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Triple-negative breast cancer (TNBC) is generally considered an aggressive breast cancer subtype associated with poor prognostic outcomes. Up to now, the molecular and cellular mechanisms underlying TNBC pathology have not been fully understood. In this manuscript, we propose a novel semiparametric model with kernel for gene-based analysis with a breast cancer GWAS data. The software of SPMGBA (semiparametric method for gene-based analysis) in MATLAB is available at GitHub (https://github.com/zliu3/SPMGBA). Genetic signatures associated with breast cancer are discovered. We further validate the prognostic power of the identified genes with a large cohort of expression data from the European Genome-Phenome Archive, and discover that SEL1L is associated with the overall survival of TNBC with the p-value of .0002. We conclude that gene SEL1L is down-regulated in TNBC and the expression of SEL1L is positively associated with patient survival.

Objective Many laboratory indicators form a skewed distribution with outliers in critically ill patients with COVID-19, for which robust methods are needed to precisely determine and quantify fatality risk factors. Method A total of 192 critically ill patients (142 were discharged and 50 died in the hospital) with COVID-19 were included in the sample. Quantile regression was used to determine discrepant laboratory indexes between survivors and non-survivors and quantile shift (QS) was used to quantify the difference. Logistic regression was then used to calculate the odds ratio (OR) and the predictive power of death for each risk indicator. Results After adjusting for multiple comparisons and controlling numerous confounders, quantile regression revealed that the laboratory indexes of non-survivors were significantly higher in C-reactive protein (CRP; QS = 0.835, p

Background Malignant peritoneal mesothelioma is the most common primary peritoneal neoplasm. The only universally recognised pathological prognostic factor is histopathological subtype. Prognostic markers based on patient features and clinical stages have been disappointing. Aims To assess the prognostic role of several clinicopathological features in a retrospective cohort of 60 patients diagnosed with peritoneal mesothelioma. Methods Sixty patients were centrally collected and were immunohistochemically analysed for the expression of osteopontin (OPN), GLUT1 and Ki‐67. Labelling was assessed by two pathologists. Complete clinical information and follow‐up were obtained from patients' records. Results OPN expression was identified in 52 (86.6%) of 60 specimens, and GLUT1 in 39 (65%) of 60 specimens. Univariate Cox regression analysis showed that a lower peritoneal carcinomatosis index (PCI), tumour‐directed treatment (chemotherapy or surgery alone or in any combination), lower Ki‐67, GLUT1 and lower OPN expression had a statistically significant positive effect on overall survival (OS). PCI (hazard ratio (HR) = 1.032 (95% confidence interval (CI): 1.000–1.067); P = 0.054) and tumour‐directed treatment (HR = 0.211 (95% CI: 0.104–0.430); P

Hypomethylating agents (HMAs) are effective therapies in myelodysplastic syndromes (MDS), but allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure MDS. According to the current literature, it is difficult to confirm whether HMAs bridging therapy is beneficial for MDS patients receiving allo-HSCT. Therefore, we tried to evaluate the effect of HMAs on long-term survival of the MDS patients. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to January 10, 2021. Patients who accepted HMAs bridging to allo-HSCT were defined as experimental group, while patients who received the best supportive care (BSC) before allo-HSCT were control group. Overall survival (OS) was the primary end point. Seven studies were included in the final analysis. The final results showed no OS differences between patients accepted HMAs before allo-HSCT and those received BSC (HR = 0.86, 95% CI: 0.64–1.15, p = 0.32), indicating that MDS patients' long-term survival did not benefit from HMAs bridging therapy before allo-HSCT. This conclusion needs to be further verified by a large number of prospective randomized controlled trials, which have guiding significance for the treatment of MDS patients.

Both electrospinning apparatus and their commercial products are extending their applications in a wide variety of fields. However, very limited reports can be found about how to implement an energy-saving process and in turn to reduce the production cost. In this paper, a brand-new type of coaxial spinneret with a solid core and its electrospinning methods are developed. A novel sort of medicated Eudragit/lipid hybrid nanofibers are generated for providing a colon-targeted sustained release of aspirin. A series of characterizations demonstrates that the as-prepared hybrid nanofibers have a fine linear morphology with the aspirin/lipid separated from the matrix Eudragit to form many tiny islands. In vitro dissolution tests exhibit that the hybrid nanofibers are able to effectively prevent the release of aspirin under an acid condition (8.7%±3.4% for the first two hours), whereas prolong the drug release time period under a neutral condition(99.7±4.2% at the seventh hour). The energy-saving mechanism is discussed in detail. The prepared aspirin-loaded hybrid nanofibers can be further transferred into an oral dosage form for potential application in countering COVID-19 in the future.

Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R0 through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development., Transmission by pre-symptomatic and asymptomatic viral carriers makes intervention and containment of the COVID-19 extremely challenging. Here, the authors construct an epidemiological model that focuses on transmission around the symptom onset, exploring specific transmission control measures.

Objectives The aim of this study was to explore the difference in target vessel failure (TVF) 3 years after intravascular ultrasound (IVUS) guidance versus angiographic guidance among all comers undergoing second-generation drug-eluting stent (DES) implantation. Background The multicenter randomized ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions) trial showed a lower incidence of 1-year TVF after IVUS-guided DES implantation among all comers compared with angiographic guidance. However, the 3-year clinical outcomes of the ULTIMATE trial remain unknown. Methods A total of 1,448 all comers undergoing DES implantation who were randomly assigned to either IVUS guidance or angiographic guidance in the ULTIMATE trial were followed for 3 years. The primary endpoint was the risk for TVF at 3 years. The safety endpoint was definite or probable stent thrombosis (ST). Results At 3 years, TVF occurred in 47 patients (6.6%) in the IVUS-guided group and in 76 patients (10.7%) in the angiography-guided group (p = 0.01), driven mainly by the decrease in clinically driven target vessel revascularization (4.5% vs. 6.9%; p = 0.05). The rate of definite or probable ST was 0.1% in the IVUS-guided group and 1.1% in the angiography-guided group (p = 0.02). Notably, the IVUS-defined optimal procedure was associated with a significant reduction in 3-year TVF relative to that with the suboptimal procedure. Conclusions IVUS-guided DES implantation was associated with significantly lower rates of TVF and ST during 3-year follow-up among all comers, particularly those who underwent the IVUS-defined optimal procedure compared with those with angiographic guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions; NCT02215915 )

BACKGROUND Occult breast cancer (OBC) is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast. Due to its low incidence and unique clinical manifestations, there is a lack of consensus on the diagnosis and treatment of OBC. We report a case of OBC treated with neoadjuvant chemotherapy combined with anlotinib. The treatment was well tolerated, and the patient achieved a pathologic complete response. CASE SUMMARY A 53-year-old woman presented with a lump in her right axillary area with no primary lesions in the breast. Pathological biopsy confirmed right axillary metastatic carcinoma. Immunohistochemical staining results were positive for progesterone receptor, cytokeratin 7, specific breast markers GATA3 and gross cystic disease fluid protein-15. Tumor cells were negative for estrogen receptor, human epidermal growth factor receptor-2, cytokeratin 5/6, cytokeratin 20, and villin. The patient was diagnosed with OBC, and she underwent neoadjuvant chemotherapy combined with anlotinib. Mastectomy plus axillary lymph node dissection was performed. The patient achieved pathologic complete response with no residual invasive tumor cells in the breast or axillary lymph nodes. Postoperatively, she received adjuvant radiotherapy and endocrine therapy. CONCLUSION Neoadjuvant chemotherapy and anlotinib had good efficacy and safety in the treatment of OBC and may be a new therapeutic option.

Background: Frozen shoulder is a common shoulder disorder characterized by pain and restriction. Various nonsurgical treatments have been reported, but there is no consensus about their comparative efficacy and the effects of moderators. Purpose: To compare the efficacy of different nonsurgical interventions and identify potential patient-specific moderating factors for frozen shoulder. Study Design: Systematic review and network meta-analysis. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception to February 18, 2019. The search was supplemented by manual review of relevant reference lists. Randomized controlled trials of participants with frozen shoulder that compared nonsurgical interventions were selected. Measured outcomes included pain, shoulder function in daily activities, and range of motion. Results: Of 3136 records identified, 92 trials were eligible, evaluating 32 nonsurgical interventions in 5946 patients. Intra-articular injection improved pain (pooled standardized mean difference [95% CI]: steroid injection, 1.68 [1.03-2.34]; capsular distension, 2.68 [1.32-4.05]) and shoulder function (steroid injection, 2.16 [1.52-2.81]; distension, 2.89 [1.71-4.06]) to a greater extent than placebo. Capsular distension and extracorporeal shockwave therapy showed the highest ranking for pain relief and functional improvement, respectively. Laser therapy also showed benefits for pain relief (3.02 [1.84-4.20]) and functional improvement (3.66 [1.65-5.67]). Subgroup analyses by disease stages revealed that steroid injection combined with physical therapy provided more benefits during the freezing phase, whereas joint manipulation provided more benefits in the adhesive phase. Adjunctive therapies, female sex, and diabetes were also identified as moderators of effectiveness. Conclusion: Capsular distension is a highly recommended choice for treatment of frozen shoulder, contributing greatly to pain relief and functional improvement; steroid injection is also a prevailing effective intervention. Among new options, extracorporeal shockwave therapy and laser therapy show potential benefits for multiple outcomes. Individualized optimal intervention should be considered, given that treatment effect is moderated by factors including the disease stage, time of assessment, adjunctive therapies, female sex, and diabetes.

In some medical researches such as ophthalmological, orthopaedic and otolaryngologic studies, it is often of interest to compare multiple groups with a control using data collected from paired organs of patients. The major difficulty in performing the data analysis is to adjust the multiplicity between the comparison of multiple groups, and the correlation within the same patient's paired organs. In this article, we construct asymptotic simultaneous confidence intervals (SCIs) for many-to-one comparisons of proportion differences adjusting for multiplicity and the correlation. The coverage probabilities and widths of the proposed CIs are evaluated by Monte Carlo simulation studies. The methods are illustrated by a real data example.

Objective To elucidate the pathophysiological process by analyzing the correlation between morphological and functional changes in patients with delayed endolymphatic hydrops (DEH). Methods Twenty-nine patients diagnosed with DEH were enrolled in this retrospective study. All patients were assessed using the caloric test, cervical and ocular vestibular evoked myogenic potentials, and gadolinium-enhanced magnetic resonance imaging (MRI) of the inner ear. Results According to the MRI, the hydrops localization was categorized as hydrops in the vestibule (saccule and utricle) (14%), hydrops in the vestibule and cochlea (72%), and hydrops in the vestibule, cochlea, and lateral semicircular canal (LSCC) (14%). Vestibular hydrops could definitely be observed as function declined; however, a dysfunction of both the saccule and utricle was not always present when vestibular hydrops was detected with MRI. In the LSCC, a decline in functional tests was not necessarily accompanied by morphological abnormalities. However, dysfunction could definitely be detected when LSCC hydrops was observed with MRI. Conclusions Hydrops can be found mainly in the vestibule as shown by MRI. In the vestibule, abnormalities are commonly morphologic rather than functional, whereas in the LSCC a functional deterioration can be detected more frequently than morphological changes. Significance Our findings can provide a new perspective on the functional and morphological characteristics of patients with DEH.

Background To evaluate an innovative open necrosectomy strategy with continuous positive drainage and prophylactic diverting loop ileostomy for the management of late infected pancreatic necrosis (LIPN). Methods Consecutive patients were divided into open necrosectomy (ON) group (n = 23), open necrosectomy with colonic segment resection (ON+CSR) group (n = 8) and open necrosectomy with prophylactic diverting loop ileostomy (ON+PDLI) group (n = 11). Continuous positive drainage (CPD) via double-lumen irrigation–suction tube (DLIST) was performed in ON+PDLI group. The primary endpoints were duration of organ failure after surgery, postoperative complication, the rate of re-surgery and mortality. The secondary endpoints were duration of hospitalization, cost, time interval between open surgery and total enteral nutrition (TEN). Results The recovery time of organ function in ON+PDLI group was shorter than that in other two groups. Colonic complications occurred in 13 patients (56.5%) in the ON group and 3 patients (27.3%) in the ON+PDLI group (p = 0.11). The length of stay in the ON+PDLI group was shorter than the ON group (p = 0.001). The hospitalization cost in the ON+PDLI group was less than the ON group (p = 0.0052). Conclusion ON+PDLI can avoid the intestinal dysfunction, re-ileostomy, the resection of innocent colon and reduce the intraoperative trauma. Despite being of colonic complications before or during operation, CPD + PDLI may show superior effectiveness, safety, and convenience in LIPN.

Dexmedetomidine, which is a highly selective α2 adrenoreceptor agonist, enhances the analgesic efficacy and prolongs the analgesic duration when administered in combination with local anesthetics. The current study aimed to evaluate the effects of dexmedetomidine combined with ropivacaine in ultrasound-guided transversus abdominis plane (TAP) block on post-operative analgesia following cesarean section (CS). A total of 70 patients scheduled for CS were divided randomly into 2 groups: The ropivacaine (R) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml 0.9% normal saline, and the dexmedetomidine (RD) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml dexmedetomidine (0.5 µg/kg). The primary outcome was pain-free duration, and secondary outcomes included heart rate (HR) and mean blood pressure (MBP) measurements, visual analogue scale (VAS) pain scores, number of patients who required rescue analgesic, time to first request for analgesia and patient satisfaction. There was no significant difference in HR and MBP between the two groups at 1 h post-surgery (P>0.05). However, VAS pain scores decreased at 6 and 8 h post-surgery [2 (1-2) vs. 0 (0-0.25) and 2 (2-3) vs. 0 (0-1), respectively; P

BackgroundEmerging functional imaging studies suggest that schizophrenia is associated with aberrant spatiotemporal interaction which may result in aberrant global and local dynamic properties.MethodsWe investigated the dynamic functional connectivity (FC) by using instantaneous phase method based on Hilbert transform to detect abnormal spatiotemporal interaction in schizophrenia. Based on resting-state functional magnetic resonance imaging, two independent datasets were included, with 114 subjects from COBRE [51 schizophrenia patients (SZ) and 63 healthy controls (HCs)] and 96 from OpenfMRI (36 SZ and 60 HCs). Phase differences and instantaneous coupling matrices were firstly calculated at all time points by extracting instantaneous parameters. Global [global synchrony and intertemporal closeness (ITC)] and local dynamic features [strength of FC (sFC) and variability of FC (vFC)] were compared between two groups. Support vector machine (SVM) was used to estimate the ability to discriminate two groups by using all aberrant features.ResultsWe found SZ had lower global synchrony and ITC than HCs on both datasets. Furthermore, SZ had a significant decrease in sFC but an increase in vFC, which were mainly located at prefrontal cortex, anterior cingulate cortex, temporal cortex and visual cortex or temporal cortex and hippocampus, forming significant dynamic subnetworks. SVM analysis revealed a high degree of balanced accuracy (85.75%) on the basis of all aberrant dynamic features.ConclusionsSZ has worse overall spatiotemporal stability and extensive FC subnetwork lesions compared to HCs, which to some extent elucidates the pathophysiological mechanism of schizophrenia, providing insight into time-variation properties of patients with other mental illnesses.

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P − group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known. We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection. We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection. We used RNA sequencing to interrogate the transcriptome of CD4+ T cells obtained from the same set of infants. After dimension reduction through principal component (PC) analysis, we performed an integrative analysis to identify significant co-variation between microbial clade and gene expression PCs. We then employed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) to estimate the clade-gene association patterns for each infant. Our network-based integrative analysis identified several clade-gene associations significantly related to the severity of RSV infection. The microbial taxa with the highest loadings in the implicated clade PCs included Moraxella, Corynebacterium, Streptococcus, Haemophilus influenzae, and Staphylococcus. Interestingly, many of the genes with the highest loadings in the implicated gene PCs are encoded in mitochondrial DNA, while others are involved in the host immune response. This study on microbiome-transcriptome interactions provides insights into how the host immune system mounts a response against RSV and specific infectious agents in nasal microbiota.

Aim of the Study: Mason type III radial head fractures are a source of concern due to the severe injury and poor recovery. At present, radial head resection, open reduction and internal fixation (ORIF), and prosthetic replacement are three common treatment methods for these fractures. The clinical efficacy and postoperative complications are controversial, which makes it difficult for physicians to determine the most appropriate regimen. Herein, this present prospective, non-randomized, parallel-controlled study was conducted to compare the therapeutic effects and identify the most effective treatment method for Mason type III radial head fracture. Materials and Methods: We assessed patients with Mason type III radial head fracture treated with resection, prosthetic replacement, and ORIF to compare preoperative and postoperative pain condition, elbow joint function, curative effect, and complication rate. A visual analog scale was used to score pain. The elbow joint function was observed using the Broberg-Morrey elbow joint score. Results: No significant differences were found in patient demographics among the resection, prosthetic replacement, and ORIF groups. The prosthetic replacement and ORIF procedures were more complex and had higher technical requirements. Prosthetic replacement and ORIF enabled higher elbow joint scores and lower pain scores than resection. Excellent and good ratings were highest and complication rates were lowest in the prosthetic replacement group, followed by the ORIF group. Conclusion: Our results showed that prosthetic replacement is more effective than ORIF and radial head resection in relieving pain, functional recovery and reducing complications in the treatment of Mason type III radial head fractures.

The objective of this investigation was to evaluate the influence of back-fat thickness (BF), at mating of sows, on the placental oxidative stress, mitochondrial injury and apoptosis. For that purpose, we performed iTRAQ labeling based proteomic analysis on term placentas obtained by vaginal delivery from BFI (15–20 mm) and BFII (21–27 mm) sows formed according to BF at mating. Proteomic analysis revealed 413 proteins to be significantly different in placenta from BFII sows by ≥1.2-fold. Gene ontology (GO) analysis identified proteins related to oxidative stress response and apoptotic process to be altered in placenta from BFII sows. Indicative of increased oxidative stress and impaired mitochondrial function, higher placental MDA, H2O2 and O2− levels and reduced CAT and SOD activities were linked to decreased mitochondrial membrane potential and reduced mitochondrial DNA copy number and increased MPTP opening activity in placenta from BFII group (P

This study aimed to assess the efficacy of double-lumen irrigation-suction tube (DLIST) in treating severe intra-abdominal infection (SIAI) induced by endoscopic sphincterotomy–related perforation (EST-rP). We enrolled 34 consecutive patients who had been transferred to our hospital with SIAI induced by EST-rP from January 2000 to June 2018. Then they were assigned into two groups based on whether or not rescue surgery had been performed: failed nonoperative treatment group (n = 9) and failed rescue surgery treatment group (n = 25). All 34 patients received DLIST for positive draining by surgery in our hospital. Data collection included demographics, indication for endoscopic retrograde cholangiopancreatography, time to rescue surgery, surgical procedure, surgical success rate, complications, hospital stay, and postoperative outcome. The research enrolled 34 patients (ages 27–79 years, mean of 57.8 ± 12.1 years). There were no significant differences in age and gender between two groups ( P > 0.05). After being admitted, they were diagnosed with sepsis induced by SIAI (Sequential Organ Failure Assessment score range of 2–6, mean of 3.6 ± 0.95). The time from endoscopic retrograde cholangiopancreatography to rescue surgery was 12 to 336 hours (mean of 73.7 ± 72.2 hours); overall hospital stay was 15 to 405 (mean of 127.5 ± 81.5) days. The hospital stay was significantly longer in the failed rescue surgery group than that of the failed nonoperative treatment group ( P < 0.05). The overall mortality rate was 11.8 per cent (4/34). The mortality rate was 16 per cent (4/25) and 0 per cent (0/9), respectively. As a modified suction technology, DLIST placement can effectively treat SIAI induced by EST-rP and lower the mortality rate of rescue surgery treatment.

Residue of veterinary antibiotics (VAs) in the animal breeding industry has become a problematic environmental issue. However, the residual levels of VAs as well as their variation tendency, degradation mechanisms and relationships with other parameters during animal wastewater disposal processes are still obscure. This study measured different samples during wastewater disposal processes from three farms, and systematically analyzed the residue, migration and removal of 58 kinds of typical VAs (6 classes) in Tianjin, China. The results showed that about 44 kinds of VAs were quantitatively detected. Tetracycline antibiotics (TCs) usually had higher residual concentrations than other classes of VAs in the raw wastewater; the highest residual concentration was 130.67 ± 5.90 μg/L which occurred for chlortetracycline (CTC). Pig farms generally had more VAs species and higher residual concentrations than dairy farms, and the proportion of different VAs was similar for dairy farms. The final removal rates of different VAs classes varied largely (negative to > 99.87%), and the highest removal rates usually occurred in biological processes for adsorption and biodegradation effects, and occasionally occurred in the final effluents. The correlation coefficients between VAs removal rates and chemical oxygen demand (COD) removal rates were much higher than those of total nitrogen (TN), total phosphorus (TP) and ammonia nitrogen (NH4-N) in pig farms, while opposite conclusion was obtained in dairy farms. Among different classes, TCs presented the highest daily mass loading of ND ~ 10,453.8 ± 471.7 mg/d in the influent and ND ~ 1141.6 ± 58.9 mg/d in the effluent in farm 1.

Background Intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation is associated with fewer major adverse cardiovascular events compared with angiography guidance for patients with individual lesion subset. However, the beneficial effect on major adverse cardiovascular event outcome of IVUS guidance over angiography guidance in all-comers who undergo DES implantation still remains understudied. Objectives This study aimed to determine the benefits of IVUS guidance over angiography guidance during DES implantation in all-comer patients. Methods A total of 1,448 all-comer patients who required DES implantation were randomly assigned (1:1 ratio) to either an IVUS guidance or angiography guidance group. The primary endpoint was target-vessel failure (TVF) at 12 months, including cardiac death, target-vessel myocardial infarction, and clinically driven target-vessel revascularization (TVR). The procedure was defined as a success if all IVUS-defined optimal criteria were met. Results At 12 months follow-up, 60 TVFs (4.2%) occurred, with 21 (2.9%) in the IVUS group and 39 (5.4%) in the angiography group (hazard ratio [HR]: 0.530; 95% confidence interval [CI]: 0.312 to 0.901; p = 0.019). In the IVUS group, TVF was recorded in 1.6% of patients with successful procedures, compared with 4.4% in patients who failed to achieve all optimal criteria (HR: 0.349; 95% CI: 0.135 to 0.898; p = 0.029). The significant reduction of clinically driven target-lesion revascularization or definite stent thrombosis (HR: 0.407; 95% CI: 0.188 to 0.880; p = 0.018) based on lesion-level analysis by IVUS guidance was not achieved when the patient-level analysis was performed. Conclusions The present study demonstrates that IVUS-guided DES implantation significantly improved clinical outcome in all-comers, particularly for patients who had an IVUS-defined optimal procedure, compared with angiography guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions [ULTIMATE]; NCT02215915)

Animals exposure to polychlorinated biphenyls (PCBs) may result in retention of hydroxylated PCBs (OH-PCBs). OH-PCBs can be accumulated in animals, including humans, through the transmission of food chain. However, there are few studies on the accumulation and metabolism of OH-PCBs exposed to the body through daily diet. Therefore, this study was conducted to investigate the fate of OH-PCBs after being ingested through dietary intake. By adding 3-OH-PCB101 and 4-OH-PCB101 to the edible tissue of crucian carp, which were used as raw materials to prepare mouse feed, with an exposure concentration of 2.5 μg/kg ww. The exposure experiment lasted for a total of 80 days. The blood, feces and 11 tissues of mice at different times were analyzed qualitatively and quantitatively. It was found that major OH-PCB101 were accumulated in intestine or excreted with feces. A small part was accumulated in heart, lung and spleen. For the first time that the conversion from OH-PCB101 to PCB101 in mice was discovered, which shows from another perspective that persistent organic pollutants are difficult to be completely degraded in the environment. 4-MeO-PCB101, 3-MeSO2-PCB101, and 4-MeSO2-PCB101 were also found in various tissues. The results of this study show that after OH-PCBs accumulated in animals re-enter the organism through the food chain, they can be metabolized again and may be reversely transformed into the parent compounds. The present research shed new light on simulating the metabolic transformation process of OH-PCBs exposed to mammals through ingestion of fish. Available data show that second-generation persistent organic pollutants in the environment still need to be continuously concerned.

Perception or imagination requires top-down signals from high-level cortex to primary visual cortex (V1) to reconstruct or simulate the representations bottom-up stimulated by the seen images. Interestingly, top-down signals in V1 have lower spatial resolution than bottom-up representations. It is unclear why the brain uses low-resolution signals to reconstruct or simulate high-resolution representations. By modeling the top-down pathway of the visual system using the decoder of variational auto-encoder (VAE), we reveal that low-resolution top-down signals can better reconstruct or simulate the information contained in the sparse activities of V1 simple cells, which facilitates perception and imagination. This advantage of low-resolution generation is related to facilitating high-level cortex to form geometry-respecting representations observed in experiments. Moreover, our finding inspires a simple artificial- intelligence (AI) technique to significantly improve the generation quality and diversity of sketches, a style of drawings made of thin lines. Specifically, instead of directly using original sketches, we use blurred sketches to train VAE or GAN (generative adversarial network), and then infer the thin-line sketches from the VAE- or GAN- generated blurred sketches. Collectively, our work suggests that low-resolution top-down generation is a strategy the brain uses to improve visual perception and imagination, and advances sketch-generation AI techniques.

Objectives Autoimmunity may play a role in endometriosis. The association between endometriosis and RA remains unknown. This study was conducted to identify any evidence for this relationship. Methods This 13-year, nationwide, population-based, retrospective cohort study analysed the risk of RA in a cohort of individuals with endometriosis. We investigated the incidence of RA among patients with endometriosis using data from the Longitudinal Health Insurance Database 2000, which is maintained by the Taiwan National Health Research Institutes. We used propensity scores to match comorbidities in the two cohorts. Kaplan–Meier analysis and Cox proportional hazard model were employed to analyse the association between endometriosis and RA among patients with different potential risks. Results Patients with endometriosis [adjusted hazard ratio (HR) 1.75, 95% CI 1.27, 2.41], aged ≥45 years (adjusted HR 1.50, 95% CI 1.06–2.13) and with autoimmune disease (adjusted HR 6.99, 95% CI 2.84–17.21) had a significantly higher risk of RA. The analyses also showed that when stratified by age, comorbidities and medication use, the risk of RA in patients with endometriosis was also higher than in those without endometriosis. Conclusions This 14-year, nationwide, population-based retrospective cohort study revealed that patients with endometriosis have a higher risk of RA. In the clinical management of patients with RA, rheumatologists should be especially mindful of the possibility of underlying endometriosis.

In order to improve its aqueous solubility and emulsifying function, zein was partially hydrolyzed by trypsin and conjugated to chitosan oligosaccharide lactate by transglutaminase. Hydrolysis and covalent linkage to chitosan oligosaccharide was confirmed by free amine content, gel electrophoresis, and infrared spectroscopy. Enzymatic glycosylation was optimized at pH 6, 44 °C, and 4 h to bind approximately 95% of the free amines in the hydrolysates to chitosan oligosaccharide. Hydrolysis and conjugation increased solubility of zein by 47.60% and 72.93%. Hydrolysis and conjugation also decreased surface hydrophobicity by more than 20% and more than doubled emulsifying activity index, emulsion stability index, and foaming capacity. This enzymatic modification has potential to be applied to improve functional properties of other prolamins.

Background Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. Trial design DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. Conclusions DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Background: Nan Ling commodity grain base is a national high-standard farmland demonstration area. Scientific evaluation of soil environmental quality is of important significance to plan land resources rationally to improve the quality and efficiency of agricultural production.Methods: This paper try to apply the equal intercept transformation radar chart --an improved radar chart--to the assessment of soil environmental quality. In the assessment, the area of equal intercept transformation radar chart is adopted to represents the soil environmental quality.Different from the other assessment methods in common use, the equal intercept transformation radar chart method, as a visual graphic data analysis method, transforms data into graphics and therefore the data information can be retained and excavated more fully. Moreover, this advanced radar chart overcomes targetedly the main defect of the conventional radar chart that the evaluation result depends heavily on the order of arrangement of indicators.Results: The results indicate that the soil environmental quality at depth of 0-60cm in low mountain area of Nan ling commodity grain base is the second grade while that in the hilly and plain area are both the first grade. The indicators of poor soil environmental quality in low mountain area are exogenous Cd and endogenous As, those in hilly area are exogenous Cd and endogenous As and Hg, and that in plain area is exogenous Cd.Conclusion: It is proved through this special case study that the application of equal intercept transformation radar chart to the assessment of soil environmental quality is feasible and more intuitive, comprehensive and fine.

Objective The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates. Study Design Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n = 3), CD (cesarean-born neonates, n = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3–V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology. Results The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the β-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins. Conclusion This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota. Key Points

Aim The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. Methods and results In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30–0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20–0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19–1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31–2.37; P = 0.772). Conclusion For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. Study registration http://www.clinicaltrials.com; Identifier: NCT02284750.

To establish a continuous reinfusion of succus entericus and enteral nutrition (EN) in complex high-output fistula (HOF). Percutaneous puncture and catheterization technique was used to establish continuous reinfusion of succus entericus and EN in complex HOF. From May 2010 to June 2018, 21 patients with complex HOF used continuous reinfusion of succus entericus and EN. Six of them were completely cured, and 15 cases were cured after definitive surgery. Percutaneous puncture and catheterization technique was shown to be a useful and effective method for establishing continuous reinfusion of succus entericus and EN in patients with complex HOF. This method can prevent succus entericus loss and remove the barrier to implementing EN in HOF.

BACKGROUND Reports showed no change of 7-day mortality after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) between 2001 and 2011 in China. National rolling one-year interventional standardized training programme began in September 2009. However, the improvement in clinical outcome following STEMI PCI after 2011 remains unclear. METHODS AND RESULTS This multicentre MOODY registry study aimed to analyse the clinical improvement after STEMI PCI. Of a total of 9265 acute MI patients registered from 24 centres, 3142 STEMIs having a first medical contact time ≤12 hours and undergoing primary PCI were assigned to the Pre Group (n = 1014, between March 1999 and October 2010) or the Post Group (n = 2128, between 2010 November and 2016 October). The primary endpoint was in-hospital cardiac death. Study endpoints were also compared between trained and untrained operators and between experienced (≥50 primary PCIs/year) and inexperienced personnel. In-hospital death after PCI was 3.0% in the Pre Group, significantly higher than 1.6% in the Post Group (P = .035). The improvements in clinical outcome after PCI between the 2016 and Pre Groups were stably sustained through one-year follow-up. The significant reduction for in-hospital death was noted when primary PCI was performed by trained (1.4% vs 5.4%, P

In order to study the transmission of rabies epidemics in vampire bats, we propose a mathematical model for vampire bat rabies virus. A threshold R0 is identified which determines the outcome of the disease. If R0<1, the disease-free equilibrium is globally asymptotically stable, and if R0>1, the endemic equilibrium is globally asymptotically stable with certain conditions. Through the numerical simulation, the correctness of the theoretical results is verified. We carry out the sensitivity analysis of the parameters which provide a theoretical basis for preventing and controlling the transmission of bat rabies.

BACKGROUND: Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI. METHODS: The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset 16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI. RESULTS: There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P

Increasing evidence has shown that fecal microbiota transplantation (FMT) could be a promising treatment option for Crohn’s disease (CD). However, the frequency of FMT for CD treatment remains unclear. This study aimed to evaluate the optimal timing for administering the second course of FMT to maintain the long-term clinical effects from the first FMT for patients with CD. Sixty-nine patients with active CD who underwent FMT twice and benefited from the first FMT were enrolled in this study. Clinical response, stool microbiota, and urine metabolome of patients were assessed during the follow-up. The median time of maintaining clinical response to the first FMT in total 69 patients was 125 days (IQR, 82.5–225.5). The time of maintaining clinical response to the second FMT in 56 of 69 patients was 176.5 days (IQR, 98.5–280). The fecal microbiota composition of each patient post the first FMT was closer to that of his/her donor. Compared to that of the baseline, patients prior to the second course of FMT showed significant differences in urinary metabolic profiles characterized by increased indoxyl sulfate, 4-hydroxyphenylacetate, creatinine, dimethylamine, glycylproline, hippurate, and trimethylamine oxide (TMAO). This study demonstrated that patients with CD could be administered the second course of FMT less than 4 months after the first FMT for maintaining the clinical benefits from the first FMT. This was supported by the host–microbial metabolism changes in patients with active CD. Trial registration: ClinicalTrials.gov, NCT01793831. Registered 18 February 2013. https://clinicaltrials.gov/ct2/show/NCT01793831?term=NCT01793831&rank=1 Electronic supplementary material The online version of this article (10.1007/s00253-018-9447-x) contains supplementary material, which is available to authorized users.

The vestibular center of the brainstem contains afferent and efferent vestibular neurons, which play an important role in information perception, processing, and sensory integration. Vestibular efferent neurons (VENs) can receive changes in vestibular afferent information and regulate peripheral vestibular function; however, it remains unclear how VENs change after vestibular afferent information increases or weakens. In this study, we used animal models with altered vestibular afferent information by electrically stimulating or destroying the vestibular medial nucleus (MVe). We confirmed the location of VENs in the brainstem by injecting five adult male Wistar rats in the vestibular region with a retrograde tracer. Following this, the MVe was stimulated electrically for 30 min in 20 naive rats. Rats were anesthetized and euthanized 1, 3, 6, and 12 h after stimulation. The MVe was electrolytically lesioned in another group (n=20); then, the rats were anesthetized and euthanized 1, 3, 5, and 7 days after lesioning. VENs were clearly identified dorsolateral to the genu of the facial nerve (g7) in coronal brainstem sections using choline acetyltransferase (ChAT) staining. The number of ChAT-positive VENs dorsolateral to g7 increased significantly on both sides compared with the control group 3 and 6 h after electrical stimulation. The number of ChAT-positive VENs dorsolateral to g7 was significantly greater on both sides compared with controls 3 and 5 days after electrolytic lesion. In summary, we found that the number of ChAT-positive VENs was significantly increased following a change in the excitability of MVe neurons. This suggests that VENs can respond to changes in afferent vestibular information and feedback, and regulate the peripheral vestibule. In addition, this shows that acetylcholine is an important neurotransmitter that plays an important role in the perception and fine regulation of the vestibular system.

To investigate the relationship between vestibular schwannoma (VS) size and the dysfunction and compensation of the vestibular system. One hundred fifty-two patients with unilateral VS were investigated using multiple auditory-vestibular function tests such as audiometry, sensory organization test (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test, and ocular VEMP (oVEMP) test. In this study, 89% of patients with unilateral VS had mild to severe hearing loss on the involved side. All patients showed higher threshold values or no response in the cVEMP and oVEMP tests, which both exhibited a lower response rate on the affected side than on the unaffected side. Patients with a tumor size ≥ 30 mm had significantly lower equilibrium scores for condition 5 and condition 6 of the SOT, which were associated with vestibular dysfunction, higher rates of canal paresis in the caloric test, and lower response rates in the cVEMP and oVEMP tests on the affected sides, compared with the results of patients with a tumor size ≤ 14 mm and patients with a tumor size of 15–29 mm. A diameter > 30 mm may be the critical threshold at which vestibular function is affected and vestibular compensation is interfered with by a VS tumor. Functional performance of the vestibular system can help clinicians predict the size of a tumor and provide a basis for the development of treatment protocols.

As one of the main sources of the air pollution, the NOx emission from combustion is difficult to avoid. In this research, a combustion method, named as Oxygen Diluted Partially Premixed and Oxygen Enriched Supplemental Combustion (ODPP/OESC) was proposed to reduce the NOx generation by adjusting the oxygen concentration. The relationships between the operating parameters were deduced. The effects of the ODPP/OESC on the NOx and CO emission were evaluated experimentally. Design of Experiments (DoE) was conducted to obtain the optimal operating parameters through the Response Surface Methodology (RSM). Further statistical analysis indicated that as the dominant operating parameter, the lower oxygen mole fraction of oxygen diluted air (Yod) resulted in lower NOx but higher CO emission. The Yod makes the most contribution to the NOx and CO emission, then the oxygen mole fraction of oxygen enriched air (Yoe) does, and the equivalence ratio of premixed gas (ERp) does the least. The regression analysis yielded two relationships between the NOx(CO), Yod, Yoe, and ERp. The optimal operating parameters were obtained by the RSM and verified experimentally. NOx and CO emission were 22.6 mg/m3 and 362 mg/m3 under the optimal condition, respectively. So the ODPP/OESC was promising and feasible for the low emission of the CH4/air combustion and the RSM can be used to control the combustion emissions.

The purpose of the study was to evaluate the feasibility of conditioning regimen with sequential chemotherapy (FLAG-IDA), followed by Fludarabine (5 days) + Busulfan (3 days) by parallel analysis of patients with refractory acute myeloid leukemia (AML) from two transplantation centers in China and France. A total of 47 refractory AML with median bone marrow blast of 35% (1–90%) and median age at 42 years (16–62) were enrolled. Thirteen patients received peripheral stem cell transplantation (HSCT) from HLA-matched sibling donor, while 18 and 16 from unrelated or haplo-identical donors, respectively. With a median follow-up of 24.3 months (1–70), 13 patients relapsed at a median time of 5.1 months (2.2–18.0) and 24 patients died due to relapse (n = 12) or non-relapsed mortality (NRM, n = 12). The estimated 3-year RR and NRM were 33.5 ± 5.7% and 25.7 ± 4.2%, respectively. The estimated 3-year overall survival (OS) and event-free survival (EFS) were 43.8 ± 7.8% and 42.3 ± 7.8%. In multivariate analysis, age (

The plasma characteristics of carbon-doped glycidyl azide polymer (GAP) are investigated ablation by nanosecond laser pulses. For the GAP energetic liquid, a specific impulse of 840 s and an ablation efficiency up to 98% are obtained, which can be attributed to the low mass loss owing to the carbon doping. A comparison between the chemical energies shows that the carbon-doped GAP provides better propulsion than pure GAP. This indicates that even for an energetic liquid, an efficient approach to enhance the thrust performance is to reduce the splashing. High ablation thrust could be achieved at a low laser fluence and high carbon content.

// Nan Zhang 1 , Nan Guo 2 , Liang Tian 3 and Zhigang Miao 3 1 Department of Thoracic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei Province, China 2 Department of Cardiology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China 3 Department of Pathology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China Correspondence to: Nan Guo, email: guo__nan2017@126.com Keywords: non-small-cell lung cancer; third-line therapy; heavily pretreated; meta-analysis Received: August 15, 2017 Accepted: October 28, 2017 Epub: March 23, 2018 Published: October 23, 2018 ABSTRACT Purpose: We performed a systematic review and meta-analysis to investigate the efficacy of third-line treatment for advanced non-small-cell lung cancer (NSCLC). Materials and Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing third-line therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). Results: A total of 1,985 advanced NSCLC patients received third-line treatment from 11 RCTs were included for analysis. The use of single targeted agent as third-line therapy for advanced NSCLC did not significantly improved PFS (HR 0.75, 95% CI: 0.28–2.04, p = 0.58) and OS (HR 1.01, 95% CI: 0.86–1.17, p = 0.95) when compared to docetaxel alone. In addition, erlotinib-based doublet combination therapy did not significantly improved PFS (HR 0.94, 95% CI: 0.78–1.13, p = 0.49) and OS (HR 1.08, 95% CI: 0.78–1.51, p = 0.65) in comparison with erlotinib alone. Conclusions: The findings of this study show that the efficacy of single novel targeted agent is comparable to that of docetaxel alone in terms of PFS and OS for heavily pretreated NSCLC patients. In addition, no survival benefits are obtained from erlotinib-based doublet therapy, thus single agent erlotinib could be recommended as third-line treatment for unselected advanced NSCLC patients.

The major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD) is due to distant metastasis. Many reports have indicated that miRNA plays a key role in tumour metastasis. The expression of miR-197 is correlated with LADprogression, however, the mechanism of miR-197 is still unknown in the processing of LAD. A Boyden chamber migration/invasion assay was used for the metastatic function study in vitro. Real-time PCR andWestern blot assays were employed to analyse the EMT hallmark changes in both the mRNA and protein levels. 3'-UTR reporter luciferase assay was used to show that HIPK2 is a directtarget of miR-197. miR-197 enhances LAD cell migration and invasion miR-197. The downregulation of miR-197 suppresses the EMT and migration ability. HIPK2 is a direct functional target of miR-197 in LAD metastasis. In summary, miR-197 controls EMT and metastasis by directly silencing HIPK2. The findings suggest that interfering with the miR-197-dependent regulation of HIPK2 could be a useful approach for the treatment of patients with late stage metastatic LAD.

Background: The relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI. Methods: A total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel. Results: Median AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z= −13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z= −3.525, P < 0.001 and 45.8% vs. 32.2%, Z= −5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033–1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017–1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%). Conclusion: Platelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel. Key words: Antiplatelet Drugs; Maximum Aggregation Rate; Obstructive Sleep Apnea; Percutaneous Coronary Intervention; Platelet Reactivity

Multifunctional capsules have great applications in biomedical fields. In this study, novel polysaccharide-based nanocapsules were prepared via a layer-by-layer technique using silica as the templates. The shell was constructed based on the electrostatic interactions between pectin and chitosan. The pectin-chitosan nanocapsules ((Pec/Cs)3Pec) could keep good colloidal stability within 96h in PBS solution and 48h in BSA solution. Meanwhile, the nanocapsules exhibited a high drug loading and pH-sensitive release property for doxorubicin hydrochloride. Moreover, (Pec/Cs)3Pec nanocapsules had no cytotoxicity to both human hepatocellular carcinoma cells (HepG2 cells) and mouse fibroblast cells (L929 cells). More importantly, (Pec/Cs)3Pec nanocapsules could be more easily uptaken by HepG2 cells when compared with L929 cells. In vitro anticancer activity tests indicated the carriers could effectively kill HepG2 cells. Overall, (Pec/Cs)3Pec nanocapsules have great potential as a novel anticancer drug carrier as a result of their pH-sensitivity, good colloidal stability and anticancer activity.

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA2 level in patients with stable angina. Methods/design This is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed. Discussion This study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris. Trial registration ClinicalTrials.gov, NCT02870764 . Registered on 13 August 2016.