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Multiview clustering refers to partition data according to its multiple views, where information from different perspectives can be jointly used in some certain complementary manner to produce more sensible clusters. It is believed that most of the existing multiview clustering methods technically suffer from possibly corrupted data, resulting in a dramatically decreased clustering performance. To overcome this challenge, we propose a multiview spectral clustering method based on robust subspace segmentation in this article. Our proposed algorithm is composed of three modules, that is: 1) the construction of multiple feature matrices from all views; 2) the formulation of a shared low-rank latent matrix by a low rank and sparse decomposition; and 3) the use of the Markov-chain-based spectral clustering method for producing the final clusters. To solve the optimization problem for a low rank and sparse decomposition, we develop an optimization procedure based on the scheme of the augmented Lagrangian method of multipliers. The experimental results on several benchmark datasets indicate that the proposed method outperforms favorably compared to several state-of-the-art multiview clustering techniques.

Purpose Endothelial dysfunction and the subsequent decrease in endothelium-dependent vascular relaxation of small arteries are major features of hypertension. Artemisinin, a well-known antimalarial drug, has been shown to exert protecting roles against endothelial cell injury in cardiac and pulmonary vascular diseases. The current study aimed to investigate the effects of artemisinin on endothelium-dependent vascular relaxation and arterial blood pressure, as well as the potential signalling pathways in spontaneously hypertensive rats (SHRs). Methods In this study, acetylcholine (ACh)-induced dose-dependent relaxation assays were performed to evaluate vascular endothelial function after treatment with artemisinin. Artemisinin was administered to the rats by intravenous injection or to arteries by incubation for the acute exposure experiments, and it was administered to rats by intraperitoneal injection for 28 days for the chronic experiments. Results Both acute and chronic administration of artemisinin decreased the heart rate and improved ACh-induced endothelium-dependent relaxation but negligibly affected the arterial blood pressure in SHRs. Incubation with artemisinin decreased basal vascular tension, NAD(P)H oxidase activity and reactive oxygen species (ROS) levels, but it also increased endothelial nitric oxide (NO) synthase (eNOS) activity and NO levels in the mesenteric artery, coronary artery, and pulmonary artery of SHRs. Artemisinin chronic administration to SHRs increased the protein expression of eNOS and decreased the protein expression of the NAD(P)H oxidase subunits NOX-2 and NOX-4 in the mesenteric artery. Conclusion These results indicate that treatment with artemisinin has beneficial effects on reducing the heart rate and basal vascular tension and improving endothelium-dependent vascular relaxation in hypertension, which might occur by increasing eNOS activation and NO release and inhibiting NAD(P)H oxidase derived ROS production., Graphical Abstract

To observe the effect of muscle regions of meridians warm needling method plus pricking Jing-Well points for blood-letting in improving nail fold microcirculation in the patients with shoulder-hand syndrome (SHS) after stroke, and the effects on hemorrheology, calcitonin gene-related peptide (CGRP) and serum substance P (SP). A total of 72 patients were randomized into an observation group and a control group by the random number table method, with 36 cases in each group. The control group was treated with physical rehabilitation training, and the observation group was treated with additional muscle regions of meridians warm needling method plus pricking Jing-Well points for blood-letting treatment. The treatment course lasted for 4 weeks. After treatment, the clinical efficacy of the two groups was compared. The changes in shoulder-hand syndrome scale (SHSS), simplified Fugl-Meyer assessment-upper extremity (FMA-UE), visual analog scale (VAS), activities of daily living (ADL), traditional Chinese medicine (TCM) syndrome score, nail fold microcirculation hemorheology indictors [whole blood viscosity (high-shear, low-shear), hematocrit, erythrocyte sedimentation rate (ESR)], CGRP and SP levels were observed. The total effective rate in the observation group was 86.1%, higher than 63.9% in the control group (P

BACKGROUND: A meta-analysis was conducted to evaluate the curative effect of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC). METHODS: Chinese and English databases were searched using free combinations of the terms “bladder cancer,” “radical cystectomy,” “muscle invasive bladder cancer,” and “bladder preservation.” Review Manager 5.3 software was used for the meta-analysis. RESULTS: A total of 12 articles were included in the meta-analysis, most of which had low-bias risk and were of medium and high quality. A funnel chart showed that the circles of some studies were basically symmetrical with the midline, suggesting that the research accuracy was high, the publications were not biased, and the final conclusions were credible. Twelve articles analyzed patients’ 5-year survival rate in randomized controlled trials (RCTs). In these RCTs, the experimental group (expt group) comprised 775 cases and the control group (ctrl group) comprised 766 cases. A heterogeneity test using the fixed-effects model (FEM) showed Chi(2) =2.19, df =11, I(2)=0%, P=1.00>0.1, Z =2.57, odds ratio (OR) =1.30, 95% confidence interval (CI): 1.06–1.59, and P=0.010.1, Z =1.42, OR =1.32, 95% CI: 0.90–1.94, and P=0.16>0.05. 6 articles analyzed 5-year distant metastasis rates (DMRs) in RCTs. The overall heterogeneity test showed Chi(2) =1.68, df =5, I(2)=0%, P=0.89>0.1, Z =1.70, OR =1.28, 95% CI: 0.96–1.71, and P=0.09>0.05). DISCUSSION: Our meta-analysis confirmed that radical cystectomy is effective in the treatment of MIBC and is worthy of clinical promotion.

Objective Cognitive frailty (CF) is associated with adverse health outcomes, but different CF models have been proposed in the literature. We explored whether cognitive impairment (CoI) assessed by the Revised Hasegawa dementia scale (HDS-R) and physical frailty (PF) assessed by the modified Frailty Phenotype can be combined to predict risks of adverse outcomes in elderly Chinese subjects. Methods The data collected in the Rugao Longevity and Aging Study were used. PF was assessed by the modified Frailty phenotype. CoI was defined as the lowest 20% of the HDS-R score. CF was defined as the co-existence of physical frailty and CoI, excluding those with severe CoI(HDR-S ≤ 10). The date and cause of death were acquired from the Death registry of Rugao's Civil Affairs Bureau. Disability was measured using the activities of daily living (ADL) scale. Results The prevalence of CF was 2.9% at baseline. During 3-year follow-up, 130 (8.1%) of the 1607 elderly subjects died. The highest mortality risk was observed among subjects with CF (hazard ratio [HR] = 2.94, 95% confidence interval [CI] = 1.28-6.78). Fully adjusted survival plots showed that CF was associated with the highest risk for 3-year mortality. The incidence of ADL disability was 6.0% after 3 years. Compared with the robust and non-CoI elderly, CF was associated with a 10.48-fold (95% CI 2.98-36.80) higher risk of ADL disability. Conclusions The CF model defined as a combination of HDS-R and Frail Phenotypes showed predictive validity for all-cause death and new-onset ADL disability 3 years later.

Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.

Background Chronic post-surgical pain (CPSP) has a negative impact on the recovery, quality of life, and physical functioning of elderly patients. This study aimed to test the superiority of parecoxib vs. placebo in preventing chronic post-hepatectomy pain in elderly patients under combined general-epidural anesthesia. Methods A total of 105 elderly patients undergoing hepatectomy under combined general-epidural anesthesia were randomized into the parecoxib or placebo group. The primary outcome was the proportion of patients with CPSP 3 months postoperatively. The secondary outcomes included the Short-Form McGill Pain Questionnaire score in CPSP-positive responders, acute pain intensity, postoperative analgesic demand, inflammatory markers change, and postoperative complications within 28 days. Results The parecoxib group provided a non-significant absolute 9.1% reduction in the rate of CPSP compared to the placebo group (P = 0.34). The average chronic pain visual analog scale in the parecoxib group was lower than that in the placebo group (P = 0.04). Significantly less moderate-to-severe acute pain at rest (P = 0.04) and with coughing (P P = 0.01), and less rescue analgesia (P P > 0.05) and postoperative complications (P = 0.65). Conclusions Parecoxib reduced the prevalence of CPSP in elderly patients after hepatectomy under combined general-epidural anesthesia from 44.4 to 35.3% with no statistical significance. Moreover, significantly alleviated CPSP intensity and improved acute pain management were observed. Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/edit.aspx?pid=56961&htm=4) on August 3, 2020 (ChiCTR-2,000,035,198).

Background The current study aimed to investigate the incidence of sepsis-induced cardiomyopathy (SICM) in patients who received general thoracic surgery, along with the risk factors and management strategies for this complication. Methods The clinical records of 163 patients with postoperative sepsis were retrospectively reviewed. After propensity score matching, 144 patients were divided into 2 groups by stroke volume: the SICM group (n=72) and the non-SICM group (n=72). Results The overall incidence of postoperative SICM was 53.99%. Multiple logistic regression analysis showed that stroke volume and C-reactive protein were independent predictors of mortality in patients with postoperative sepsis. Statistical analysis by t-test and χ2 test indicated that mortality (P=0.000), B-type natriuretic peptide (P=0.001), left ventricular ejection fraction (P=0.000), the mitral peak velocity of early filling/early diastolic mitral annular velocity (E/e') (P=0.049), C-reactive protein (P=0.016), procalcitonin (P=0.013), serum creatinine (P=0.016), platelets (P=0.028), and lactic acid (P=0.002) were significantly associated with the occurrence of postoperative SICM. Among these parameters, B-type natriuretic peptide was identified as the best biomarker for predicting SICM by receiver operating characteristic (ROC) curve analysis. Conclusions It is vital to improve the diagnosis and standard management of SICM. A combined strategy comprising early detection of suspected infection, adequate use of antibiotics, close monitoring, effective drainage, and supportive care may improve the outcomes of patients with postoperative SICM.

Stimulated by the dramatical service demand in the logistics industry, logistics trucks employed in last-mile parcel delivery bring critical public concerns, such as heavy cost burden, traffic congestion and air pollution. Unmanned Aerial Vehicles (UAVs) are a promising alternative tool in last-mile delivery, which is however limited by insufficient flight range and load capacity. This paper presents an innovative energy-limited logistics UAV schedule approach using crowdsourced buses. Specifically, when one UAV delivers a parcel, it first lands on a crowdsourced social bus to parcel destination, gets recharged by the wireless recharger deployed on the bus, and then flies from the bus to the parcel destination. This novel approach not only increases the delivery range and load capacity of battery-limited UAVs, but is also much more cost-effective and environment-friendly than traditional methods. New challenges therefore emerge as the buses with spatiotemporal mobility become the bottleneck during delivery. By landing on buses, an Energy-Neutral Flight Principle and a delivery scheduling algorithm are proposed for the UAVs. Using the Energy-Neutral Flight Principle, each UAV can plan a flying path without depleting energy given buses with uncertain velocities. Besides, the delivery scheduling algorithm optimizes the delivery time and number of delivered parcels given warehouse location, logistics UAVs, parcel locations and buses. Comprehensive evaluations using a large-scale bus dataset demonstrate the superiority of the innovative logistics UAV schedule approach.

Background: Oncolytic adenovirus-mediated gene therapy is an emerging strategy for cancer treatment. However, oncolytic adenoviruses are mainly administered locally at tumor site. Intravenous administration of oncolytic adenovirus for cancer gene therapy is a problem that needs to be solved urgently. Methods: We constructed recombinant oncolytic adenovirus KGHV500 carrying anti-p21Ras scFv and employed CIK cells to deliver KGHV500. TUNEL, wound healing, MTT, and Transwell invasion assays were used to determine the anti-tumor efficacy of KGHV500 on liver cancer cells in vitro. Nude mouse xenograft model was used to examine the anti-tumor efficacy of CIK cells combined with KGHV500 in vivo. Furthermore, KGHV500 accumulation in different organs was detected to assess the safety. Results: KGHV500 inhibited the migration, proliferation, invasion, and induced the apoptosis of liver cancer cells. CIK cells carrying KGHV500 reached tumor site and exerted much better anti-tumor efficacy than CIK cells or KGHV500 alone in nude mouse xenograft model. Moreover, we detected KGHV500 and anti-p21Ras scFv in different organs of nude mice, with little effects on the organs. Conclusions: We develop a novel strategy for the treatment of Ras-driven liver cancer by combining CIK cells with oncolytic adenovirus expressing anti-p21Ras scFv. Intravenous injection of CIK cells carrying KGHV500 in vivo significantly inhibits tumor growth, has little effect on normal organs, and is relatively safe.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069–1.430; and HR: 1.600, 95% CI: 1.350–1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054–1.434; and HR: 1.658, 95% CI: 1.389–1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853–3.225) and RFS (HR: 2.405, 95% CI: 1.802–3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Pulmonary arterial hypertension (PAH) is a progressive disease with a complex aetiology and high mortality. Functional and structural changes in the small pulmonary arteries lead to elevated pulmonary arterial pressure, resulting in right heart failure. The pathobiology of PAH is not fully understood, and novel treatment targets in PAH are desperately needed. The renin-angiotensin system is critical for maintaining homeostasis of the cardiovascular system. The system consists of the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang-(1–7)-Mas receptor axis. The former, the ACE-Ang II-AT1R axis, is involved in vasoconstrictive and hypertensive actions along with cardiac and vascular remodelling. The latter, the ACE2-Ang-(1–7)-Mas axis, generally mediates counterbalancing effects against those mediated by the ACE-Ang II-AT1R axis. Based on established functions, the ACE2-Ang-(1–7)-Mas axis may represent a novel target for the treatment of PAH. This review focuses on recent advances in pulmonary circulation science and the role of the ACE2-Ang-(1–7)-Mas axis in PAH.

Hepatectomy is an effective therapeutic strategy for many benign and malignant liver diseases, while the complexity of liver anatomy and the difficulty of operation lead to complications after hepatectomy. Among them, post-hepatectomy liver failure (PHLF) is the main factor threatening the life of patients. At present, liver transplantation is an effective approach for PHLF. However, the application of liver transplantation has been largely limited due to the shortage of donors and the high cost of such operation. Therefore, it is urgently necessary to develop a new treatment for PHLF. Mesenchymal stem cells (MSCs) have become a new treatment regimen for liver diseases because of their easy access and low immunogenicity. Our study found that there were some subtle connections between MSCs and liver lipid metabolism in the PHLF model. We used MSC transplantation to treat PHLF induced by 90% hepatectomy. MSC transplantation could restore the mitochondrial function, promote the β-oxidation of fatty acid (FA), and reduce the lipid accumulation of hepatocytes. In addition, interleukin 10 (IL-10), a cytokine with immunoregulatory function, had an important role in lipid metabolism. We also found that MSCs transplantation activated the mammalian target of rapamycin (mTOR) pathway. Therefore, we explored the relationship between mitochondrial damage and lipid metabolism abnormality or PHLF. MSCs improved mitochondrial function and corrected abnormal lipid metabolism by affecting the mTOR pathway in the treatment of PHLF. Collectively, MSC transplantation could be used as a potential treatment for PHLF.

Objectives: The roles of innate immunity including macrophages in radiation-induced abscopal effect (RIAE) are ambiguous. In this study, we evaluated the role of macrophage in RIAE and the interaction of cytokines in tumor microenvironment after irradiation. Materials and Methods: Transplanted tumor of breast cancer cells in BalB/C mice, severe combined immunodeficiency (SCID) mice and non-obese diabetic (NOD)-SCID mice were irradiated with fractionation doses to observe anti-tumor abscopal effect. The underlying mechanism of RIAE was investigated by treating the mice with TNF-α inhibitor or macrophage depletion drug and analyzing the alteration of macrophage distribution in tumors. A co-culture system of breast cancer cells and macrophages was applied to disclose the signaling factors and related pathways involved in the RIAE. Results: The growth of nonirradiated tumor was effectively suppressed in mice with normal or infused macrophages but not in mice with insufficiency/depletion of macrophage or TNF-α inhibition, where M1-macrophage was mainly involved. Investigation of the bystander signaling factors in vitro demonstrated that HMGB1 released from irradiated breast cancer cells promoted bystander macrophages to secret TNF-α through TLR-4 pathway and further inhibited the proliferation and migration of non-irradiated cancer cells by PI3K-p110γ suppression. Conclusions: HMGB1 and TNF-α contributes to M1-macrophages facilitated systemic anti-tumor abscopal response triggered by radiotherapy in breast cancer, indicating that the combination of immunotherapy and radiotherapy may has important implication in enhancing the efficiency of tumor treatment.

To investigate the expression and role of nicotinic acetylcholine α7 subunit (nAChRα7) in the hippocampus of rats with Parkinson's disease (PD) and Parkinson's disease dementia (PDD). PD model was established with 6-hydroxydopa. Then, methyllycaconitine was further used to prepare a PDD model. The behavioral indexes and malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. The mRNA level and protein level of nAChRα7 in hippocampus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western-blot, respectively. The α7nAchR and NeuN protein was detected by immunofluorescence. Compared with the PD model group, the escape latency of the PDD model group was significantly prolonged while the times of crossing platforms was significantly reduced (p

Introduction Because of its high morbidity and mortality, sepsis remains the leading cause of death in the ICU. Microparticles (MP) have been largely studied as potential diagnostic or prognostic markers in various diseases including sepsis. Objective The biological and clinical relevance of neutrophil-derived microparticles (NDMPs) within the MP population remains unclear. The objective of this study was to elucidate the relationship between plasma NDMPs and the prognosis of patients with sepsis and/or septic shock. Methods The study was designed as an observational, noninterventional clinical study. The cohort for this study included 40 sepsis and 40 septic shock patients together with 10 healthy controls admitted to the Intensive Care Unit (ICU) and the Health Surveillance Center in the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China, from January to November 2018, respectively. The degree of critical disease for sepsis and septic shock was evaluated, with data analyses conducted from 2018 to 2019. Results On days 1, 3 and 5 post-admission a series of data including plasma NDMP levels, patient demographics, TNF-α levels, IL-6 levels, sTREM-1 levels, and the sepsis severity score measurements were collected. A survival curve was plotted against levels of plasma NDMPs. Levels of NDMPs were observed to be higher in the septic shock patients than in the sepsis patients on days 1, 3, and 5 post-ICU admission (p < 0.05). NDMP levels were significantly increased in sepsis and septic shock patients with a parallel increase in pro-inflammatory mediators and sepsis severity score (p < 0.05) as well as mortality. Conclusion Our data suggest that NDMPs may be a biomarker of sepsis severity and mortality although its implications on sepsis prognosis warrant further study.

The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

Background Dual antiplatelet aggregation therapy leads to better outcomes in patients with carotid artery stenosis, intracranial artery stenosis, minor strokes, or transient ischaemic attacks. However, carriers of the CYP2C19 loss-of-function allele may not experience the desired effects. We attempted to increase the clopidogrel dose to determine whether it would improve the outcomes of stroke patients who carry a single loss-of-function allele. Methods We recruited 131 patients with minor ischaemic stroke, within less than 7 days of stroke onset and a CYP2C19 loss-of-function allele, who had moderate-to-severe cerebral artery stenosis. Patients were divided into the high dose group (clopidogrel 150 mg per day + aspirin 100 mg per day over 21 days.) and a normal dose group (clopidogrel 75 mg per day + aspirin 100 mg per day over 21 days). The reported outcomes included any vascular or major bleeding events as the primary and safety endpoints, respectively. Results One and six vascular events occurred in the high dose and normal dose groups during the 3-months follow-up period, respectively. However, no significant difference was found between the two groups when adjusted for history of diabetes (hazard ratio, 5482; 95% confidence interval, 0.660 to 45.543; P = 0.115). No major bleeding events occurred. Conclusions In patients with ischaemic stroke who had a single CYP2C19 loss-of-function allele and moderate to severe cerebral stenosis, fewer vascular events occurred within 3 months with high dose of clopidogrel and aspirin than with normal dose of clopidogrel and aspirin. However, the difference between the two groups was not significant. Trial registration Clinical study of clopidogrel in the treatment of patients with symptomatic moderate to severe cerebral artery stenosis with intermediate metabolites of CYP2C19, URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR1800017411, 07/28/2018

External evaluation is an important issue in the population pharmacokinetic analysis of antibiotics. The purpose of this review was to summarize the current approaches and status of external evaluations and discuss the implications of external evaluation results for the future individualization of dosing regimens. We systematically searched the PubMed and EMBASE databases for external evaluation studies of population analysis and extracted the relevant information from these articles. A total of 32 studies were included in this review. Vancomycin was investigated in 17 (53.1%) articles and was the most studied drug. Other studied drugs included gentamicin, tobramycin, amikacin, amoxicillin, ceftaroline, meropenem, fluconazole, voriconazole, and rifampicin. Nine (28.1%) studies were prospective, and the sample size varied widely between studies. Thirteen (40.6%) studies evaluated the population pharmacokinetic models by systematically searching for previous studies. Seven (21.9%) studies were multicenter studies, and 27 (84.4%) adopted the sparse sampling strategy. Almost all external evaluation studies of antibiotics (93.8%) used metrics for prediction-based diagnostics, while relatively fewer studies were based on simulations (46.9%) and Bayesian forecasting (25.0%). The results of external evaluations in previous studies revealed the poor extrapolation performance of existing models of prediction- and simulation-based diagnostics, whereas the posterior Bayesian method could improve predictive performance. There is an urgent need for the development of standards and guidelines for external evaluation studies.

Background Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary disorder caused by mutations of the MEN1 gene. It is characterized by hyperparathyroidism and involves the pancreas, anterior pituitary, duodenum, and adrenal gland. Here, we report a 40-year-old male patient with MEN1 who first manifested as thymic carcinoid, then primary hyperparathyroidism and prolactinoma, and a decade later pancreatic neuroendocrine tumor. Case summary The patient underwent a thymectomy because of the thymic carcinoid 10 years prior and a prolactinoma resection 2 years prior. His sister suffered from prolactinoma. His parents displayed a typical triad of amenorrhea, galactorrhea, and infertility. Computed tomography revealed a strong signal in the upper portion of the left lobes and posterior portion of the right lobes of the thyroid and irregular soft tissue densities of the pancreatic body. Positron emission tomography/computed tomography imaging further showed strong 18F-flurodeoxyglucose uptake in the tail of the pancreatic body and segment IV of the liver. The patient underwent pancreatic body tail resection, pancreatic head mass enucleation, and ultrasound-guided radio-frequency ablation for liver cancer. Pathology results reported neuroendocrine tumor grade 2. Whole exome sequencing revealed a verified pathogenic mutation c.378G>A (p.Trp126*) in the MEN1 gene. The diagnosis of MEN1 was confirmed. At the 1.5-year follow-up, the patient appeared healthy without any sign of reoccurrence. Conclusion The present case may add some insight into the diagnosis and treatment of patients with MEN1.

Compared to the conventional gate driver for the insulated gate bipolar transistor (IGBT), the active gate driver (AGD) not only reduces the switching delay but also suppresses voltage or current overshoot, however, at the expense of increasing the switching losses unavoidably. In this article, a self-adaptive active gate driver (SAGD) is proposed to further optimize IGBT switching performance, which is particularly suitable for applications where the load current varies over time or the dc bus voltage is changed. Since in such applications, AGD with fixed overshoot suppression ability will cause unnecessary switching loss, especially when the load current or the dc bus voltage is low. In contrast, with neither A/D nor D/A converters applied, the proposed SAGD indirectly detects the load current and dc bus voltage as time quantities, based on status monitoring, then self-adaptively chooses the optimal gate resistance increment online during the specific voltage or current rising phase. In this way, the current or voltage with overshoot is suppressed to be inside the safe operation area of IGBT while the switching loss is minimized, thus a better tradeoff between overshoots and switching losses is achieved. Finally, the feasibility of the proposed SAGD is verified by experiments.

The n-type filled and doped skutterudites GaxCo4Sb12.3 and Ga0.2Co4Sb11.3Te composites with the well-distributed GaSb nanoinclusions are synthesized through the manipulating of metastable Ga fillers and enrichment of Sb by an in-situ method with a proper annealing procedure. Ga atoms can fill the icosahedron cages of skutterudite at high temperature, but at low temperature, they are driven out from the lattice voids and form the second phase of GaSb at grain boundaries. The presence of GaSb second phases reduces the thermal conductivity effectively. Te doping leads to a significant increase in carrier concentration of Ga0.2Co4Sb11.3Te, thus largely suppresses the bipolar effect of GaxCo4Sb12.3, resulting in a great enhancement in power factor. Moreover, Te doping induces mass and strain fluctuation, which decreases the lattice thermal conductivity further. Consequently, the maximum ZT is increased from 0.56 for Ga0.2Co4Sb12.3 at 573 K to 1.48 for Ga0.2Co4Sb11.3Te at 873 K, which is advantageous to improve the thermoelectric conversion efficiency for commercial application. Keywords: Thermoelectric, Skutterudite, Second phase, Bipolar effect

In recent years, a large number of commercial airplanes equipped with sensors have been contributing to collecting the atmospheric composition and meteorological data. Based on a worldwide commercial airplane dataset, we identify an inherent limitation of such an airplane-based sensing system as airplanes fly through airspace with spatiotemporal dynamic. As a result, the sensed data is coarse-grained and incomplete. Moreover, naive methods such as installing sensors on more airplanes, cannot effectively address the issue. In this paper, we propose a collaborative airspace sensing strategy auSense to improve the sensing performance. In auSense, UAVs (Unmanned Aerial Vehicles) are employed to sense the airspace when the airspace is not sensed by airplanes. Particularly, auSense leverages the existing worldwide commercial airplane tracking infrastructure and fine-grained trajectory data to estimate whether and when one airspace will be sensed by airplanes. Then auSense schedules the UAV paths to improve the sensing performance. We implement auSense in different airspaces based on a 1-month airplane trajectory data. The experiments demonstrate the superior performance of our data-driven UAV and commercial airplane collaborative strategy over the ground truth and other benchmarks.

Data dissemination in Internet of Things (IoT) networks provides a fundamental service for many critical applications. However, traditional dissemination schemes were investigated for an isolated IoT network, and did not fit the coexistence scenario of heterogeneous IoT networks. Motivated by the latest innovations in cross-technology communication (CTC) techniques, this article proposes CDD, a framework utilizing a WiFi-based access point (AP) to simultaneously conduct fast data diffusion in heterogeneous IoT networks (e.g., WiFi and ZigBee). We shed light on the network features in the coexistence scenario and then review the key challenges of coordinating dissemination based on CTC techniques. With these network features and challenges in mind, the CDD framework includes a series of designs to conduct efficient data dissemination in heterogeneous networks using a WiFi AP. The framework is implemented and evaluated on a real-world testbed. The results demonstrate that CDD can reduce the dissemination delay and significantly outperform the state-of-the-art approaches.

Background/objectives Acral lentiginous melanoma (ALM) is a melanoma subtype associated with atypical locations on the hands and feet and advanced disease at diagnosis. There is a limited understanding of whether the survival is similar for nail, non-nail, lower limb and upper limb ALM patients. We therefore explored clinicopathologic characteristics and melanoma-specific survival of ALM patients according to tumour location. Methods A prospectively collected cohort study was performed of all primary invasive cutaneous acral lentiginous melanomas with known thickness and tumour location reviewed at a tertiary referral centre over 21 years. Results A total of 101 ALM patients were reviewed from 1994 until 2016. The majority of cases (82/101) occurred on the feet. Hand ALMs were thicker and more likely to be ulcerated than feet ALMs (P = 0.05 and 0.02, respectively); however, survival was not statistically different between these two groups (univariate HR 0.48 P = 0.11, 95% CI, 0.20-1.17; multivariate HR 0.67 P = 0.40, 95% CI, 0.27-1.69, respectively). Non-nail ALM patients had longer survival when compared to nail ALM on univariate analysis (HR 0.40, 95% CI, 0.17 to 0.90) which was accounted for by Breslow thickness and ulceration (multivariate HR 0.56, 95% CI, 0.24 to 1.34). Conclusions The reduced melanoma-specific survival in nail ALM patients was likely due to their greater thickness and ulceration. Although hand ALMs are thicker and more frequently ulcerated, this is likely due to the higher proportion of nail ALMs present in this location.

BACKGROUND: To investigate the efficacy and safety of icotinib plus pleurodesis or icotinib alone in epidermal growth factor receptor (EGFR) positive mutant lung cancer patients after malignant pleural effusion (MPE) drainage. METHODS: In this retrospective study from initially reviewed case reports of 230 lung adenocarcinoma patients with MPE who were EGFR mutation positive and treated in our hospital between Jan 2014 and Dec 2016 consecutively, 51 patients who met the inclusion criteria were divided into treated with oral icotinib plus pleurodesis and without pleurodesis after pleural effusion drainage groups. Case records including patient gender, age, smoking status and local treatments, as well as adverse events were collected and retrospectively analyzed. The clinical outcomes which were measured by progression free survival (PFS), objective response rate (ORR) & adverse reactions were analyzed by a Kaplan-Meier curve and a log-rank test after follow-ups. RESULTS: The median PFS of patients who received icotinib plus pleurodesis was 8.4 months, while the median PFS of icotinib alone patients was 9.0 months (P=0.996, χ(2)=7.241). Similarly, the ORR for MPEs, with or without pleurodesis were not significantly difference (64.29% vs. 67.57%, P=0.824, χ(2)=0.049). Adverse reactions of pleurodesis were mainly fever, chest pain, gastrointestinal reactions and myelosuppression. CONCLUSIONS: Our results suggested that pleurodesis after MPE drainage had no difference on outcomes of icotinib therapy patients. However, pleurodesis may increase some adverse reactions, which might be inconvenient for patients in clinical practice.

Multi-view Clustering has become a vital task with the rapidly growing amount of data in multiple representations. Under the context of unsupervised learning, the existing clustering methods show limited capability in leveraging the discriminative information from multiple views. View-independent noises and distribution differences among views are two main causes that may degrade the clustering performances. By introducing the inter-and-intra-view low rank decomposition, we propose Multi-view Clustering via Intra and Inter-view Low Rank Fusion (MCIIF). The proposed method facilitates clustering with the discriminative intra-view low rank structures that complement the shared inter-view transition. By recovering complementary low rank transitions from the differences between the shared inter-view transition and individual-view transitions, we pursue a more accurate transition probability matrix by combining the complementary intra-view transitions with the shared inter-view transition in an additive manner. To solve the corresponding optimization problem, we propose a procedure based on the Alternating Direction Method of Multipliers (ADMM) scheme with convergence guarantees. Experimental results on various real-world datasets verify the effectiveness of the proposed method over the state-of-art multi-view clustering methods.

Summary Background Colonoscopy with computer-aided detection (CADe) has been shown in non-blinded trials to improve detection of colon polyps and adenomas by providing visual alarms during the procedure. We aimed to assess the effectiveness of a CADe system that avoids potential operational bias. Methods We did a double-blind randomised trial at the endoscopy centre in Caotang branch hospital of Sichuan Provincial People's Hospital in China. We enrolled consecutive patients (aged 18–75 years) presenting for diagnostic and screening colonoscopy. We excluded patients with a history of inflammatory bowel disease, colorectal cancer, or colorectal surgery or who had a contraindication for biopsy; we also excluded patients who had previously had an unsuccessful colonoscopy and who had a high suspicion for polyposis syndromes, inflammatory bowel disease, and colorectal cancer. We allocated patients (1:1) to colonoscopy with either the CADe system or a sham system. Randomisation was by computer-generated random number allocation. Patients and the endoscopist were unaware of the random assignment. To achieve masking, the output of the system was shown on a second monitor that was only visible to an observer who was responsible for reporting the alerts. The primary outcome was the adenoma detection rate (ADR), which is the proportion of individuals having a complete colonoscopy, from caecum to rectum, who had one or more adenomas detected. The primary analysis was per protocol. We also analysed characteristics of polyps and adenomas missed initially by endoscopists but detected by the CADe system. This trial is complete and is registered with http://www.chictr.org.cn , ChiCTR1800017675. Findings Between Sept 3, 2018, and Jan 11, 2019, 1046 patients were enrolled to the study, of whom 36 were excluded before randomisation, 508 were allocated colonoscopy with polyp detection using the CADe system, and 502 were allocated colonoscopy with the sham system. After further excluding patients who met exclusion criteria, 484 patients in the CADe group and 478 in the sham group were included in analyses. The ADR was significantly greater in the CADe group than in the sham group, with 165 (34%) of 484 patients allocated to the CADe system having one or more adenomas detected versus 132 (28%) of 478 allocated to the sham system (odds ratio 1·36, 95% CI 1·03–1·79; p=0·030). No complications were reported among all colonoscopy procedures. Polyps initially missed by the endoscopist but identified by the CADe system were generally small in size, isochromatic, flat in shape, had an unclear boundary, were partly behind colon folds, and were on the edge of the visual field. Interpretation Polyps initially missed by the endoscopist had characteristics that are sometimes difficult for skilled endoscopists to recognise. Such polyps could be detected using a high-performance CADe system during colonoscopy. The effect of CADe during colonoscopy on the incidence of interval colorectal cancer should be investigated. Funding None.

Influence maximization is an important technique in advertisement post, viral marketing, and public opinion monitoring. Seed set identification is one of the key issues in influence maximization. In reality, there exist heterogeneous nodes, such as user nodes, message nodes in social networks. The complex association relationship among heterogeneous nodes, which are seldom considered, significantly increases the complexity of the seed set identification. In this paper, we propose a Measuring Influence (MIF) model to capture social influence with heterogeneity. MIF considers the interaction among adjacent nodes, the tag of users, the users’ social friendships and the similarity in user interests, and studies the interaction based influence, tag based influence, friendship based influence, and topic based influence, respectively. As obtaining the seed set in social networks has been proved to be a NP-hard problem, we propose an algorithm called Influence Maximization Greedy Algorithm (IMGA) to solve this problem by maximizing the marginal influence of selected seed nodes. Series of experiments are designed to evaluate the performance of the proposed model and algorithm. Our results show that MIF model and IMGA algorithm have better influence spread effects and higher quality of the seed set identification comparing to the approaches under IC, LT, CDNF, MIA, and BBA, models.

Acute kidney injury (AKI) is an independent risk factor for the increased risk of death in patients with sepsis. In the current study, we first investigated the expression of circMTO1 in sepsis-induced AKI, and the underlying mechanism was further elucidated. The results showed that circMTO1 expression level was significantly decreased in serums and kidney tissues of US rats and RMCs treated with LPS. Besides, circMTO1 overexpression promoted cell viability, suppressed cell apoptosis and cytokines production of LPS-treated RMCs. Bioinformatics analysis showed that circMTO1 served as a sponge for miR-337. Furthermore, circMTO1 could inhibit the expression of KLF6. Altogether, our study first reported that circMTO1 expression was decreased in sepsis-induced AKI rat models and RMCs treated with LPS. CircMTO1 overexpression could attenuate AKI development by sponging miR-337 and regulating KLF6 expression, which may provide new ideas for evaluation the pathogenesis and the treatment of sepsis-induced AKI.

OBJECTIVE Insulin resistance (IR) has been established as a major risk factor for nonalcoholic fatty liver disease (NAFLD) where it exerts effects on plasma glucose homeostasis, cellular anabolism, and organ glucose uptake. Owing to paucity of studies focused on peripheral IR in relation to pathological outcome, we aim to investigate homeostatic model assessment of insulin resistance (HOMA-IR) by histological characteristics of NAFLD. METHODS Liver biopsy of 588 patients was screened. After excluding etiologies other than NAFLD and factors contributing to IR, serum HOMA-IR was compared with patients' histologic features. Univariate and multivariate analyses were conducted to assess their relationship. Area under the receiver operating characteristic (AUROC) was calculated to assess the discriminatory ability of homeostatic model assessment of IR for advanced lobular inflammation (LI). RESULTS We observed higher serum level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and low-density lipoprotein as HOMA-IR increased. HOMA-IR is significantly associated with severity of LI (odds ratio = 1.222, 95% confidence interval = 1.135-1.315, P

The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.

The core carrier working substances of heat accumulation of solar thermal generator units are analyzed through computer numerical simulation analysis and simulation experiments, including the selection criteria of working substances, the mechanism of heat accumulation system, the correlation between power generation efficiency and the evaporation temperature of working substance, the correlation between the condensing temperature and condensing pressure of working substance, and the influence of working substance velocity on heat accumulation capacity. The results show that under the same radiation intensity, the greater the flow velocity of the working substance is, the worse the heat accumulation and heat conduction of the working substance is. As the condensing temperature of the working substance increases, the condensing pressure also increases. As the evaporation temperature of the working substance increases, the power generation efficiency of the working substance also increases significantly. In summary, the heat accumulation system based on the high efficiency working substances is vital for the normal operation of solar thermal generator units. Once the solar radiation intensity cannot meet the needs of power generation, the heat accumulation system will output previously-stored thermal energy. Meanwhile, its collection and release of thermal energy depend on the photovoltaic intensity. The constructed hot-oil working substance-based heat accumulation system satisfies the normal operation needs for thermal generator units, which is significant for subsequent research.

Purpose To identify the effectiveness and feasibility of blindfold training on preventing pediatric psychological behavior disorders during the anesthesia recovery period. Design This study investigated the effect of blindfold training through the assessment of anxiety, delirium, and pain in children during the anesthesia recovery period. Methods This study was a prospective, randomized, controlled trial. Pediatric patients were randomized into either a control (routine practice) or blindfold training group (routine practice + blindfold training). Anxiety, delirium, and pain levels of children were assessed by the modified Yale Preoperative Anxiety Scale, Pediatric Anesthesia Emergence Delirium scale, and the Face, Legs, Activity, Cry, Consolability scale. Findings The blindfold training group had significantly lower scores for emergence delirium, anxiety, and pain during the anesthesia recovery period and a lower incidence of anesthesia complications (all P's Conclusions Preoperative blindfold training was able to reduce anxiety, pain, and the incidence of delirium during the anesthesia recovery period in pediatric patients.

This paper demonstrates the use of amplitude variance in combination with only one time of 4th power transformation and fast Fourier transform (FFT) for modulation format identification (MFI) in digital coherent receiver. The incoming signals are firstly classified into two main categories, polarization-division multiplexing (PDM) m -ary phase-shift keying modulation ( m PSK) and m -ary quadrature amplitude modulation ( m QAM), based on the amplitude variance after constant modulus algorithm (CMA) equalization. Then, the sub-categories of PDM- m PSK or PDM-mQAM are further identified by utilizing the logical regression (LR) algorithm on a two-dimensional (2-D) plane which is constructed by using the mean and maximum value after 4th power transformation and FFT. The feasibility is firstly verified via numerical simulation for 28GBaud/s PDM-QPSK/8PSK/16QAM/32QAM signals transmitted through additive Gaussian noise channel as well as long-distance standard single mode fiber (SSMF) channel. The simulation results demonstrate that 100% identification accuracy for all these modulation formats can be achieved at the optical signal noise ratio (OSNR) much lower than their respective 7% FEC thresholds and as high as 99% identification accuracy can be achieved even at the OSNR much lower or close to their respective 20% FEC thresholds. 100% identification accuracy can be also obtained in the presence of obviously nonlinear impairments. Proof-of-concept experiments are finally implemented to evaluate the MFI performance among 28GBaud/s PDM-QPSK/8PSK/16QAM, and 21.5GBaud/s PDM-32QAM signals, which further confirm the feasibility of our proposed MFI scheme.

Background: To investigate the effects of recombinant human thrombopoietin (rhTPO) and interleukin-2 (IL-2) on a basic gemcitabine (GEM) plus carboplatin (GC) treatment regimen in a murine lung carcinoma model. Methods: Fifty nude mice with subcutaneous tumors derived from human lung cancer cells were divided into 5 groups, each comprised of 10 mice: A blank group (intraperitoneal injection of saline), a control group (GC) (intraperitoneal injections of GC), a rhTPO group (same as the control group plus subcutaneous injection of rhTPO), an IL-2 group (same as the control group plus subcutaneous injection of IL-2) and a rhTPO + IL-2 group (same as the rhTPO group plus subcutaneous injection of IL-2). Tumor development and histology as well as CD4+, phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated-protein kinase B (p-AKT), phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-phosphoinositide 3-kinase (p-pI3K) and GTPase RAS1 expression in tumor tissues were measured and blood analyses performed. Results: Tumor sizes from all treated mice were significant smaller than the controls, as were the tumors of IL-2 plus GC treated mice compared to other treated groups. CD4+ expressing cells were increased in tumors after IL-2 and rhTPO treatment and the application of rhTPO significantly restored the blood platelet count. The expression of p-AMPK, p-AKT, p-ERK, p-pI3K and RAS1 in tumor cells were all significantly diminished after the addition of rhTPO and IL-2 to the GC regimen. Conclusions: The supplementation of rhTPO and IL-2 to a GC regime effectively reduced tumor sizes and restored the platelet count in a human lung cancer mouse model.

Background and Aims: Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 ( PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism. Methods: The variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest. Results: The distribution of PNPLA3 genotypes was CC: 27.5%, CG: 48.2%, and GG: 24.3%. Higher VFA was associated with greater risk of having SF (adjusted-odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02-1.04, pConclusions: PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD. Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.

Transient parotid gland swelling could happen as complication after per oral endoscopy or intubation. We reported a 53-year-old man who developed transient unilateral parotid gland swelling following esophagogastroduodenoscopy (OGDS) with dilatation of achalasia cardia. The swelling of the parotid gland was transient and resolved completely without any intervention.

Background Extra nodal NK/T cell lymphoma (ENKTL) is rarely occurred in the gallbladder, and it is generally difficult to diagnose before surgery. Here we present a case of primary ENKTL of gallbladder. Case presentation A 61-year-old female with pain in the right upper abdomen, and Murphy's sign was positive. Ultrasonography showed that a submucosal tumor-like lesion in the neck of the gallbladder, and the gallbladder wall thickness was 0.6cm; there were several high-signal stone shadows. Microscopic examination revealed coagulative necrosis in the lamina propria of the mucosa, the tumor cells were grown diffusely infiltrating, which with medium to large size and inconspicuous or small nucleoli. Immunohistochemistry showed that the tumor cells were positively expressed CD3, CD2, CD56, CD43, TIA-1, Perforin, Granzyme-B, and EBER-ISH (-). Based on these findings, the pathological diagnosis was ENKTL of the gallbladder. The patient received CHOP chemotherapy regimens, who has been free of recurrence for 8 months after the surgery. Conclusion In the early stage, histological diagnosis of ENKTL is difficult, and the patient may not have obvious symptoms, for patients with the gallbladder wall thickens and has protrusions, ENKTL should be regarded as one of the differential diagnosis.

BACKGROUND/OBJECTIVES Increased rates of histopathological misdiagnosis of melanoma have been associated with incisional punch more so than shave biopsy when compared with complete excisional biopsy. It is unknown how the increasing utilisation of shave biopsy may impact melanoma diagnosis. The extent to which the provision of clinical information to the pathologist may improve diagnostic accuracy remains unclear. This study assessed the impact of both initial biopsy technique and provision of adequate clinical information to pathologists on the accuracy of histopathological diagnosis of melanoma and disease progression. METHODS We conducted a retrospective cohort with nested case-control study of all histopathological false-negative and false-positive melanoma diagnoses from January 2014 to May 2019 from the Victorian Melanoma Service electronic database. Cases were assessed for the initial biopsy type, provision of clinical information on pathology request forms and disease progression associated with false-negative diagnosis. RESULTS Partial shave biopsy had higher odds of false-negative (OR 5.19, 95% CI 2.89-9.32; P

Ganoderma lucidum (Lingzhi) polysaccharide peptide (GL-pp) is a component of the globally acknowledged traditional Chinese medicine Ganoderma lucidum; Ganoderma lucidum is known for its sedative, hypnotic, immune regulatory, antitumor, and other pharmacological effects. In recent years, sleep disorders have been linked to many diseases and human body disorders, including cancer. Some experimental studies in mice found that sleep fragmentation could promote tumor development and progression. However, effects on GL-pp on tumor metastasis under circumstances of sleep disorders have rarely been studied. Thus, in this study, we used mice with sleep fragmentation (SF) bearing B16-F10-luc-G5 melanoma tumors to investigate the effect of SF on melanoma metastasis. Furthermore, we investigated the antitumor and antimetastatic effects of GL-pp (80 mg/kg) in mice suffering from SF and bearing B16-F10-luc-G5. Then, whole proteomics was used to analyze the differences in protein expression in the lung tissue between SF mice bearing B16-F10-luc-G5 with and without GL-pp administration. High-throughput pyrosequencing of 16S rRNA was also used to analyze the impact of GL-pp on the gut microbiota composition in SF mice bearing B16-F10-luc-G5. Last, the effects of GL-pp on macrophage polarization and TNF-α serum levels were detected. Collectively, we found that SF significantly facilitated the B16-F10-luc-G5 melanoma tumor metastasis in mice, while GL-pp significantly reduced B16-F10-luc-G5 melanoma tumor metastasis under the condition of SF, in which proteomics and gut microbiota had been changed greatly.

Background: The presence of significant liver fibrosis is a key determinant of long-term prognosis in non-alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non-invasive fibrosis biomarkers. Methods: We used a cohort of 553 adults with biopsy-proven NAFLD, who were randomly divided into a training cohort (n = 278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n = 275). Significant fibrosis was defined as fibrosis stage F ≥ 2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. Results: In the training cohort, the variables selected by LASSO algorithm were body mass index, pro-collagen type III, collagen type IV, aspartate aminotransferase and albumin-to-globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC: 0.902, 95% CI 0.869-0.904) for identifying fibrosis F ≥ 2. The LRM AUROC was 0.764, 95% CI 0.710-0.816 and significantly better than the AST-to-Platelet ratio (AUROC 0.684, 95% CI 0.605-0.762), FIB-4 score (AUROC 0.594, 95% CI 0.503-0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95% CI 0.470-0.644). In the validation cohort, MLA also showed the highest AUROC (0.893, 95% CI 0.864-0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered. Conclusions: Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F ≥ 2 in patients with biopsy-confirmed NAFLD.

An increasing number of epidemiological studies have suggested that birth weight (BW) may be a determinant of bone health later in life, although the underlying genetic mechanism remains unclear. Here, we applied a pleiotropic conditional false discovery rate (cFDR) approach to the genome-wide association study (GWAS) summary statistics for lumbar spine bone mineral density (LS BMD) and BW, aiming to identify novel susceptibility variants shared between these two traits. We detected 5 novel potential pleiotropic loci which are located at or near 7 different genes (NTAN1, PDXDC1, CACNA1G, JAG1, FAT1P1, CCDC170, ESR1), among which PDXDC1 and FAT1P1 have not previously been linked to these phenotypes. To partially validate the findings, we demonstrated that the expression of PDXDC1 was dramatically reduced in ovariectomized (OVX) mice in comparison with sham-operated (SHAM) mice in both the growth plate and trabecula bone. Furthermore, immunohistochemistry assay with serial sections showed that both osteoclasts and osteoblasts express PDXDC1, supporting its potential role in bone metabolism. In conclusion, our study provides insights into some shared genetic mechanisms for BMD and BW as well as a novel potential therapeutic target for the prevention of OP in the early stages of the disease development.

Under the background of centralized access of large-capacity high-voltage direct current (HVDC) transmission and high-ratio renewable energy (RE) generation, this paper studied the mechanism and impact factors of transient overvoltage under large disturbance considering dynamic characteristic of wind turbine generators (WTG). Firstly, the theoretical equations calculating the magnitude of transient overvoltage on the converter station (CS) side and the WTG side after AC/DC disturbance were derived. Then, the mechanism of transient overvoltage caused by AC/DC disturbance were analyzed. Finally, the impact of different factors such as WTG active/reactive power characteristics during low-voltage ride through (LVRT) on transient overvoltage was analyzed combined with simulation. All the conclusions were verified through simulation of practical case systems. The study results reflected that the LVRT characteristic makes the WTGs be another ‘reactive power source’ resulting in transient overvoltage besides the CS, the higher of the transient overvoltage is caused by the smaller of the WTG active output and the larger of the WTG reactive output.