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Despite significant advances in targeted and immune therapy for non-small cell lung cancer (NSCLC), effective therapies for wild-type epidermal growth factor receptor/anaplastic lymphoma kinase ( EGFR/ALKWT) with low expression of programmed death ligand-1 (PD-L1) NSCLC remain elusive. Numerous studies have shown that ferroptosis plays an essential role in antitumor activity. To identify the molecular regulation patterns associated with ferroptosis, 351 EGFR/ALKWT NSCLC samples with low-level PD-L1 were extracted from The Cancer Genome Atlas (TCGA) and clustered using the k-means clustering technique. The two clusters associated with ferroptosis showed significantly different prognoses. In total, 169 differential expression genes (DEGs) were identified. Cluster differential analysis revealed that Cluster 1 had a significantly poorer overall survival (OS) and was associated with more negative immune regulation. In addition, TCGA samples were randomly assigned in a 7:3 ratio to a training group or testing group. A signature of eight genes associated with ferroptosis was established in the training cohort using DEGs and validated in the test cohort and three independent cohorts (GSE72049, GSE41271, and GSE50081). The 5-year area under the curve (AUC) was 0.713, which was significantly higher than that of other predictors, including TNM stage and age. Furthermore, the risk score was associated with immune function, immune infiltration, and immunotherapy response, with high-risk patients having a worse prognosis, an immune-suppressing phenotype, and a poor response to immune checkpoint inhibitors. This study aims to contribute to our understanding of the biological role of ferroptosis in EGFR/ALKWT NSCLC with low-level PD-L1, laying the groundwork for the development of novel therapeutic strategies.

This study aimed to assess the clinical characteristics affecting outcomes after immune checkpoint inhibitors (ICI) therapies in non-small cell lung cancer (NSCLC) patients, and the underlying mechanism in tumor immune micro-environment (TIME).A total of 144 patients treated with ICI-based strategies were retrospectively analyzed. Expression of 10 immune antibodies in tumor tissues from other 60 untreated NSCLC patients were sequentially tested using multiplexed immunofluorescence (mIF) staining method. Correlation of clinical characteristics with ICI treatment outcomes and TIME characteristics were analyzed.Multivariate logistic and cox regression indicated that BoM negatively affected disease control rate (OR = 0.32, 95%CI: 0.13-0.82, P = 0.018), progression free survival (HR = 3.44, 95% CI:1.97-6.00, P 0.001) and overall survival (HR = 3.24, 95% CI:1.62-6.50, P = 0.001), irrespective of programmed death-ligand 1 (PD-L1) expression. BoM patients were with significantly lower PD-L1, and this heterogeneity of TIME was then confirmed in the mIF staining, where 36 (61.0%) patients were clustered into immune-subtype A, with low expression of all the detected immune markers, similar to "cold" tumors, and 23 (39.0%) in cluster B with likely "hot" tumors. More patients in immune-subtype A were non-smokers (63.9% vs. 39.1% P = 0.063), with BoM (66.7% vs. 21.7%, P = 0.001), in stage IV(88.9% vs. 65.2%, P = 0.045), and with adenocarcinoma (91.7% vs. 69.6%, P = 0.037). Multivariate logistic regression indicated that BoM was independently associated with the "cold" immune characteristics (OR = 0.19, 95% CI:0.04-0.84, P = 0.028). Combination therapy with chemotherapy /antiangiogenesis or use of bisphosphonate during ICI treatment significantly improved clinical outcomes in BoM patients.BoM displays adverse impact on clinical outcomes after ICI treatments in NSCLC patients. The "cold" characteristics of TIME may be the underlying mechanism for the attenuated efficacy of ICIs in bone metastatic NSCLC patients.

To observe the efficacy of acupuncture on symptom burden in patients with gastric cancer during adjuvant chemotherapy after gastrectomy.A total of 58 patients were randomized into a high-dose acupuncture group (19 cases, 5 cases dropped off), a low-dose acupuncture group (20 cases, 6 cases dropped off) and a control group (19 cases, 2 cases dropped off). Conventional chemotherapy and antiemetic treatment were adopted in the control group. On the basis of the treatment in the control group, acupuncture was applied 7 times each chemotherapy cycle for totally 21 times in the high-dose acupuncture group, and 3 times each chemotherapy cycle for totally 9 times in the low-dose acupuncture group. Baihui (GV 20), Zusanli (ST 36), Neiguan (PC 6), etc. were selected in the two acupuncture groups, as well as back-The symptom burden was worst within 7 days of each cycle of chemotherapy in the 3 groups. After the 3rd chemotherapy cycle, the total score of ESAS in the low-dose acupuncture group was lower than the control group (Acupuncture shows promising effect in controlling symptom burden during adjuvant chemotherapy in gastric cancer patients after gastrectomy.

High-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 (The mRNA and protein expression ofThis study showed that

The goal of this study was to identify genes that were differentially methylated and differentially expressed and their related signaling pathways in ovarian endometriosis tissue. First, the DNA methylation and gene expression profiles in the endometrial tissue of patients with ovarian endometriosis were studied using Illumina 450K methylation microarray analysis and the GSE141549 gene expression dataset. Second, differentially methylated and differentially expressed genes, herein referred to as differentially methylated/expressed genes, were identified and protein-protein interaction networks and functional analysis of these genes were determined. Third, qPCR and immunohistochemistry of patient samples was used to confirm the differential expression of a subset of differentially methylated/expressed genes. Finally, the GSE7305 dataset was used confirm the expression profile of differentially methylated/expressed genes and to determine the potential usefulness of these genes for diagnosis of endometriosis. A total of 37 hypermethylated low-expression genes and 66 hypomethylated high-expression genes were identified in ovarian endometriosis patients. Protein-protein interaction and functional analysis highlighted 8 hypermethylated low-expression genes (KRT19, KRT8, ESR1, PRL, SFN, IL20RA, IL2RB, and PAX8) and 4 hypomethylated high-expression genes (CYP11A1, NR5A1, ME1, and GSTM1). Significantly, both of these gene sets had a diagnostic value for patients with ovarian endometriosis. Signaling pathways that were identified included JAK-STAT (involving IL20RA and IL2RB), prolactin (involving PRL and ESR1), Staphylococcus aureus infection (involving KRT19), viral protein interaction with cytokine and cytokine receptor (involving IL20RA and IL2RB), cytokine-cytokine receptor interaction (involving IL20RA and IL2RB), and drug metabolism-cytochrome P450 (involving GSTM1). The differentially methylated/expressed genes and enriched signaling pathways identified in this study are likely to be associated with the process of ovarian endometriosis.

Background: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. Methods: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients’ endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). Results: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02–1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01–2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. Conclusion: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of采用文献调研和德尔菲专家共识，总结针刺治疗癌痛的重要穴位，为制订《针刺治疗癌痛临床实践指南》提供证据基础。通过系统检索中、英文数据库，纳入针刺治疗癌痛的临床研究28项，归纳分析选穴方法和高频使用的穴位，据此设计德尔菲调查问卷，对30名国内外针灸、肿瘤相关领域专家进行两轮问卷调查。认为针刺治疗癌痛应采用个性化取穴方案，取穴以足三里、合谷、太冲、三阴交、阳陵泉和阿是穴为主。结合临床研究证据与专家调研结果得出针刺治疗癌痛的重要穴位，然而临证选穴仍有待进一步研究和细化。.

To explore the relationship between effect of induction chemotherapy and prognosis in acute myeloid leukemia (AML) patients.The clinical data of 146 adult AML patients treated in Affiliated Hospital of Chifeng University from March 2015 to March 2018 were enrolled and retrospectively analyzed. Day 14 bone marrow biopsy (D14BM) cellularity and blast proportion, daily peripheral blood blast (PBB) clearance rate, time to PBB clearance and etc. were primarily observed after induction chemotherapy. All the patients were divided into Non-relapse survival group, Relapse survival group, Non-relapse death group and Relapse death group according to survival and recurrence situation during 2-year follow-up. The survival of the patients was analyzed by Kaplan-Meier. Univariate analysis of prognostic factors were performed by ordinal Logistic regression, and ROC curve was used to assess the prediction efficiency of those factors for the 2-year overall survival (OS) and relapse of the patients.A total of 138 patients were included since 8 cases failed to be assessed clinically. Their 2-year OS rate was 65.94%. Age of the patients in Non-relapse survival group was lower than that in Relapse death group. The D14BM cellularities in Non-relapse survival group and Relapse survival group were lower than those in Relapse death group (P0.05). Daily PBB clearance rates in Non-relapse survival group and Relapse survival group were higher than those in Non-relapse death group and Relapse death group (P0.05). There was a statistical difference among the four groups in the number of cycles of induction chemotherapy (P0.05). The survival rate within 2 years in the patients with D14BM cellularity≤10% was higher than that in patients with cellularity10%, while it was higher in patients with daily PBB clearance rate20% than those with clearance rate≤20% (P0.05). Age (HR=1.102, P=0.000), D14BM cellularity (HR=1.252, P=0.000) and the cycles of induction chemotherapy≥3 (HR=1.703, P=0.000) were the risk factors affecting the prognosis of AML patients, while daily PBB clearance rate was a protective factor (HR=0.799, P=0.000). The AUC of age, daily PBB clearance rate and D14BM cellularity in predicting 2-year OS of AML patients was 0.738, 0.817 and 0.807, respectively, whereas in predicting relapse within 2 years it was 0.691, 0.647 and 0.711, respectively. There was no statistical difference among the three factors in the sensitivity of 2-year OS (68.11%, 85.12%, 74.49%) and 2-year relapse (50.00%, 64.13%, 61.60%) (P0.05).Bone marrow biopsy results and PBB clearance rate are related to prognosis in AML patients, which can offer certain predictive value in assessing 2-year OS of patients.AML患者诱导化疗疗效与预后关系分析.探讨急性髓系白血病（AML）患者诱导化疗的治疗效果与预后的关系。.收集并回顾性分析2015年3月至2018年3月本院收治的146例AML成年患者的临床资料，主要观察指标为诱导治疗d 14骨髓（D14BM）增生程度及原始细胞的比例，外周血白血病细胞（PBB）清除时间及日减少率等。根据随访2年患者的存活和复发情况分为无复发存活组、复发存活组、无复发死亡组、复发死亡组。采用Kaplan-Meier法行生存分析，有序Logistic回归分析对预后相关因素行单因素分析，绘制ROC曲线并评估上述指标对患者2年总生存期（OS）和复发的预测效能。.共纳入138例患者，2年OS率65.94%；无复发存活组年龄低于复发死亡组，无复发存活组和复发存活组D14BM增生度低于复发死亡组（均P0.05）；无复发存活组和复发存活组PBB日减少率均高于无复发死亡组和复发死亡组（均P0.05）；4组化疗次数比较差异有统计学意义（P0.05）；D14BM增生≤10%的患者2年内存活率高于增生10%的患者，PBB日减少率20%的患者存活率高于≤20%者（均P0.05）；年龄（HR=1.102，P=0.000）、D14BM增生度（HR= 1.252，P=0.000）、化疗次数≥3次（HR=1.703，P=0.000）为影响AML患者预后的危险因素，而PBB日减少率（HR= 0.799，P=0.000）为保护因素；年龄、PBB日减少率、D14BM增生度预测患者2年OS的AUC分别为0.738、0.817、 0.807，预测患者2年内复发的AUC分别为0.691、0.647、0.711，三者预测患者2年OS（68.11%、85.12%、74.49%）和2年内复发（50.00%、64.13%、61.60%）的敏感性均无明显差异（P0.05）。.骨髓活检结果、PBB清除率与AML患者预后相关，可为患者2年OS提供一定预测价值。.

Owing to the high morbidity and mortality, novel biomarkers in the occurrence and development of colorectal cancer (CRC) are needed nowadays. In this study, the CRC-related datasets were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. After screening the differentially expressed genes (DEGs) in R software, a total of 238 upregulated and 199 downregulated DEGs were revealed simultaneously. Then the Kaplan-Meier survival analysis and Cox regression analysis were used to reveal the prognostic function of these DEGs. Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) were two outstanding independent overall survival (OS) and relapse-free survival (RFS) prognostic genes of CRC in TCGA database. We next verified the expression of NXPE4 and PARM1 messenger RNA (mRNA) levels were significantly lower in CRC tumor tissue than in the adjacent noncancerous tissue in our clinical samples, and NXPE4 mRNA expression level was related to the tumor location and tumor size, while PARM1 was related to tumor location, lymph nodes metastasis, and tumor size. This study demonstrated that NXPE4 and PARM1 might be two potential novel prognostic biomarkers for CRC.

Aim: The present study aimed to assess the association between IGF2/H19 genetic variants and susceptibility to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Methods: A total of 43 platinum-resistant (PR) and 138 platinum-sensitive (PS) EOC patients were recruited in our study. 21 polymorphisms in IGF2/H19 locus were genotyped by Sequenom MassARRAY assay. Results: The frequencies of GG genotype in both rs3842761(C/G) and rs4244809(A/G) were significantly lower in PR group compared with those in PS group (9.76 vs 23.36%, p = 0.049; 9.76 vs 26.09%, p = 0.045; respectively). Compared with the AA genotype, rs4244809 GG genotype was associated with significantly reduced risk of platinum resistance (adjusted OR: 0.30; 95% CI: 0.10–0.91; p = 0.033). Further stratified analyses revealed that the SNPs of rs3842761 and rs4244809 were greatly related to PR risk in FIGO stage III–IV (rs3842761GG/CC+CG: adjusted OR: 0.15; 95% CI: 0.02–1.21; rs4244809 GG/AA+AG: adjusted OR: 0.24; 95% CI: 0.07–0.84; respectively) and serous adenocarcinoma subgroups (rs3842761 GG/CC+CG: adjusted OR: 0.21; 95% CI: 0.05–0.94; rs4244809 GG/AA+AG: adjusted OR: 0.19; 95% CI: 0.04–0.5; respectively), while rs7924316 polymorphism was associated with reduced risk of PR in serous adenocarcinoma subgroup as analyzed by a recessive model (rs7924316 GG/TT+TG: adjusted OR: 0.22; 95% CI: 0.05–0.98). In addition, both TCT haplotypes of rs3741206/rs3842761/rs7924316 and TC haplotype of rs3741206/rs3842761 were associated with elevated risk of PR (for the TCT haplotype of rs3741206/rs3842761/rs7924316: p = 0.049; OR: 1.69; 95% CI: 1.00–2.87; for the TC haplotype of rs3741206/rs3842761: p = 0.044; OR: 1.71; 95% CI: 1.01–2.88). Conclusion: These results suggest that polymorphisms in IGF2/H19 gene locus are associated with PR risk in EOC.

Context Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. Objectives This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. Methods In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. Results Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). Conclusion EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

Background The precise etiology of anterior inferior cerebellar artery (AICA) infarction is difficult to identify because of the high anatomic variability of vertebrobasilar arteries and the limitations of conventional vascular examinations. Basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) can reveal the outer contour of the intracranial vertebrobasilar arteries, which may be helpful to distinguish the arteriosclerosis from congenital dysplasia and dissection. Case presentation In this study, we reported 3 cases of AICA infarction and discussed the diagnostic value of BPAS-MRI in the evaluation of vascular etiology. Conclusions The BPAS-MRI could be considered as an important supplementary in the diagnosis of vascular etiology of infarction in AICA territory.

More than 20 types of ALK fusion variant subtypes have been identified, including different fusion partner genes or EML4-ALK fusions with different breakpoints. However, different ALK fusions show different sensitivities to ALK-tyrosine kinase inhibitors (ALK-TKIs) and the emergence of rare fusions brings great challenges to the target therapy in clinic. We report a rare EML4-ALK (E6;A18) fusion in a patient with lung adenocarcinoma that responded well to alectinib. This is the second case of this rare variant reported but the first report of response to an ALK-TKI. This evidence is the first to show that alectinib may be effective for this rare fusion type of non–small cell lung cancer, and these findings have important implications for drug selection in patients with this subtype. Further studies are needed to understand the function of this variant.

Background To facilitate biomedical studies of disease mechanisms, a high-quality interactome that connects functionally related genes is needed to help investigators formulate pathway hypotheses and to interpret the biological logic of a phenotype at the biological process level. Results Interactions in the updated version of the human interactome resource (HIR V2) were inferred from 36 mathematical characterizations of 6 types of data that suggest functional associations between genes. This update of the HIR consists of 88,069 pairs of genes representing functional associations that are of strengths similar to those between well-studied protein interactions. Among these functional interactions, 57.04% may represent protein interactions, which are expected to cover 32.48% of the true human protein interactome. The gene set linkage analysis (GSLA) tool is developed based on the high-quality HIR V2 to identify the potential functional impacts of observed transcriptomic changes, helping to elucidate their biological significance and complementing the currently widely used enrichment-based gene set interpretation tools. Conclusions We present the HIR V2, a high-quality functional interactome of human genes, along with the gene set linkage analysis (GSLA) webtool, which utilizes the HIR V2 to interpret the biological significance of transcriptionally changed genes. A case study shows that the annotations reported by the HIR V2/GSLA system are more comprehensive and concise compared to those obtained by widely used gene set annotation tools such as PANTHER and DAVID. The HIR V2 and GSLA are available at http://human.biomedtzc.cn .

To analyze vascular damage-related risk factors for ED in patients with type 2 diabetes mellitus (DM) and develop a nomogram for the prediction of the factors.A total of 181 patients with type 2 DM were included for sexual function assessment, and the clinical data on vascular damage were retrieved from the patients system. After preprocessing, the data were described by the number and percentage of different types of cases and subjected to statistical analysis with the R software. The Lasso regression model was used to optimize feature selection. On the premise of the sample size required for logistic regression analysis according to the number of events per variable, multivariable logistic regression analysis was performed on the selected variables and a nomogram was developed for diabetes-induced erectile dysfunction (DIED). Then, the performance of the nomogram was evaluated with respect to its calibration, discrimination and clinical utility using Harrell's concordance index (C-index), the calibration plot and decision curve analysis, as well as bootstrapping for internal validation.ED was diagnosed in 90 (49.7%) of the 181 patients. The risk factors subjected to logistic regression analysis included the duration of DM (OR = 4.440, 95% CI: 1.594－13.105; OR = 7.667, 95% CI: 1.444－48.733), status of carotid intima-media thickness (c-IMT) (OR = 3.767, 95% CI: 1.194－12.691), diabetic retinopathy (DR) (OR = 5.382, 95% CI: 1.373－28.301), diabetic kidney disease (DKD) (OR = 4.959, 95% CI: 1.156－27.728), low-density lipoprotein cholesterol (LDL-C) (OR = 8.210, 95% CI: 2.027－43.507), red blood cell distribution width (RDW) (OR = 2.418, 95% CI: 1.021－5.826), and plasma fibrinogen (Fbg) (OR = 4.649, 95% CI: 2.001－11.339). The C-index of the DIED model was 0.911 (95% CI: 0.869－0.954). The curve representing the performance of the nomogram fit in well with that representing a perfect prediction by the calibration plot. Decision curve analysis indicated that the nomogram was clinically useful for predicting DIED in the type 2 DM patients at the possibility threshold of 6% to 93%.A nomogram was preliminarily developed for predicting the risk of DIED in type 2 DM patients with respect to the seven independent influencing factors, including the duration of DM, status of c-IMT, DR, DKD, LDL-C, RDW, and Fbg.

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs.

Breast cancer (BC) is the most malignant tumor in women. The molecular mechanisms underlying tumorigenesis still need to be further elucidated. It is necessary to investigate novel candidate genes involved in breast cancer progression and prognosis. In this study, we commit to explore candidate genes that associate with prognosis and therapy in BC by a comprehensive bioinformatic analysis. Four GEO datasets (GSE5764, GSE7904, GSE20711, and GSE29431) and the BC-related transcriptome data in TCGA database were downloaded and used to identify the differently expressed genes (DEGs). The function of DEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. The protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. Prognostic candidate genes were identified through survival analysis. In addition, potential therapeutic targets were identified by constructed gene-drug interaction network through Comparative Toxicogenomics Database. A total of 547 DEGs (302 up and 245 down) were identified. Three core-subnetwork and 25 hub genes were identified in PPI network. Seven genes (namely COL12A1, QPRT, MRPL13, KRT14, KRT15, LAMB3, and MYBPC1) were identified as crucial prognostic candidate genes, which significantly associated with breast cancer overall survival. Furthermore, two representative candidate genes (COL12A1 and LAMB3) were optionally chosen for verification by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR). What's more, the gene-drugs interaction analysis indicates several antitumor drugs that could affect the expression of these prognostic markers, such as doxorubicin, cisplatin, and tamoxifen. These results identified seven crucial candidate genes that may serve as prognosis biomarkers and novel therapeutic targets of breast cancer, which may facilitate further understanding the molecular pathogenesis and providing potential therapeutic strategies for BC.

Polymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes.A total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database.The results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05-2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09-2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29-1.91, P 0.001 and HR = 1.31, 95% CI = 1.06-1.63, P = 0.013, respectively).TIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.

Background and Aim: We have previously shown that high-mobility group box 1 (HMGB1) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis. Methods: Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 (BRG1) was examined by immunohistochemistry. Results: The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues. Conclusions: Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1-mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.

The house mouse or Mus musculus has become a premier mammalian model for genetic research due to its genetic and physiological similarities to humans. It brought mechanistic insights into numerous human diseases and has been routinely used to assess drug efficiency and toxicity, as well as to predict patient responses. To facilitate molecular mechanism studies in mouse, we present the Mouse Interactome Database (MID, Version 1), which includes 155,887 putative functional associations between mouse protein-coding genes inferred from functional association evidence integrated from 9 public databases. These putative functional associations are expected to cover 19.32% of all mouse protein interactions, and 26.02% of these function associations may represent protein interactions. On top of MID, we developed a gene set linkage analysis (GSLA) web tool to annotate potential functional impacts from observed differentially expressed genes. Two case studies show that the MID/GSLA system provided precise and informative annotations that other widely used gene set annotation tools, such as PANTHER and DAVID, did not. Both MID and GSLA are accessible through the website http://mouse.biomedtzc.cn.

Lung cancer organoids (LCOs) have sprung up in more and more researching fields, because of their ability to recapitulate the three-dimensional structure and functions of the in vivo counterpart organs. However, the culture system for LCOs is still immature, resulting in limited success rate and low tumor purity when culturing LCOs. This is mainly due to the deficiency of an optimal formula of culture medium specially for LCOs. Various cytokines and small molecules have been added in the LCOs culturing system. Compound screening, considering both the mechanism of these molecules and the complexity of lung cancer types is warranted to optimize LCOs culture medium. As methods to culture LCOs increase in sophistication, this model will undoubtedly stand its ground in the coming years in every aspect of cancer researches, especially with major advantages in the field of personalized medicine and tumor microenvironment researches.

Our study aimed to assess the associations of plasma magnesium with prediabetes and type 2 diabetes (T2D) among Chinese adults. We conducted a case-control analysis of 4447 participants: 867 newly diagnosed prediabetes patients, 1475 newly diagnosed T2D patients and 2105 normal glucose tolerance (NGT) individuals. In a subsample of 599 apparently healthy individuals, we measured plasma hs-CRP levels to examine their relation to plasma magnesium. Plasma magnesium and hs-CRP were measured by inductively coupled plasma mass spectrometry and an enzyme-linked immunosorbent assay, respectively. Plasma magnesium decreased from NGT to prediabetes to T2D, and was inversely associated with prediabetes and T2D. After adjustment for potential confounding factors, the ORs from the lowest to highest quartiles of plasma magnesium were 1, 0.57 (95%CI, 0.44–0.74), 0.49 (0.37–0.65) and 0.51 (0.37–0.70) for prediabetes, and 1, 0.26 (0.20–0.33), 0.15 (0.12–0.20) and 0.15 (0.11–0.20) for T2D. Consistently, plasma magnesium was inversely correlated with plasma hs-CRP in our subsample analysis; the geometric mean hs-CRP concentration for ascending quartiles of plasma magnesium were 1.29 (1.06–1.57), 1.16 (0.95–1.41), 1.00 (0.81–1.22), and 0.71 (0.58–0.88) mg/l. Plasma magnesium was independently and inversely associated with prediabetes and T2D in Chinese adults.

This study aimed to evaluate neonatal surgical outcomes of patients diagnosed with complex congenital heart disease (CHD) during pregnancy and treated by the newly initiated "perinatal integrated diagnosis and treatment program (PIDTP)".We reviewed clinical data of 207 neonates (surgical age ≤ 28 days) who underwent cardiac surgeries in a single center from January 2017 to December 2018, including 31 patients with referrals from the "PIDTP" (integration group) and 176 patients with routine referral treatment (non-integrated group).In the integration group, median admission age was 0 days and median age at surgery was 4 days. In the non-integrated group, median admission age was 8 days (P = 0.001) and median age at surgery was 13 days (P = 0.001). The emergency surgery rate in patients with duct-dependent defects was 36% in the integration group and 59% (P = 0.042) in the non-integrated group, respectively. The in-hospital mortality was 16% in the integration group and 14% (P = 0.78) in the non-integrated group. The 2-year cumulative survival rate after surgery was 83.9% ± 6.6% in the integration group and 80.3% ± 3.1% (P = 0.744) in the non-integrated group. According to multivariable regression analysis, independent risk factors for early mortality of overall neonatal cardiac surgery were low body weight, high serum lactate level, postoperative extracorporeal membrane oxygenation (ECMO) support and prolonged cardiopulmonary bypass (CPB) time.PIDTP shortens the postnatal transit interval, reduces the emergency operation rate of neonatal critical CHD, and provides better preoperative status for surgery. Patients treated by the PIDTP tend to have more complicated anatomical deformity and a greater requirement for the operation and postoperative management, but early outcome and follow-up prognosis are satisfactory.

To investigate the association between SNPs in human IGF2/H19 gene locus and epithelial ovarian cancer (EOC) risk, we performed a case-control study in 422 individuals (219 EOC patients and 203 cancer-free controls). Four SNPs (rs2525885, rs2839698, rs3741206, rs3741219) were found to be related with EOC risk. Specifically, the minor allele C of rs2525885 and allele A of rs2839698 was associated with elevated EOC genetic susceptibility under both dominant and recessive models (TC + CC vs TT: adjusted OR: 1.61, P = .031; CC vs TT + TC: adjusted OR: 4.87, P = .014; GA + AA vs GG: adjusted OR: 1.63, P = .023; AA vs GG + GA: adjusted OR: 2.43, P = .007). For rs3741206, the genotype TC + CC was associated with a significant decrease in EOC risk with the TT genotype as reference in a dominant genetic model (adjusted OR: 0.44, P = .003), while for rs3741219, genotype AA was associated with a 59% decrease in EOC risk only in the recessive model (adjusted OR: 0.41, P = .038). In the stratified analysis, an increased risk associated with the variant genotypes was observed in only subjects aged >47 years for rs2525885 (adjusted OR = 2.04, P = .024), rs2839698 (adjusted OR = 2.50, P = .047) and rs3741206 (adjusted OR = 0.37, P = .009), respectively. What's more, the TC + CC genotype of rs2525885 was significantly associated with advanced FIGO stage (III vs II, adjusted OR = 2.73, P = .040).

Prostate cancer (PCa) is the most common malignancy in men and in the absence of any effective treatments available. For the development of potential anticancer agents, 24 kinds of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety were synthesized and characterized by using spectroscopic methods. Their pharmacological activities were evaluated against human PCa cell lines (PC-3 and LNCaP) and a1-adrenergic receptors (a1-ARs; α1a, α1b, and α1d-ARs). The structure–activity relationship of these designed arylpiperazine derivatives was rationally explored and discussed. Among these derivatives, 3c, 3d, 3h, 3k, 3o, and 3s exhibited the most potent activity against the tested cancer cells, and some derivatives with potent anticancer activities exhibited better a1-AR subtype selectivity than others did (selectivity ratio > 10). This work provided a potential lead compound for the further development of anticancer agents for PCa therapy.

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

Twenty-one polycyclic polyprenylated acylphloroglucinols, including three new compounds named as hyperichoisins A (

Background Preeclampsia (PE) is a severe pregnancy complication and is an important cause for maternal and child death, premature delivery, and limited intrauterine growth and development. The aim of this study was to investigate the role of NGAL and cystatin C, alone and in combination, for early prediction of PE at 10 - 14 weeks of gestation. Methods Serum levels of NGAL and cystatin C were assessed in women at 10 - 14 weeks of gestation who subsequently developed PE (n = 128) and normal pregnancy outcome (n = 183). Comparison of clinical characteristics, NGAL, and cystatin C levels between normal pregnancy and PE groups were analyzed using Mann-Whitney test. The receiver operating characteristic curve (ROC curve) was used to analyze the value of serum NGAL and cystatin C levels in predicting PE. Results The levels of cystatin C and NGAL in the serum were significantly higher in the PE group [0.64 mg/L (0.52 - 0.78)] and [34.9 ng/mL (24.4 - 55.2), respectively] than in the normal pregnancy group [0.56 mg/L (0.49 - 0.65)] and [20.2 ng/mL (13.8 - 26.9), respectively]. ROC curve analysis showed that serum NGAL levels predicted the area under the curve in the PE period 0.739 (95% CI: 0.618 to 0.860). Serum cystatin C levels predicted the area under the curve in the PE period 0.722 (95% CI: 0.592 to 0.853). The combination of serum NGAL and cystatin C levels predicted the area under the curve in the PE period 0.877 (95% CI: 0.811 to 0.943). Conclusions NGAL and cystatin C levels in serum appear to be ideal biomarkers for PE prediction at 10 - 14 weeks. The combination of NGAL and cystatin C will also be more valuable in discriminating patients at risk of developing PE from other pregnancy complications early in gestation.

A novel scaffold of arylpiperazine derivatives was discovered as potent androgen receptor (AR) antagonist through rational drug designation based on our pre-work, leading to the discovery of a series of new antiproliferative compounds. Compounds 10, 16, 27, 29 and 31 exhibited relatively strong antagonistic potency against AR and exhibited potent AR binding affinities, while compounds 5, 6, 10, 14, 16, 19, 21, 27 and 31 exhibited strong cytotoxic activities against LNCaP cells (AR-rich) as well as also displayed the higher activities than finasteride toward PC-3 (AR-deficient) and DU145 (AR-deficient). Docking study suggested that the most potent antagonist 16 mainly bind to AR ligand binding pocket (LBP) site through hydrogen bonding interactions. The structure-activity relationship (SAR) of these designed arylpiperazine derivatives was rationally explored and discussed. These results indicated that the novel scaffold compounds demonstrated a step towards the development of novel and improved AR antagonists, and promising candidates for future development were identified.

Inhibin B, a glycoprotein produced predominantly by Sertoli cells and preferentially suppressing the production and secretion of follicle-stimulating hormone (FSH) in the pituitary, is closely related to spermatogenesis. Varicocele is the abnormal dilatation and tortuosity of the pampiniform plexus veins, which may contribute to spermatogenic dysfunction and male infertility. More and more evidence has shown that the level of serum inhibin B is negatively correlated with the severity of varicocele. Determination of the inhibin B level may help assess the severity of spermatogenic dysfunction of the patient and predict the outcomes of varicocele repair and therefore has a potential application value in the diagnosis and treatment of varicocele.抑制素B主要由睾丸支持细胞合成的可特异性地抑制垂体FSH合成与分泌的一种糖蛋白激素，与生精功能密切相关。精索静脉曲张指精索内蔓状静脉丛的异常迂曲、扩张，可以引起睾丸生精功能障碍，是导致男性不育常见的病因。越来越多的证据表明，血清抑制素B水平与精索静脉曲张程度呈负相关，检测血清抑制素B水平能评估精索静脉曲张患者生精功能的损害程度，并可预测精索静脉曲张术后的疗效，在精索静脉曲张疾病的诊疗中有潜在的应用价值。.

With the development of high-performance fighters, the function of pilot helmets is also constantly upgrading, and helmet-mounted display (HMD) has become a future development trend. To solve the inter-restriction between the eye position control and the pressure comfort under high overloads of pilot helmets, this paper optimizes the helmet design by building a head-helmet finite element model: (1) Under a 10 G overload, the deformation of helmet soft liner should not exceed 2 mm; and (2) The combination of liner materials used in various areas should satisfy the requirements of most comfortable head pressure distribution (Pfront: Ptop: Pside: Pback = 2:2:1:3). The study on 46 different combinations of materials finds that the helmet can meet both the eye position maintenance requirement under overloads and the requirement of comfortable pressure distribution when linear elastic materials with Young's modulus of 1000 pa, 55000 pa and 65000 pa are used for the side, top and front parts of the head, and nonlinear elastic hyperfoam material with two-fold stress variation is used for the head back area.

Objective: The aim of this study was to identify heart failure (HF)-specific circulating micro-RNAs (miRNA), and examine whether the selected miRNAs correlate with myocardial fibrosis and are reflective of the incidence of adverse cardiovascular events in patients with stage C or D HF. Methods: Circulating miRNAs which were expressed in end-stage HF patients and matched healthy controls were detected by microarray analysis and validated by quantitative real-time polymerase chain reaction. Multivariate Cox regression analysis was performed to determine whether the selected circulating miRNAs could be prognostic factors in HF patients. Results: In a cohort of 7 healthy controls and 9 patients with stage C or D HF, 7 miRNAs were differentially expressed. These miRNAs were further investigated in a second cohort of 80 patients with stage C or D HF and 30 healthy controls. Only miR-197-5P correlated with fibrosis as seen in cardiac magnetic resonance imaging in patients under the age of 50 years with stage C or D HF (r = 0.42, p = 0.008). Multivariate analyses revealed that miR-197-5P was also a risk factor for composite endpoint events in patients under the age of 50 years with stage C or D HF. Conclusion: miR-197-5P is a circulation miRNA that correlates with MF and adverse cardiac events in HF patients under the age of 50 years.

Background Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. Methods Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway. Results CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway. Conclusion The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0722-6) contains supplementary material, which is available to authorized users.

Background: Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients' experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). Methods: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients' medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. Conclusion: The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities.

The main objective of the current research work was to investigate the antitumor effects of papaverine in PC-3 human prostate cancer cells along with testing its toxicity in the normal human fibroblast (NHF) cells.The cytotoxic effects of papaverine were examined by the MTT cell viability assay. Flow cytometry using annexin V-FITC/PI was used to study the effects on apoptosis, including its quantification. Effects on cell cycle progression were analyzed by flow cytometry while as effects on apoptosis-related proteins, NF-kB and PI3K/Akt pathways were estimated by Western blot assay.The results indicated that papaverine could induce significant, highly selective and dose-dependent cytotoxic effects in PC-3 cells without causing too much toxicity in normal cells. Papaverine also led to induction of early and late apoptosis along with inducing sub-G1 cell cycle arrest in a dose-dependent manner. Papaverine induced a dose-dependent reduction in the expression levels of Blc-2 proteins and a dose-dependent increase in the expression levels of Bax protein. The expression levels of NF-kB were decreased markedly in comparison to the untreated control. Papaverine treatment also led to a dose-dependent downregulation of PI3K and phospho-Akt expression.Papaverine showed selective antitumor properties against PC-3 human prostate cancer cells by inducing early and late apoptosis, sub-G1 cell cycle arrest, modulation of apoptosis-related proteins like Bcl-2, Bax, Bid, XIAP and cytochrome C along with downregulation of NFkB, PI3K/Akt signalling pathway.

Objective The purpose of the present study was to assess the efficacy of the long-term results after video-assisted pulmonary vein isolation and left atrial appendage excision for lone atrial fibrillation (AF) and to determine the most significant risk factors for the long-term results. Methods From December 2006 to December 2012, 332 consecutive patients with lone AF underwent minimally invasive surgical ablation at our center. Of the 332 patients, 91, who had undergone video-assisted pulmonary vein isolation >5 years earlier, were evaluated in the present study (48 with paroxysmal AF, 21 with persistent AF, and 22 with long-standing persistent AF). The median follow-up period was 66 months. The primary endpoint was the success rate of video-assisted pulmonary vein isolation, defined as the absence of any atrial arrhythmia recurrence lasting >30 seconds at the clinical visit and on the electrocardiogram or long-term cardiac rhythm recording after discharge. Results During the follow-up period, 1 patient (1.1%) experienced a stroke and 4 (4.4%) died of noncardiac disease. At the 5-year follow-up point, 43 of 78 patients (55.1%) were in normal sinus rhythm. Of the 39 patients with paroxysmal AF and 39 with nonparoxysmal AF, 27 (69.2%) and 16 (44.1%) were in normal sinus rhythm, respectively. The results of the univariate and multivariate analyses of the preoperative risk factors for AF recurrence showed a left atrial diameter of ≥44 mm (hazard ratio, 5.56; 95% confidence interval, 1.68-18.387; P = .005) and an AF duration of ≥31.5 months (hazard ratio, 3.67; 95% confidence interval, 1.50-8.95; P = .004) were the most significant independent risk factors. Conclusions Patients with lone AF with a large preoperative left atrial diameter and long AF duration will not be suitable for video-assisted pulmonary vein isolation alone and might need to undergo ablation of the lesions.

Purpose The aims of this study were to present an uncommon intracranial germinoma manifesting as skull base extension and analyze its clinical characteristics to give valuable insight into such uncommon radiologic variant. Methods This is a clinical study of a 15-year-old girl with intracranial germinoma manifesting as skull base extension. Clinical characteristics, magnetic resonance imaging scan observations, pathologic findings, and flow of the treatment procedure were presented and analyzed. Results She had a 5-month history of diuresis and diplopia. magnetic resonance imaging observation displayed a neoplasm located in the right-side central skull base and suprasellar area with wide extension into the cavernous sinus, intraorbital region, ethmoidal sinus, sphenoid sinus, and pituitary fossa. After administration of contrast medium, strong and heterogeneous enhancement of the mass was observed, with a dural tail sign along the right cerebellar tentorial. Right pterional approach was performed, and intraoperative histologic examination suspected the diagnosis of germinoma; partial resection was achieved, and postoperative radiotherapy was administered. Cranial nerve palsy improved greatly 6 months postoperatively. Conclusions Although highly unusual, germinoma should be included in the differential diagnosis of all masses with extension along the midline region of skull base, especially when it happens in young female patients.

Background Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis. Methods By performing Solexa/Illumina's digital gene expression (DGE) profiling, we analyzed gene expression profiles of PBMCs from 6 quiescent (grade 0) and 6 rejection (grade 2R&3R) heart transplant recipients at more than 6months after transplantation. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out in an independent validation cohort of 47 individuals from three rejection groups (ISHLT, grade 0,1R, 2R&3R). Results Through DGE sequencing and qPCR validation, 10 genes were identified as informative genes for detection of cardiac transplant rejection. A further clustering analysis showed that the 10 genes were not only effective for distinguishing patients with acute cardiac allograft rejection, but also informative for discriminating patients with renal allograft rejection based on both blood and biopsy samples. Moreover, PPI network analysis revealed that the 10 genes were connected to each other within a short interaction distance. Conclusions We proposed a 10-gene signature for heart transplant patients at high-risk of developing severe rejection, which was found to be effective as well in other organ transplant. Moreover, we supposed that these genes function systematically as biomarkers in long-time allograft rejection. Further validation in broad transplant population would be required before the non-invasive biomarkers can be generally utilized to predict the risk of transplant rejection.

To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer.We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013.By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4(+)/CD8(+) ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions.Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.

Chronic inflammation plays an important role in nasopharyngeal carcinoma (NPC) development and progression. Aim of this study is to determine whether inflammation-related parameters predict distant metastasis in NPC patients.335 newly diagnosed non-metastatic NPC patients were recruited. The values of the C-reactive protein (CRP), lactate dehydrogenase, albumin, globulin, white blood cell and neutrophil at baseline were measured.Among the above six parameters, only CRP was independently associated with distant metastasis-free survival (DMFS). CRP concentration of advanced T-/TNM-classification patients was higher than those with early classification (P = 0.001). Higher-CRP (CRP ⩾ 2.46 mg/L) predicted shorter overall survival, disease-free survival and DMFS than lower-CRP (CRP2.46 mg/L). In a multivariable model, higher-CRP and advanced N-classification were independent predictors of distant metastasis. On the basis of these two parameters, a prognostic NC-model was developed as following: (1) low-risk (early N-classification and lower-CRP); (2) intermediate-risk (advanced N-classification or higher-CRP) and (3) the high-risk distant metastasis (advanced N-classification and higher-CRP). When compared with the low-risk group, the hazard ratios (HRs) for distant metastasis and death for the intermediate-/high-risk patients were 3.6/16.1 and 2.26/7.61, respectively (both P0.001).We developed a new prognostic model based on CRP and N-classification for predicting distant metastasis and death of NPC patients, which may facilitate patient counselling and individualised treatment.

The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

BackgroundThis study assessed the role of surgical ablation for atrial fibrillation (AF) in decreasing tricuspid regurgitation (TR) and right‐sided heart remodeling in patients after mitral valve procedure.Methods and ResultsBetween 1994 and 2014, 1568 consecutive patients withAFundergoing mitral valve procedure were identified. In 26.0% (n=408), surgical ablation ofAFwas used. Propensity‐score matching (PSM) was performed on the basis of 41 known perioperative risk variables. Survival, reoperation, stroke, and moderate‐to‐severeTR, as well as echocardiography indices in long‐term follow‐up, were compared in 406 matched patient pairs (ablated and nonablated groups). The nonablated group showed significantly higher risks of death (hazard ratio [HR], 1.644; 95%CI, 1.081–2.501;P=0.020), reoperation (HR, 2.644; 95%CI, 1.299–5.466;P=0.008), and moderate‐to‐severeTR(HR, 1.436; 95%CI, 1.059–1.948;P=0.020), associated with a significantly deteriorated cardiac function, progression ofTR, and right‐sided heart remodeling after 5‐year follow‐up. In a subgroup comparison of ablated patients with sinus rhythm versusAFrecurrence, aPSManalysis was performed at the 5‐year follow‐up. The recurrent group showed significantly higher risks of moderate‐to‐severeTR(HR, 2.427; 95%CI, 1.261–4.671;P=0.008).AFrecurrence was associated with progressiveTRand significant deterioration in right‐sided heart remodeling.ConclusionsIn a retrospectivePSManalysis, mitral valve disease withAFwas associated withTRprogression as well as right‐sided heart remodeling, which are alleviated by surgical ablation.

Papillary meningioma is an uncommon meningioma subtype of World Health Organization grade III. It could show some radiologic profiles pointing to malignant behavior, such as a cystic change, a heterogeneous enhancement, and an ill- defined border. However, to date, the radiologic profile described in this article has not been reported in previous literatures, and it is just the characteristic being considered as the major cause for patients’ death. A 16-year-old adolescent boy with a 6-month history of headache was admitted to our department on June 28, 2012. Magnetic resonance imaging showed a giant well-defined mass in the left temporal region, with a severe flow void on T2-weighted image and an abundant stripelike enhancement on T1-weighted contrast-enhanced scan. In view of its middle cranial fossa location (one predilection site for meningioma), meningioma was suspected preoperatively. A regular left frontotemporal craniotomy was performed. Unexpectedly, extreme hemorrhage happened intraoperatively, and it was difficult to stop the bleeding. After identification of no hemorrhage in the operative cavity through intraoperative magnetic resonance imaging, the operation was finished, with an overall blood loss of 15,000 mL. The patient died of brain stem dysfunction the second day after the operation.

BACKGROUND Dual-specificity phosphatase 6 (DUSP6) inactivates different target kinases to regulate cell proliferation and differentiation. Altered DUSP6 expressions or gene polymorphisms are associated with human cancer development including non-small cell lung cancer (NSCLC). DNA topoisomerase II alpha (TOP2A) regulates chromosome condensation and chromatid separation, and altered TOP2A expressions are associated with drug resistance development. This study assessed DUSP6 and TOP2A single nucleotide polymorphisms (SNPs) associated with NSCLC patient survival. METHODS This study included 152 surgically resected NSCLC patients and 277 chemoradiotherapy treated inoperable cases. DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used to evaluate the association between these variants and NSCLC overall survival. RESULTS DUSP6 rs2279574 A/A genotype was associated with significantly poor inoperable NSCLC patient overall survival (A/A vs. C/C, adjusted HR = 1.549, 95% CI = 1.019-2.355). Stratification analysis against clinical stage, histology, weight loss, and ECOG performance status revealed that the DUSP6 rs2279574 A/A variant homozygous genotype is associated with a decrease in survival of stage IV NSCLC patients compared to those with the C/C genotype (log-rank, p = 0.003). No association was found among histology, weight loss, and ECOG performance status. Moreover, there was no association of TOP2A SNPs between clinicopathological and survival data. CONCLUSIONS Data obtained from the current study demonstrated that functional DUSP6 rs2279574 polymorphism was able to predict inoperable NSCLC patient survival after chemoradiotherapy.

Background The outcomes of atrial fibrillation (AF) between biatrial maze (BAM) and left atrial maze (LAM) are still controversial. The purpose of this study was to compare the clinical and rhythm outcomes between BAM and LAM in patients with AF. Methods Electronic databases and article references were systematically searched (1990-2014) to access relevant studies. Odds ratio (OR) and weight mean difference (WMD) with 95% confidence interval (CI) were reported. Results Fourteen studies with 2,075 patients were finally involved in the present meta-analysis. The rate of restored sinus rhythm (SR) was similar in BAM and LAM groups (OR: 1.25, 95% CI: 0.91-1.72, p = 0.163). BAM reduced the prevalence of atrial flutter during follow-up (OR: 0.12, 95% CI: 0.01-0.96, p = 0.046). Compared with BAM, LAM shorten aortic cross-clamping time (WMD = 9.05 minutes, 95% CI: 1.28-16.82, p = 0.023) and cardiopulmonary bypass time (WMD = 20.21 minutes, 95% CI: 7.40-33.03, p = 0.002). No significant difference was found between groups in the risk of death (OR: 1.22, 95% CI: 0.70-2.14, p = 0.233), cerebrovascular events (OR: 1.44, 95% CI: 0.51-4.06, p = 0.493), and reoperation for bleeding (OR: 1.34, 95% CI: 0.70-2.55, p = 0.374). However, the risk for implantation of permanent pacemaker was significantly higher in BAM group (OR: 2.60, 95% CI: 1.09-6.20, p = 0.031). Conclusion No significant difference was found between BAM and LAM in the rate of restored SR, the risk of death, cerebrovascular events, and reoperation for bleeding. BAM is superior to LAM in reducing the prevalence of atrial flutter during follow-up, but LAM shortens the aortic cross-clamping time and cardiopulmonary bypass time, and decreases the risk of permanent pacemaker implantation.

To compare the image quality of T1WI fat phase,T1WI water phase, short time inversion recovery (STIR) sequence, and diffusion weighted imaging (DWI) sequence in the evaluation of multiple myeloma (MM).Totally 20MM patients were enrolled in this study. All patients underwent scanning at coronal T1WI fat phase, coronal T1WI water phase, coronal STIR sequence, and axial DWI sequence. The image quality of the four different sequences was evaluated. The image was divided into seven sections(head and neck, chest, abdomen, pelvis, thigh, leg, and foot), and the signal-to-noise ratio (SNR) of each section was measured at 7 segments (skull, spine, pelvis, humerus, femur, tibia and fibula and ribs) were measured. In addition, 20 active MM lesions were selected, and the contrast-to-noise ratio (CNR) of each scan sequence was calculated.The average image quality scores of T1WI fat phase,T1WI water phase, STIR sequence, and DWI sequence were 4.19 ± 0.70,4.16 ± 0.73,3.89 ± 0.70, and 3.76 ± 0.68, respectively. The image quality at T1-fat phase and T1-water phase were significantly higher than those at STIR (P=0.000 and P=0.001) and DWI sequence (both P=0.000); however, there was no significant difference between T1-fat and T1-water phase (P=0.723)and between STIR and DWI sequence (P=0.167). The SNR of T1WI fat phase was significantly higher than those of the other three sequences (all P=0.000), and there was no significant difference among the other three sequences (all P0.05). Although the CNR of DWI sequences was slightly higher than those of the other three sequences,there was no significant difference among all of them (all P0.05).Imaging at T1WI fat phase,T1WI water phase, STIR sequence, and DWI sequence has certain advantages,and they should be combined in the diagnosis of MM.

There is increasing concern about neurologic injury due to deep hypothermia with low flow during repair of complex congenital heart defects in neonates and infants. Twenty infants with ventricular septal defect and pulmonary hypertension were randomly assigned to cardiac repair under deep hypothermia with circulatory arrest or deep hypothermia with low flow. Measurements of static pulmonary compliance, airway resistance, and respiratory index were performed before institution of cardiopulmonary bypass and at 5 minutes and 2 hours after cessation of cardiopulmonary bypass. Both groups had significant pulmonary dysfunction in terms of static pulmonary compliance, airway resistance, and respiratory index. There was greater impairment of pulmonary compliance and respiratory index after deep hypothermia with low flow, and this group required longer intensive care unit stay.

Multiple myeloma is an incurable malignancy developed in the bone marrow plasma cell system. It usually consists of focal lesions of the bone,soft tissue lesions,and diffuse bone marrow infiltration. Currently,the diagnosis and follow-up of multiple myeloma are highly dependent on various medical imaging techniques.