Search

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

Background:. Patients’ recovery after surgery is the major concern for all perioperative clinicians. This study aims to minimize the side effects of peri-operative surgical stress and accelerate patients’ recovery of gastrointestinal (GI) function and quality of life after colorectal surgeries, an enhanced recovery protocol based on pre-operative rehabilitation was implemented and its effect was explored. Methods:. A prospective randomized controlled clinical trial was conducted, patients were recruited from January 2018 to September 2019 in this study. Patients scheduled for elective colorectal surgeries were randomly allocated to receive either standardized enhanced recovery after surgery (S-ERAS) group or enhanced recovery after surgery based on pre-operative rehabilitation (group PR-ERAS). In the group PR-ERAS, on top of recommended peri-operative strategies for enhanced recovery, formatted rehabilitation exercises pre-operatively were carried out. The primary outcome was the quality of GI recovery measured with I-FEED scoring. Secondary outcomes were quality of life scores and strength of handgrip; the incidence of adverse events till 30 days post-operatively was also analyzed. Results:. A total of 240 patients were scrutinized and 213 eligible patients were enrolled, who were randomly allocated to the group S-ERAS (n = 104) and group PR-ERAS (n = 109). The percentage of normal recovery graded by I-FEED scoring was higher in group PR-ERAS (79.0% vs. 64.3%, P 0.050). Conclusions:. Peri-operative rehabilitation exercise might be another benevolent factor for early recovery of GI function and life of quality after colorectal surgery. Newer, more surgery-specific rehabilitation recovery protocol merits further exploration for these patients. Trial Registration:. ChiCTR.org.cn, ChiCTR-ONRC-14005096

Wind speed predictions are essential for wind power management and wind farm operation. However, due to the high volatility and nonstationarity of measured wind data, it is often difficult to achieve an accurate prediction. This study proposes a hybrid approach that consists of two stages, i.e., data preprocessing and wind speed predicting, to improve the accuracy of short-term wind speed prediction. A preprocessing algorithm for the transformation and standardization of hourly mean wind speed is utilized to remove the non-Gaussian distribution of wind data and diurnal nonstationarity. Several statistical models and artificial intelligence models are then adopted in the second stage of the prediction process, including a persistence model, autoregressive model, autoregressive moving average model and backpropagation neural network. The proposed approach is developed based on the weighted averaging of these models and error optimization theory. Finally, wind speed data for 12 months from two meteorological towers located in Yanan, China, are investigated to demonstrate the effectiveness and accuracy of the proposed approach for multistep wind speed predictions, and its performance is then compared with several existing prediction models. The results indicate that the prediction accuracy improves significantly after preprocessing with the proposed approach, outperforming all the existing aforementioned models.

The advent of the era of big data has provided a new way of development for Internet financial credit collection. The traditional methods of credit risk identification of Internet financial enterprises cannot get the characteristics of credit risk zoning, leading to large errors in the results of credit risk identification. Therefore, this paper proposes a new method of credit risk identification based on big data for Internet financial enterprises. According to the big data perspective, the credit risk assessment steps of Internet financial enterprises are analyzed and the weight of assessment indicators is calculated using the improved analytic hierarchy process (AHP), and the linear weighted synthesis method is applied to comprehensively assess the credit of clients. Using the unique characteristics of big data credit risk region division, the big data credit risk is determined by rule-based matching method. The eXtreme Gradient Boosting (XGBoost) machine learning algorithm is used to establish a credit risk identification model of Internet financial enterprises. The kappa coefficient and ROC curve are used to evaluate the performance of the proposed method. Experimental results show that the proposed method can accurately assess the credit risk of Internet financial enterprises.

Flavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 µM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10–1000 µM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 µM). Pre-incubation with SCU (500 µM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 µM) was added. The brain slice staining test in rats’ model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal. Graphic Abstract

CD1d-restricted natural killer T (NKT) cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia. Here, we show that lung-infiltrated and activated NKT cells are the major cellular source of LIGHT/TNFSF14, which determines the severity of pulmonary pneumonia by highly deteriorative influenza A virus (IAV) infection. Compared to wild-type mice, LIGHT−/− mice exhibit much lower morbidity and mortality to IAV, due to alleviated lung damage and reduced apoptosis of alveolar macrophages (AMs). LIGHT preferentially promotes cell death of lymphotoxin β receptors positive (LTβR+) AMs but not herpesvirus entry mediator positive (HVEM+) AMs. Therefore, these results suggest that NKT-derived LIGHT augments cell death of the tissue protective AMs in exacerbating lung pathology and susceptibility to fatal influenza infection. Suppression of LIGHT signaling might be a viable option in the treatment of influenza-associated acute respiratory distress syndrome.

Lichang Chen,1,&ast; Lingling Wu,1,&ast; Dongzhu Lu,1 Mei Zi,2 Huapeng Yu1 1Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huapeng YuDepartment of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510220, People’s Republic of ChinaTel +86 020 61643175Fax +86 020 84306143Email huapengyu@aliyun.comPurpose: To evaluate the contribution of fractional exhaled nitric oxide (FeNO) and impulse oscillometry (IOS) and spirometric parameters in predicting bronchial hyperresponsiveness (BHR) in adults with chronic cough.Patients and Methods: In total, 112 patients with chronic cough were enrolled in this prospective diagnostic study. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic efficiency and optimal cut-off values of FeNO and IOS and spirometric parameters in predicting BHR. Optimal combinations of FeNO and IOS and spirometric parameters for BHR prediction were investigated using univariate and multivariate logistic regression models. Bootstrapping was employed for internal validation. Model discrimination and calibration were assessed using indices and calibration plots.Results: Rhinitis and values of FeNO, IOS parameters (resonant frequency (Fres), reactance at 5 Hz (X5), and integrated area of low-frequency X (AX)) and spirometric parameters (FEV1, PEF, MEF75, MEF50, MEF25, MMEF) were significantly different between patients with BHR and those without BHR (P < 0.05). After adjusting for rhinitis, logistic analyses showed that FeNO combined with Fres, FeNO combined with MMEF, or the combination of FeNO, Fres and MMEF had high predictive value in diagnosing BHR; the areas under the ROC curves (AUCs) of the corresponding three models were 0.914, 0.919 and 0.927, respectively. In addition, the three models displayed good discrimination, with high C-index values and good calibration.Conclusion: FeNO combined with Fres or MMEF or a combination of these three parameters may be conveniently used as indicators in BHR prediction.Keywords: maximum mid-expiratory flow, resonant frequency, cough variant asthma, ROC curve, diagnosis

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

Cloud services with the property of elasticity are always bearing different loads over time. The efficiency of cloud management can be improved through the accurate prediction for cloud loads, which can be served as the foundation and recommendation for the future developing of the network scheme. As the basis and premise for management and decision making, a good prediction depends on suitable models and research methods. However, the interaction of users and the cloud network is high variability in the time and spatial dimensions, so traditional linear forecasting models cannot always process cloud computing loads well because of nonlinear changes. In this paper, a novel cloud load prediction model is proposed by improving whale optimization algorithm based on the hybrid strategy (HWOA) and combined with extreme learning machine (ELM) for strong nonlinear mapping ability. The proposed cloud load forecasting model is to employ HWOA optimizer to optimize the ELM model random parameters. Main research work includes that (1) the HWOA optimizer is to solve the whale optimizer local extremum problem; (2) the proposed HWOA optimizer reduces the ELM random parameters on cloud load forecasting; (3) the convergence performance is verified by benchmark testing functions; and (4) three groups of simulation experiments are conducted to evaluate the cloud load forecasting results. The results prove that the HWOA optimizer has a good convergence and outperforms the several conventional popular swarm intelligence optimizers. Also, the prediction results verify that our proposed model is more competitive for providing a solid foundation for efficient resource management and maximized economic benefits in cloud environment. For cloud load research groups and practitioners, this paper provides a new idea of cloud load forecasting.

Most studies focus on the first and second signals of T cell activation. However, the roles of cytokines in immunotherapy are not fully understood, and cytokines have not been widely used in patient care. Clinical application of cytokines is limited due to their short half-life in vivo, severe toxicity at therapeutic doses, and overall lack of efficacy. Several modifications have been engineered to extend their half-life and increase tumor targeting, including polyethylene glycol conjugation, fusion to tumor-targeting antibodies, and alteration of cytokine/cell receptor-binding affinity. These modifications demonstrate an improvement in either increased antitumor efficacy or reduced toxicity. However, these cytokine engineering strategies may still be improved further, as each strategy poses advantages and disadvantages in the delicate balance of targeting tumor cells, tumor-infiltrating lymphocytes, and peripheral immune cells. This review focuses on selected cytokines, including interferon-α, interleukin (IL)-2, IL-15, IL-21, and IL-12, in both preclinical studies and clinical applications. We review next-generation designs of these cytokines that improve half-life, tumor targeting, and antitumor efficacy. We also present our perspectives on the development of new strategies to potentiate cytokine-based immunotherapy.

Asphalt overlay or concrete overlay on existing pavements is a common strategy for pavement maintenance. Interlayer bonding performance between asphalt and concrete layers is a critical concern in achieving optimal long-term structural performance due to the possible cracking along the interface. In this study, bonding behaviors of asphalt concrete interface were characterized by employing mode I fracture tests conducted at −10 and 25°C, respectively. Two typical interface conditions were manually prepared. A tack coat material was applied on the interface with four distinct rates: 0.1, 0.2, 0.3, and 0.4 L/m2. Parameters including fracture strength, stress intensity factor (KIC), facture energy (GF), and energy release rate (J integral) were selected to evaluate the fracture performance. Results showed that optimum tack coat rates were 0.1 and 0.3 L/m2 for specimens with unmilled and milled surfaces. At the optimum tack coat rates, KIC and GF increased with the increase of interface roughness at −10°C, while, at 25°C, J integral of specimens with unmilled interface was larger than that of specimens with milled interface at the optimum tack coat rates. Analysis of variance (ANOVA) was conducted to evaluate the significance of the factors on the fracture loads and found that surface roughness is significant at −10°C and becomes nonsignificant at 25°C. Temperature and tack coat rate were significant factors considering a given interface.

Summary Over 85 590 000 individuals have been infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although there have been an increasing number of reports on coronavirus disease 2019 (COVID-19), it is unclear why infected children show milder symptoms than adults. A retrospective case study was performed at two designated hospitals for COVID-19. Patients (56 children and 63 adults) with confirmed SARS-CoV-2 infection and mild pneumonia were randomly enrolled in this study. The median age of the children was 7.0 years, and 51.79% of them were boys. The median age of the adults was 57 years, and 47.62% were men. The most common symptoms were fever, cough, sputum and diarrhoea. There were no significant differences in symptoms between children and adult patients. In terms of immunological indices on admission, adult patients displayed typical leukopenia and markedly higher levels of IL-2, IL-4, and IL-6 than child patients. The elevation of IL-2, IL-4 and IL-6 in adults induced more extensive lung injury. The effective and non-aggressive immune response successfully resisted SARS-CoV-2 invasion and maintained mild symptoms in child patients. The correlation of higher IL-2, IL-4, and IL-6 with the lung injury might be evidence that preventing excessive cytokine production can avoid further lung damage in these patients.

A case of abducens nerve palsy was introduced in this paper. A female patient, 37 years old, she complained double vision for 4 days. Acupuncture was applied and no other treatment was cooperated. Main acupoints included Jīngming (睛明BL1), Chengqi (承泣ST1), Tongzĭliao (瞳子髎GB1), Shuĭgōu (水沟GV26), belly side of lateral rectus muscle and Fēngchi (风池GB20). After consecutive treatment for 10 days, the orientation of the right eye was corrected and the patient narrated that double vision disappeared, the symptoms such as dizziness, distending pain of the eyeball disappeared. This therapy provided a new thought and approach to the treatment of abducens nerve palsy.

Objectives: Comparative analysis of laboratory data in moderate-to-severe COVID-19 patients presenting with or without ground-glass opacities (GGOs). Methods: This retrospective study examined 61 patients with moderate-to-severe COVID-19, as defined by the report of the WHO-China Joint Mission on COVID-19. All patients were admitted to the Department of Infectious Diseases, Wuhan Union Hospital from Dec 28, 2019 to Feb 22, 2020 and classified into a GGO group or a non-GGO group based on CT results. The clinical characteristics and laboratory data of the two groups were compared. Data were analyzed using univariate and multivariate analysis, and using receiver operating characteristic (ROC) analysis. Results: Forty-five patients were in the GGO group (73.8%, 21 females, 24 males, mean age 54.8±17.8 years) and 16 were in the non-GGO group (26.2%, 11 females, 5 males, mean age 53±14.9 years). The levels of IL-2, IL-4, and IFN-γ were greater in the GGO group (all P

Background Pleomorphic adenoma (PA) is the most common benign tumor that occurs in the salivary glands; however, tracheobronchial PA is rarely observed. To the best of our knowledge, fewer than 50 cases have been reported in the literature. We report a 49-year-old woman who had been treated for asthma for 2 years before being diagnosed with PA of the trachea. Case summary A 49-year-old woman was referred to our hospital due to dyspnea upon exertion and chronic cough with wheezing for 2 years. Laboratory tests showed an elevated white blood cell count, absolute neutrophil count, and percentage of neutrophils. A chest computerized tomography scan showed a well-defined, soft-tissue density lesion measuring 2.4 cm × 2.1 cm in the lower trachea. Flexible bronchoscopy revealed that nearly 90% of the tracheal lumen was obstructed. The histopathological and immunohistochemistry features suggested PA of the trachea. Furthermore, we review the characteristics of 29 patients with tracheobronchial PA over the last 30 years. Conclusion Tracheobronchial PA occurs without gender predominance, mostly in the lower or upper trachea, and has a low recurrence rate. The median age at diagnosis is 48 years. The most common symptoms are cough, stridor, dyspnea, and wheezing.

We retrospectively evaluated the echocardiographic data of ambrisentan-treated patients with pulmonary arterial hypertension (PAH) (NCT01808313).Change from baseline in right ventricle (RV) systolic function, right heart structure, and pulmonary artery systolic pressure (PASP) prognosis to Weeks 12 and 24 was evaluated by echocardiography.In the overall population, the mean tissue Doppler-derived tricuspid lateral annular systolic velocity (S') increased by 0.6 cm/s at both Weeks 12 (p 0.001) and 24 (p = 0.004) and tricuspid annular plane systolic excursion increased by 0.13 cm at Week 12 and 0.15 cm at Week 24 (both p 0.001). A marked decrease in transverse and longitudinal RV and RA diameter at Weeks 12 and 24 was observed. A significant decrease in diastolic eccentricity index at both Weeks 12 (-0.1; p = 0.02) and 24 (-0.1; p = 0.001). The decrease in PASP from baseline was significant at both Weeks 12 (-9.5 mmHg; p0.001) and 24 (-7.6 mmHg; p0.001), while a decrease in the estimated right atrium pressure was found to be significant at Week 24 (-0.8mmHg; p = 0.01).Significant improvements in a number of RV echocardiographic parameters were observed at Weeks 12 and 24 after ambrisentan treatment in patients with PAH.

Organic-inorganic hybrid perovskite materials possess advantages over other candidate classes for chemo-sensory materials because of their structural tunability and stability. In this work, we prepared highly qualitied MAPbBr3 perovskite crystals to provide a high carrier mobility to enhance the sensing on gas, where the response time of sensing below 0.1 s is obtained. Because the perovskite field effect transistor provides a large surface to adsorb gas, the sensitivity of detection can reach 0.2 ppm. Furthermore, combining with theoretical simulation, we analyzed the binding energy, electronic structure, and charge transfer density between perovskite surface (including PbBr2-terminated surface and CH3NH3Br-terminated surface) and gas molecules to study the mechanism behind the phenomena. It is obtained that enhancing the interfacial charge transfer density and then suppressing the recombination of transferred charges will effectively increase the sensitivity of the sensor.

Objectives. Metabolic syndrome (MetS) is now becoming a serious public health threat. Some behaviors risk factors were considered to be associated with MetS and interacted to adversely affect MetS. However, the clustering effects of behavior risk factors of MetS among Chinese population remain unclear. The aim of this study is to observe the behavior risk factors and their clustering effects of MetS in China. Methods. A cross-sectional study design was used. Subjects were recruited in the departments of Cardiology Clinic, Endocrine Clinic, and Health Management from March to December 2019. A demographic sheet was designed to collect the demographic and clinical characteristics of the subjects. International Physical Activity Questionnaire-Short was applied to evaluate the level of PA in this study. Other behavior risk factors were observed by the questionnaire. The stepwise logistic regression analysis was performed to identify the determinants of MetS. The multiple logistic regression analysis was used to analyze the clustering effects of behavior risk factors in MetS. Results. There are a total of 532 eligible subjects (56.6% females; mean age was 48.4±15.3 years), and approximately 33.3% were diagnosed as MetS. The subjects with a smoking habit (heavy and long-time history) had a 1.833-fold higher risk for MetS than their counterparts (none and light smoking), and the subjects that preferred salty taste had a 1.626-fold higher risk for MetS than the comparison cohort. Smoking and alcohol drinking had the highest clustering effect on MetS among the behavior risk factors. Conclusions. The main finding of this study was that smoking and salty taste preference were the independent determinants of MetS. Smoking and alcohol consumption had the highest clustering effect on southern Chinese MetS.

AIM: To observe the effect of different concentrations Buddleja offcinalis eye drops (BOED) to inflammatory factors of lacrimal gland cells of castrated male rabbit with dry eye. METHODS: Forty-two healthy adult New Zealand rabbits were randomly divided into 7 groups, 6 rabbits each group. Group A: blank group, Group B: model group, Group C: low concentrations BOED group, Group D: medium concentrations BOED, Group E: high concentrations BOED, Group F: the placebo group, Group G: testosterone groups. All rabbits of group B to G were cut off bilateral testis and epididymis except group A. The rabbits of group C, D, E and F were dropped relevant eye drops except groups A and B. All rabbits were tested Schimer I test (SIT) and break-up time (BUT) before operation and 4wk after operation. Expressions of inflammatory factors of TNF-α, IL-1β from lacrimal gland cells were checked in immunohistochemical staining method. RESULTS: 1) Comparison of SIT and BUT: Compared with the groups D, E and G, group C had statistical significance (P0.05); 2) Comparison of inflammatory factors of TNF-α, IL-1β after operation: Compared with value of the average optical density of TNF-α and IL-1β of group C, those of group D, E and G were obviously different after operation (P0.05).

The purpose of this work was to use near-infrared reflectance spectroscopy (NIRS) to investigate the spectral characteristics and frontal lobe activation in patients with obsessive-compulsive disorder (OCD) during a verbal fluency task. Thirty-seven patients with OCD, who met the diagnostic criteria of International Classification of Diseases 10 (ICD-10), were recruited. The total score of the Symptom Checklist (SCL-90, grade 1-5) was ≥160 points. The total score of the Yale-Brown Obsessive Compulsive Scale was ≥7 points. The changes in frontal lobe blood flow were measured by NIRS when completing a verbal fluency task. Then, the differences between obsessive-compulsive thoughts and obsessive-compulsive behaviors in OCD, and the concentration variation of oxygenate hemoglobin (Oxy-Hb) and deoxygenate hemoglobin (Deoxy-Hb) were investigated. The difference was significant (P

The application of resting state functional MRI (RS-fMRI) in Parkinson’s disease (PD) was widely performed using standard statistical tests, however, the machine learning (ML) approach has not yet been investigated in PD using RS-fMRI. In current study, we utilized the mean regional amplitude values as the features in patients with PD (n = 72) and in healthy controls (HC, n = 89). The t-test and linear support vector machine were employed to select the features and make prediction, respectively. Three frequency bins (Slow-5: 0.0107–0.0286 Hz; Slow-4: 0.0286–0.0821 Hz; conventional: 0.01–0.08 Hz) were analyzed. Our results showed that the Slow-4 may provide important information than Slow-5 in PD, and it had almost identical classification performance compared with the Combined (Slow-5 and Slow-4) and conventional frequency bands. Similar with previous neuroimaging studies in PD, the discriminative regions were mainly included the disrupted motor system, aberrant visual cortex, dysfunction of paralimbic/limbic and basal ganglia networks. The lateral parietal lobe, such as right inferior parietal lobe (IPL) and supramarginal gyrus (SMG), was detected as the discriminative features exclusively in Slow-4. Our findings, at the first time, indicated that the ML approach is a promising choice for detecting abnormal regions in PD, and a multi-frequency scheme would provide us more specific information.

Acute intermittent porphyria (AIP) is a rare inherited disorder, which is caused by the partial deficiency of hydroxymethylbilane synthase (HMBS), an enzyme of the heme biosynthetic pathway. Abdominal pain, neuropsychiatric disturbance and neuropathy are the typical manifestations of the disease. Complications such as posterior reversible encephalopathy syndrome (PRES), a rare type of brain lesion present on MRI, are also observed in patients with AIP. The present study reports on the case of a 36‑year‑old Chinese female patient with AIP and PRES. Genomic DNA were obtained from peripheral blood leukocytes and genomic regions of the HMBS gene were amplified as 2 fragments, which together contained all the exons and flanking intronic regions. Sanger sequencing of the amplified DNA fragments from the patient and the patient's family revealed a novel frameshift deletion (c.405‑406delAA) in exon 8 of the HMBS gene. This mutation leads to a subsequent truncated protein (p.Glu135AspfsX74). The recombinant mutant protein had 62% activity relative to the wild‑type protein but similar thermostability. It was confirmed that this novel mutation was the cause of AIP. Accumulation of D‑aminolevulinic acid (ALA) due to HMBS dysfunction is a potential mechanism of PRES. The manifestation of PRES may be associated with ALA‑induced cytotoxicity and the destruction of the blood‑brain barrier. In summary, in the present study, a novel pathogenic HMBS mutation was identified, expanding on the molecular heterogeneity of AIP.

Invigorating blood and dissolving stasis method is a kind of unique therapy of traditional Chinese medicine treatment, which efficacy has become increasingly prominent in the treatment of ophthalmology, with the further studies of blood stasis and invigorating blood and dissolving stasis therapy, it is widely used in clinical ophthalmology, and get good effects beyond thought, especially when western medicine has no curative effects, which improve the cure rate of fundus oculi disease from the eyelids, conjunctiva, lacrimal sac, vitreous body to the choroid and retina, optic nerve and macula lutea, from surface to fundus. Pathological changes related to inflammation, degeneration, necrosis, atrophy, hyperplasia of fibrous tissue hyperplasia. This paper is aim to explain the definition of invigorating blood and dissolving stasis and make a summary of basic research and clinical application about it in several diseases.

Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1+ dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1+ macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B., A ferritin nanoparticle that delivers the preS1 domain of the large hepatitis B surface protein to two specific myeloid cell populations provides a therapeutic vaccination strategy for the treatment of chronic hepatitis B.

A simplified method for predicting the nonlinear dynamic response of composite caisson-piles foundation (CCPF) under scour conditions is proposed. The Hardin-Drnevich model is employed to represent...

Supplemental Digital Content is available in the text, Background: Post-operative pain is unpleasant for patients and may worsen surgical recovery. Peri-operative multimodal analgesia has been used for many years; however, its efficacy still needs improvement. In the present study, a thorough peri-operative pain counseling and stratified management program based on risk assessment was implemented, with the goal of improving post-operative analgesia and patient satisfaction. Methods: This prospective, controlled, pilot study included 361 patients who underwent elective surgery. Of these 361 patients, 187 received peri-operative pain risk assessment and stratified analgesia and counseling (stratified analgesia group), while 174 received conventional multimodal analgesia (conventional group). The two groups were compared regarding the post-operative pain intensity, rescue analgesia administration, post-operative quality of recovery as assessed via the quality of recovery 40 questionnaire, total dosage of peri-operative opioids, analgesic satisfaction, and analgesic costs. Results: Compared with the conventional group, the stratified analgesia group reported decreased pain intensity during motion at 24 h post-operatively and required lower dosages of rescue analgesia (P = 0.03). The total quality of recovery 40 questionnaire score and the scores for physical wellbeing and pain were significantly better in the stratified analgesia group than the conventional group (P = 0.04); the stratified analgesia group also reported better scores for analgesic satisfaction (P = 0.03) and received lower dosages of opioids (P = 0.03). Analgesic costs were lower in the stratified analgesia group than the conventional group; the cost-effective ratio was 109 in the conventional group and 62 in the stratified analgesia group. Conclusions: The analgesic efficacy was improved by the implementation of stratified analgesia based on surgical pain risk assessment and counseling. This stratified analgesia protocol increased the patients’ analgesic satisfaction and improved the quality of recovery without increasing healthcare costs. The present findings may help improve the efficacy of peri-operative multimodal analgesia in clinical practice. Clinical Trial Registry: NCT02728973; https://clinicaltrials.gov/ct2/show/NCT02728973?term=NCT02728973&draw=2&rank=1.

Histamine H1 receptor (H1R) and histamine H4 receptor (H4R) are essential in allergic inflammation. The roles of H4R have been characterized in T cell subsets, whereas the functional properties of H4R in monocytes remain unclear. In the current study, the responses of H4R in peripheral monocytes from patients with allergic rhinitis (AR) were investigated. The results confirmed that H4R has the functional effects of mediating cytokine production (i.e., down-regulating IFN-γ and up-regulating IL-6) in cells from a monocyte cell line following challenge with histamine. We demonstrated that when monocytes from AR patients were stimulated with allergen extracts of house dust mite (HDM), IFN-γ secretion was dependent on H4R activity, but IL-6 secretion was based on H1R activity. Furthermore, a combination of H1R and H4R antagonists was more effective at blocking the inflammatory response in monocytes than treatment with either type of antagonist alone.

According to the previous reports, hypothyroidism has been shown to be strongly correlated with increased circulating concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Notably, thyroid hormones are confirmed to modulate the production, clearance, and transformation process of cholesterol within circulation of mammals. Moreover, emerging evidence suggests that the thyroid-stimulating hormone could also participate in modulating serum lipid metabolism independently of thyroid hormones, which further induces the pathological development of dyslipidemia. However, the underlying mechanism is still not fully elucidated. Recently, several research studies have demonstrated that the pathogenic progression of hypothyroidism-related dyslipidemia might be correlated with the decreased serum concentrations of thyroid hormones and the increased serum concentrations of thyroid-stimulating hormones. Thus, this indicates that hypothyroidism could induce dyslipidemia and its related cardio-metabolic disorder diseases. In addition, several newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play an important role in the regulation of dyslipidemia induced by hypothyroidism. Furthermore, under the status of hypothyroidism, significantly dysfunctional HDL particles could also be observed. In the current review, we summarized the recent knowledge of the relationship between the development of hypothyroidism with dyslipidemia. We also discussed the updated understanding of the mechanisms whereby hypothyroidism induces the risk and the development of dyslipidemia and cardio-metabolic diseases.

BackgroundConcurrent chemoradiotherapy (CRT) is the preferred treatment strategy for inoperable esophageal cancer (EC). However, the effect of CRT needs to be improved.MethodsThis study comprehensively analyzed targeted agents combined with CRT for the treatment of EC by a network meta-analysis. The search was performed in public databases from incipient to 5 August 2021. Randomized controlled trials comparing the effect of targeted agents combined with CRT and CRT alone on EC patients were included.ResultsTen studies were included. For progression-free survival (PFS), nivolumab (67.4%) and erlotinib (64.6%) had advantages based on Cox analysis. Regarding the frequency of PFS, cetuximab (OR: 1.39; 95% CI: 1.01, 1.91; p=0.042) and nivolumab (OR: 1.81; 95% CI: 1.34, 2.44; pConclusionIn conclusion, compared to CRT alone, cetuximab and nivolumab combined with CRT were found to significantly improve the PFS rate only based on the frequency results. However, there was no benefit in terms of OS. For epCR and ORR, nimotuzumab was better than the blank control. Considering the limitations in this study, more well-designed RCTs are needed in the future to validate the results.

Background Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to patients with hypertensive pulmonary Takayasu's arteritis (PTA), another chronic obstructive pulmonary vascular disease, remains unclear. Purpose To investigate the potential efficacy and safety of PTPA for hypertensive PTA. Methods All consecutive patients with hypertensive PTA who completed PTPA in our center between January 1, 2016 and December 31, 2019 were prospectively enrolled. Hemodynamics, exercise capacity and oxygen saturation were measured at baseline and at least 3 months after the last PTPA session. PTPA procedure related complications, restenosis and all-cause deaths during follow-up were recorded. Results A total of 50 patients were enrolled, with the median age of 41 (IQR, 30–49) years and female predominance (82.0%). After PTPA, significant improvements in hemodynamics including mean pulmonary artery pressure (from median 48 [39–60] to 37 [31–42] mm Hg, p Conclusion PTPA appears to be a promising therapeutic option for patients with hypertensive PTA. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Key Research and Development Program of China Efficacy of PTPA

Objective: Accidental pharyngeal fishbone ingestion is a common complaint in ear, nose, and throat clinics. Approximately two-thirds of the accidentally ingested fishbones can be removed using tongue depressors and indirect laryngoscopy. However, the remaining third is challenging to identify and remove using these methods. These difficult fishbones require identification and removal via more advanced approaches. Video-guided laryngoscope is used to deal with difficult fishbones in our center. This study aimed to explore the risk factors for difficult fishbones. Methods: A prospective study was performed at a teaching hospital on 2080 patients. Univariate and multivariate analyses were performed to identify the risk factors. Results: The common fishbone locations were the tonsils (39.8%; defined as STEP-I), tongue base (37.1%), vallecula (13.3%; STEP-II), and hypopharynx (9.8%; STEP-III). With increasing STEP level, the ratio of difficult fishbones correspondingly increased (Z = 13.919, P < .001), and the proportions were 21.1%, 41.9%, and 70% in STEP-I, II, and III, respectively. In particular, fishbones in STEP-III (vs STEP-I) had a higher risk of difficult fishbones (odds ratio [OR]: 11.573, 95% CI: 7.987-16.769). Complaints of neck pain (yes vs no), foreign body sensation (yes vs no), and shorter length of fishbones always had a lower risk of difficult fishbones (OR: 0.455, 95% CI: 0.367-0.564; OR: 0.284, 95% CI: 0.191-0.422; OR: 0.727, 95% CI: 0.622-0.85). Missing teeth (yes vs no), swallowing behavior after fishbone ingestion (yes vs no), and male patients (vs female) had a higher risk of difficult fishbones (OR: 1.9, 95% CI: 1.47-2.456; OR: 1.631, 95% CI: 1.293-2.059; OR: 1.278, 95% CI: 1.047-1.56). Conclusions: Neck pain, foreign body sensation, fishbone length, patient age and sex, tooth status, and swallowing behavior after fishbone ingestion are independent risk factors for difficult fishbones.

This paper describes a work of EMI treatment for a large electrical vehicle (EV), and the practical debugging methods, used materials and tools are presented. Being different from the EMI treatment for consumer and IT products, usually there are many diverse electronic and electrical facilities being equipped in a large electrical vehicle, say, an electrical bus, and that makes the EMI environment very complex and hard to be solved.

Asthma is an important cause of subacute cough. The concentration of alveolar nitric oxide (CANO) is a sensitive inflammatory indicator in peripheral airways, and it has received much less attention than the fraction of exhaled nitric oxide (FeNO50). The main objective of this study was to explore the correlation between CANO and clinical parameters in asthmatic and non-asthmatic subacute cough, which might promote understanding of the clinical utility of CANO in these special patient populations. 155 patients with subacute cough were included consecutively, of which 25 were diagnosed as asthmatic. Data for demographic characteristics, FeNO50, CANO, baseline spirometry, bronchial provocation test (or bronchodilation test) and response dose ratio (RDR) were collected. Differences between the asthmatic and non-asthmatic groups were analyzed. Spearman’s correlation coefficient (ρ) was used to evaluate the correlation between FeNO50, CANO and other clinical parameters. In patients with subacute cough, baseline CANO values did not differ between asthmatic and non-asthmatic patients (4.4(1.3, 11.4) versus 4.0(2.1, 6.8) ppb, P > 0.05). Besides, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO50. For asthmatic subacute cough, CANO was inversely correlated with FEV1/FVC (ρ = −0.69, P < 0.01) and small airway parameters including MEF25 (ρ = −0.47, P < 0.05) and MMEF (ρ = −0.45, P < 0.05). For non-asthmatic subacute cough, CANO was inversely correlated with MEF25 (ρ = −0.19, P < 0.05) and RDR (ρ = −0.21, P < 0.05). In subacute cough, asthmatic and non-asthmatic patients had similar values of baseline CANO. In both asthmatic and non-asthmatic subacute cough, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO50. A low CANO value in non-asthmatic subacute cough corresponded to a higher value of RDR, which implied a stronger tendency towards airway responsiveness.

Purpose To evaluate the value of impulse oscillometry (IOS) and quantitative HRCT parameters for differentiating asthma-COPD overlap (ACO) in COPD patients. Patients and Methods We enrolled 44 controls and 66 COPD patients, divided into the pure COPD group (n=40) and the ACO group (n=26). Spearman correlation analysis was utilized to assess the relationship between the quantitative HRCT and IOS parameters. A binary logistic regression analysis was performed to analyze the associations between the different variables and the risk of ACO. Receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff and assess the diagnostic value of relative volume change -856 HU to -950 HU (RVC-856 to -950), decrease in the resistance from 5 Hz to 20 Hz (R5-R20) and their combination in predicting ACO. Bootstrapping validation was used to evaluate the internal validation. The concordance index (C-index) and calibration plot were calculated to assess the discrimination and calibration of the prediction model. Results Binary logistic regression analysis indicated that RVC-856 to -950 and the IOS parameters (R5-R20, R5, X5) were independently correlated with a higher risk of developing ACO after adjusting for age, sex, body mass index (BMI), history of smoking, exacerbation and atopy or allergic rhinitis. A correlation analysis showed a good correlation between the pulmonary function parameters and RVC-856 to -950, with a weaker correlation with the % area of low attenuation (LAA%) in ACO patients. Combining RVC-856 to -950 and R5-R20 to predict ACO, the AUC was 0.909, and the optimal cutoff value was >-0.62 for RVC-856 to -950 and >0.09 for R5-R20. Good calibration and favorable discrimination were displayed with a higher C-index. Conclusion More serious small airway impairment exists in ACO patients. The combination of RVC-856 to -950 and R5-R20 could be applied to differentiate ACO from COPD patients.

Background Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer’s disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects. Methods Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD. Results Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1. Conclusions Our study reveals the underlying mechanism of memantine in the treatment of AD mice.

Background: Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and convenient nomogram for patients with HBV-related ACLF.Methods: A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898).Results: Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort (P < 0.001). The results were confirmed in the validation cohort.Conclusions: The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

This study proposes a novel cloud load prediction model and combines hybrid whale optimizer (HWOA) and extreme learning machine (ELM) together for strong nonlinear mapping ability. Accurate cloud load prediction improves the cloud service efficiency and serves as the foundation for network scheme due to traditional linear forecasting models are unable to predict cloud computing resources with nonlinear changes on massive multiplication and cloud computing data complexity, effectively. The proposed cloud load forecasting model is to employ HWOA optimizer to optimize the ELM model random parameters. The contributions of this study are as follows. (1) the HWOA optimizer is to solve the whale optimizer local extremum problem; (2) the proposed HWOA optimizer reduces the ELM random parameters on cloud load forecasting; (3) the convergence performance verifies the benchmark testing functions; and (4) three simulation experiments are conducted to test the cloud load forecast effect. The result indicated that the convergence analysis reveals the HWOA optimizer outperforms the prior optimizers. The proposed cloud load prediction model obtains better forecasting results. The mean absolute percentage error and root mean square error of the proposed model are less than 14% and 11, respectively. Accurate cloud load forecasting lays a foundation for effective deployment of cloud computing resources and maximization of economic benefits.

AimsThis study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu’s arteritis-associated pulmonary hypertension (TA-PH).Methods and resultsWe conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu’s arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77–16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03–1.06), P ConclusionPatients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators’ personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.

While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, and propensity to amplify Treg cells are major barriers that prevent IL-2 from being widely used for cancer therapy. In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes (CTLs). We also observe that pre-existing CTLs within the tumor are sufficient and essential for sumIL-2 therapy. This next-generation IL-2 can also overcome targeted therapy-associated resistance. In addition, preoperative sumIL-2 treatment extends survival much longer than standard adjuvant therapy. Finally, Ab-sumIL2 overcomes resistance to immune checkpoint blockade through concurrent immunotherapies. Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potentiate combined cancer therapies., Interleukin-2 (IL-2) based cancer therapy is limited by severe toxicity and strong Treg amplification at the therapeutic dosage. Here, the authors develop a recombinant IL-2 immunocytokine which is comprised of a tumor-targeting antibody fused to a super mutant IL-2 and show in mouse models that this next-generation IL2 has reduced toxicity and enhanced antitumor activity.

Pacific white shrimp is the major farmed shrimp species in the world. It is known to be very sensitive to the environmental and management changes such as intensification, which is one of the primary necessities to increase shrimp production, but represents a stressful condition, and needs to be managed properly to diminish its negative effects in aquaculture. In this study, juvenile Pacific white shrimp were fed diets supplementing with equal quantities of Astragalus membranaceus, Codonopsis pilosula and Glycyrrhiza uralensis extracts in different concentrations (0, 1.0, 2.0 and 3.0 g/kg) for 8 weeks. We subsequently estimated the effects of supplemented diets on growth performance, haematological parameters, and histological changes of hepatopancreas. Results revealed that the supplemented mixture had no benefits on growth and survival rate, but had favourable effects on haemocyte count, number of granulocytes, and hemocyanin concentration in the haemolymph (p > 0.05). We observed that R cells and B cells were increased in hepatopancreatic tubules of shrimps fed on supplemented diets. Besides, a diet containing 2.0 g/kg of extract mixture maintained the decreased levels of alanine aminotransferase (p 0.05). Among the used concentrations, 2.0 g/kg seemed to be the most suitable concentration.

Purpose: Neoadjuvant chemoradiotherapy (neoCRT) is a standard treatment for locally advanced rectal cancer (LARC); however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to identify factors involved in the radioresistance of colorectal cancer and to clarify the underlying mechanisms. Experimental Design: A genome-wide RNAi screen was used to search for candidate radioresistance genes. After RFC4 knockdown or overexpression, colorectal cancer cells exposed to X-rays both in vitro and in a mouse model were assayed for DNA damage, cytotoxicity, and apoptosis. Moreover, the regulatory effects and mechanisms of RFC4 in DNA repair were investigated in vitro. Finally, the relationships between RFC4 expression and clinical parameters and outcomes were investigated in 145 patients with LARC receiving neoCRT. Results: RFC4, NCAPH, SYNE3, LDLRAD2, NHP2, and FICD were identified as potential candidate radioresistance genes. RFC4 protected colorectal cancer cells from X-ray–induced DNA damage and apoptosis in vitro and in vivo. Mechanistically, RFC4 promoted nonhomologous end joining (NHEJ)-mediated DNA repair by interacting with Ku70/Ku80 but did not affect homologous recombination–mediated repair. Higher RFC4 expression in cancer tissue was associated with weaker tumor regression and poorer prognosis in patients with LARC treated with neoCRT, which likely resulted from the effect of RFC4 on radioresistance, not chemoresistance. Conclusions: RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in colorectal cancer cells. In addition, the expression level of RFC4 predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in patients with LARC.

An unheard of growth in mobile data traffic has drawn attention from academia and industry. Mobile cloud computing is an emerging computing paradigm combining cloud computing and mobile networks to alleviate resource-constrained limitations of mobile devices, which can greatly improve network quality of service and efficiency to make good use of available network resource. Mobile cloud computing not only inherits the advantages of strong computing capacity and massive storage of cloud computing, but also overcomes the time and geographical restrictions, bringing benefits for mobile users to offload complex computation to powerful cloud servers for execution anytime and anywhere. To this end, an optimal task workflow scheduling scheme is proposed for the mobile devices, based on the dynamic voltage and frequency scaling technique and the whale optimization algorithm. Through considering three factors: task execution position, task execution sequence, and operating voltage and frequency of mobile devices, this study makes a tradeoff between performance and energy consumption by solving the joint optimization for task completion time and energy consumption simultaneously. Finally, a series of extensive simulation results has demonstrated and verified the scheme has distinguished performance in terms of efficiency and operational cost, providing feasible solutions to similar optimization problems of mobile cloud computing.

The purpose of this research was to estimate the effects of different meditation exercises on the improvement of sleep disorders in older people using pairwise and network meta-analyses. Qigong, Yoga, and Tai Chi could help older people improve their sleep disorders. Meditation exercises may have a role in the management of insomnia in older people. Chronic sleep loss or sleep disorders is a public health problem affecting older people and cause many health problems. We aim to estimate the effects of different meditation exercises on relieving and improvement of sleep disorders in older people using the pairwise and network meta-analyses. Randomized controlled trials, which were published in English and reported on meditation exercises for sleep disorders in the older people, were retrieved from PubMed and EMBASE up to May 2018. Publication bias of the included studies were assessed by the Cochrane Collaboration recommendations. Network meta-analysis was performed by ADDIS, and all test models used random-effects model. Pooled effect sizes were presented with weighted mean differences (WMDs) and 95% confidence interval (CI). A total of ten studies were included in our research. Pairwise comparisons indicated that Qigong could significantly improve the quality of sleep in older people with sleep disorders compared with Activities (WMD = − 4.28, 95% CI − 5.75 to − 2.81). In addition, there were significant differences in Education vs. Usual care (WMD = 2.60, 95% CI 1.03–4.17) and Tai Chi vs. Activities (WMD = − 1.05, 95% CI − 1.73 to − 0.38). With great consistence and convergence, network meta-analysis showed that there was a significant difference in Qigong vs. Activities (WMD = − 4.23, 95% CI − 8.31 to − 0.21). Moreover, Qigong showed a best outcome in relieving sleep disorders, followed by Yoga. Qigong, Yoga, and Tai Chi improved sleep disorders in the older people, and Qigong intervention had the best effect followed by Yoga. A long-term clinical verification should be needed in the future.

Objectives: Patients with early-stage distal rectal cancer, if treated with radical surgery, usually suffer a poor quality of life. Definitive radiotherapy or chemoradiotherapy may be another treatment option for them. The aim of this study was to evaluate the role of definitive external beam radiotherapy or chemoradiotherapy in treating distal rectal cancer with stage cT1-2N0. Methods: We performed a retrospective study of 231 distal rectal cancer patients who were staged as cT1-2N0 from March 2002 to March 2015. All patients were treated by definitive radiotherapy or chemoradiotherapy. Overall survival (OS), progression-free survival (PFS), and short-term efficacy were analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with PFS, local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) for the whole group. Results: For the whole group, 135 patients (58.4%) achieved clinical complete response (cCR). The 5-year OS, PFS, and LRFS were 86.19%, 83.30%, and 92.50%, respectively. Patients with cCR acquired better survival than those with non-cCR. In multivariable analysis, it revealed that clinical stage, carcinoembryonic antigen (CEA level) and concurrent chemotherapy were independent predictors of PFS. Conclusion: Definitive radiotherapy or chemoradiotherapy may be feasible in some early-stage distal rectal cancer regarding its favorable efficacy.

Kai-yun You,1,* Hai-hua Peng,2,* Yan-hui Jiang,1,* Zhuo-fei Bi,1 Xing-sheng Qiu11Department of Radiation Oncology, SunYat-Sen Memorial Hospital, SunYat-Sen University; 2Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510075, People’s Republic of China*These authors contributed equally to this workBackground: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy.Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS).Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS.Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.Keywords: cervical cancer, chemotherapy, radiotherapy &nbsp

Background Acidic preconditioning (APC) has been demonstrated to protect against ischemia-reperfusion (IR)-induced lung injury, which could occur during lung transplantation or cardiopulmonary bypass. However, the pathophysiological mechanisms underlying IR lung injury and APC protection are not completely understood. The key factors responsible for the protective effects of APC are not clear. In this study, bioinformatics was used to predict the potential key factor in IR lung injury and explore the important mediator of the APC protective effect in IR lung injury. Methods First, we screened GSE6730, which is related to both lung injury and IR in Gene Expression Omnibus, and STRING was used later to select the genes in GSE6730 needed in the future. Animal models were established and classified to validate the effect of matrix metalloproteinase 9 (MMP-9) on lung injury after IR by adding a selective inhibitor (4-phenoxyphenylsulfonyl) methylthiirane, MMP-9 inhibitor. Next, for better understanding of APC inhibition of the expression of MMP-9 in lung injury, assessment of lung tissues, Western blot analysis, and RNA extraction and reverse transcription quantitative polymerase chain reaction were conducted. Results MMP-9 was identified to be overexpressed after IR according to the analysis on GSE67370. MMP-9 was an unknown gene in relation to acute lung injury and found to be associated with interleukin (IL)-1B, IL-6, and IL-8. The expressions of these inflammatory factors, including MMP-9, were all elevated in IR. Furthermore, lung injury was ameliorated, and the level of MMP-9 was lower when an MMP-9 inhibitor, (4-phenoxyphenylsulfonyl) methylthiirane, was added. Compared with group IR, APC reversed the ischemia-induced lung injury, and the level of MMP-9 was lower, and the concentrations of IL-1β, IL-6, and IL-8 were decreased. Conclusions Our findings reveal a novel mechanism indicating that IR induces higher expression of MMP-9 in lung injury by increasing the expression of inflammation-related factors. APC might protect against IR lung injury by inhibiting the expression of MMP-9.

Aesthetic ability is an advanced cognitive function of human beings. Human dancers in front of mirrors estimate the aesthetics of their own dance poses by fusing multimodal information (visual and non-visual) to improve their dancing performances. Similarly, if a robot could perceive the aesthetics of its own dance poses, the robot could demonstrate more autonomous and humanoid behavior during robotic dance creation. Therefore, we propose a novel automatic approach to estimate the aesthetics of robotic dance poses by fusing multimodal information. From the visual channel, the shape features (including eccentricity, density, rectangularity, aspect ratio, Hu-moment Invariants, and complex coordinate based Fourier descriptors) are extracted from an image; from the non-visual channel, joint motion features are obtained from the internal kinestate of a robot. The above two categories of features are fused to portray completely a robotic dance pose. To automatically estimate the aesthetics of robotic dance poses, the following ten machine learning methods are deployed: Naive Bayes, Bayesian logistic regression, SVM, RBF network, ADTree, random forest, voted perceptron, KStar, DTNB, and bagging. Experimental results show the feasibility and good performance of the proposed mechanism, which was implemented in a simulated robot environment. The highest correct ratio of aesthetic evaluation is 81.6%, which comes from the ADTree, based on the above mixed features (joint + shape).