Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study.

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Balanced influence maximization in social networks based on deep reinforcement learning.

Balanced influence maximization aims to balance the influence maximization of multiple different entities in social networks and avoid the emergence of filter bubbles and echo chambers. Recently, an increasing number of studies have drawn attention to the study of balanced influence maximization in social networks and achieves success to some extent. However, most of them still have two major shortcomings. First, the previous works mainly focus on spreading the influence of multiple target entities to more users, ignoring the potential influence of the correlation between the target entities and other entities on information propagation in real social networks. Second, the existing methods require a large amount of diffusion sampling for influence estimation, making it difficult to apply to large social networks. To this end, we propose a Balanced Influence Maximization framework based on Deep Reinforcement Learning named BIM-DRL, which consists of two core components: an entity correlation evaluation module and a balanced seed node selection module. Specifically, in the entity correlation evaluation module, an entity correlation evaluation model based on the users' historical behavior sequences is proposed, which can accurately evaluate the impact of entity correlation on information propagation. In the balanced seed node selection module, a balanced influence maximization model based on deep reinforcement learning is designed to train the parameters in the objective function, and then a set of seed nodes that maximize the balanced influence is found. Extensive experiments on six real-life network datasets demonstrate the superiority of the BIM-DRL over state-of-the-art methods on the metrics of balanced influence spread and balanced propagation accuracy.

Enteral feeding strategies in patients with acute gastrointestinal injury: From limited to progressive to open feeding.

Acute gastrointestinal injury (AGI) is very common in critically ill patients, and its severity is positively correlated with mortality. Critically ill patients with digestive and absorption dysfunction caused by AGI face higher nutritional risks, making nutritional support particularly important. Early enteral nutrition (EN) support is extremely important because it can promote the recovery of intestinal function, protect the intestinal mucosal barrier, reduce microbiota translocation, reduce postoperative complications, shorten hospital stay, and improve clinical prognosis. In recent years, many nutritional guidelines have been proposed for critically ill patients; however, there are few recommendations for the implementation of EN in patients with AGI, and their quality of evidence is low. The use of EN feeding strategies in critically ill patients with AGI remains controversial. The aim of this review was to elaborate on how EN feeding strategies should transition from limited to progressive to open feeding and explain the time window for this transition.

Small peptide formulas versus standard polymeric formulas in critically ill patients with acute gastrointestinal injury: a systematic review and meta-analysis.

Small peptide formulas versus standard polymeric formulas for enteral nutrition in critically ill patients with acute gastrointestinal injury (AGI) have been a topic of debate. A systematic review and meta-analysis were conducted to compare their clinical and nutritional outcomes. Relevant studies from January 1980 to June 2022 were searched in PubMed, Cochrane, and Embase databases. Randomized controlled trials involving AGI grade I-IV patients were included, while children, non-AGI patients, and non-critically ill patients were excluded. Results indicated no significant difference in all-cause mortality. Patients receiving small peptide formulas showed higher daily protein intake, greater albumin growth, and higher prealbumin levels. They also had shorter lengths of stay in the intensive care unit and hospital. Conversely, patients receiving standard polymeric formulas had a higher daily calorie intake. In conclusion, the choice of formula may not affect mortality in critically ill patients with AGI. Small peptide formulas were more conducive to increase daily protein intake, decrease intensive care unit and hospital length of stay. Further large-scale randomized controlled trials evaluating the effects of these two nutritional formulas on clinical and nutritional outcomes in critically ill patients with AGI are needed to confirm these results.

Development and validation of a nomogram for predicting enteral feeding intolerance in critically ill patients (NOFI): Mixed retrospective and prospective cohort study.

OBJECTIVE: Developing and validating a clinical prediction nomogram of enteral feeding intolerance (NOFI) in critically ill patients. So as to help clinicians implement pre-intervention for patients with high risk of enteral feeding intolerance (FI), formulate individualized feeding strategies, and reduce the probability of FI occurrence. METHODS: From March 2018 to April 2023, patients who met the inclusion criteria but did not meet the exclusion criteria constituted the development cohort for retrospective analysis, and NOFI was developed. Patients recruited consecutively between May 2023 and July 2023 constituted the validation cohort for the prospective analysis for independent external validation of NOFI. Initially, a backward stepwise method was employed to conduct a multivariate logistic regression analysis in the development cohort, aiming to identify the optimal-fit model. Subsequently, a nomogram was derived from this model. The validation of the nomogram was carried out in an independent external validation cohort, where discrimination and calibration were evaluated. Additionally, a decision curve analysis was conducted to assess the net benefit of utilizing the nomogram for decision-making. RESULTS: A total of 628 and 143 patients, 49.0 % and 51.7 % of patients occurred FI, were included in the development and validation cohort, respectively. We developed a NOFI in severely ill patients and the primary diagnosis, Acute gastrointestinal injury (AGI) grade, and APACHE II score were independent predictors of FI, with the OR of the primary diagnosis of circulatory disease being 2.281 (95 % CI, 1.364-3.816; P = 0.002); The OR of respiratory diseases was 0.424 (95 % CI, 0.259-0.594; P = 0.001); The OR of AGI grade was 4.920 (95 % CI, 3.773-6.416; P < 0.001), OR of APACHE II score was 1.100 (95 % CI, 1.059-1.143; P < 0.001). Independent external validation of the prediction model was performed. This model has good discrimination and calibration. The decision curve analysis of the nomogram provided better net benefit than the alternate options (full early enteral nutrition or delayed enteral nutrition). CONCLUSIONS: The prediction of enteral feeding intolerance can be conveniently facilitated by the NOFI that integrates primary diagnosis, AGI grade, and APACHE II score in critically ill patients.

Role and efficacy of capecitabine in the anthracycline-free regimen in breast cancer patients: a systematic review and meta-analysis.

PURPOSE: Capecitabine has extensive utilization in the treatment of diverse solid tumors, and its efficacy has been substantiated. Its oral administration and minimal toxicity in clinical practice render it advantageous. Nevertheless, uncertainty remains regarding whether capecitabine can substitute anthracycline drugs in chemotherapy regimens to achieve a lower risk of anthracycline-induced degradation. Consequently, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the potential of capecitabine as a replacement for anthracycline drugs in chemotherapy regimens for breast cancer. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register (CENTRAL) to retrieve eligible studies published before July 18, 2023. Two independent reviewers extracted relevant data from the included studies using a pre-established data extraction form. The primary endpoints of interest encompassed overall survival (OS) and progression-free survival (PFS) for postoperative adjuvant therapy, as well as pathological complete response (PCR) following neoadjuvant therapy. Adverse events were considered as secondary outcomes. The statistical analysis was performed using Revman 5.4.1. RESULTS: A total of six studies involving 2348 breast cancer patients were deemed eligible according to the selection criteria. The pooled meta-analysis revealed that there were no statistically significant differences observed in the primary outcomes of overall survival (OS) (HR 1.06, 95% CI 0.88-1.28) and progression-free survival (PFS) (HR 1.10, 95% CI 0.90-1.34) across the four postoperative adjuvant chemotherapy trials, as well as in the two neoadjuvant chemotherapy trials with respect to the primary outcome of pathological complete response (PCR) (OR 1.65, 95% CI 0.93-2.95) when comparing regimens containing anthracycline drugs to those without. In terms of adverse events, the probability of experiencing diarrhea (OR 3.94, P = 0.004) and hand-foot syndrome (OR 10.89, P = 0.004) was significantly higher in the capecitabine group, attributable to the drug characteristics. Conversely, the likelihood of developing neutropenia (OR 0.50, P = 0.03) was higher in the anthracycline group. CONCLUSIONS: According to the current evidence, there was no statistically significant difference in the primary outcomes when capecitabine was substituted for anthracycline drugs. Thus, capecitabine can be regarded as a feasible alternative in the subset of patients who necessitate the exclusion of anthracyclines.

Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy.

Sepsis-induced coagulopathy (SIC) is a life-threatening complication characterized by the systemic activation of coagulation in sepsis. The diagnostic criteria of SIC consist of three items, including Sequential Organ Failure Assessment (SOFA) score, platelet count, and prothrombin time (PT)-international normalized ratio (INR). SIC has a high prevalence and it can lead to a higher mortality rate and longer length of hospital and ICU stay. Thus, the early detection of SIC is extremely important. It is unfortunate that there is still no precise biomarker for early diagnosis and assessment of the prognosis of SIC. We reviewed the current literature and discovered that some potential biomarkers, such as soluble thrombomodulin (sTM), thrombin-antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), α2-plasmin inhibitor-plasmin complex (PIC), C-type lectin-like receptor 2 (CLEC-2), neutrophil extracellular traps (NETs), prothrombin fragment 1.2 (F1.2), Angiopoietin-2 (Ang-2), plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be useful for early diagnosis, evaluation, and prognosis of SIC. Early initiation of treatment without missing any therapeutic opportunities may improve SIC patients' prognosis. Further large-scale clinical studies are still needed to confirm the role of these biomarkers in the diagnosis and prognosis assessment of SIC.

Changes in Early T-Cell Subsets and Their Impact on Prognosis in Patients with Sepsis: A Single-Center Retrospective Study.

Objective: To analyze the early changes in CD3+, CD4+, and CD8+T-cell subset counts in patients with sepsis and their correlation with prognosis to provide a feasible basis for clinical immunomodulation in sepsis. Methods: This is a single-center retrospective study. The study enrolled sepsis patients (meeting SEPSIS 3.0 definition) who were admitted to the Department of Intensive Care Unit at the First Hospital of Jilin University from July 5th, 2018 to December 5th, 2019 and were aged 18 years or above. In addition, these patients underwent cellular immune testing (CD3+, CD4+, CD8+ T lymphocyte counts, and CD4+/CD8+ ratio) within 24 hours of ICU admission. Patient's clinical data including age, gender, infection site, APACHE II score, SOFA score, length of ICU stay, mechanical ventilation time, ICU mortality, 28-day mortality, and 3-year survival status were collected. The prognostic indicators and survival of the decreased and nondecreased groups of different subsets of T lymphocyte counts and CD4+/CD8+ ratio were compared. Results: A total of 206 patients were enrolled, with 76.7% having a decrease in CD3+ T lymphocyte count, 76.7% having a decrease in CD4+ T lymphocyte count, and 63.6% having a decrease in CD8+ T lymphocyte count. Furthermore, 21.8% had a lower CD4+/CD8+ ratio. Analysis showed that the CD3+ T lymphocyte count decreased group had a longer length of ICU stay [11 d (4, 21) vs. 7 d (4, 17), P=0.03], increased percentage of mechanical ventilation (67.5% vs. 51.0%, P=0.04), and extended mechanical ventilation time [144 h (48, 360) vs. 96 h (48, 144), P=0.04] compared to the nondecreased group. The 28-day mortality was higher in the decreased group of CD4+/CD8+ ratio compared to the nondecreased group (33.3% vs. 25.5%, P=0.29); however, the difference did not reach statistical significance. Logistic regression analysis revealed no significant correlation between the decrease in CD4+/CD8+ ratio and 28-day mortality (P=0.11). The 3-year follow-up revealed that the CD4+/CD8+ decreased group had a lower survival rate than the nondecreased group (33.3% vs. 53.4%, P=0.01). Conclusions: In the early stage of sepsis, most patients showed a decrease in CD3+, CD4+, and CD8+T-cell subsets, as well as in the CD4+/CD8+ ratio. The decrease in CD3+ and CD4+/CD8+ was related to some poor prognosis.

Coupled plasma filtration adsorption for the treatment of sepsis or septic shock: a systematic review and meta-analysis.

BACKGROUND: The effect of coupled plasma filtration adsorption (CPFA) for the treatment of sepsis or septic shock is controversial. A systematic review and meta-analysis was performed to evaluate the impact of CPFA on all-cause mortality in patients with sepsis or septic shock. METHODS: We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of May 2022. We included studies involving patients (˃ 14 years) with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality (hospital mortality, 28-day mortality or 30-day mortality). Results were expressed as odds ratio (OR) with accompanying 95% confidence interval (CI). RESULTS: Six studies including 537 patients were included. The primary outcome of this meta-analysis showed that the all-cause mortality was about 54.2% (119/243 in the CPFA group and 172/294 in the control group). There was no statistically significant difference in the all-cause mortality between two groups (odds ratio [OR] = 0.75; 95% CI 0.53 to 1.06; P = 0.11; Chi2 = 14.04; I2 = 64%). CONCLUSIONS: The treatment of CPFA failed to decrease all-cause mortality of sepsis or septic shock patients. Further large-scale randomized controlled trials (RCTs) evaluating the ability of this therapy to improve clinical outcomes are still required to confirm these results.

Comparisons between short-peptide formula and intact-protein formula for early enteral nutrition initiation in patients with acute gastrointestinal injury: a single-center retrospective cohort study.

Background: Early enteral nutrition (EN) in critically ill patients is important and most of them have suffered acute gastrointestinal injury (AGI). In this study, we investigated the influence of short-peptide EN formula and intact-protein EN formula on the prognosis of patients with AGI grades I-II to provide some guidance. Methods: A retrospective cohort study was performed. The primary outcomes were the percentage of EN calories (25 kcal/kg/d) and protein (1.2 g/kg/d) on the 3rd and 7th days of intensive care unit (ICU) admission, EN percent elevation in calories and protein on days 3-7, and the incidence of gastric retention and diarrhea after EN administration. Secondary outcomes included ICU and 28-day mortality, length of ICU stay, total hospitalization cost, and ventilator-free days. Univariate and multivariate Cox regression analysis was used to identify factors associated with gastric retention and diarrhea. And we used Kaplan-Meier survival curves to compare 28-day mortality rates between the two groups. Results: There were no statistically significant differences in ICU and 28-day mortality, ICU length of stay, total hospitalization cost, or ventilator-free days in the short-peptide formula group compared with the intact-protein formula group. Kaplan-Meier survival curves of 28-day mortality also showed no statistically significant difference. The EN percent elevation in calories and protein on days 3-7 in the short-peptide formula group was significantly higher than the intact-protein formula group (48% vs. 38%, P=0.03 and 37% vs. 38%, P=0.04, respectively). For gastrointestinal (GI) adverse events, the incidence of gastric retention (15.5% vs. 29.8%, P=0.03) and diarrhea (8.5% vs. 19.8%, P=0.04) were lower in the short-peptide group. In the multivariate-adjusted model, the use of short-peptide formula was the only independent variable of reduction in gastric retention and diarrhea [HR =0.469 (95% CI: 0.239-0.922), P=0.028; and HR =0.394 (95% CI: 0.161-0.965), P=0.041, respectively]. Conclusions: Short-peptide formula is more easily tolerated by patients in the acute phase of AGI and can quickly achieve nutritional goals by EN provision, making it the preferred formula for the initiation of EN in the acute phase of AGI.

ROS-Triggered Autophagy Is Involved in PFOS-Induced Apoptosis of Human Embryo Liver L-02 Cells.

The liver is the primary target organ for perfluorooctane sulphonate (PFOS), a recently discovered persistent organic pollutant. However, the mechanisms mediating hepatotoxicity remain unclear. Herein, we explored the relationship between reactive oxygen species (ROS) and autophagy and apoptosis induced by PFOS in L-02 cells, which are incubated with different concentrations of PFOS (0, 50, 100, 150, 200, or 250 µmol/L) for 24 or 48 hrs at 37°C. The results indicated that PFOS exposure decreased cell activities, enhanced ROS levels in a concentration-dependent manner, decreased mitochondrial membrane potential (MMP), and induced autophagy and apoptosis. Compared with the control, 200 µmol/L PFOS increased ROS levels; enhanced the expression of Bax, cleaved-caspase-3, and LC3-II; induced autophagy; decreased MMP; and lowered Bcl-2, p62, and Bcl-2/Bax ratio. The antioxidant N-acetyl cysteine (NAC) protected MMP against PFOS-induced changes and diminished apoptosis and autophagy. Compared with 200 µmol/L PFOS treatment, NAC pretreatment reversed the increase in ROS, Bax, and cleaved-caspase-3 protein caused by PFOS, lowered the apoptosis rate increased by PFOS, and increased the levels of MMP and Bcl-2/Bax ratio decreased by PFOS. The autophagy inhibitor 3-methyladenine and chloroquine decreased apoptosis and cleaved-caspase-3 protein level and increased the Bcl-2/Bax ratio. In summary, our results suggest that ROS-triggered autophagy is involved in PFOS-induced apoptosis in L-02 cells.

LncRNA SNHG6 promotes breast cancer progression and epithelial-mesenchymal transition via miR-543/LAMC1 axis.

PURPOSE: Breast cancer (BC) is the most prevalent cancer in women with an estimated incidence of 10% and the leading cause of mortality due to its heterogenous property and high metastasis rate. Development of novel therapy is very necessary and requires an understanding of molecular mechanisms. We investigated the function of SNHG6/miR-543/LAMC1 axis in BC. METHODS: Human BC tissues were obtained from diagnosed patients. BC cell lines and normal breast cells were used. QRT-PCR and Western blotting were employed to measure expression levels of SNHG6, miR-543, LAMC1, EMT-related proteins, and PI3K/AKT pathway. Dual-luciferase assay was performed to validate interactions of SNHG6/miR-543 and miR-543/LAMC1. Colony formation assay, flow cytometry, scratch wound healing assay, and transwell assay were utilized to assess the proliferation, apoptosis, migration, and invasion of BC cells. Nude mouse xenograft model was used the evaluate the function of SNHG6/miR-543 in tumor growth in vivo. RESULTS: SNHG6 and LAMC1 were elevated, but miR-543 was reduced in BC tissues and cells. SNHG6 interacted directly with miR-543, while miR-543 targeted LAMC1. Knockdown of SNHG6 suppressed BC cell proliferation, migration, invasion, EMT, and PI3K/AKT pathway, but promoted cell apoptosis, while miR-543 inhibitor or overexpression of LAMC1 reversed those effects. Overexpression of LAMC1 also blocked the effects of miR-543 on BC cell proliferation, migration, invasion, and EMT. Knockdown of SNHG6 restrained BC growth in vivo, while miR-543 inhibitor inhibited that suppression. CONCLUSION: SNHG6 promoted EMT and BC cell proliferation and migration by acting as a miR-543 sponge and disinhibiting LAMC1/PI3K/AKT pathway. SNHG6/miR-543/LAMC1 axis could serve as candidates for the development of therapeutic strategies for BC.

Surgical treatment for antiplatelet intracerebral hemorrhage (SAP-ICH): protocol for a prospective cohort study of emergency surgery for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment.

BACKGROUND: Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT. METHODS: As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage. RESULTS: In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established. CONCLUSIONS: In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future. ETHICS AND DISSEMINATION: The research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023. TRIAL REGISTRATION: Name: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment. ChiCTR1900024406 . Date of registration is July 10, 2019.

Electrochemical synthesis of EuVO4 for the adsorption of U(VI): Performance and mechanism.

The efficient removal of uranium from aqueous solution remains of great challenge in securing water environment safety. In this paper, we reported a high temperature electrochemical method for the preparation of EuVO4 with different morphologies from rare earth oxides and vanadate, which solved the problems of rare earth and vanadium recovery. The effects of pH, ionic strength, contact time, initial concentration and reaction temperature on the adsorption of U(VI) by prepared adsorbent were studied by static batch experiments. When the concentration of U(VI) standard is 100 mg g-1, the maximum adsorption capacity of EuVO4 is 276.16 mg g-1. The adsorption mechanism was elucidated with zeta potential and XPS: 1) negatively charged EuVO4 attracted UO22+ by electrostatic attraction; 2) exposed Eu, V, and O atoms complexed with U(VI) through coordination; 3) the hybrid of Eu was complex, which accommodated different electrons to interact. In the multi-ion system with Al3+, Zn2+, Cu2+, Ni2+, Cr2+ and Mn2+, EuVO4 also showed good selective adsorption properties for U(VI). Five adsorption and desorption cycle experiments demonstrated that EuVO4 possessed good renewable performance.

Integrative omics analysis reveals relationships of genes with synthetic lethal interactions through a pan-cancer analysis.

Synthetic lethality is thought to play an important role in anticancer therapies. Herein, to understand the potential distributions and relationships between synthetic lethal interactions between genes, especially for pairs deriving from different sources, we performed an integrative analysis of genes at multiple molecular levels. Based on inter-species phylogenetic conservation of synthetic lethal interactions, gene pairs from yeast and humans were analyzed; a total of 37,588 candidate gene pairs containing 7,816 genes were collected. Of these, 49.74% of genes had 2-10 interactions, 22.93% were involved in hallmarks of cancer, and 21.61% were identified as core essential genes. Many genes were shown to have important biological roles via functional enrichment analysis, and 65 were identified as potentially crucial in the pathophysiology of cancer. Gene pairs with dysregulated expression patterns had higher prognostic values. Further screening based on mutation and expression levels showed that remaining gene pairs were mainly derived from human predicted or validated pairs, while most predicted pairs from yeast were filtered from analysis. Genes with synthetic lethality were further analyzed with their interactive microRNAs (miRNAs) at the isomiR level which have been widely studied as negatively regulatory molecules. The miRNA-mRNA interaction network revealed that many synthetic lethal genes contributed to the cell cycle (seven of 12 genes), cancer pathways (five of 12 genes), oocyte meiosis, the p53 signaling pathway, and hallmarks of cancer. Our study contributes to the understanding of synthetic lethal interactions and promotes the application of genetic interactions in further cancer precision medicine.

WITHDRAWN: Analysis of Infection Factors after Radical Mastectomy for Breast Cancer by CT Image and AUTO-plan Intelligent Analysis under Regional Nerve Block.

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

hPSD: A Hybrid PU-Learning-Based Spammer Detection Model for Product Reviews.

Spammers, who manipulate online reviews to promote or suppress products, are flooding in online commerce. To combat this trend, there has been a great deal of research focused on detecting review spammers, most of which design diversified features and thus develop various classifiers. The widespread growth of crowdsourcing platforms has created large-scale deceptive review writers who behave more like normal users, that the way they can more easily evade detection by the classifiers that are purely based on fixed characteristics. In this paper, we propose a hybrid semisupervised learning model titled hybrid PU-learning-based spammer detection (hPSD) for spammer detection to leverage both the users' characteristics and the user-product relations. Specifically, the hPSD model can iteratively detect multitype spammers by injecting different positive samples, and allows the construction of classifiers in a semisupervised hybrid learning framework. Comprehensive experiments on movie dataset with shilling injection confirm the superior performance of hPSD over existing baseline methods. The hPSD is then utilized to detect the hidden spammers from real-life Amazon data. A set of spammers and their underlying employers (e.g., book publishers) are successfully discovered and validated. These demonstrate that hPSD meets the real-world application scenarios and can thus effectively detect the potentially deceptive review writers.

Overexpression of Epidermal Growth Factor Receptor (EGFR) and HER-2 in Bladder Carcinoma and Its Association with Patients' Clinical Features.

BACKGROUND The aim of this study was to determine the expression of EGFR/HER-2 and investigate their association with patients' clinical features in bladder transitional cell carcinoma (BTCC). MATERIAL AND METHODS Immunohistochemistry was utilized in our study to explore the expression of EGFR/HER-2 of 56 human bladder cancer samples and 10 normal bladder samples. RESULTS EGFR and HER-2 expressions were both significantly higher in bladder transitional cell carcinoma (BTCC) than that in non-cancer bladder samples; the EGFR positivity rate was 55.4% among BTCC samples and 37.5% for HER-2a. A statistically significant correlation was also present between the increasing EGFR or HER-2 expression levels and the clinical stages, pathologic grades, and tumor recurrence. The expression level of EGFR increased along with higher clinical stages and pathologic grades of BTCC, and the obviously increased expression of HER-2 was statistically associated with clinical stages and tumor recurrence. In addition, the expression level of HER-2 increased along with the higher clinical stage of BTCC. EGFR expression and HER-2 levels were positively associated in BTCC samples. CONCLUSIONS Our findings demonstrate that high EGFR and HER-2 expressions are dramatically increased in the BTCC tissues and are closely related to the clinical stages, pathologic grades, and tumor recurrence. Therefore, the evaluation of EGFR and HER-2 expression in BTCC may contribute to identifying patients who are at increased risk of disease progression and recurrence.

Lanthanum-modified drinking water treatment residue for initial rapid and long-term equilibrium phosphorus immobilization to control eutrophication.

This study presents an approach for developing inactivating materials to achieve an initial rapid and a long-term equilibrium P immobilization to control eutrophication based on drinking water treatment residue (DWTR), which is a byproduct of potable water production. By taking advantage of the long-term equilibrium P adsorption by DWTR, the La chemical properties, and the previous success of using La-modified bentonite clay (Phoslock®), we used DWTR as a La carrier with different ratios to develop the specific materials. The La loading mechanisms, the potentially toxic effect of La-modified DWTR on snail Bellamya aeruginosa (within 120 d), and the short- and long-term (within 80 d) P immobilization characteristics of the modified DWTR were investigated to understand the performance of the developed materials. The results showed that La loading into DWTR was based on ligand exchanges and the formation of new particles; DWTR loaded with <5% La had no toxicity against the snail. Most importantly, the loading of 5% La to DWTR substantially enhanced the rapid immobilization capacity of DWTR, achieving an initial rapid and a long-term equilibrium P adsorption in aqueous solutions. This study promotes the beneficial recycling of DWTR and results in a win-win situation for lake restoration.

Effect of the tyrosinase inhibitor (S)-N-trans-feruloyloctopamine from garlic skin on tyrosinase gene expression and melanine accumulation in melanoma cells.

In our searching for novel tyrosinase inhibitors from natural sources, (S)-N-trans-feruloyloctopamine isolated from garlic skin was found to be a potential mushroom tyrosinase inhibitor. Here, we examined the effects of the potential tyrosinase inhibitor in B16F10 cells on intracellular melanin contents, cytotoxicity, and the signaling mechanism involved in the expression of tyrosinase. The results showed the inhibitor displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin contents in a dose-dependent manner in the α-MSH-stimulated B16F10 cells. Real-time PCR and Western blot analysis showed that it inhibits melanogenesis signaling by down-regulates mRNA and protein expression levels of tyrosinase, which leads to a lower melanin contents. These results suggested that (S)-N-trans-feruloyloctopamine was an ideal tyrosinase inhibitor, and could be used in food and medical industry.