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Background Esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy as a safe and feasible minimally invasive technique has gained attention recently. But the occurrence of Intraoperative events is inevitable. It's necessary to investigate and discuss the intraoperative events and countermeasures during operation. Methods Intraoperative events were retrospectively reviewed in 60 patients who underwent esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy in the recent 3 years. Results There was no perioperative death and no aortic or bronchial injury. Bronchial artery injury occurred in 2 cases (3.34%), bronchial artery combined with azygos vein hemorrhage occurred in 1 case (1.67%). The pleura were injured in 3 cases (5%). Recurrent laryngeal nerve injury was noticed in 7 cases (11.67%). Thoracic duct injury occurred in 1 case (1.67%). Conclusions As a new surgical method, esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy is considered safe and feasible, but requires improvement when compared with traditional surgical methods. Due to the influence of surgical space and with experienced surgeons, the incidence of intraoperative events such as intraoperative bleeding and thoracic duct injury is not dominant when compared with the traditional surgical methods. Thoracic surgeons should continuously improve their clinical knowledge as well as skills. Careful preoperative examination and evaluation of the patients, being familiar with the anatomical structure and various methods, wise selection of energy devices and calmly dealing with all kinds of events are the key factors for successful surgeries with fewer intraoperative events.

The aim of this article is to demonstrate the interest of the optimized clustering method (OCM) when dealing with the yield analysis of ring oscillators, given uncertain assumptions over inputs. Indeed, the complementary metal–oxidesemiconductor (CMOS) integrated circuit domain is facing a major challenge since these devices are subjected to noticeable fluctuations (mostly due to transistor constant scaling down at sub-micron sizes), with utmost expectationsregarding their performances (e.g., for digital circuits). Whether the classical approach requires use of Monte Carlo methods coupled with classical circuitsolver (e.g., Spice and/or transistor model), the natural complexity of systems and varying inputs needs to provide alternative techniques, such as OCM. The foundations of the method and its efficiency will be presented and illustrated through ring oscillator applications.

International audience; A particularly original negative group delay (NGD) theory of-topology is developed in the present paper. The NGD three-port topology is a passive circuit purely constituted by capacitors network. The model of the proposed-topology impedance 3-D matrix is analytically established in function of the capacitor elements. Then, the S-matrix model is derived by using the Y-to-S transform. By considering the S-matrix frequency responses, a bandpass (BP) NGD analysis of the capacitive-topology is originally elaborated. It is theoretically demonstrated that the passive-topology is susceptible to behave as a BP NGD circuit under an analytical condition between the constituting capacitor values. The design feasibility of the BP NGD function is experimentally verified with lumped capacitor components-based-circuit proof of concept. An electronic circuit board constituted by purely capacitive-network-circuit is fabricated as an original-circuit prototype. The tested board is constituted by arbitrary chosen capacitors, 100 nF, 10 nF and 0.1 nF. As expected, the calculation, simulation and measurement results, which are in very good agreement, confirm the BP NGD behavior. It is observed from measurement that it generates NGD of about −18.1 ns at a frequency of about 0.55 MHz and, lower and upper cutoff frequencies of about 0.33 MHz and 1.71 MHz. It is noteworthy that the transmission and reflection coefficients at very low frequency are independent of the capacitor values and analytically equal to 2/3 and 1/3, respectively. INDEX TERMS Bandpass (BP) negative group delay (NGD), passive topology,-topology, three-port circuit, S-parameter modeling, NGD theory, capacitive network.

This paper develops an innovative model of shielded coaxial cable illuminated by high power electromagnetic pulse. This Kron-Branin model is a flexible and efficient way of wave-circuit hybrid calculation, which is based on Branin’s transmission line (TL) model and tensorial analysis of network (TAN). The traditional equivalent circuit is transferred into a topology graph consists of basic elements like nodes, branches, meshes, and cords. Electromagnetic and circuit equations can be derived and transferred according to the graph. The graph topology and equivalent transmission line equation of illuminated shielded cable structure is presented in this paper. A good correlation between the analytical calculation of the KB model and commercial simulation software is obtained.

With the rapid development of modern industry and the emphasis on cost saving, high efficiency, high power density, high reliability of isolated switching power supplies demand more and more. In order to continuously improve the efficiency and power density of the power module, high-frequency and miniaturization has become the development trend of switching power supply. As the volume and weight of magnetic components take up a large proportion in the whole DC/DC power supply module, it is very important to reduce the volume and loss of planar transformer and improve the efficiency at the same time. In this paper, through ANSYS Maxwell finite element simulation, high frequency electromagnetic field modeling of different transformer design schemes were carried out, and the simulation results were extracted and analyzed to obtain an integrated magnetic transformer with low loss, small volume, high efficiency and good electromagnetic compatibility.

The outbreak of COVID-19 caused by SARS-CoV-2 infection has become a serious hazard to global health. Apart from attacking respiratory system, it can induce multiorgan dysfunction, including cardiovascular system, liver, kidney, gastrointestinal, nervous system, and immune system. However, there are few reviews focusing on summary and comparison of diagnostic methods and complications induced by SARS-CoV-2 infection, which places a significant limit on the effective management.This review is a blend of evidence obtained by literature retrieval from PubMed, clinical experience, and the authors' opinions. We searched PubMed using the terms 'COVID-19diagnosis' and 'COVID-19complications' and selected the most relevant articles. Here we summarize the diagnostic methods that are available in clinic and discuss their different characters. Furthermore, the review offers an insight into the symptoms, incidence, and clinical strategies of complications associated with SARS-CoV-2 infection.COVID-19 has been a global pandemic, which requires rapid response. The comparison between different characters of the diagnostic methods and the summary of the symptoms, incidence, and clinical strategies of complications given in this review are not only significant for the optimal use of diagnostic methods, but also beneficial for the prevention and management of complications.

Objective To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and cognitive dysfunction of children with OSA. Methods Twenty children with OSA (7.2 ± 3.1 years, apnea hypopnea index (AHI): 16.5 ± 16.6 events/h) and 29 healthy controls (7.7 ± 2.8 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent resting-state fMRI (rs-fMRI) and T1-wighted imaging. Some children were sedated for MRI scanning. We compared amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) of children with OSA with those of healthy controls. During resting-state, the former reflects the intensity of the spontaneous neural activities, whereas the latter reflects temporal similarity of the spontaneous neural activities within a local brain region. Pearson correlation analysis was performed between these features of rs-fMRI and cognitive scores among children with OSA. Results Compared with controls, children with OSA showed decreased ALFF in the left angular gyrus but increased ALFF in the right insula, and decreased ReHo in the left medial superior frontal gyrus, right lingual gyrus, and left precuneus. Additionally, among children with OSA, the ReHo value in the right lingual gyrus was negatively correlated with FIQ and VIQ, whereas that in the left medial superior frontal gyrus was positively correlated with VIQ. Conclusions Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions with the former possibly being the neural mechanism of the latter.

Objective The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis are to verify this issue and further provide reference for clinical practice. Methods Seven databases were searched for randomized controlled trials (RCTs) up to September 30, 2019. The literature screening and data extraction were performed by two independent researchers. Adverse reactions from trials were also recorded. Meta-analysis was performed and analyzed heterogeneity. Methodological and evidence quality were followed by to evaluate according to Cochrane handbook. Results A total of 4 RCTs including 305 children with mild to moderate OSA were involved. Compared with placebo, we found that oral montelukast (OM) significantly improved polysomnography (PSG) monitoring parameters, typical and relevant symptoms including snoring and mouth breathing, and adenoid morphology in children with OSA. When compared with routine drugs, not only PSG monitoring parameters and adenoid morphology, but also sleep-disordered breathing (SDB)-related questionnaire scores were improved in patients with OSA treated by combination of OM and routine drugs. In addition, compared with single nasal spray of mometasone furoate, the present study also showed that OM combined with nasal spray of mometasone furoate significantly improved PSG monitoring parameters, symptoms of snoring and mouth breathing and reduced tonsil morphology in pediatric OSA. In terms of treatment safety, one study reported adverse reactions of OM such as headache, nausea and vomiting, while no adverse events were reported after OM treatment in another study. Conclusion As a classic leukotriene receptor antagonist, montelukast can be used to treat children with mild to moderate OSA in the short term and improve clinical characteristics. The promotion and application of OM in clinic is considered to be a noninvasive option to avoid surgical treatment.

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the first-line treatment of patients with metastatic or advanced non-small cell lung cancer (NSCLC) whose tumors have specific EGFR mutations. Pulmonary toxicity is one of the fatal adverse effects of gefitinib and the underlying mechanism remains unclear. Here we demonstrated that alveolar macrophages contributed to gefitinib-induced pulmonary toxicity through promoting alveolar epithelial cells to undergo epithelial to mesenchymal transition (EMT) and inducing activation and antiapoptotic effect in fibroblasts. Further, we found that alveolar macrophage-secreted MCP-1 worked as a key factor in the pathologic changes of these two cell types. Gefitinib increased Mcp-1 transcription level via the nuclear import of the transcription factor STAT3. In conclusion, our data uncovered the underlying mechanisms of macrophage-promoted pulmonary toxicity in the presence of gefitinib. MCP-1 antibody or inhibition of STAT3 activation may represent novel therapeutic strategies for preventing gefitinib-induced pulmonary toxicity.

Vascular endothelial growth factor (VEGF) is a key target in cancer therapy. However, cardiovascular safety has been one of the most challenging aspects of anti-VEGF/VEGF receptor (VEGFR) agent development and therapy. While accurate diagnostic modalities for assessment of cardiac function have been developed over the past few decades, a lack of an optimal definition and precise mechanism still places a significant limit on the effective management of cardiovascular toxicity.Here, we report the cardiovascular toxicity profile associated with anti-VEGF/VEGFR agents and summarize the clinical diagnoses as well as management that are already performed in clinical practice or are currently being investigated. Furthermore, the review discusses the potential molecular toxicological mechanisms, which may provide strategies to prevent toxicity and drive drug discovery.Cardiovascular toxicity associated with anti-VEGF/VEGFR agents has been a substantial risk for cancer treatment. To improve its management, the development of guidelines for prevention, monitoring and treatment of cardiovascular toxicity has become a hot topic. The summary of cardiovascular toxicity profile, mechanisms and management given in this review is not only significant for the optimal use of existing anti-VEGF/VEGFR agents to protect patients predisposed to cardiovascular toxicity but is also beneficial for drug development.

This paper proposes a decoupling capacitor placement optimization method based on the cavity model and Lagrange multiplier. The variable conditions associating with coordinates (x,y) of input impedance expression based on the cavity model are combined with the Lagrange multiplier method. The decoupling capacitor optimum placement within a defined area of the board can be found through the proposed analytical method. The example of finding an optimum location of the decoupling capacitor within a defined area of the power delivery network is exposed, the results are compared to the brute-force method to prove the effectiveness of the proposed method.

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1β, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO2, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.

We assessed the influence of allergic rhinitis (AR) on sleep disordered breathing (SDB) in children with adenotonsillar hypertrophy (ATH), and compared sleep quality and polysomnographic data in habitually snoring children with or without AR.Children with snoring resulting from adenoid/tonsils hypertrophy were recruited between Jan 1st, 2018 and Jun 30th, 2018. The exclusion criteria were congenital disorders, metabolic disorders, neurological disorders and pulmonary diseases, such as, asthma etc. Overnight polysomnography (PSG) and Sleep Questionnaire (SQ) were assessed on each participant to identify children with obstructive sleep apnea (OSA). Cross-sectional study design was used to examine PSG and SQ data. The diagnosis of AR was based upon history of allergies and positive clinical examinations, then confirmed by allergen test. Participants were categorized into four groups (AR and Non-OSA group; AR and OSA group; Non-AR and Non-OSA group; Non-AR and OSA group). Non-parametric rank sum test was used for statistical analysis.Six hundred and sixty children (age between 3yrs and 14yrs) with SDB were enrolled in the study (mean age 6.7 ± 2.1yrs, 67.4% male). The number of children diagnosed with OSA was 495 (74.3%). The prevalence of AR among all participating SDB children was 25.8%, and AR with OSA was19.4%. The behavioral problems scores in SQ showed significant difference among SDB children with AR (P.0001). No difference was observed in the OAHI (obstructive apnea-hypopnea index) and AHI (apnea-hypopnea index) between the groups of children with and without AR regardless whether OSA was coexisting. The percentage of time spent in the rapid eye movement (REM) sleep stage was shortened among children with AR without OSA (P = 0.031), however, the percentage of time spent in the REM sleep stage was not different among children with OSA (P = 0.98). The total sleep time was shorter among children with AR (OSA P = 0.02; without OSA P = 0.03).Despite the high prevalence of AR in patients with SDB, AR is not an aggravating factor for the severity of AHI. High risk behavioral problems link to SDB with AR. AR is associated with shortened REM sleep stage in children with SDB without sleep apnea, and shortened total sleep time in children with SDB.

Numerous protein kinases encoded in the genome have become attractive targets for the treatment of different types of cancer. As of January 2020, a total of 52 small-molecule kinase inhibitors (SMKIs) have been approved by the FDA. With the numerous clinical trials and a heavy focus on drug safety, SMKI-induced cardiotoxicity, which is a life-threatening risk, has greatly attracted the attention of researchers. In this review, the SMKIs with cardiotoxicity incidence were described exhaustively. The data were collected from 42 clinical trials, 25 FDA-published documents, seven meta-analysis/systematic reviews, three case reports and more than 50 other types of articles. To date, 73% (38 of 52) of SMKIs have reported treatment-related cardiotoxicity. Among the 38 SMKIs with known cardiotoxicity, the rates of incidence of cardiac adverse events were QT prolongation: 47% (18 of 38), hypertension: 40% (15 of 38), left ventricular dysfunction: 34% (13 of 38), arrhythmia: 34% (13 of 38), heart failure: 26% (10 of 38) and ischemia or myocardial infarction: 29% (11 of 38). In the development process of novel SMKIs, more attention should be paid to balancing the treatment efficacy and the risk of cardiotoxicity. In preclinical drug studies, producing an accurate and reliable cardiotoxicity evaluation model is of key importance. To avoid the clinical potential cardiotoxicity risk and discontinuation of a highly effective drug, patients treated with SMKIs should be proactively monitored on the basis of a global standard. Moreover, the underlying mechanisms of SMKI-induced cardiotoxicity need to be further studied to develop new therapies for SMKI-induced cardiotoxicity.

This paper focuses on novel modeling of radiated electromagnetic compatibility (EMC) coupling onto the multilayer printed circuit board (PCB). Kron's method integrates the electromagnetic (EM) emission, Taylor's, and field-to-interconnect coupling models. The equivalent graph of the field-to-interconnect coupling is established. The modeling methodology consists in defining the primitive sub-network elements (vias, interconnect lines, pads, and ground plane). Kron's graph equivalent to the EMC problem is elaborated. Finally, the coupling voltages are calculated via the tensorial equation translated from the graph. The radiated EMC Kron's model is validated with a four-layer PCB from 0.4 to 1.4 GHz by two scenarios of EM radiation. As proof-of-concept, a prototype of four-layer PCB was designed, fabricated, tested, and simulated in full wave with a commercial three-dimensional EM tool. For the first case, the multilayer PCB was illuminated by plane wave emission propagating in different directions. The numerical computation from Kron's formalism was compared with simulation and measurement. The other case is the field-to-interconnect coupling between a microstrip I-line PCB, as an EM field emitter, and the multilayer PCB, as a receiver, in 1-m distance. For both cases, the simulated and calculated voltage couplings onto the multilayer PCB are in good agreement.

Background The known risk factors of childhood OSAS include tonsillar and adenoidhypertrophy, obesity, craniofacial anomalies, neuromuscular disorders and African-American (AA) ancestry. Whether other factors such as allergic rhinitis (AR), premature, environmental tobacco smoking (ETS) are associated with OSAS are inconsistent in different studies. Our study enrolled children of a broad age range and included potential risk factors of OSAS derived from previous studies and our own experience. Our objective is to identify risk factors of OSAS in children in a clinical setting. Methods Children between 2 and 15 years of age exhibiting snoring symptoms who visited the sleep center for polysomnography (PSG) were enrolled. All children completed a questionnaire, physical examination and PSG. The questionnaire included demographic data and information related to potential risk factors for sleep disorders. A physical examination included measurements of height, weight, neck circumference, waist and hip ratio, visual evaluation of the tonsils and the degree of adenoid obstruction. Children with obstructive apnea-hypopnea index (OAHI) ≥ 1 were defined as OSAS. Results A total of 1578 children were enrolled and1009 children exhibited OSAS. Univariate analyses showed that snoring occurring for ≥ 3 months, male gender, preterm birth, breastfeeding, obesity, neck circumference ≥ 30 cm, waist/hip ratio ≥ 0.95, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. The proportion of low educational level was higher in parents who breastfed their babies than those who didn’t. Multivariate analysis showed that snoring for ≥ 3 months, male gender, obesity, breastfeeding, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. Confounders such as socioeconomic status, parental occupation, and health-related behaviors should be explored further to investigate the relationship between breastfeeding and OSAS. Conclusion The independent risk factors for OSAS in children included snoring ≥ 3 months, male gender, obesity, breastfeeding, tonsillar and adenoid hypertrophy. The study was registered on Clinical Trials government (NCT02447614). The name of the trial is “Follow-up Studies of Primary Snoring (PS) and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in Chinese Children” and the URL is https://clinicaltrials.gov/.

It is increasingly evident that the molecular and biological functions of long non-coding RNAs (lncRNA) are vital for understanding the molecular biology and progression of cancer. The lncRNA-HEIH, a newly identified lncRNA, has been demonstrated to be up-regulated in hepatocellular cancer. However, little is known about its role in oesophageal squamous cell carcinoma (ESCC). In the present study, an obvious up-regulation of lncRNA-HEIH was observed in ESCC compared to the adjacent normal tissues. Meanwhile, patients with high expression of lncRNA-HEIH have significantly poorer prognosis than those with low expression. We further found that lncRNA-HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association led to the repression of TP53. These findings indicate that lncRNA-HEIH may serve as a prognostic marker and a potential therapeutic target for ESCC.

This paper develops an unfamiliar modelling of printed circuit board (PCB) interconnect behaving as HH-tree. The developed model is based on the tensorial analysis of networks (TAN) formalism. The ...

International audience; This paper introduces a tensorial analysis of networks (TAN) applied to a tree asymmetrical structure. To illustrate the TAN concept easily, the present investigation is applied to a three-port structure represented by a Y-tree topology. The unfamiliar method of TAN circuit modelling is elaborated from the graph topology. The fast formulation of the Y-matrix model of the structure is established from branch and mesh space TAN analyses. The TAN model is validated with commercial tool simulation and measurements from DC up to 0.5 GHz in the frequency domain and two different waveform signals in the time domain. The proof of concept circuit is implemented in microstrip technology on an FR4-epoxy dielectric substrate. Mapping sensitivity analysis with respect to the Y-tree RLC-parameters is realized by showing that local variations around initial set of R, L, and C do not equally influence reflection and transmission coefficients over the frequency bandwidth. If a similar impact is observed at the lowest frequency, maximum variations up to 250% show the importance of parameters ranking to improve both microstrip design and modelling.

Dasatinib shows remarkable activity against imatinib-refractory chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL). However, severe cardiovascular toxicity limits the clinical applications of dasatinib. Since the underlying mechanism of dasatinib-induced cardiotoxicity is still elusive, we aim to clarify this. Recent studies have shown that necroptosis and apoptosis participate in multiple toxicity development. Here, we first report that dasatinib could directly induce cardiomyocytes death, as analyzed by the Sulforhodamine B (SRB) assay. This type of cardiomyocytes death was mediated by the necrosis pathway rather than apoptosis, as determined by using flow cytometry to characterize the mode of dasatinib-induced cell death. Inhibition of receptor-interacting protein kinase 1 (RIP1)activity and knockdown of receptor-interacting protein kinase 3 (RIP3)expression can block dasatinib-evoked cardiotoxicity, which further confirmed the involvement of necroptosis. We next found that the classic substrates of RIP3, mixed lineage kinase domain-like protein (MLKL) and Ca2+-calmodulin-dependent protein kinase II (CaMKII) were not involved in dasatinib-induced cardiomyocytes necroptosis. What's more, unlike the inflammation-associated necroptosis, dasatinib-triggered necroptosis was dependent on intracellular instead of secreted High-mobility group box 1 (HMGB1) protein. Collectively, our study revealed that dasatinib-induced cardiotoxicity acted via leading cardiomyocytes to HMGB1-mediated necroptosis, indicating a viable strategy for prevention of dasatinib-induced cardiotoxicity.

A fast, sensitive and high-resolution colorimetric method for sensing benzoyl peroxide (BPO) was proposed by using orange sheath-like Au@Ag nanorods (NRs) as the signal transducer. BPO can oxidize Ag nanoshells on the surface of Au@Ag NRs; the etching of Ag nanoshells changes the aspect ratio of Au nanostructures and causes a red-shift of longitudinal local surface Plasmon resonance (LSPR) peak, resulting in a sharp-contrast multicolor change within 2 min. Under the optimal conditions, the red-shift of longitudinal LSPR peak was in linear with the BPO concentration over the range of 0–100 μmol L−1 with a limit of detection of 0.75 μmol L−1. Furthermore, a simple, inexpensive and portable test kit was designed for the visual detection of BPO. A color variation can be distinguished by naked eyes at a concentration of BPO as low as 20 mg kg−1 in flour samples. The colorimetric sensor shows a great potential application for the rapid and on-site assay of BPO in flour samples.

The multilayer technology constitutes the ultimate solution for the design of high-density printed circuit board (PCB). Challenging modeling method is required to predict the signal integrity (SI) of the multilayer PCB. This paper addresses an unfamiliar direct time-domain model of a 3-D multilayer hybrid PCB. The subnetwork primitive elements of the equivalent graph are constituted by lumped components, interconnect lines, vias, pads, and anti-pads. The tensorial analysis of networks (TANs) is used to solve the problem related to the graph topology in the function of the PCB design parameters. The TAN concept is based on the interaction between the primitive elements. The mesh currents constitute the proposed computational unknowns. The unfamiliar model is validated with a three-port network prototype constituted by the six-layer PCB, including passive SMD components. In the frequency domain, S-parameter validation from 100 kHz to 5 GHz is presented. By using 80-Mb/s and 0.5-Gb/s rate data patterns, the proposed TAN model is validated by both simulations and measurements in the time domain. The transient results present vector magnitude relative error accuracy lower than 15%. Thanks to the computation speed and adaptability to multilayer hybrid structures, the TAN model is a prominent approach for the SI and power integrity analyses of 3-D multilayer structures.

Background: Physical rehabilitation training as an effective measure was proposed by relevant government sector recently. Many compulsory isolated detoxification centers had already implemented the measure, but rarely a systematically comprehensive research was published. Therefore, the purpose of this paper was to evaluate the effect of “5433” training program as an exercise intervention on addicts during drug treatment and rehabilitation, in order to provide the experimental data for the research about the effects of mental quality and physical quality of addicts. Methods: The 2132 male addicts were randomly divided into experimental group (n = 1020) and control group (n = 1112), experimental group was training by “5433” program, and control group ordinary was managed alone. Before and after one year training, in accordance with the “SCL-90” and “Standards of People’s Republic of China national physique”, the SCL-90 scores, height/weight, vital capacity, step index, grip strength, vertical jump, push-ups, sit-and-reach, one-leg standing with eye-closed, choice reaction index of two groups were detected. Results: 1) The scores of depression, anxiety, paranoia and psychosis in two groups before the experiment are both lower than those after the experiment, and the experimental group decreased more (P 0.05). Conclusion:These initial findings show that The “5433” Training Program was effective more than a simple kinesiotherapy, thereby opening avenues for the rehabilitation of Chinese drug addicts.

Background: It is known that short sleep duration adversely affects children’s behavior and physical development. This study aimed to investigate the status of sleep duration in 3–14-year-old children in Beijing and explore the related factors of sleep loss with them. Methods: In this study, a cross-sectional study of random stratified cluster sampling was conducted on 3–14-year-old children and adolescents in Beijing. According to the proportion of children in each district and school, the final cohort included a total of 11 kindergartens, 7 primary schools, and 8 junior high schools from 7 districts of Beijing. Children of sampled classes were included, and their parents were invited to fill a series of questionnaires including the simplified Chinese version of Pediatric Sleep Questionnaire, Sleep Questionnaire Scale, and Hong Kong-Children Sleep Questionnaire about the performance of the last 6 months. Results: Out of the total 11,420 questionnaires, 9198 questionnaires were valid and effective with the response rate of 80.54%. The age of the investigated children was 8.8 ± 3.8 years, including 4736 males and 4462 females. The daily sleep duration of children in Beijing was 9.7 ± 0.7 h. The prevalence of sleep loss (

Background: Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumour and has poor prognosis. Currently, systematic chemotherapy is the only approach to prolong survival. Thus the development of new treatment regimens is urgently needed to improve the therapeutic efficacy. Our study intended to assess the combination of dasatinib and irinotecan against HCC and made an effort to develop a potential medical choice for advanced HCC patients. Methods: We used SRB colorimetric assay and clonogenic assay to assess antitumour effect in vitro and HCC xenograft model to assess antitumour effect in vivo. We applied flow cytometry and western blotting to explore the mechanism of the combined therapy. Knockdown and overexpression of PLK1 are also applied for validation. Results: We confirmed that dasatinib has synergistic effect with irinotecan (or SN38) on HCC both in vitro and in vivo. The effect is due to arisen apoptosis rate of HCC cells that is accompanied by mitochondria dysfunction. The enhanced antitumour efficacy of SN38 could be explained by additional inhibition of PLK1, which is triggered by dasatinib. Unlike existed PLK1 inhibitors, dasatinib does not inhibit PLK1 activity in a direct way. Instead, we found that dasatinib reduces PLK1 level by interfering with its protein synthesis progress. We validated that this kind of downregulation of PLK1 level has a key role in the synergistic effect of the two agents. Conclusions: Dasatinib is able to reinforce the anti-HCC efficacy of irinotecan/SN38 by downregulation of PLK1 synthesis. The combination of the two agents might be a potential medical choice for HCC therapy.

Capecitabine, as the first-line treatment for multiple tumor types, has a serious drawback of hand-foot-syndrome (HFS) that limits its clinical use. However, the pathophysiology and mechanism of capecitabine-induced HFS is rarely known. Here we built the experimental mouse model of HFS induced by capecitabine at first and it was shown that 3 of 6 mice appeared HFS in the 5th day and 5 mice occurred HFS in the 30th day. The corneous layer was reduced in capecitabine-induced HFS in vivo. Moreover, we found that capecitabine could significantly induce keratinocytes cells death in vitro through activated apoptosis pathway and decreased mitochondrial membrane potential. In conclusion, these results suggested that HFS of capecitabine may be developed from reduction of corneous layer through stimulation of intracellular mitochondrial dysfunction following activation of caspase-dependent apoptosis pathway.

Hand–foot skin reaction (HFSR), among the most significant adverse effects of sorafenib, has been limiting the clinical benefits of this frontline drug in treating various malignant tumors. The mechanism underlying such toxicity remains poorly understood, hence the absence of effective intervention strategies. In the present study, we show that vascular endothelial cells are the primary cellular target of sorafenib-induced HFSR wherein soluble heparin-binding epidermal growth factor (s-HBEGF) mediates the crosstalk between vascular endothelial cells and keratinocytes. Mechanistically, s-HBEGF released from vascular endothelial cells activates the epidermal growth factor receptor (EGFR) on keratinocytes and promotes the phosphorylation of c-Jun N-terminal kinase 2 (JNK2), which stabilizes sirtuin 1 (SIRT1), an essential keratinization inducer, and ultimately gives rise to HFSR. The administration of s-HBEGF in vivo could sufficiently induce hyper-keratinization without sorafenib treatment. Furthermore, we report that HBEGF neutralization antibody, Sirt1 knockdown, and a classic SIRT1 inhibitor nicotinamide could all significantly reduce the sorafenib-induced HFSR in the mouse model. It is noteworthy that nicotinic acid, a prodrug of nicotinamide, could substantially reverse the sorafenib-induced HFSR in ten patients in a preliminary clinical study. Collectively, our findings reveal the mechanism of vascular endothelial cell-promoted keratinization in keratinocytes and provide a potentially promising therapeutic strategy for the treatment of sorafenib-induced HFSR.

Background The peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility. Methods This systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS). Results In sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18). Conclusions This systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.

Medical exchanges are an important part of scientific and technological exchanges between China and the West. The Jesuits spread Chinese medicine mainly through letters, works and translations. Although the spread efficiency is relatively low, they still make important contributions to the spread of Chinese medicine to the west. With the development of new media, TCM communication faces new opportunities, and TCM communication should be closely combined with science and technology to improve communication efficiency. This paper reviews the contribution of jesuits to TCM communication, and puts forward TCM communication strategies based on the background of informatization.

Background: Magnolol has shown anti-cancer activity against a variety of cancers, such as liver, breast, lung and colon cancer. However, the role of magnolol in esophagus cancer cells is unknown. Methods: In this study, esophagus cancer cell lines including TE-1, Eca-109 and KYSE-150 were used to evaluate the cytotoxic effect of magnolol on cell proliferation, apoptosis and migration. Results: We found that magnolol inhibits cellular proliferation of all three cell lines in a time- and dose-dependent manner; 20 µM magnolol markedly inhibited the migration ability of KYSE-150 cell which was accompanied with a decreased expression of MMP-2. Treatment with 100 μM magnolol significantly increased KYSE-150 cell apoptosis. We found that cleaved caspase-3, cleaved capsese-9 and Bax protein expression was increased and Bcl-2 protein expression was decreased after magnolol treatment. In addition, Magnolol had no effect on JNK but induced the phosphorylation of p38 and ERK1/2 in a concentration-dependent manner, suggesting the involvement of these kinases in the initiation of the apoptosis process. Finally, magnolol treatment significantly suppressed KYSE-150 tumor cell growth in nude mouse xenograft models. Conclusions: The results of this study provide a basis for the understanding and development of magnolol as a potential novel drug for esophagus cancer.

Objective This study aimed to identify the heterogeneity of obstructive sleep apnea syndrome clinical presentation in children. Participants Children who were 3–14 years old and with obstructive sleep apnea syndrome after polysomnography monitoring (apnea and hypopnea index>5 or obstructive apnea index>1) in the sleep center of Beijing Children's Hospital were included. Methods A sleep disorder questionnaire including different combinations of symptoms and co-morbidities of obstructive sleep apnea syndrome in children was used. A cluster analysis was used to classify the data. Results The apnea hypopnea index alone is not adequate to predict clinical phenotypes. Based on symptoms and co-morbidities of obstructive sleep apnea syndrome, three distinct clusters were identified. They were “nocturnal snoring and daytime sleepiness group” (cluster 1), “hyperactivity group” (cluster 2), and “minimally symptomatic group” (cluster 3). A prediction model was built according to eight variables which showed statistical significance by pairwise comparison among clusters. Overall accuracy of the prediction model could reach 86%. Both the sensitivity and specificity of cluster 2 and 3 prediction were around 90%. Conclusion Children with obstructive sleep apnea syndrome have different patterns of clinical presentation and the identification of the different clinical profiles of obstructive sleep apnea syndrome can provide clues for more personalised diagnoses and therapies.

Parkinson’s disease is a chronic neurodegenerative disease that affects the daily lives of tens of thousands of middle-aged and elderly people. The intelligent classification method of Parkinson’s disease has received extensive attention in recent years. The paper proposes a new auxiliary classification model of Parkinson’s disease based on principal component analysis and support vector machine. The model first samples and preprocesses the collected handwritten sensor data, then performs dimensionality reduction by principal component analysis, and finally inputs the dimensionality reduction data into a linear kernel support vector machine for Parkinson’s disease classification and prediction. The experiment uses 5-fold cross-validation for dataset segmentation and performance verification. The average performance results obtained on the Meander r dataset are: accuracy is 70.86%, specificity is 67.23%, sensitivity is 75.98%, and F1-Score is 69.72%, and the average performance results obtained on the Spiral dataset are: accuracy is 77.45%, specificity is 70.26%, sensitivity is 85.58%, and F1-Score is 77.10%.

The tumor suppressor protein p53 participates in the control of key biological functions such as cell death, metabolic homeostasis and immune function, which are closely related to various diseases such as tumors, metabolic disorders, infection and neurodegeneration. The p53 gene is also mutated in approximately 50% of human cancer cells. Mutant p53 proteins escape from the ubiquitination-dependent degradation, gain oncogenic function and promote the carcinogenesis, malignant progression, metastasis and chemoresistance. Therefore, the stability of both wild type and mutant p53 needs to be precisely regulated to maintain normal functions and targeting the p53 stability is one of the therapeutic strategies against cancer. Here, we focus on compound-induced degradation of p53 by both the ubiquitination-dependent proteasome and autophagy-lysosome degradation pathways. We also review other posttranslational modifications which control the stability of p53 and the biological functions involved in these processes. This review provides the current theoretical basis for the regulation of p53 abundance and its possible applications in different diseases.

Objective The objectives of this study were to characterise age-specific normal polysomnography values in healthy children and to establish reference values for paediatric sleep studies. Methods Healthy children and adolescents aged 3–14 years were recruited from families of hospital employees. The subjects were divided into young (three to five years old) and old (6–14 years old) groups. Each child was subjected to overnight polysomnography. The polysomnographic parameters of sleep architecture, respiratory events and oxygen saturations of the two groups were compared. Results Ninety-nine subjects, including 33 3–5 year olds and 66 6–14 years olds, were recruited. The old group yielded a higher per cent of N2 sleep and lower per cent of R sleep than the young group. Sleep efficiency and latency were similar between the two groups. The average of the total apnoea/hypopnoea index (AHI) was different between the two groups (1.02 ± 0.99 vs 0.51 ± 0.57, p = 0.007). The average central apnoea index (CAI) in the young group was higher than that of the old group (0.7 ± 0.82 vs 0.28 ± 0.42, p = 0.001), with 97.5 percentile of 3.8 and 1.4, respectively. The obstructive apnoea index (OAI) and obstructive apnoea hypopnoea index(OAHI) were similar in the two groups (OAI: 0.08 ± 0.12 and 0.07 ± 0.14, and OAHI: 0.18 ± 0.21 and 0.19 ± 0.26, respectively). The mean lowest SaO 2 in the young group was significantly lower than that of the old group because of central apnoea events. Conclusions The findings were consistent with previously published data regarding sleep architecture, oxygen saturations, and relative rarity of respiratory events in normal children. The occurrence of central apnoea varied with age. Therefore, it is suggested that different normal cut-off values be used for children in different age groups.

Cisplatin is a widely used chemotherapy drug that is first-line therapy for a variety of tumors. Unfortunately, its adverse effects on various normal tissues and organs, especially nephrotoxicity, threaten the life of patients. Although the mechanism of cisplatin nephrotoxicity has been confirmed to be related to oxidative stress, apoptosis of renal tubular epithelial cells and inflammatory response, there is no effective prevention strategy in the clinic. Here, we found that bisdemethoxycurcumin (BDMC), a natural compound, can significantly attenuates cisplatin-induced apoptosis of renal tubular epithelial cells in vitro at the concentration of 5–20 μM and has a significant protective effect on cisplatin-induced kidney injury in mice at the dose of 50 mg/kg. Mechanistically, BDMC attenuates cisplatin-induced apoptosis of renal tubular epithelial cells by inhibiting cisplatin-induced up-regulation of p53. Meanwhile, BDMC counteracts oxidative stress by inhibiting cisplatin-induced down-regulation of nuclear factor erythroid-2-related factor 2 (Nrf2). BDMC also significantly reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) proteins, as well as the expression and translocation of the p65 subunit of nuclear factor-κB (NF-κB p65) into the nucleus, all of which were increased in the kidney by cisplatin treatment. Collectively, BDMC might be an effective prevention strategy which could against cisplatin-induced nephrotoxicity, and our research may shed a new light on treatment of drug toxicity.

Introduction This study was performed to investigate the differences in blood pressure among different groups of snoring children and among different sleep stages.In recent years, the incidence of OSAS in children has increased year by year. Blood pressure research of OSAS children can better understand the occurrence of OSAS related complications. Early detection and intervention of blood pressure changes in children with OSAS can effectively reduce the incidence of cardiovascular disease in adulthood and lower the disease burden. Methods Habitually snoring children (snoring frequency of ≥3 nights per week) aged 3to 11 years were recruited from Beijing Children’s Hospital, Capital Medical University from 1 January 2017 to 30 June 2018. All children underwent polysomnography, and their blood pressure was monitored and calculated by the pulse transit time. The children were divided into those with primary snoring (PS), mild obstructive sleep apnea syndrome (OSAS), and moderate to severe OSAS according to their obstructive apnea-hypopnea index (OAHI). Results In total, 140 children were recruited. Ninety-seven had PS, 24 had mild OSAS, and 19 had moderate to severe OSAS. There were no differences in age, sex, or body mass index z-score among the groups. Statistically significant differences were found in the OAHI, oxygen desaturation index 3%, respiratory arousal index, and lowest oxygen saturation among the three groups. Children with moderate to severe OSAS had higher systolic and diastolic blood pressure than those with mild OSAS and PS (P < 0.001). In all children, systolic and diastolic blood pressure was higher in the rapid eye movement (REM) sleep stage than in the non-REM sleep stage (P < 0.05). Conclusion Children with moderate to severe OSAS had higher blood pressure than those with PS and mild OSAS. Blood pressure in the REM sleep stage was higher than that in other sleep stages in all groups of children. Support The Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority (XTYB201807);Capital Health Research and Development of Special Funding (2018-1-2091);National Key Research and Development Plan (2017YFC0112502)