodes DNM1, a GTPase involved in synaptic vesicle fission for receptor-mediated endocytosis on the presynaptic plasma membrane. A human induced pluripotent stem cell (iPSC) line, termed as FDCHI007-A, was generated using non-integrating episomal vector technique from peripheral blood mononuclear cells (PBMCs) of a 3-year-old female DDE31 patient, who had a heterozygous (c.545C A P. Ala 182Asp) mutation in the DNM1 gene. FDCHI007-A offers a useful cell resource to investigate pathogenic mechanisms in DEE31, as well as a cell-based model for drug development for DEE31.

In the present study, a comprehensive and sensitive method for simultaneous determination of 21 PIs (nine benzophenones, eight amine co-initiators, and four thioxanthones) in human plasma using high-performance liquid chromatography coupled with tandem mass spectrometry was developed and validated. Two different pre-treatment approaches (liquid-liquid extraction (LLE) and LLE coupled with solid-phase extraction (SPE)) and eight extraction solvents were studied to optimize sample treatment to obtain good recoveries and reduce any matrix effects. The procedure of LLE+SPE was selected as final sample treatment procedure because it obtained higher recoveries as well as lower matrix effects than that performed by LLE alone. The recoveries of 21 target analytes at three spiked concentrations (0.05, 0.5, and 5 ng/mL) ranged from 81% to 109%. The intra- and inter-day relative standard deviations were between 2.5% and 13%. Accuracy and precision data indicated that the detection method was accurate and precise for most of the PIs. The linearities of the labeled dilution calibration curves at 10 concentration levels (iLOQ to 100 ng/mL or iLOQ to 200 ng/mL) were good with correlation coefficients ranged from 0.995 to 0.999. The method quantification limits were in the range of 1.7-16 pg/mL. The analytical method was applied to the analysis of PIs in 14 human plasma samples collected from pregnant women in Guangdong Province, China. Fifteen PIs were detected with total concentrations ranging from 318 to 2772 pg/mL. The ubiquitous contamination of human plasma with PIs suggests that there is widespread exposure to these compounds. Consequently, there should be increased awareness of these pollutants in the environment.

Background Pregnancy can be stressful for women and families, so the life satisfaction of pregnant women may face significant challenges. This study aimed to identify the relationship among anxiety symptoms, perceived social support and life satisfaction, and to further explore whether perceived social support can play a mediating role. Methods This cross-sectional study was conducted from June to September in Shenyang City, China in 2019. 290 effective questionnaires were collected. The Satisfaction with Life Scale (SWLS), the Zung’s Self-Rating Anxiety Scale (SAS), the Multi-Dimensional Scale of Perceived Social Support (MSPSS) as well as demographic variables were included in each questionnaire. Hierarchical multiple regression was conducted to explore the mediating role of perceived social support in the relationship between anxiety symptoms and life satisfaction. Then the mediation model was examined by the PROCESS macro for SPSS. Results After adjusting control variables, anxiety symptoms were negatively associated with life satisfaction and explained 14.7% of the variance. Higher level of perceived social support was related to higher level of life satisfaction, explaining 21.0% of the variance. Perceived social support partly mediated the relationship between anxiety symptoms and life satisfaction for pregnant women. Conclusions Perceived social support played a mediating role between anxiety symptoms and life satisfaction among pregnant women. Strategies and measures to improve perceived social support may be expected to buffer the impact of anxiety symptoms on pregnant women’s life satisfaction.

SUMMARY Peroral endoscopic myotomy (POEM) has been increasingly accepted as the first-line treatment of achalasia. However, laparoscopic Heller myotomy or esophagectomy still remains as the mainstay treatment for advanced achalasia featured with megaesophagus and/or sigmoid-shaped esophagus. Although the efficacy of POEM for advanced achalasia with sigmoid-shaped esophagus has been described, little is known about the role of POEM for patients with megaesophagus. The aim of our study is to evaluate the efficacy and safety of POEM for advanced achalasia with megaesophagus. Patients who received initial examinations and underwent POEM in our hospital from June 2013 to December 2018 were identified and data were retrospectively analyzed. The advanced achalasia was defined as megaesophagus with a diameter of ≥6 cm. The primary outcome was clinical success. The secondary outcomes were technical success and adverse events. A total of 112 patients (50 females, 44.6%) were included with a mean age of 44.8 years. The median symptom duration was 6.5 years (IQR:3.0–13.0 years). Modified POEM techniques were used in 27.7% (31/112) of patients. Technical success rate was 99.1% (112/113) per procedure. Clinical success was seen in 93.1% patients with median Eckardt score decreasing from 8.0 to 1.0 (P

Background Recently, copy number alteration (CNA) of 9p24.1 were demonstrated in 10% of diffuse large b-cell lymphoma (DLBCL), with gene expression and mutation profiles that were similar to those of primary mediastinal large B-cell lymphoma (PMBCL). However, their CNA-based profile and clinical impact still remain unclear. Methods Multiplex ligation-dependent probe amplification were employed to investigate the prevalence of JAK2/PD-L2 amplification in DLBCL and their CNA-based pattern of driver genes. The clinical outcome and characteristics were also analyzed. Results Using unsupervised hierarchical clustering, a small group of DLBCL (10.5%, 8/76) was clustered together with PMBCL as Cluster_2, demonstrating amplification of JAK2 (100%,8/8) and PD-L2 (75.0%,6/8). This subgroups of DLBCL demonstrated significant higher expression of PD-L1 than those with MYD88 L265P mutation(p = 0.024). And they exhibited dismal OS and PFS as compared with DLBCL_others(p = 0.003 and 0.001, respectively), which is similar to DLBCL with MYD88 L265P mutation. Conclusions DLBCL with amplification of JAK2/PD-L2 exhibits CNA pattern that is similar to PMBCL, and demonstrates unfavorable clinical outcome that resembles those with MYD88 L265P mutation. It is essential to identify this subgroup of DLBCL who may acquire more benefits from the JAK2 and PD-L1 signaling inhibition.

There is increasingly concern that PM

Background Pulmonary sarcomatoid carcinomas (PSCs) constitutes a heterogeneous group of NSCLCs, which show poor prognosis even with aggressive surgical treatment and postoperative chemotherapy. The detection MET exon14 skipping (METex14 skipping) in PSCs suggests the targeted therapeutic opportunities with MET TKIs. Patients and methods We detected MET exon14 alterations using both targeted DNA- and RNA-based Next Generation Sequencing (NGS) and elucidated the driver mutation profile of 77 Chinese PSC patients. We also collected and analyzed the demographic features and clinical outcomes of patients harboring METex14 skipping mutation. Results METex14 skipping was detected in 20.8% of PSCs. A concordance of 96.1% was observed for DNA- and RNA-based NGS. 13 different genomic variants were revealed to induce METex14 skipping, including indels (N = 1) at splice acceptor sites, base substitutions (N = 4) and indels (N = 5) at splice donor sites, indels (N = 2) in the ∼20bp intronic noncoding region adjacent to the splice acceptor site, and indels (N = 1) in the exonic region. Patients harboring METex14 skipping tended to be older than others. In most cases, METex14 skipping were exclusive to other tumor driver alterations, however, we detected one case with METex14 skipping and a concurrent KRAS mutation. In survival analysis, we identified METex14 skipping as an unfavorable factor for Disease Free Survival (DFS) of PSCs. Conclusion Although a high concordance of 96.1% was observed for DNA- and RNA-based NGS in detecting METex14 skipping, RNA-based sequencing appears the most accurate method, because some somatic variants not covering METex14 splices sites might also induce skipping. Without targeted treatment, patients with METex14 skipping had a shorter DFS. Because of the clinical significance of METex14 skipping and emerging effective treatment with MET TKI, the clinical screening for METex14 skipping should be encouraged, particularly in PSC patients who have poor prognosis with no effective treatments.

Background The MET gene has been recognized as a potential important therapeutic target in non–small-cell lung cancer (NSCLC). We sought to investigate the MET exon 14 mutations in a cohort of Chinese patients with NSCLC. Methods We tested 461 NSCLCs for MET exon 14 mutations by sequencing whole exon 14 and its flanking introns. The protein expression was determined by immunohistochemical analysis. Results In this study, we identified MET exon 14 mutations in 9 (2.0%) of 461 NSCLCs. Of these 9 mutations, 7 (77.8%) were located in the splice sites of MET exon 14, with MET overexpression in 6. One point mutation c.3010C>T (p.Arg1004Ter) was nonsense mutation with no MET expression. One insertion mutation was within exon 14 of MET with MET overexpression. MET protein localization in tumor cells with MET exon 14 mutations was different between mutation types. Three point mutations that disrupted the splice donor site of intron 14 were membranous staining, whereas the other mutations were cytoplasmic staining. Patients with MET exon 14 splice site mutations were significantly older. The incidence of MET exon 14 mutations in sarcomatoid carcinoma was significantly higher than in other histologic types (P = .034). Conclusion Distinct MET protein localization is associated with MET exon 14 mutation types in patients with NSCLC. Different MET exon 14 mutation types were identified in a subset of Chinese patients with NSCLC who could possibly benefit from MET targeted therapy.

Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients. T790M always coexisted with a sensitizing EGFR mutation. Primary T790M more commonly coexisted with L858R, whereas acquired T790M was more likely to coexist with exon 19 deletions. Moreover, next-generation sequencing (NGS) showed that concomitant sensitizing EGFR and primary T790M mutant allele frequencies (MAFs) were highly concordant, but acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs. Sixteen acquired T790M-mutant patients received osimertinib. The median progression-free survival (PFS) was 8.1 months. Four primary T790M-mutant patients received osimertinib and the median PFS was 8.0 months. Together, our study demonstrates that primary and acquired T790M-mutant patients show distinct differences in some clinical and molecular characteristics, but may both respond to osimertinib treatment.

Next‐generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI‐naive and 107 TKI‐relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with

BACKGROUND AND AIMS Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long-term outcomes of upgrading from pacemakers to CRT with (CRT-D) or without (CRT-P) defibrillation in patients with no history of sustained ventricular arrhythmias. METHODS AND RESULTS In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT-P or CRT-D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4 - 7.0]). In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10-1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05-1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96-1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36-0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34-0.79) and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40-0.82) were lower after CRT-D than after CRT-P. CONCLUSION Upgrading from pacemakers to CRT was associated with a similar long-term risk of mortality and morbidity to de novo CRT. After upgrade, CRT-D was CRT-D was associated with lower mortality than CRT-P. This article is protected by copyright. All rights reserved.

Background Women are underrepresented in cardiac resynchronization therapy ( CRT ) trials. Some studies suggest that women fare better than men after CRT . We sought to explore clinical outcomes in women and men undergoing CRT ‐defibrillation or CRT‐pacing in real‐world clinical practice. Methods and Results A national database (Hospital Episode Statistics for England) was used to quantify clinical outcomes in 43 730 patients (women: 10 890 [24.9%]; men: 32 840 [75.1%]) undergoing CRT over 7.6 years, (median follow‐up 2.2 years, interquartile range, 1–4 years). In analysis of the total population, the primary end point of total mortality (adjusted hazard ratio [ aHR ], 0.73; 95% CI, 0.69–0.76) and the secondary end point of total mortality or heart failure hospitalization ( aHR , 0.79, 95% CI 0.75–0.82) were lower in women, independent of known confounders. Total mortality ( aHR , 0.73; 95% CI, 0.70–0.76) and total mortality or heart failure hospitalization ( aHR , 0.79; 95% CI, 0.75–0.82) were lower for CRT ‐defibrillation than for CRT ‐pacing. In analyses of patients with ( aHR , 0.89; 95% CI, 0.80–0.98) or without ( aHR , 0.70; 95% CI, 0.66–0.73) a myocardial infarction, women had a lower total mortality. In sex‐specific analyses, total mortality was lower after CRT ‐defibrillation in women ( aHR , 0.83; P =0.013) and men ( aHR , 0.69; P Conclusions Compared with men, women lived longer and were less likely to be hospitalized for heart failure after CRT . In both sexes, CRT ‐defibrillation was superior to CRT ‐pacing with respect to survival and heart failure hospitalization. The longest survival after CRT was observed in women without a history of myocardial infarction.

Aims Randomized controlled trials have shown that cardiac resynchronization therapy (CRT) prolongs survival in patients with heart failure. No studies have explored survival after CRT in relation to individuals in the general population (relative survival, RS). We sought to determine observed and RS after CRT in a nationwide cohort undergoing CRT. Methods and results A national administrative database was used to quantify observed mortality for patients undergoing CRT. Relative survival (RS) was quantified using life tables. In 50 084 patients [age 72.1 ± 11.6 years (mean ± standard deviation)] undergoing CRT with (CRT-D) (n = 25 273) or without (CRT-P) defibrillation (n = 24 811) over 8.8 years (median follow-up 2.7 years, interquartile range 1.3-4.8), expected survival decreased with age. Device type, male sex, ischaemic heart disease, diabetes, and chronic kidney disease predicted excess mortality. In multivariate analyses, excess mortality (analogue of RS) was lower after CRT-D than after CRT-P in all patients [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.76-0.84] as well as in subgroups with (aHR 0.79, 95% CI 0.74-0.84) or without (aHR 0.82, 95% CI 0.74-0.91) ischaemic heart disease. A Charlson Comorbidity Index (CCI) ≥3 portended a higher excess mortality (aHR 3.04, 95% CI 2.76-3.34). Relative survival was higher in 2015-2017 than in 2009-2011 (aHR 0.64, 95% CI 0.59-0.69). Conclusion Reference RS data after CRT is presented. Sex, ischaemic heart disease, diabetes, chronic kidney disease, and CCI were major determinants of RS after CRT. CRT-D was associated with a higher RS than CRT-P in patients with or without ischaemic heart disease. Relative survival after CRT improved from 2009 to 2017.

Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney’s detailed anatomy and correctly corresponds to the targeted human cadaver’s upper urinary tract. Soft materials with a tensile modulus of 0.8–1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.

BACKGROUND This study aimed to study the brain structural and functional changes after 8 courses of electroconvulsive therapy (ECT) on patients with major depressive disorder (MDD). MATERIAL AND METHODS MRI scans were performed on 12 depressive patients before and after 8 courses of ECT and compared with those of 15 normal controls. Data were analyzed by voxel-based morphometry (VBM) using SPM8 software. Functional MRI (fMRI) and regional homogeneity (ReHo) analyses were used to assess the functional changes after ECT. RESULTS Grey matter volumes were smaller in the right cingulate gyrus of depressive patients before ECT compared with normal controls. After false discovery rate (FDR) correction, post-ECT grey matter volumes were increased in bilateral amygdala and hippocampus compared with pre-ECT. Resting-state ReHo maps showed significant differences in brain activity pre- and post-ECT. Compared with healthy controls, MDD patients treated with 8 courses of ECT showed higher ReHo values in the bilateral frontal lobe, bilateral parietal lobe, and right caudate nucleus. Decreased ReHo values were observed in the right medial temporal gyrus, right superior temporal gyrus, right cingulate gyrus, and left anterior cerebellar lobe. CONCLUSIONS Results suggested that there were both structural and functional differences between the brains of MDD patients and healthy controls. After ECT, both structural and functional changes occurred, but without complete recovery to normal. ECT may display effects through regulating other brain regions to compensate for the original defects.

// Yun Ling 1,* , Xin Yang 2,* , Wenbin Li 1 , Zhuo Li 1 , Lin Yang 1 , Tian Qiu 1 , Lei Guo 1 , Lin Dong 1 , Lin Li 1 , Jianming Ying 1 , Dongmei Lin 2 1 Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2 Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China * These authors have contributed equally to this work Correspondence to: Jianming Ying, email: // Dongmei Lin, email: // Keywords : activating EGFR mutation, mutation-specific antibodies, immunohistochemistry, survival, non-small cell lung cancer Received : December 10, 2015 Accepted : April 07, 2016 Published : July 13, 2016 Abstract Background: Epidermal growth factor receptor (EGFR) is a novel target for therapy in a subset of non-small cell lung cancer (NSCLC). Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemistry (IHC) to detect EGFR L858R and del E746-A750 mutations in NSCLC patients and predict EGFR TKIs response. Methods: We collected specimens from 200 patients with NSCLC whose EGFR mutation status had been validated by direct DNA sequencing. IHC analyses using EGFR mutation-specific antibodies were employed for all samples. After staining and scoring, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: The sensitivity, specificity, PPV, and NPV of IHC using EGFR del E746-A750 and L858R mutation antibodies were 95.0%/95.1%, 85.7%/94.1%, 74.0%/91.8%, and 97.6%/96.5%, respectively. When score 2+ and 3+ were considered as positive, the sensitivity, specificity, PPV, and NPV were 53.3%/36.6%, 99.3%/100%, 97.0%/100%, and 83.2%/65.3%, respectively. The median progression-free survival (PFS) after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (31.0 versus 13.0 months, p

To investigate the use of molecular testing on cytological specimens in selecting advanced non-small cell lung cancer (NSCLC) patients who are adequate for targeted treatment, a total of 137 NSCLC cases were analyzed by fluorescence in situ hybridization (FISH) for anaplastic lymphoma kinase (ALK) rearrangements, and Epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were evaluated by quantitative real-time PCR (qRT-PCR) platform combining amplification refractory mutation system (ARMS) primers and TaqMan probes. Cytological specimens included 91 fine-needle aspirates, 5 fibreoptic bronchoscopic derived samples and 41 pleural effusions. Among 137 NSCLCs analyzed for ALK FISH, 16 (11.7%, of 137) were detected to harbor ALK rearrangement. FISH positive cases were all defined as adenocarcinoma (ADC) histologic subtype and the FNA samples showed the highest ALK positive rate (13.2%, 12/91). Of the 9 ALK FISH positive patients who received crizotinib treatment, 8 (88.9%) patients exhibited tumor regression. In addition, 60 (44.8%, of 134) cases were found to harbor EGFR mutations and 22 patients with EGFR sensitive mutations who received gefitinib or erlotinib treatment showed a median PFS of 16.0 months. Mutations of KRAS occurred in 8 (6.0%, of 134) cases and this was mutually exclusive from EGFR mutation. Our results demonstrated that ALK FISH and EGFR, KRAS mutational analysis on cytological specimens are sensitive methods for screening advanced stage NSCLC patients who are adequate for targeted treatment.

Objective Wolffian adnexal tumors (WATs) are rare, and metastasis is uncommon. We present the case of a 53-year-old female with a recurrent WAT. Case Report The patient presented with abdominal distension, and ultrasound revealed heterogeneous echoes (130 × 93 × 116 mm 3 ) around the uterus and ascites. Her cancer antigen 125 (CA125) and CA19-9 levels were elevated. Hysterectomy, bilateral oophorectomy, and tumor resection were performed. The histopathological diagnosis was a WAT. Two years later, multiple abdominal and pelvic masses were found on ultrasonography and computed tomography. Laparotomy revealed nodules in the omentum, mesentery, and pelvic peritoneum. Resection of the pelvic masses and partial resection of the omentum were performed. Immunohistochemistry revealed that the lesions were inhibin A, calretinin, estrogen receptor, progesterone receptor, cluster of differentiation 99, and Pax2 positive. Despite postoperative chemotherapy, she developed liver and renal failure 2 months after surgery, and died of the disease. Conclusion This case further suggests that WATs have malignant potential, and close follow-up is necessary.

Background Characterization of genetic alterations has been revealed to be important to predict the outcomes of targeted therapy in cancer. We here aimed to assess the mutation profiling of 526 colorectal cancer (CRC) patients by next-generation sequencing (NGS) to enable a more personalized anti-EGFR treatment. Methods Tumors were analyzed using NGS to determine hotspot mutations in 22 cancer-related genes. Results Mutations were observed in 13 genes in 436 of 526 (82.9%) tumors, and the most common mutations occurred in TP53 and KRAS. PIK3CA mutations usually coexisted with KRAS, NRAS or BRAF mutations. A higher frequency of concomitant PIK3CA mutations was observed in tumors with KRAS outside codon 13 mutations, with NRAS codon 61 mutations and with BRAF kinase-activated mutations. Moreover, KRAS, PIK3CA, AKT1 and FBXW7 mutations were statistically associated with some clinicopathological features, including location, age or metastasis of CRC patients. For RAS wild-type patients treated with cetuximab, longer progression-free survival (PFS) was observed in patients identified as wild type in all 22 genes compared with patients with mutations in one or more genes. Conclusions A wild-type result in all 22 cancer-related genes detected by NGS is associated with a better outcome of cetuximab treatment. Determining mutation patterns by NGS may aid to understand the molecular mechanisms of CRC and improve targeted therapy prediction.

Background Experimental evidence indicates that left ventricular ( LV ) apical pacing is hemodynamically superior to nonapical LV pacing. Some studies have shown that an LV apical lead position is unfavorable in cardiac resynchronization therapy. We sought to determine whether an apical LV lead position influences cardiac mortality after cardiac resynchronization therapy. Methods and Results In this retrospective observational study, the primary end point of cardiac mortality was assessed in relation to longitudinal (basal, midventricular, or apical) and circumferential (anterior, lateral, or posterior) LV lead positions, as well as right ventricular (apical or septal), assigned using fluoroscopy. Lead positions were assessed in 1189 patients undergoing cardiac resynchronization therapy implantation over 15 years. After a median follow‐up of 6.0 years (interquartile range: 4.4–7.7 years), an apical LV lead position was associated with lower cardiac mortality than a nonapical position (adjusted hazard ratio: 0.74; 95% confidence interval, 0.56–0.99) after covariate adjustment. There were no differences in total mortality or heart failure hospitalization. Death from pump failure was lower with apical than nonapical positions (adjusted hazard ratio: 0.69; 95% confidence interval, 0.51–0.94). Compared with a basal position, an apical LV position was also associated with lower risk of sudden cardiac death (adjusted hazard ratio: 0.34; 95% confidence interval, 0.13–0.93). No differences emerged between circumferential LV lead positions or right ventricular positions with respect to any end point. Conclusions In recipients of cardiac resynchronization therapy, an apical LV lead position was associated with better long‐term cardiac survival than a nonapical position. This effect was due to a lower risk of pump failure and sudden cardiac death.

Electroconvulsive therapy (ECT) is one of the most effective treatments for major depression disorder (MDD). ECT can induce neurogenesis and synaptogenesis in hippocampus, which contains distinct subfields, e.g., the cornu ammonis (CA) subfields, a granule cell layer (GCL), a molecular layer (ML), and the subiculum. It is unclear which subfields are affected by ECT and whether we predict the future treatment response to ECT by using volumetric information of hippocampal subfields at baseline? In this study, 24 patients with severe MDD received the ECT and their structural brain images were acquired with magnetic resonance imaging before and after ECT. A state-of-the-art hippocampal segmentation algorithm from Freesurfer 6.0 was used. We found that ECT induced volume increases in CA subfields, GCL, ML and subiculum. We applied a machine learning algorithm to the hippocampal subfield volumes at baseline and were able to predict the change in depressive symptoms (r = 0.81; within remitters, r = 0.93). Receiver operating characteristic analysis also showed robust prediction of remission with an area under the curve of 0.90. Our findings provide evidence for particular hippocampal subfields having specific roles in the response to ECT. We also provide an analytic approach for generating predictions about clinical outcomes for ECT in MDD.

Major depressive disorder (MDD) is a prevalent mood disorder. Treatment of MDD includes a variety of biopsychosocial approaches. Glutamate receptor, metabotropic 4 (GRM4) has been implicated in the regulation of MDD and it is seen as an attractive target for drug discovery and development. Here we reported using cellular assays and blood samples from MDD patients and showed that miR-335 was downregulated in individuals with depression compared with healthy controls. Additionally, we confirmed that miR-335 can directly target GRM4, which can further regulated the expression of miR-335. Antidepressant drug treatment with citalopram can upregulate miR-335 expression and downregulate GRM4 expression. These results suggest that miR-335 is associated with the pathophysiology of depression and is a potential target for new antidepressant treatments.

Allogeneic lymphocytes of paternal origin or supplied by a male third party have been used for the treatment of recurrent spontaneous abortion. Few studies, however, have examined the use of female third party lymphocytes. Our purpose was to determine whether female third party lymphocytes could be used for immunotherapy of women with recurrent spontaneous abortion.In this retrospective non-randomised cohort-controlled study, the medical records of patients with three or more spontaneous abortions who received immunotherapy with lymphocytes from their partner, a male third party or a female third party, as well as those who received no immunotherapy, from 1996 to 2012 were reviewed. All patients were negative for mixed lymphocyte culture reaction (MLR)-blocking antibodies. Immunotherapy was performed in 302 patients in two courses, while 53 patients received no immunotherapy.The pregnancy rates in patients who received lymphocytes from their partners, a male third party or a female third party, and in those not immunised, were 85.6%, 87.3%, 89.7%, and 79.3%, respectively (p = 0.523);the live birth rates were 87.3%, 75.8%, 84.6%, and 40.5%, respectively (p0.001).We conclude that female third party lymphocytes can be used for immunotherapy in patients with recurrent spontaneous abortion.

Background In cardiac resynchronization therapy ( CRT ), quadripolar ( QUAD ) left ventricular ( LV ) leads are less prone to postoperative complications than non‐ QUAD leads. Some studies have suggested better clinical outcomes. Methods and Results Clinical events were assessed in 847 patients after CRT ‐pacing or CRT‐defibrillation using either QUAD (n=287) or non‐ QUAD (n=560), programmed to single‐site site LV pacing. Over a follow‐up period of 3.2 years (median [interquartile range, 1.90–5.0]), QUAD was associated with a lower total mortality (adjusted hazard ratio [ aHR ]: 0.32, 95% confidence interval [ CI ], 0.20–0.52), cardiac mortality ( aHR : 0.36, 95% CI , 0.20–0.65), and heart failure ( HF ) hospitalization ( aHR : 0.62, 95% CI , 0.39–0.99), after adjustment for age, sex, New York Heart Association class, HF etiology, device type ( CRT ‐pacing or CRT ‐defibrillation), comorbidities, atrial rhythm, medication, left ventricular ejection fraction, and creatinine. Death from pump failure was lower with QUAD ( aHR : 0.33; 95% CI , 0.18–0.62), but no group differences emerged with respect to sudden cardiac death. There were no differences in implant‐related complications. Re‐interventions for LV displacement or phrenic nerve stimulation, which were lower with QUAD , predicted total mortality ( aHR : 1.68, 95% CI , 1.11–2.54), cardiac mortality ( aHR : 2.61, 95% CI , 1.66–4.11) and HF hospitalization ( aHR : 2.09, 95% CI, 1.22–3.58). Conclusions CRT using QUAD , programmed to biventricular pacing with single‐site LV pacing, is associated with a lower total mortality, cardiac mortality, and HF hospitalization. These trends were observed for both CRT ‐defibrillation and CRT ‐pacing, after adjustment for HF cause and other confounders. Re‐intervention for LV lead displacement or phrenic nerve stimulation was associated with worse outcomes.

Background Recent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. Objectives The aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (−) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. Methods Clinical events were quantified in patients with NICM who were +MWF (n = 68) or −MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. Results In the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for −MWF). In separate analyses of +MWF and −MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in −MWF. Conclusions In patients with NICM, CRT-D was superior to CRT-P in +MWF but not −MWF. These findings have implications for the choice of device therapy in patients with NICM.

Background PCDH10, one of the non-clustered protocadherins, is identified as a tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10 was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes, suggesting that its epigenetic aberrance is essential to the lymphomagenesis. However, there are few studies on the clinicopathological relevance and prognostic significance of PCDH10 methylation status in DLBCL. Methods One hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to extract genomic DNA and perform bisulfite modification. Their methylation status of PCDH10 promoter were accessed by methylation-specific PCR (MSP) with methylated and unmethylated primers. Analysis of overall survival and clinicopathological correlation were conducted. Results PCDH10 hypermethylation were found in 54.2% (58/107) of DLBCL cases, but only 12.5% (1/8) in reactive lymph node/follicular hyperplasia. In RCHOP-treated cohort, promoter methylation of PCDH10 is an independent prognostic indicator of worse overall survival (p = 0.017; HR 4.045; 95%CI 1.287–12.711) and worse progress-free survival (p = 0.014; HR 2.977; 95%CI 1.245–7.119). Whereas, PCDH10 hypermethylation wasn’t correlated with MYC translocation and cell of origin classification using Hans model. Conclusions PCDH10 methylation status could serve as a valuable biomarker for risk classification, and a potential therapeutic target for demethylating drugs in DLBCL in the future. Electronic supplementary material The online version of this article (10.1186/s12885-017-3810-7) contains supplementary material, which is available to authorized users.

The current study explored the influences of genetic and environmental factors on the mental health of twins between ages 6 and 16. A total of 41 monozygotic (MZ) twins and 35 dizygotic twins were recruited. The psychological attributes and environmental information of children were evaluated. A significant correlation was found between twins in the diagnostic categories of any psychiatric disorder and attention deficit/hyperactivity disorder (ADHD)/hyperkinesis based on the Strengths and Difficulties Questionnaire scale in MZ twins. Furthermore, fathers' authoritarian parenting style was positively correlated with the probability of any psychiatric disorders and oppositional/conduct disorders, whereas mothers' authoritative parenting style was negatively correlated with the probability of any psychiatric disorders and ADHD/hyperkinesis. The probability of emotional disorders was negatively correlated with scores on the Stressful Life Events Scale. These results collectively suggest that genetic and environmental elements, such as parental rearing style and stressful life events, may influence children's mental health. [ Journal of Psychosocial Nursing and Mental Health Services, 54 (8), 29–34.]

Breast carcinoma is the most common malignancy in Chinese women. The purpose of this study is to evaluate the predictive value of serum anti-p53 antibodies (p53 Abs), carcino-embryonic antigen (CEA), carbohydrate antigen (CA) 15-3, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2 in taxane-based and anthracycline-based neoadjuvant chemotherapy (NAC). Sixty-eight patients with locally advanced breast carcinoma were included. Thirty-two were treated with taxane (the taxane group) and 36 with anthracycline (the anthracycline group). The standard dosage of docetaxel was 100 mg/m2 (day 1) and those of cyclophosphamide, adriamycin and 5-flurouracil were 500 mg/m2 (day 1-8), 40 mg/m2 (day 1) and 500 mg/m2 (day 1-8), respectively. The p53 Abs were detected by enzyme-linked immunosorbent assay; CEA and CA15-3 were detected by Elecsys 2010 Disc System; ER, PR and HER-2 were detected by immunohistochemistry staining. The biomarkers p53 Abs, CEA and CA15-3 were detected in serum samples, and the immunohistochemistry staining for ER, PR and HER-2 was performed in tumor samples before and after NAC. The expression of p53 Abs was significantly reduced by taxane (P = 0.006). The serum CEA and CA15-3 levels were significantly affected by both taxane (P = 0.004 and P = 0.008) and anthracycline (P = 0.002 and P = 0.000) drugs. HER-2-negative status (pre-neoadjuvant) was correlated with a high objective response rate (OR) in both taxane-based and anthracycline-based chemotherapy (P = 0.022 and P = 0.025), whereas p53 Ab-negative status (pre-neoadjuvant) was correlated with high OR rate in anthracycline-based chemotherapy (P = 0.039). This study shows that the serum p53 Ab level is easily changed by taxane. CEA and CA15-3 levels are easily changed by taxane and anthracycline. The p53 Ab-negative patients may predict a high clinical OR rate in anthracycline-based NAC. HER-2-negative may predict a high OR in both taxane-based and anthracycline-based NAC.

Ovarian cancer has been one of the most common malignant tumor among women in China. The aims of this research were to increase the detection efficiency of anti-p53 antibodies in the sera from patients with ovarian cancer and to assist the diagnosis for patients with ovarian cancer.The hybrid phage displaying the immunodominant epitope SQAMDDLMLS in p53 N-terminal region was constructed and the fusion protein was prepared and purified. Ninety-two nonselected Chinese women with ovarian cancer were involved in this study. Tumor p53 overexpression was assessed by immunohistochemical analysis of tissue sections. Serum antibodies to p53 were also detected by enzyme-linked immunosorbent assay (ELISA) using recombinant human wild-type p53 protein and the hybrid phage as the coating antigen respectively. Furthermore, the correlations between the anti-p53 antibodies and clinicopathological parameters were analyzed.The positive rate of anti-p53 antibodies in the patients with ovarian cancer was increased (39.1%, 36/92) through the combination of the two ELISA methods compared with each method. The anti-p53 antibodies were not associated with the clinicopathologic parameters, while there was a significant correlation between the presence of p53 Abs and tissue overexpression of p53 in ovarian cancer.These preliminary results demonstrate that the combination of the two ELISA methods increased the positive rate of anti-p53 antibodies in patients with ovarian cancer and provided a useful marker to complement routine clinical diagnosis for patients with ovarian cancer.

Background : Gastric carcinoma is one of the most frequently occurring cancers. The aim of this research was to increase the detection efficiency of anti-p53 antibodies in the sera of patients with gastric carcinoma and to improve the diagnosis for patients with gastric carcinoma. Methods : We prepared phage-displayed peptide DO7 and established an enzyme-linked immunosorbent assay method to detect the anti-p53 antibodies. We detected the anti-p53 antibodies of 61 patients with gastric carcinoma using the method and our previous ELISA method assisted by the recombinant wild-type human p53 protein to detect the anti-p53 antibodies. We studied the correlation between the anti-p53 antibodies and the clinicopathological data including sex, age, carcinoembryonic antigen, tumor size, tumor TNM staging, and lymph-node status. Results : The anti-p53 antibodies positive rate for patients with gastric carcinoma was increased (31.1%, 19/61) through the combination of p53-ELISA and phage-ELISA. We found that the positive anti-p53 antibodies correlated significantly with tumor size ( P =0.047). The combination of the anti-p53 antibodies and carcinoembryonic antigen could improve the diagnosis for patients with gastric carcinoma. Conclusions : This approach indicated an increased anti-p53 antibodies positive rate for patients with gastric carcinoma and provided a useful marker for clinical diagnosis for patients with gastric carcinoma.

The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI. They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions. Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain. Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD.

Background Modified electroconvulsive therapy (MECT) has been regarded as the most effective antidepressant therapy, despite its cognitive side effects. However, how MECT influences problem-solving capacity in major depressive disorder (MDD), as well as its underlying neurobiological mechanisms, remains unclear. The present study aimed to assess alterations in problem-solving capacity after MECT and to explore spontaneous brain activity using amplitudes of low-frequency fluctuations (ALFF)/fractional ALFF. Methods Thirteen first-episode, treatment-naive MDD patients treated by MECT were recruited. We collected resting-state functional magnetic resonance imaging, and we evaluated their Modified Card Sorting Test performance before and after single-session MECT. Another 11 MDD patients without MECT were also recruited and interviewed with Modified Card Sorting Test twice as a control group. Results After a single MECT, MDD patients showed significantly decreased ALFF in the right cerebellar posterior lobe. Compared to the control group, perseverative errors significantly decreased after MECT, controlling for practice effects. Some cognitive functional changes significantly correlated to changed ALFF in several brain regions, including Brodmann areas BA9, BA19, BA 21, and BA48, right thalamus, left cerebellum, and right postcentral gyrus. Conclusions The MECT could improve problem-solving capacity, even after controlling for practice effects, and it could induce changes in spontaneous brain activity. These changes in cognitive functioning might result from changes in the cerebral functions of some regions, including frontal cortex, a key region for problem-solving capacity.

An investigation of interactive effects of exogenous and endogenous factors and tumor molecular changes can lead to a better understanding of tumor molecular signatures in colorectal cancer. We here report a molecular pathological epidemiology study in a large cohort of 945 colorectal cancer patients. Mutations of KRAS (36.6%) and BRAF (3.46%) were nearly mutually exclusive. KRAS-mutated tumors were more common in female patients (odds ratio [OR] = 1.68; P = 0.0001) and never smokers (OR = 1.60; P = 0.001). Whereas BRAF-mutated tumors demonstrated no discrepancy in aspects of gender and smoking status compared with wild-type tumors. In addition, tumors with BRAF or KRAS mutations were in correlation with elevated serum level of carbohydrate antigen (CA19-9) and carcinoma embryonic antigen (CEA) and the combination of serum biomarkers and molecular mutation status may enhance the more precise risk stratification of CRC patients. Further studies are needed to define the mechanism brought about by the aforementioned epidemiologic and clinicopathologic characteristics that may help optimize cancer prevention and precision therapy.

Identification of multi-gene variations has led to the development of new targeted therapies in lung adenocarcinoma patients and identification of an appropriate patient population with a reliable screening method is the key to the overall success of tumor targeted therapies. In this study, we used the Ion Torrent next-generation sequencing (NGS) technique to screen for mutations in 89 cases of lung adenocarcinoma metastatic lymph node specimens obtained by fine-needle aspiration cytology (FNAC). Of the 89 specimens, 30 (34%) were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations. Seven (8%) samples harbored KRAS mutations and three (3%) samples had BRAF mutations involving exon 11 (G469A) and exon 15 (V600E). Eight (9%) samples harbored PIK3CA mutations. One (1%) sample had a HRAS G12C mutation. Thirty-two (36%) samples (36%) harbored TP53 mutations. Other genes including APC, ATM, MET, PTPN11, GNAS, HRAS, RB1, SMAD4 and STK11 were found each in one case. Our study has demonstrated that NGS using the Ion Torrent technology is a useful tool for gene mutation screening in lung adenocarcinoma metastatic lymph node specimens obtained by FNAC and may promote the development of new targeted therapies in lung adenocarcinoma patients.

Epidermal growth factor receptor (EGFR) and KRAS must be detected mutation status before patients of lung cancer use targeted drugs. The aim of this study is to elucidate the significance of EGFR and KRAS mutation in fine needle aspiration (FNA) cytology suspension specimens of non-small cell lung carcinoma.EGFR gene exons 18-21 and KRAS codons 12, 13 of exons 2 were performed by Real-time PCR methods in fine needle aspiration cytology suspension specimens of lymph nodes.85 metastasis lymph nodes were detected in fine needle aspiration cytology samples of lung cancer. EGFR mutation rate was 37.3%. KRAS mutation rate was 7.2%. 19 formalin fixed paraffin-embedded tissue specimens were available and match cytology specimens. Analysis of EGFR mutation status in those samples revealed agreement with the results obtained in cytological samples (kappa=1.0). Clinical follow-up was available for 13 who presented with stage IV disease. Based on the identification of such mutations, these patients received subsequent therapy with a TKI in clinic. We observed two cases complete remission (16.7%) and 8 cases partial remission (66.7%) and three had ongoing stable disease.Fine-needle aspiration cytology samples were detected EGFR and KRAS mutation. The method which collects samples was easier, simple and convenient. This method has higher application value in clinical treatment. .背景与目的 肺癌患者靶向药物治疗前，需要检测表皮生长因子受体（epidermal growth factor receptor, EGFR）和KRAS基因是否突变。本研究旨在探讨细针吸取悬浮液标本检测非小细胞肺癌EGFR、KRAS基因突变的意义。方法 细胞学悬浮液标本，Real-time PCR法检测EGFR 18-21号外显子，KRAS 2号外显子12、13密码子突变。结果 检测85例肺癌转移淋巴结针吸标本，EGFR突变率37.3%，KRAS突变率7.2%。19例组织切片标本，与细胞学结果一致（kappa=1.0）。13例有EGFR突变，临床分期IV期患者， 使用酪氨酸激酶抑制剂治疗，2例完全缓解（complete remission, CR）（16.7%）；8例部分缓解（partial remission, PR）（66.7%）；3例最佳稳定疾病（stable disease, SD）（25.0%）。结论 细针吸取标本检测EGFR、KRAS基因突变，标本取材容易、简单、方便，具有较高的临床实用性。.

KRAS mutation occurs in 35%-40% of colorectal cancer (CRC). The aim of our study was to evaluate the pathological and molecular features of specific KRAS mutated colorectal carcinomas. KRAS and BRAF V600E mutation tests were performed in 762 primary tumors from a consecutive cohort study of Chinese CRC patients. DNA mismatch repair (MMR) status was determined by immunohistochemistry (IHC) staining. Assessment of KRAS and BRAF V600E mutational status was performed using a multiplex allele-specific PCR-based assay. Mutations of KRAS (34.8%) and BRAF V600E (3.1%) were nearly mutually exclusive. Both KRAS- and BRAF- mutated tumors were more likely to be located at proximal colon than wild-type (WT) carcinomas. KRAS-mutated carcinomas were more frequently observed in female patients (47.5% vs 37.1%, p = 0.005) and mucinous differentiation (34.7% vs 24.8%, p = 0.004), but have no difference between lymph node (LN) metastases and among pTNM stages. Whereas, BRAF-mutated carcinomas more frequently demonstrated histologic features such as proximal location (60.9% vs 20.9%, p = 0.001), low-grade histology (43.5% vs 18.0%, p = 0.005), mucinous differentiation (69.6% vs 25.9%, p = 0.001) and deficient MMR (dMMR) (21.7% vs 7.6%, p = 0.03). In particular, KRAS codon 12 mutated carcinomas had increased lymph node metastasis (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.04 to 1.65; P = 0.02) and were more likely in higher disease stage (III-IV) than that of WT carcinomas (OR = 1.30; 95% CI = 1.03 to 1.64; P = 0.03). However, there were no significant differences in lymph node metastasis and disease stage between KRAS codon 13 mutated carcinoma and WT carcinoma patients. In summary, KRAS codon 12 mutation, but not codon 13 mutation, is associated with lymph node metastasis and higher tumor stages.

To study the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and its association with clinicopathologic features.Two hundred and ninety-two patients with primary PTC encountered during the period from December 2010 to December 2012 and underwent surgery in Cancer Hospital, Chinese Academy of Medical Science were enrolled into the study. Polymerase chain reaction was used to amplify exon 15 of the BRAF gene from paraffin-embedded thyroid tumor specimens, followed by direct sequencing to detect the BRAF V600E mutation. Statistical analysis was performed with SPSS 16.0 for Windows. Association between BRAF mutation and clinicopathologic parameters was tested with the χ(2) test or Fisher exact test as appropriate.There were 87 males and 205 females in the cohort. The age of patients ranged from 13 to 84 years (mean = 43.1 years). BRAF V600E mutation was found in 190 cases (65.1%). The presence of BRAF V600E mutation correlated with age at diagnosis (older than 45 years), tumor volume (larger than 1 cm), extrathyroidal extension, classic type/tall-cell variant and advanced disease stage (P0.05). BRAF V600E mutation did not correlate significantly with gender, multicentricity, lymph node metastasis or anatomic location (P0.05).BRAF V600E mutation is associated with high-risk clinicopathologic characteristics in patients with PTC. The BRAF V600E mutation may be a potential prognostic factor in PTC patients.

Objectives Tumor heterogeneity, which causes different EGFR mutation abundance, is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. Frequent EGFR amplification and its common affection in EGFR mutant allele promote the hypothesis that EGFR mutant abundance might be determined by EGFR copy number variation and therefore examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment. Materials and methods In this study, 86 lung ADC patients, who harbored EGFR activating mutations and received EGFR-TKI treatment, were examined for EGFR amplification and expression by Dual-color Silver in situ Hybridization (DISH) and immunohistochemistry analysis, respectively. Results and conclusion Forty-one of 86 (47.7%) samples with EGFR activating mutations were identified with EGFR amplification. Patients with EGFR gene amplification had a significantly longer PFS than those without (16.3 vs. 9.1 months, p =0.004). The EGFR expression was then examined by immunohistochemistry analysis. Thirty-nine of 86 (45%) tumors had EGFR overexpression, which was significantly correlated with EGFR amplification ( p =0.000). However, patients with EGFR overexpression exhibited no difference in PFS (14.1 vs. 13.3 months, p =0.797). In conclusion, EGFR amplification occurs frequently in lung ADC patients harboring EGFR activating mutations, and could serve as an indicator for better response from EGFR-TKI treatment.

Objective. Electroconvulsive therapy (ECT) is considered one of the most effective and fast-acting treatment options for depressive episodes. Little is known, however, about ECT’s enabling brain (neuro)plasticity effects, particular for plasticity of white matter pathway.Materials and Methods. We collected longitudinal diffusion tensor imaging in the first-episode, drug-naïve major depressive disorder (MDD) patientsn=24before and after a predefined time window ECT treatment. We constructed large-scale anatomical networks derived from white matter fiber tractography and evaluated the topological reorganization using graph theoretical analysis. We also assessed the relationship between topological reorganization with improvements in depressive symptoms.Results. Our investigation revealed three main findings: (1) the small-worldness was persistent after ECT series; (2) anatomical connections changes were found in limbic structure, temporal and frontal lobes, in which the connection changes between amygdala and parahippocampus correlate with depressive symptom reduction; (3) significant nodal strength changes were found in right paralimbic network.Conclusions. ECT elicits neuroplastic processes associated with improvements in depressive symptoms that act to specific local ventral frontolimbic circuits, but not small-world property. Overall, ECT induced topological reorganization in large-scale brain structural network, opening up new avenues to better understand the mode of ECT action in MDD.

Cortical surface area (CSA) has particular relevance for understanding development, behavior, and the connection between brain structure and function. Little is known about genetic and environmental determinants of CSA during development. We utilized bivariate twin methods to identify global and regionally specific genetic factors which influence CSA in a preliminary sample of typically-developing adolescents, with hypotheses based on findings in middle-aged adults. Similar to previous findings, we observed high heritability for total CSA. There was also significant evidence for genetic influences on regional CSA, particularly when these were not adjusted for total CSA, with highest heritability in frontal cortex and relatively fewer genetic contributions to medial temporal cortical structures. Adjustment for total CSA reduced regional CSA heritability dramatically, but a moderate influence of genetic factors remained in some regions. Both global and regionally-specific genetic factors influence regional CSA during adolescence.

To evaluate the sensitivity and specificity of fully automated immunohistochemistry (IHC), with comparison to FISH, in the detection of EML4-ALK rearrangement in lung adenocarcinoma (ADC); and the use of IHC as a pre-screening tool.A total of 404 paraffin-embedded NSCLC samples from surgical resections were tested by IHC with Ventana anti-ALK rabbit monoclonal antibody (D5F3) and ultrasensitive detection kit. ALK rearrangement was further confirmed by FISH.Twenty-nine of 404 lung ADCs (7.2%) were positive for ALK by IHC. ALK positive tumor cells demonstrated strong and diffused granular cytoplasmic staining. All the ALK IHC-positive cases were confirmed to harbor ALK rearrangement by FISH. None of the ALK IHC-negative cases was FISH-positive.IHC can effectively detect ALK rearrangement in lung cancer. It may provide a reliable and cost-effective diagnostic approach in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy.

To analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.Fifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.(1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50).Immunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.