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Hostile attribution bias (HAB) has been considered as a risk factor of various types of psychosocial adjustment problem, and contributes to displaced aggression (DA). The neural basis of HAB and the underlying mechanisms of how HAB predicts DA remain unclear.The current study used degree centrality (DC) and resting-sate functional connectivity (RSFC) to investigate the functional connection pattern related to HAB in 503 undergraduate students. Furthermore, the "Decoding" was used to investigate which psychological components the maps of the RSFC-behavior may be related to. Finally, to investigate whether and how the RSFC pattern, HAB predicts DA, we performed mediation analyses.We found that HAB was negatively associated with DC in bilateral temporal poles (TP) and positively correlated with DC in the putamen and thalamus; Moreover, HAB was negatively associated with the strength of functional connectivity between TP and brain regions in the theory of mind network (ToM), and positively related to the strength of functional connectivity between the thalamus and regions in the ToM network. The "Decoding" showed the maps of the RSFC-behavior may involve the theory mind, autobiographic, language, comprehension and working memory. Mediation analysis further showed that HAB mediated the relationship between some neural correlates of the HAB and DA.The current results need to be further tested by experimental methods or longitudinal design in further studies.These findings shed light on the neural underpinnings of HAB and provide a possible mediation model regarding the relationships among RSFC pattern, HAB, and displaced aggression.

Gastric cancer (GC) is one of the most aggressive malignant tumors worldwide. Ferroptosis is a kind of iron-dependent cell death, which is proved to be closely related to tumor progression. In this study, we aim at constructing a ferroptosis-related lncRNAs signature to predict the prognosis of GC and explore potential therapies.Ferroptosis-Related LncRNAs Signature for GC patients (FRLSG) was constructed through univariate Cox regression, the LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, receiver operating characteristic curves, and risk score plot were applied to verify the predictive power of FRLSG. Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses were conducted to explore the potential clinical value of the FRLSG. In addition, drug sensitivity prediction was applied to identify chemotherapeutic drugs with potential therapeutic effect.Five ferroptosis-related lncRNAs (AC004816.1, AC005532.1, LINC01357, AL355574.1 and AL049840.4) were identified to construct FRLSG, whose expression level in GC were confirmed by experimental validation. Kaplan-Meier curve and ROC curve proved the reliability and effectiveness of the FRLSG in predicting the prognosis for GC patients. Several immune-related pathways were enriched in the high-FRLSG group, and further immune infiltration analyses demonstrated the high immune infiltration status of the high-FRLSG group. In addition, 19 and 24 candidate drugs with potential therapeutic effect were identified for the high- and low-FRLSG groups, respectively.FRLSG was an effective tool in predicting the prognosis of GC, which might help to prioritize potential therapeutics for GC patients.

Background and AimOver 10% of hepatocellular carcinoma (HCC) cases recur each year, even after surgical resection. Currently, there is a lack of knowledge about the causes of recurrence and the effective prevention. Prediction of HCC recurrence requires diagnostic markers endowed with high sensitivity and specificity. This study aims to identify new key proteins for HCC recurrence and to build machine learning algorithms for predicting HCC recurrence.MethodsThe proteomics data for analysis in this study were obtained from the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database. We analyzed different proteins based on cases with or without recurrence of HCC. Survival analysis, Cox regression analysis, and area under the ROC curves (AUROC > 0.7) were used to screen for more significant differential proteins. Predictive models for HCC recurrence were developed using four machine learning algorithms.ResultsA total of 690 differentially expressed proteins between 50 relapsed and 77 non-relapsed hepatitis B-related HCC patients were identified. Seven of these proteins had an AUROC > 0.7 for 5-year survival in HCC, including BAHCC1, ESF1, RAP1GAP, RUFY1, SCAMP3, STK3, and TMEM230. Among the machine learning algorithms, the random forest algorithm showed the highest AUROC values (AUROC: 0.991, 95% CI 0.962–0.999) for identifying HCC recurrence, followed by the support vector machine (AUROC: 0.893, 95% Cl 0.824–0.956), the logistic regression (AUROC: 0.774, 95% Cl 0.672–0.868), and the multi-layer perceptron algorithm (AUROC: 0.571, 95% Cl 0.459–0.682).ConclusionsOur study identifies seven novel proteins for predicting HCC recurrence and the random forest algorithm as the most suitable predictive model for HCC recurrence.

Introduction: Gut dysbiosis has been reported to be closely associated with gout. Washed microbiota transplantation (WMT) is considered as an effective way to restore a healthy gut microbiota with less adverse events than the conventional fecal microbiota transplantation. In this study, we aimed to evaluate the effects of WMT on serum uric acid levels, symptoms, and the intestinal barrier function in patients with acute and recurrent gout. Methods: We performed a pilot study of WMT for acute and recurrent gout. The primary outcome was the changes in the serum uric acid level and gout symptoms. The secondary outcomes included the changes in levels of diamine oxidase (DAO), D-lactic acid, and endotoxin. Results: Eleven patients received WMT treatment. The averaged serum uric acid levels in patients with gout reduced after WMT (p = 0.031), accompanied with a decrease in the frequency and duration time of acute gout flares (p < 0.01). The levels of DAO, D-lactic acid, and endotoxin were higher in patients than in healthy donors (p < 0.05). After WMT treatment, the levels of DAO and endotoxin decreased (p < 0.05). Conclusions: WMT is effective for reducing serum uric acid levels and improving gout symptoms in patients with gout and contributes to improve their impaired intestinal barrier function.

Objective Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD. Methods This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated. Results By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity. Conclusion The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD. Electronic supplementary material The online version of this article (10.1007/s11596-021-2475-2) contains supplementary material, which is available to authorized users.

In order to reveal the Spatial distribution characteristics of heavy metal(loid)s health risk in soil on the town-scale, 788 topsoil samples were collected from a town in the hinterland of Chengdu Plain, with 5 subordinate communities and 17 administrative villages as the research sub regions. The USEPA health risk assessment model was used to assess the health risks of heavy metal(loid)s Cd, Hg, As, Cu, Pb, Cr, Zn and Ni in the soil, the health risk analysis method system based on the geographic detector and the optimized rank-size theory model are used to clarify the spatial differentiation and risk level difference of health risk in the study area. The results showed that the average values of Cd, Hg, As, Pb, Cr, Cu, Ni and Zn in the soil of the study area were 0.221, 0.155, 9.76, 32.2, 91.9, 35.2, 37.1 and 108.8 mg/kg, respectively. The health risks of heavy metal(loid)s in soil to adults and children are generally within the acceptable range, but the maximum hazard index of children and the maximum non-carcinogenic risk value of Cr to children are 2.653303 and 1.213098 respectively, which were exceeding the acceptable range. The carcinogenic risk of Cr and As to adults and children and the carcinogenic risk of Cd to children are at 1 × 10–4 to 1 × 10–6, exceeding the 10–6 health threshold. The q-value range of heavy metal(loid)s health risk spatial differentiation of soil in the study area is 0.016–0.425. The spatial differentiation of non-carcinogenic risk of Hg, As, Ni, Pb, Cd and Cr and the spatial differentiation of carcinogenic risk of Cr and As are larger, which needs further attention. The strictly controlled area of heavy metal(loid)s health risk in the soil of the study area (R ≥ 1.1) is mainly concentrated in the central, western and northeast sub regions, and most sub regions belong to the safe utilization area (0.9

To study the application of triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) combined with liver function indexes to predict metabolic-associated fatty liver disease (MAFLD).A total of 2971 outpatients diagnosed with MAFLD and 2794 healthy controls were enrolled, and their relevant data were collected. Two-sample Mann-WhitneyThe TG/HDL-C of MAFLD patients was significantly higher than that of healthy controls. In multivariate analysis, after adjusting for body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, uric acid and creatinine, the odds ratio of TG/HDL-C was 2.356 (95% confidence interval [TG/HDL-C is an independent risk factor for MAFLD. TG/HDL-C can well predict MAFLD when it is used in combination with ALT, AST, and ALB.

Purpose To investigate the dosimetric impact of deep learning-based auto-segmentation of organs at risk (OARs) on nasopharyngeal and rectal cancer. Methods and materials Twenty patients, including ten nasopharyngeal carcinoma (NPC) patients and ten rectal cancer patients, who received radiotherapy in our department were enrolled in this study. Two deep learning-based auto-segmentation systems, including an in-house developed system (FD) and a commercial product (UIH), were used to generate two auto-segmented OARs sets (OAR_FD and OAR_UIH). Treatment plans based on auto-segmented OARs and following our clinical requirements were generated for each patient on each OARs sets (Plan_FD and Plan_UIH). Geometric metrics (Hausdorff distance (HD), mean distance to agreement (MDA), the Dice similarity coefficient (DICE) and the Jaccard index) were calculated for geometric evaluation. The dosimetric impact was evaluated by comparing Plan_FD and Plan_UIH to original clinically approved plans (Plan_Manual) with dose-volume metrics and 3D gamma analysis. Spearman’s correlation analysis was performed to investigate the correlation between dosimetric difference and geometric metrics. Results FD and UIH could provide similar geometric performance in parotids, temporal lobes, lens, and eyes (DICE, p > 0.05). OAR_FD had better geometric performance in the optic nerves, oral cavity, larynx, and femoral heads (DICE, p p p = 0.05). Only one significant correlation was found between the mean dose of the femoral head and its HD index (R = 0.4, p = 0.01), there is no OARs showed strong correlation between its dosimetric difference and all of four geometric metrics. Conclusions Deep learning-based OARs auto-segmentation for NPC and rectal cancer has a nonsignificant impact on most PTV and OARs dose-volume metrics. Correlations between the auto-segmentation geometric metric and dosimetric difference were not observed for most OARs.

Objectives This study aimed to investigate whether plasma levels of adenosine, adenosine deaminase (ADA), and certain cytokines change in patients with chronic insomnia disorder (CID), and if so, whether these alterations are associated with poor sleep quality and cognitive dysfunction. Methods Fifty-five CID patients were selected for the study, along with fifty-five healthy controls (HC) matched to the patients according to their basic data. All subjects completed sleep, emotion, and cognition assessments, with some CID patients also completing an overnight polysomnography. The plasma level of adenosine was measured using liquid chromatography–tandem mass spectrometry, while ADA level was quantified using a quantitative sandwich enzyme-linked immunosorbent assay. Levels of cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ, were measured using Luminex liquid chip technology. Results CID patients had a lower adenosine level, and higher levels of ADA and some of the cytokines (IL-1β, IL-2, IL-6, IL-10 and TNF-α) compared with controls. In the CID group, plasma concentrations of adenosine were negatively correlated with Pittsburgh Sleep Quality Index scores, while concentrations of IL-1β, IL-6 and TNF-α were positively correlated with these scores. Concentrations of IL-1β and TNF-α were negatively correlated with scores on the Chinese-Beijing Version of the Montreal Cognitive Assessment. Moreover, levels of IL-1β, TNF-α, IL-6, and IL-2 were positively correlated with memory test errors by CID patients after controlling for confounding factors. Conclusions The reduced adenosine and elevated cytokine levels of CID patients were associated with the severity of insomnia and/or cognitive dysfunction.

To analyze and compare the efficacy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of thrombocytopenia after chemotherapy in acute leukemia patients.180 patients with acute leukemia complicated with thrombocytopenia after chemotherapy in the First Affiliated Hospital of Anhui Medical University were analyzed retrospectively. Among them, 50 patients who treated with rhTPO and did not receive platelet transfusion were set as group A, 50 patients treated with rhTPO and receive platelet transfusion were set as group B, Forty patients treated with rhIL-11 without platelet transfusion were set as group C, Forty patients who treated with rhIL-11 and received platelet transfusion were set as group D. The duration of PLT below 20×10The duration of PLT20×10In the treatment of acute leukemia patients with thrombocytopenia after chemotherapy, compared with rhIL-11, rhTPO can significantly shorten the duration for patients in a status with extremely low levels of PLT and the recovery time of PLT to normal range. In addition, PLT transfusion cannot speed up the time for patients to raise platelets to a safe range, nor can it shorten the duration of low PLT levels, but it can reduce the incidence of high bleeding risk events.rhTPO与rhIL-11对白血病化疗后血小板减少的疗效分析.分析比较重组人血小板生成素（rhTPO）与重组人白介素-11（rhIL-11）在急性白血病化疗后血小板(PLT)减少患者治疗中的效果.回顾分析安徽医科大学第一附属医院180例急性白血病化疗后并发血小板减少症患者，其中50例使用rhTPO治疗且未进行血小板输注的为A组，50例使用rhTPO治疗且进行血小板输注的为B组，40例使用rhIL-11治疗且未进行血小板输注的为C组，40例使用rhIL-11治疗且进行血小板输注的为D组, 比较各组患者PLT 在 20×10A组PLT＜20×10在急性白血病化疗后血小板减少患者的治疗中，与rhIL-11比较，rhTPO能明显缩短患者血小板处于极低水平状态及升至正常的时间，而血小板的输注不能加快患者血小板升高至安全范围的时间，也不能缩短患者处在低血小板水平持续的时间，但可以减少患者高出血风险事件的发生率.

Displaced aggressive behaviour is associated with many negative outcomes. Although certain personality traits predict displaced aggressive behaviour, the uniquely longitudinal effect of indigenous interpersonal traits on displaced aggressive behaviour is ignored. To address this gap, we explored the longitudinal relationship among an indigenously interpersonal trait of China (interpersonal openness), hostile attribution bias, and self-reported displaced aggressive behaviour. Additionally, we tested whether hostile attribution bias mediated the relationship between interpersonal openness and self-reported displaced aggressive behaviour. The Interpersonal Self-Support Scale for Undergraduate Students, Word Sentence Association Paradigm for Hostility, Displaced Aggression Questionnaire, and the NEO Personality Inventory-3 were administered to 942 undergraduates on two occasions, 6 months apart. A cross-lagged model showed that, after controlling for the Big Five personality traits, interpersonal openness predicted subsequent hostile attribution bias, and hostile attribution bias predicted self-reported displaced aggressive behaviour 6 months later. Hostile attribution bias at time 2 mediated the relationship between interpersonal openness at time 1 and self-reported displaced aggressive behaviour at time 2. These results were consistent with the interpersonal self-support theory's appraisals of interpersonal openness, and they extended the social information processing and general aggression models to explain displaced aggressive behaviour.

Background The pathogenesis of gastroesophageal reflux disease (GERD) is closely associated with the intestinal bacteria composition and their metabolites. Aim To investigate whether washed microbiota transplantation (WMT) improves symptoms of nonerosive reflux disease (NERD) with proton pump inhibitor (PPI) dependency. Methods Patients with recurrent NERD and PPI dependency at the First Affiliated Hospital of Guangdong Pharmaceutical University from 2017 to 2018 were included and divided into a WMT or PPI group treated with PPI with/without WMT. The endpoint was NERD symptom frequency evaluated 1 mo after WMT using reflux disease questionnaire (RDQ) and GERD questionnaire (GERDQ) scores, remission time, PPI dose, and the examination of intestinal mucosal barrier function. Results In the WMT (n = 15) and PPI (n = 12) groups, the total remission rate at 1 mo after treatment was 93.3% vs 41.7%. Compared with the PPI group, the WMT group showed better results in GERDQ (P = 0.004) and RDQ (P = 0.003) and in remission months (8 vs 2, P = 0.002). The PPI dose was reduced to some extent for 80% of patients in the WMT group and 33.3% in the PPI group. In 24 patients, intestinal mucosal barrier function was examined before treatment, and changes in the degree of damage were observed in 13 of these patients after treatment. Only one of the 15 patients had minor side effects, including a mushy stool two or three times a day, which resolved on their own after 1 wk. Conclusion This study is the first to demonstrate that WMT may be safe and effective for relieving NERD symptoms and reducing PPI dependency and recurrence.

Improved methods are needed to predict outcomes in biliary tract cancers (BTCs). We aimed to build an immune-related signature and establish holistic models using machine learning. Samples were from 305 BTC patients treated with curative-intent resection, divided into derivation and validation cohorts in a two-to-one ratio. Spatial resolution of T cell infiltration and PD-1/PD-L1 expression was assessed by immunohistochemistry. An immune signature was constructed using classification and regression tree. Machine learning was applied to develop prediction models for disease-specific survival (DSS) and recurrence-free survival (RFS). The immune signature composed of CD3+, CD8+, and PD-1+ cell densities and PD-L1 expression within tumor epithelium significantly stratified patients into three clusters, with median DSS varying from 11.7 to 80.8 months and median RFS varying from 6.2 to 62.0 months. Gradient boosting machines (GBM) outperformed rival machine-learning algorithms and selected the same 11 covariates for DSS and RFS prediction: immune signature, tumor site, age, bilirubin, albumin, carcinoembryonic antigen, cancer antigen 19-9, tumor size, tumor differentiation, resection margin, and nodal metastasis. The clinical-immune GBM models accurately predicted DSS and RFS, with respective concordance index of 0.776–0.816 and 0.741–0.781. GBM models showed significantly improved performance compared with tumor-node-metastasis staging system. The immune signature promises to stratify prognosis and allocate treatment in resected BTC. The clinical-immune GBM models accurately predict recurrence and death from BTC following surgery.

Self-control is a well-known inhibitor of aggression, but the effect of self-control on different kinds of aggression (such as reactive-proactive aggression) and the underlying mediating mechanisms of these effects are unclear. We developed a mediation model to address these issues. A three-wave study was conducted with a sample of 1203 qualifying Chinese undergraduates to test the model. The results showed that self-control at Wave 1 negatively predicted reactive aggression at Wave 3 through mediating effects of hostile rumination and moral disengagement at Wave 2 at the same time, while self-control at Wave 1 negatively predicted proactive aggression at Wave 3 only through moral disengagement at Wave 2. Furthermore, the longitudinal relationship between hostile rumination and moral disengagement is mutual. The current findings support our hypotheses regarding the mediation model of self-control inhibiting reactive-proactive aggression and suggest that moral disengagement should be a common and basic variable to predict most kinds of aggression; further, hostile rumination only has a particular effect on reactive aggression. The present study used motivation theory to explain its mediation model, which develops aggressive theory regarding varied common influencing factors and underlying mediating mechanisms of reactive and proactive aggression.

Sustained expression of B-cell receptor (BCR) critically contributes to the development of diffuse large B-cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull-down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull-down, and mRNA stability assays. Smurf2-mediated BCR ubiquitination was investigated using co-immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up-regulated in and essentially maintained multiple malignant behaviors of BCR-dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE-PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.

Postoperative abdominal infectious complication (AIC) is associated with metastasis in locally advanced gastric cancer (GC) patients after radical gastrectomy. However, the underlying mechanism remains unclear. Herein, we report that neutrophil extracellular traps (NETs), the DNA meshes released by neutrophils in response to infection, could promote GC cells proliferation, invasion, migration and epithelial–mesenchymal transition dependent on TGF-β signaling. Then we model nude mice with cecal puncture without ligation to simulate postoperative AIC and find that NETs in peripheral blood and ascites fluid facilitate GC cells extravasation and implantation into liver and peritoneum for proliferation and metastasis. Notably, TGF-β signaling inhibitor LY 2157299 could effectively impede liver and peritoneal metastasis but not concurrently aggravate sepsis in those AIC-bearing nude mice. These findings implicate that targeting downstream effectors of NETs such as TGF-β signaling might provide potential therapeutic prospect to reduce the risk of GC metastasis.

Hypoxic tumor microenvironment(TME) is a universal feature in solid carcinoma and is associated with unfavorable prognosis. Tumor-derived exosomes are now significantly implicating in mediating cellular communication and interactions in TME. The aim of this study was to identify exosomal miR-301a-3p involved in gastric cancer(GC) progression and metastasis. Here, we found hypoxia promote GC exosomes release and miR-301a-3p expression in an HIF-1α-dependent manner. In hypoxic TME, enriched miR-301a-3p could be transmitted between GC cells via exosomes and then contributed to inhibit HIF-1α degradation through targeting PHD3, that were capable to hydroxylate HIF-1α subunits to ubiquitinate degradation. This synergistical positive feedback loop between HIF-1α and miR-301a-3p facilitated GC proliferation, invasion, migration, and epithelial-mesenchymal transition. In clinical samples, we further discovered circulating exosomal miR-301a-3p in serum was positively related with peritoneal metastasis. Collectively, these data indicate that GC cells could generate miR-301a-3p-rich exosomes in the hypoxic TME, which then help to HIF-1α accumulation and promote GC malignant behaviors and metastasis. Exosomal miR-301a-3p/HIF-1α signaling axis may serve as a promising predictor and potential therapeutic target of GC with metastasis.

Background and aim This study aimed to investigate the postoperative quality of life (QOL) between laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) and laparoscopy-assisted distal gastrectomy with Billroth I anastomosis (LADGBI) in patients with middle-third early gastric cancers (EGC). Methods From January 2015 to August 2017, a total 91 patients with EGC underwent LAPPG or LADGBI procedure with complete QLQ-C30 and QLQ-STO22 in Ren Ji Hospital. Not only do surgical and oncological safety as well as clinicopathologic characteristics analyze, but also chronological changes of QOL and nutritional status were compared for the evaluation of functional advantages. Results There was no significant difference in clinicopathologic characteristics and perioperative recovery between LAPPG and LADGBI. During postoperative 2-year follow up, LAPPG showed significant advantages over LADGBI in emotional functioning, insomnia, appetite loss, reflux, and taste problem and presented larger area in global and functional scales and less area in symptom scales, which means that LAPPG tended to present better improvement and less symptoms than LADGBI for QOL 2 years after surgery. Furthermore, LAPPG could bring about significant improvement in total protein and hemoglobin compared to LADGBI at postoperative 2 years. Conclusion LAPPG obtains QOL as well as total protein and hemoglobin superiority and could be recommended to patients with EGC whose tumor located in the middle third of the stomach.

To propose a clinically feasible automatic planning solution for external beam intensity-modulated radiotherapy, including dose prediction via a deep learning and voxel-based optimization strategy.The dose distribution of patients was predicted using a U-Net-based deep learning network based on the patient's anatomy information. One hundred seventeen patients with nasopharyngeal cancer (NPC) and 200 patients with rectal cancer were enrolled in this study. For NPC cases, 94 cases were included in the training dataset, 13 in the validation dataset, and 10 in the testing dataset. For rectal cancer cases, 172 cases were included in the training set, 18 in the validation set, and 10 in the testing set. A voxel-based optimization strategy, "Voxel," was proposed to achieve treatment planning optimization by dividing body voxels into two parts: inside planning target volumes (PTVs) and outside PTVs. Fixed dose-volume objectives were attached to the total objective function to realize individualized planning intended as the "hybrid" optimizing strategy. Automatically generated plans were compared with clinically approved plans to evaluate clinical gains, according to dosimetric indices and dose-volume histograms (DVHs).Similarities were found between the DVH of the predicted dose and clinical plan, although significant differences were found in some organs at risk. Better organ sparing and suboptimal PTV coverage were shown using the voxel strategy; however, the deviations in homogeneity indices (HIs) and conformity indices (CIs) of the PTV between automatically generated plans and manual plans were reduced by the hybrid strategy ([manual plans]/[voxel plans[/[hybrid plans]: HI of PTV70 [1.06/1.12/1.02] and CI of PTV70 [0.79/0.58/0.76]). The optimization time for each patient was within 1 min and included fluence map optimization, leaf sequencing, and control point optimization. All the generated plans (voxel and hybrid strategy) could be delivered on uRT-linac 506c (United Imaging Healthcare, Shanghai, China).Deliverable plans can be generated by incorporating a voxel-based optimization strategy into a commercial treatment planning system (TPS). The hybrid optimization method shows the benefit and clinical feasibility in generating clinically acceptable plans.

Background Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. Methods/design This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. Discussion This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. Trial registration ClinicalTrials.govNCT03607656. Registered on 1 July 2018. The final protocol version is V1.1.

Background Displaced aggression is a specific form of attack prompted by rumination on anger experiences and revenge thought which might lead to expression of anger on innocent people. There is sufficient evidence demonstrating the potential role of agreeableness in reducing displaced aggression in theory. However, little is known about the neural basis of displaced aggression and how agreeableness and the underlying neural mechanisms link to displaced aggression. Methods In this investigation, we examined these issues on 123 college students by assessing resting-state brain activity (i.e. amplitude of low-frequency fluctuation, ALFF) and connectivity (i.e. resting-state functional connectivity, RSFC). Results Whole-brain correlation analysis revealed that a higher level of displaced aggression was linked with decreased ALFF in the left dorsomedial prefrontal cortex (dmPFC) and decreased RSFC between the left dmPFC and left ventromedial prefrontal cortex (vmPFC). Mediation analysis further revealed that left dmPFC activity and the left dmPFC–vmPFC connectivity mediated the relationship between agreeableness and displaced aggression, as well as agreeableness mediated the relation between left dmPFC activity and the left dmPFC–vmPFC connectivity and displaced aggression. Limitations Only ALFF and RSFC were used as indicators of brain function in this study. The two mediation models need to be further tested by longitudinal design or experimental methods in further studies. Conclusions This study suggested that dmPFC and vmPFC might be the functional neural markers of displaced aggression and provided two possible mediation models regarding the relationship among the resting-state brain activity and connectivity, agreeableness and displaced aggression.

The majority of research regarding hostile attribution bias focuses on its effect on aggression. However, little is known about the brain structure associated with trait hostile attribution bias and the mediating mechanism underlying this link. The current study uses voxel-based morphometry (VBM) to identify the brain regions related to individual differences in trait hostile attribution bias, measured by a Word Sentence Association Paradigm - Hostility in a sample of 176 undergraduate students. Subsequently, two mediation models with regard to brain structure, trait hostile attribution bias, and attitudes toward violence (measured by the Attitudes toward Violence Scale) were analyzed. The results reveal that trait hostile attribution bias is positively correlated with gray matter volume (GMV) in the left orbitofrontal cortex (OFC) and negatively associated with the left lingual gyrus (LG). Furthermore, attitudes toward violence acted as a mediator underlying the association between the left OFC volume and trait hostile attribution bias. Such bias also mediated the relationship between the left OFC and attitudes toward violence. We argue that attitudes toward violence and trait hostile attribution bias seem to predict each other, and the GMV in the left OFC may involve the underlying cognitive mechanism of the bidirectional relationship between the two variables. These results and ideas may shed light on the current understanding of the relationships of the brain's anatomical features, attitudes toward violence, and trait hostile attribution bias.

Complete surgical resection, accessible therapeutic targets and effective tyrosine kinase inhibitors (TKIs) have not completely cured gastrointestinal stromal tumours (GISTs), with most patients suffering from residual tumours and recurrence. The existence of nerve infiltration in GIST provides a way for tumour cells to escape local resection and systemic targeted therapy, which may challenge the previous understanding of its behaviour patterns and inspire the development of more radical excision and more precise targeted therapy. Moreover, tumour dormancy has emerged as a major cause of drug resistance and tumour relapse. Among these pathways, the nerve-tumour regulatory axis GDNF-GFRA1 is activated in GISTs, assists tumour cells in achieving dormancy and protects them from apoptosis under environmental stress by enhancing autophagic flux. The concrete mechanism is that the GDNF-regulating interaction between GFRA1 and the lysosomal calcium channel MCOLN1 activates Ca

We try to develop an atlas-guided automatic planning (AGAP) approach and evaluate its feasibility and performance in rectal cancer intensity-modulated radiotherapy. The developed AGAP approach consisted of four independent modules: patient atlas, similar patient retrieval, beam morphing, and plan fine-tuning modules. The atlas was setup using anatomy and plan data from Pinnacle auto-planning (P-auto) plans. Given a new patient, the retrieval function searched the top similar patient by a generic Fourier descriptor algorithm and retrieved its plan information. The beam morphing function generated an initial plan for the new patient by morphing the beam aperture from the top similar patient plan. The beam aperture and calculated dose of the initial plan were used to guide the new plan optimization in the plan fine-tuning function. The AGAP approach was tested on 96 patients by the leave-one-out validation and plan quality was compared with the P-auto plans. The AGAP and P-auto plans had no statistical difference for target coverage and dose homogeneity in terms of V100%(p=0.76) and homogeneity index (HI)(p=0.073), respectively. The CI index showed they had a statistically significant difference. but the ΔCI was both 0.02 compared to the perfect CI index of 1. The AGAP approach reduced the bladder mean dose by 152.1cGy (p

In this study, 130 surface soil samples were collected at an industrial pollution site in Beijing and the contents of As, Be, Cd, Cu, Cr, Hg, Ni, Pb, Sb, Ti, Zn, and 16 PAHs were determined. The positive matrix factorization (PMF) model was used to analyze the sources of heavy metals and PAHs, and the contributions of these sources to carcinogenic risk and hazard index in the study area were calculated. The results showed that the contents of Cd, Cu, Pb, Hg, As, Zn, and Cr in the soil exceeded the background values in different degrees; Cd, Hg, Pb, Zn, and Cu exceeded the background values by50%. Low molecular weight PAHs (two and three rings) and high molecular weight PAHs (four to six rings) accounted for 39.6% and 60.4% of the total content of 16 PAHs. The PAH content at 77% of the sampling points at the target site was more than 1000 μg ·kg

Rationale: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model. Patient concerns: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection. Diagnoses: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis. Interventions: The patient was treated with a total of 4 individual courses of FMT. Outcomes: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors. Lessons: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.

Aims: This study aims to evaluate and validate a simple quantitative ultrasound (US) method for determining the hepatic fat content (HFC) based on the combination of quantitative US hepatic/renal ratio (US-HRR) and quantitative US hepatic echo-intensity attenuation rate (US-HAR) as compared with [1H]-magnetic resonance spectroscopy (1H-MRS).Material and methods: There were a total of 242 subjects recruited in the present study. All subjects were examined for HFC by quantitative US and 1H-MRS methods. The QUS-HRR and QUS-HAR were calculated from ordinary ultrasound images of liver and kidney with a triple modality 3D abdominal phantom using the Image J software.Results: The results found that US-HRR and US-HAR correlated with 1H-MRS HFC (US-HRR: r=0.946, p

Background hsa_circ_0000826 has been previously linked to CRC through the competing endogenous RNA network; however, the upstream driver of hsa_circ_0000826 elevation remains unknown. In this study, we aim to elucidate the effect of hypoxia‐induced hsa_circ_0000826 on CRC tumorigenesis and metastasis. Methods RNA scope assay was used to evaluate the expression of hsa_circ_0000826 in CRC cells under hypoxia condition. The effects of hsa_circ_0000826 on phenotypes of CRC cells were evaluated through cell migration and invasion assay. The nude, AOM‐DSS model mice and APCMin /+ mice were used to investigate the relationship between circ_0000826, hypoxia, and CRC in mice. A total of 100 CRC tissue samples, as well as the paired adjacent tissues, were collected, and qRT‐PCR assay was used to detect the expression of hsa_circ_0000826 in these samples. Results Hypoxia‐induced hsa_circ_0000826 overexpression can increase the malignant phenotypes, tumor formation, and metastasis capability of CRC cells in vitro. mmu_circ_0000826 levels were significantly increased in the CRC tissues from AOM‐DSS and APC mice model under hypoxia conditions. Further, the hypoxia‐induced upregulation of mmu_circ_0000826 can also promote CRC tumorigenesis and liver metastasis in vivo. The expression of hsa_circ_0000826 in serum was significantly increased in CRC tissues in 100‐pair of CRC and according to the adjacent normal tissues by qRT‐PCR assays. Moreover, the expression levels of hsa_circ_0000826 in serum of patient with liver metastasis were significantly increased than those without metastasis. Conclusion Our results suggested that hsa_circ_0000826 was induced by the hypoxia in CRC, which can be a potential biomarker of CRC liver metastasis.

Objective This study aimed to study the effects of laparoscopic-assisted radical gastrectomy (LAG) and open radical gastrectomy (OG) on immune function and inflammatory factors in patients with early gastric cancer. Methods Seventy-five patients with pT1N0M0 gastric cancer in Ren Ji Hospital from August 2017 to January 2018 were studied. Lymphocytes subsets and interleukins were compared preoperatively and on the third postoperative day (POD3) and seventh postoperative day (POD7). Results There were no significant differences in age, sex, body mass index, duration of the operation, estimated blood loss, total gastrectomy rate, postoperative first fluid diet, and the levels of preoperative lymphocytes subsets and interleukins between the two groups. The number of CD4+ T cells and the CD4+/CD8+ ratio in the LAG group were significantly higher than those in the OG group on POD3. However, the number of CD8+ T cells, and interleukin-6 and interleukin-8 levels in the LAG group were significantly lower than those in the OG group on POD3. Conclusions Laparoscopy can effectively reduce the levels of inflammatory factors and has less effect on the immune system than OG.

Direct Black G (DBG) is a highly toxic synthetic azo dye which is difficult to degrade. Biological treatment seems to be a promising option for the treatment of azo dye containing effluent. A thermophilic bacterial strain (Anoxybacillus sp. PDR2) previously isolated from the soil can effectively remove DBG. However, the molecular underpinnings of DBG degradation and the microbial detoxification ability remains unknown. In the present study, the genetic background of PDR2 for the efficient degradation of DBG and its adaptation to azo dye-contaminated environments was revealed by bioinformatics. Moreover, the possible biodegradation pathways were speculated based on the UV–vis spectral analysis, FTIR, and intermediates identified by LC-MS. Additionally, phytotoxicity and the comet experiment studies clearly indicated that PDR2 converts toxic azo dye (DBG) into low toxicity metabolites. The combination of biodegradation pathways and detoxification analysis were utilized to explore the molecular degradation mechanism and bioremediation of azo dye for future applications. These findings will provide a valuable theoretical basis for the practical treatment of azo dye wastewater.

Electroconvulsive therapy (ECT) is the most effective and rapid treatment for severe major depressive disorder (MDD) in elderly patients. The mechanism of ECT is unclear, and studies on ECT in elderly MDD patients by resting-state functional magnetic resonance imaging are rare. Thirteen elderly MDD patients were scanned before and after ECT using a 3.0T MRI scanner. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuations (ALFF) were processed to compare resting-state function before and after treatment. Depression and anxiety symptoms of all patients abated after ECT. Decreased ReHo values in the bilateral superior frontal gyrus (SFG) were observed after ECT, and the values of right SFG significantly correlated with an altered Hamilton depression rating scale score. Increased ALFF values in the left middle frontal gyrus, right middle frontal gyrus, orbital part, and decreased ALFF values in the left midcingulate area, left precentral gyrus, right SFG/middle frontal gyrus after ECT were also observed. These results support the hypothesis that ECT may affect the regional resting state brain function in geriatric MDD patients.

Preoperative evaluation of vasculobiliary anatomy in the umbilical fissure (U-point) is pivotal for perihilar cholangiocarcinoma (PCCA) applied to right-sided hepatectomy. The purpose of our study was to review the vasculobiliary anatomy in the U-point using three-dimensional (3D) reconstruction technique, to investigate the diagnostic ability of 2D scans to evaluate anatomic variations, and to discuss its surgical implications.A retrospective study of 159 patients with Bismuth type I, II, and IIIa PCCA, who received surgery at our institution from November 2012 to September 2016, was conducted. Anatomic structures were assessed using multidetector computed tomography (MDCT) by one hepatobiliary surgeon, whereas 3D images were reconstructed by an independent radiologist. Normal confluence pattern of left biliary system was defined as the left medial segmental bile duct (B4) joining the common trunk of segment II (B2) and segment III (B3) ducts, whereas aberrant confluence patterns were classified into 3 types: type I, triple confluence of B2, B3, and B4; type II, B2 draining into the common trunk of B3 and B4; type III, other patterns. Surgical anatomy of B4 was classified into the central, peripheral, and combined type according to its relation to the hepatic confluence. The lengths from the bile duct branch of Spiegel's lobe (B1l) to the orifice of B4 and the junction of B2 and B3 were measured on 3D images. The anatomy of left hepatic artery (LHA) was classified according to different origins and the spatial relationship related to the U-point.3D reconstruction revealed that normal confluence pattern of left biliary system was observed in 71.1% (113/159) of all patients, and variant patterns were type I in 11.9% (19/159), type II in 12.6% (20/159), and type III in 4.4% (7/159). The length from B1l to the junction of B2 and B3 was 12.1 ± 3.1 mm in type I variation, which was significantly shorter than that in normal configuration (30.0 ± 6.8 mm, P 0.001) but significantly longer than that in type II variation (9.6 ± 3.4 mm, P = 0.019). Surgical anatomy of B4: the peripheral type was most commonly seen (74.2%, 118/159), followed by central type (15.7%, 25/159) and combined type (10.1%, 16/159). The distance between the B1l and B4 was 8.4 ± 2.4 mm in central and combined type, which was significantly shorter than that in peripheral type (14.5 ± 4.1 mm, P 0.001). A replaced or accessory LHA from the left gastric artery was present in 6 (3.8%) and 9 (5.7%) patients, respectively. LHA running along the left caudal position of U-point was present in 143 cases (89.9%), along the right cranial position of U-point in nine cases (5.7 %), and combined position in seven cases (4.4%). Interobserver agreement of two imaging modalities was almost perfect in biliary confluence pattern (kappa = 0.90; 95% confidence interval: 0.79-1.00), substantial in surgical anatomy of B4 (kappa = 0.74; 95% confidence interval: 0.62-0.86), and perfect in LHA (kappa = 1.00).Thoroughly understanding the imaging characters of surgical anatomy in the U-point may be benefit for preoperative evaluation of PCCA by successive review of 2D images alone, whereas 3D reconstruction technique allows detailed hepatic anatomy and individualized surgical planning for advanced cases.

Aim Diabetic foot has become the main cause of non-traumatic amputation. Stem cell therapy, especially mesenchymal stem cells (MSCs), holds a great promise as a therapy for diabetic foot with ischemia limb arterial disease. The aim of this pilot study is to evaluate the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment for diabetic patients with critical limb ischemia (CLI). Methods Four eligible diabetic patients with CLI were consecutively enrolled in this pilot study. On the base of the standard-of-care treatment, these patients accepted P-MSCs treatment by intramuscular injection for successive 3 times at an interval of 4 weeks, and the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment were evaluated. Results There were no serious adverse events during the period of P-MSCs injection and the 24-weeks follow-up period. The clinical ischemic features of patients were improved 24 weeks after P-MSCs treatment. The scores of resting pain and limb coldness significantly decreased, and pain-free walking distance significantly increased from baseline to 24 weeks after P-MSCs therapy. The resting ankle brachial index increased, but no statistically significant difference was found. The findings of magnetic resonance angiography showed the increase of collateral vessel formation in one patient, but there were no significant changes observed in the other patients. Conclusions The data in this pilot study indicated that multiple intramuscular P-MSCs injections may be a safe and effective alternative therapy for diabetic patients with CLI, and larger, placebo-controlled, perspective studies are needed to prove these results.

The idea that influential factors for two subtypes of aggression (reactive and proactive aggression) should be different is popular, but the common influential factors have not been examined. Such an examination could help understand the influential factors of aggression from the perspective of multiple motivations affecting the development of aggressive motivations over time. The present study argued that angry rumination would be a common influential factor for both reactive and proactive aggression. In addition, consideration of future consequences (CFC) may moderate the longitudinal effect of angry rumination on proactive aggression. Two studies were conducted to test these hypotheses. In Study 1, a cross-lagged analysis with a 6-month interval was employed. A total of 505 undergraduate students (46% males) completed the questionnaires twice. Results indicated that after a 6-month period, angry rumination predicted reactive aggression but not proactive aggression. Furthermore, reactive aggression predicted angry rumination over time. In Study 2, a moderation analysis was performed with another 437 participants (130 males). The results partly supported our hypotheses, indicating that CFC-immediate (CFC-I) moderated the longitudinal effect of angry rumination on proactive aggression. The present results extended prior research regarding the predictors of proactive and reactive aggression and may contribute to a greater understanding of the development of aggressive motivation. In addition, our research suggested that high CFC-I may be an important factor for the motivation change from reactive aggression to proactive aggression.

Angry rumination and hostile attribution bias are important cognitive factors of aggression. Although prior theoretical models of aggression suggest that aggressive cognitive factors may influence each other, there are no studies examining the longitudinal relationship between angry rumination and hostile attribution bias. The present study used cross-lagged structural equation modeling to explore the longitudinal mutual relationship between hostile attribution bias and angry rumination; 941 undergraduate students (38.5% male) completed questionnaires assessing the variables at two time points. The results indicate that hostile attribution bias showed a small but statistically significant effect on angry rumination 6 months later, and angry rumination showed a quite small but marginally significant effect on hostile attribution bias across time. The present study supports the idea that hostile attribution bias influences angry rumination, and argue that the relationship between angry rumination and hostile attribution bias may be mutual. Additionally, the results suggest that there may be a causal relation of different aggression-related cognitive factors.

Background Laparoscopic-assisted pylorus-preserving gastrectomy (LAPPG) is a minimally invasive function-preserving surgery for early gastric cancer. This study was designed to investigate the clinical outcomes between LAPPG and laparoscopy-assisted distal gastrectomy (LADG) by objective evaluation. Methods A total 167 pT1N0M0 gastric cancer patients underwent LAPPG(n = 70) and LADG(n = 97) were retrospectively analyzed. By evaluating the functional advantages, objective short-term and one year follow-up outcomes were compared. Results There is no significant difference in perioperative clinical characteristics as well as pathologic results between LAPPG and LADG group while the cost is higher in latter(p = 0.004). The Clavien–Dindo grade II or higher complications were 15.7 and 13.4% in LAPPG and LADG group respectively(p = 0.824). In one year follow-up, nutritional status was significantly better in LAPPG group accompanied by better pylorus function preserving. Conclusion LAPPG is an acceptable surgical procedure for pT1N0M0 middle portion gastric cancer patients in terms of nutritional and economic advantage. Trial registration Chinese Clinical Trial Registry (ChiCTR-PIC-17012358, Date of Registration:2017-08-14).

This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its prognostic value. For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. The radiomics signature comprised eight LN-status–related features and showed significant association with LN metastasis in both cohorts (p

Objective Semaphorin 3C (Sema3C) may regulate tumor metastasis and prognosis. We determined the biological roles of Sema3C in the hepatic metastasis of gastric adenocarcinoma and evaluated its clinical significance as a potential biomarker. Methods Sema3C expression in gastric cancer (GC) cell lines and tissues was measured using RT-qPCR and western blotting. Moreover, Sema3C functions were analyzed using Transwell assays and in vitro metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of Sema3C on the prognosis of 80 randomly selected patients with GC was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in GC tissues. Results Sema3C expression was significantly upregulated in highly metastatic GC cell lines and tissues. Additionally, Sema3C promoted invasion, migration and hepatic metastasis in GC cells. Moreover, Sema3C expression was positively correlated with clinicopathological features in GC and paired hepatic metastatic tissues, and Sema3C expression was an independent prognostic factor. Finally, Sema3C expression was associated with node metastasis, hepatic metastasis and EMT marker expression. Conclusions Sema3C may play roles in regulating the EMT and metastasis of gastric adenocarcinoma, highlighting its potential use as a prognostic factor for hepatic metastasis and poor prognosis in gastric adenocarcinoma.

Background: Recent researches and relevant patents have been reported to prove the significant value of Caveolin-1 (Cav-1) in cancer diagnosis and treatment. Objective: Our study aimed to study the role of Cav-1 in gastric cancer progression and investigate the relationship between Cav-1/E-cadherin expression and the clinical status of gastric cancer. Method: Immunohistochemistry was applied to detect the expression of Cav-1 and E-cadherin in gastric cancer in a tissue microarray. Real-time PCR was used to further detect the mRNA expression of Cav-1 and E-cadherin in tumor-derived and peritumoral tissues and in different gastric cancer cell lines. The expression of E-cadherin was analyzed by Western Blot and the cell migration ability was examined by Transwell migration assays after downregulation of Cav-1 using siRNA. Results: The staining of Cav-1 and E-cadherin were both strong in all 5 of the normal gastric tissues, while in gastric cancer tissues the staining of Cav-1 and E-cadherin were downregulated (44&33 negative, 21&22weak and 5&15 strong). And their level was correlated with tumor clinical stage, pathological grade, and metastasis status. Moreover, there was a positive correlation between Cav-1 expression and E-cadherin expression in gastric cancer tissues(r = 0.42, P < 0.05). Knockdown of Cav-1 resulted in decreased expression of E-cadherin, cell morphology changes and elevated migration ability of gastric cancer cells. Conclusion: Decreased expression of Cav-1 and E-cadherin may play an important role in the progression of gastric cancer; Knockdown of Cav-1 may promote EMT of gastric cancer by targeting E-cadherin.

While the relationship between personality, hostility, and hostile attribution bias (HAB) has been explored in previous studies, their longitudinal relationship is unclear, and no related study has utilized the indigenous Chinese personality. This research explored the longitudinal relationships of interpersonal openness (IO; an indigenous Chinese personality construct), hostility, and HAB. The 942 valid participants (38.5% male, mean age = 20.83, standard deviation = 1.04) were from six different provinces in China. Measurements were completed on two separate occasions (Times 1 and 2), with a 6-month interval. Results showed that IO has longitudinal effects on hostility, after controlling for the Big Five, and HAB could be longitudinally predicted by IO and hostility as well. Moreover, hostility served as a mediator in the relationship between IO and HAB. These results suggest that IO can affect the development of hostility and HAB, and some indigenous Chinese personality factors may complement Western personality theories.

A fluorescence probe, Cz-BDP-NBD, for detecting biothiols with two photon excited fluorescence has been designed and used under irradiation from sapphire pulsed lasers at 800 nm. Upon addition of biothiols, NBD was removed through a SNAr reaction and the fluorophore Carbazyl BODIPY (Cz-BDP) was released simultaneously. A two photon excited fluorescence was turned on and accompanied by a strong red emission at 660 nm, the two-photon absorption (TPA) cross section of the Cz-BDP reached a value of 198.5 GM at 800 nm. Moreover, Hcy/Cys and GSH could be distinguished between by a two emission channel, which resulted from the different mechanisms. For Hcy and Cys, N-NBD-Hcy and N-NBD-Cys were formed through a 5/6-membered cyclic transition, they displayed distinct fluorescent turn-on signal changes at 540 nm (Φ = 0.28, Φ = 0.24) and 670 nm, while GSH only has a single emission channel at 670 nm. Therefore, the Cz-BDP-NBD can distinguish GSH, Hcy and Cys with a fast response time (within one minute), high selectivity and sensitivity. In addition, it has been successfully applied for the detection of Cys/Hcy and GSH in living cells and ratio imaging. The Cz-BDP-NBD probe could be used for discriminative sensing of intracellular Cys, Hcy and GSH, and has the potential for use in biological applications.

The dose data produced by treatment plan system(TPS)in intensity-modulated radiation therapy(IMRT)has many gradient edge points.Considering this feature we proposed a new interpolation algorithm called treatment plan dose interpolation algorithm based on gradient feature in intensity-modulated radiation therapy(TDAGI),which improves the Canny algorithm to detect the gradient edge points and non-edge points by using the gradient information in the dose data plane.For each gradient edge point,the corresponding gradient profile was traced and the profile’s sharpness was calculated,and for each non-edge point,the dispersion was calculated.With the sharpness or dispersion,the kernel coefficients of bi-cubic interpolation can be obtained and can be used as the central point to complete the bi-cubic interpolation calculation.Compared with bi-cubic interpolation and bilinear interpolation,the TDAGI algorithm is more accurate.Furthermore,the TDAGI algorithm has the advantage of gradient keeping.Therefore,TDAGI can be used as an alternative method in the dose interpolation of TPS in IMRT.

Hypoxia is a hallmark of pancreatic cancer (PC) and is associated with gemcitabine resistance. However, the mechanisms underlying hypoxia-induced gemcitabine resistance in PC remain greatly unknown. Our previous work showed that miR-301a, a hypoxia-sensitive miRNA, is involved in PC metastasis under hypoxia via regulation of its target gene P63. Here, we showed that miR-301a was upregulated in a NF-κB independent manner and promoted gemcitabine resistance under hypoxic conditions in vitro. In addition, TAp63, a member of the P63 family, reversed hypoxia-induced gemcitabine resistance by promoting degradation of HIF-1α. Furthermore, we proved that TAp63 was a functional downstream target of miR-301a and mediated the biological properties of miR-301a in PC. Taken together, these findings indicate that miR-301a exerts as a critical regulator involved in hypoxia-induced gemcitabine resistance in PC and may have potentials to be a therapeutic target for PC patients.

Background: To investigate the efficacy of febuxostat in hyperuricemic patients with chronic kidney disease (CKD), relevant randomized clinical trials (RCTs) were analyzed. Methods: We used PubMed, Medline, ISI Web of Science, CBMdisc, and Cochrane Library databases to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). We conducted subgroup analysis, sensitivity analysis, and analyzed publication bias, to comprehensively estimate the renoprotective effects of febuxostat in hyperuricemic patients with CKD. Results: Among 296 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that serum estimated glomerular filtration rate (eGFR) was improved after febuxostat treatment in hyperuricemic patients with CKD, with an SMD (95% CI) of 0.24 [−0.17 to 0.43] and P = .67 (fixed-effects model). No heterogeneity was observed across studies (I2 = 0% and P = .67). Subgroup analysis suggested that treatment-related reductions in serum eGFR levels were not related to drug doses, intervention times, or region. Conclusions: The present meta-analysis suggests that febuxostat may slow the progression of mild-to-moderate CKD. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term renoprotective effects of febuxostat in hyperuricemic patients with CKD.

Neural stem cells (NSCs) have emerged as a promising treatment for spinal cord injuries. However, the increasing expression of bone morphogenetic proteins (BMPs) in spinal cord injury lesion sites seems to have contributed to the limited oligodendroglial differentiation and the majority of the astroglial differentiation of NSCs. In the present study, we demonstrate that BMPs promote NSCs differentiation toward astrocytes and prevent them from differentiating into oligodendrocytes. This effect is accompanied by the increasing expression of Id2 and the reduction in Oilg1/2 expression. Treatment with bone marrow stromal cells (BMSCs) can enhance the development of oligodendrocytes in the presence of BMPs. The analysis of Id2, as well as Olig1 and Olig2 gene expression, reveals that the effect of BMPs on these gene expressions is reversed with the addition of BMSCs. In sum, these data strongly suggest that BMSCs can promote the differentiation of NSCs into oligodendrocytes through mediating Id2 and Olig1/2 expression by blocking the BMP/Smad signaling pathway.

Rationale Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our knowledge, we report the first case of a pregnant female with IAS. Patient concerns The 26-year-old patient with Graves disease and 10 weeks pregnant developed IAS after approximately 6 months treatment with methimazole. The patient exhibited recurrent spontaneous hypoglycemia. Diagnoses On evaluation, laboratory findings detected both high fasting insulin (>1000 mIU/L) and insulin autoantibodies. An oral glucose tolerance test showed elevated insulin concentrations with disproportionately elevated C-peptide levels. The imaging study showed nomasslesionsinthepancreas,and the patient was clinically diagnosed with IAS. Interventions The patient had an abortion, discontinued methimazole and switched to oral prednisone (30 mg once daily) and propylth- iouracil (100 mg 3 times daily) for 3 months. Outcomes At the 3-month follow-up visit, hypoglycemic episodes had disappeared and insulin antibody levels were no longer detectable. Lessons We have described this case and reviewed the relevant literature concerning diagnosis and treatment of IAS. Importantly, this case indicates that clinicians should view pregnancy as another factor of hypoglycemia in IAS.

Rationale Diabetic foot ulcer (DFU) is a chronic complication of diabetes characterized by continuity, repeatability, and nonhealing. In recent years, mesenchymal stem cells hydrogel complex has been a new emerging technique in the treatment of DFU. The placenta-derived mesenchymal stem cells (PDMSCs) hydrogel is multipotent, and can secrete growth factors, cytokines, and immunomodulatory substances which could accelerate wound healing. Patient concerns In this case report, we present a 57-year-old female with type 2 diabetes mellitus and a 20-day DFU.A wound bed located at the dorsalis pedis of the right foot, and conventional therapies had no effect on the foot. Diagnoses The patient was confirmed a diagnosis of type 2 DM with diabetic foot (Wagner classification III). Interventions To assess the efficacy and safety of PDMSCs hydrogel in wound repair and to improve the rate of wound healing, we administered PDMSCs hydrogel (cell number: 1 × 10/cells/cm) topically into the wound with the patient's permission. Outcomes The patient's foot ulcer was almost healed, and foot function in walking was well preserved. No complications were observed. No recurrence occurred in the subsequent 6 months. Lessons To the best of our knowledge, this is the first patient globally to receive PDMSCs hydrogel to treat DFU. The present case study suggests that PDMSCs hydrogel may provide a new approach to DFU treatment. Clinical Trial Registration-URL: http://www.chictr.org.cn/searchproj.aspx:chiCRT-ONC-16008732.

// Xiang Xia 1,* , Kundong Zhang 1 , Gang Cen 1 , Tao Jiang 1 , Jun Cao 1 , Kejian Huang 1 , Chen Huang 1,* , Qian Zhao 2 and Zhengjun Qiu 1 1 Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, China 2 Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis and National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Qian Zhao, email: // Zhengjun Qiu, email: // Keywords : miR-301a-3p; SMAD4; pancreatic ductal adenocarcinoma; xenograft tumor; prognosis Received : February 10, 2015 Accepted : May 02, 2015 Published : May 12, 2015 Abstract Background: Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo . Methods: By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. Results: Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo . Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues. Conclusion: MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4 .

Transforming growth factor-β (TGF-β) regulates cell functions and has key roles in pancreatic cancer development. SMAD4, as one of the Smads family of signal transducer from TGF-β, mediates pancreatic cell proliferation and apoptosis and is specifically inactivated in half of advanced pancreatic cancers. In recent years, many advances concerning SMAD4 had tried to unravel the complex signaling mechanisms of TGF-β and its dual role of tumor-suppressive and tumor-promoting efforts in pancreatic cancer initiation and progression through SMAD4-dependent TGF-β signaling and SMAD4-independent TGF-β signaling pathways. Meanwhile, its potential prognostic value based on immunohistochemical expression in surgical sample was variably reported by several studies and short of a systematic analysis. This review aimed to discuss the structure, functions, and regulation of this principal protein and its effects in determining the progression and prognosis of pancreatic cancer.