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BACKGROUND Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence. METHODS Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression-based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post-admission. RESULTS By distinguishing recurrence-associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non-recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy. CONCLUSIONS Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment.

miRNAs in circulating extracellular vesicles (EVs) are promising biomarkers for cancer. However, their diagnostic ability for early‐stage non‐small‐cell lung cancer (NSCLC) is not well known. In this study, the circulating EV miRNAs profiling was initially performed in 36 untreated NSCLC patients and 36 healthy controls by TaqMan Low Density Array (TLDA). Subsequently, we performed quantitative reverse‐transcription PCR assay (RT‐qPCR) validation in several independent cohorts that included 159 NSCLC patients, 120 age/sex‐matched healthy controls and 31 benign nodule patients enrolled from three different clinical centres. In addition, 38 cases of NSCLC were analysed before and after surgery. We demonstrated that miR‐520c‐3p and miR‐1274b were significantly and steadily increased in NSCLC patients in comparison with healthy controls and benign nodule patients (P, Sensitive and specific biomarkers for the detection of non‐small‐cell lung cancer (NSCLC) are urgently needed. Here, we investigated the diagnostic potential of extracellular vesicle (EV) miRNAs as biomarkers for NSCLC in a multiphase case–control study. We report that EV‐miR‐520c‐3p and miR‐1274b hold potential as novel diagnostic biomarkers for early‐stage NSCLC.

INTRODUCTION Interleukin (IL)-25 is a T helper (Th) type-2 cytokine implicated in the pathogenesis of asthma. Fibrocytes are progenitor cells that can migrate into circulation and inflamed bronchial epithelium. OBJECTIVES We aim to test the hypothesis that circulating fibrocytes may be the novel cellular targets of IL-25 and the recruitment of IL-25R+ circulating fibrocytes may correlate with asthmatic airway obstruction. METHODS By using flow cytometry analysis, IL-25R+ fibrocytes (i.e., IL-17RB+ fibrocytes) in the freshly isolated peripheral blood mononuclear cells (PBMCs) from 15 control subjects and 35 patients with asthma were enumerated and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of IL-25. RESULTS We found the percentage of total and IL-25R+ (IL-17RB+ ) fibrocytes in PBMCs was significantly increased in patients with asthma when compared with control subjects. Subgroup analysis further showed that the percentage of circulating total and IL-25R+ fibrocytes in PBMCs was markedly increased in asthma patients with severe-to-very severe fixed airflow limitation. Furthermore, IL-25R+ circulating fibrocytes in asthma patients were shown to significantly correlate with forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC), FEV1 % predicted, blood eosinophils, serum IgE and plasma IL-25 levels. CONCLUSION We concluded that circulating fibrocytes are the novel potential cellular targets of IL-25. IL-25R+ fibrocytes are increased in asthma patients. Increased proportions of IL-25R+ fibrocytes predict a distinct asthma phenotype with fixed airflow limitation. Biological therapy-targeting IL-25-fibrocytes axis may offer great promise for the control of asthma patients with severe airway remodelling and obstruction.

Background Mugwort and house dust mite (HDM) are two of the most common inhalant allergens in Asia, however, whether mugwort affects polysensitized HDM+ allergic rhinitis (AR) patients has not been elucidated. Methods Overall, 15,884 AR outpatients were assessed for clinical status. Amino acid sequences of mugwort were determined by mass spectrometry. Afterward, cross-reactivity between mugwort tropomyosin and Dermatophagoides pteronyssinus 10 (Der p10) was analysed by ELISA inhibition and basophil activation experiments. To compare immunologic responses eliciting by two different tropomyosins, peripheral blood mononuclear cells (PBMCs) of HDM-monosensitized patients were stimulated by mugwort, HDM, Der p10 and synthetic peptides representing mugwort tropomyosin respectively. Results Polysensitized HDM+AR patients were mainly sensitized to cat and mugwort, and the positive rate of monosensitized HDM+AR out-clinic patients was increased during the mugwort pollen season. Tropomyosin protein was able to find in mugwort. Synthetic tropomyosin peptide of mugwort activated basophils which were primed by HDM-specific IgE; ELISA inhibition experiment showed synthetic tropomyosin peptide of mugwort inhibited IgE binding to HDM tropomyosin, Der p10. Unlike HDM and Derp 10, mugwort and mugwort tropomyosin mainly induced IFN-γ and IL-17 release in PBMCs of monosensitized HDM+AR patients, but not IL-5. Conclusions Pan-allergen tropomyosin accounts for the cross-reactivity between mugwort and HDM, which reminds HDM+ patients to reduce mugwort exposure in mugwort pollen season in virtue of the tropomyosin induced mild inflammation.

BACKGROUND: Sinonasal symptoms were usually reported to appear initially, yielding the symptoms important for the early detection of coronavirus disease 2019 (COVID-19). This study was conducted retrospectively to investigate the detailed sinonasal manifestations and dynamic profile of real-time reverse transcription polymerase chain reaction (RT-PCR) results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients longitudinally. METHODS: This retrospective study included 11 consecutive patients. The prevalence, timing and severity of sinonasal manifestations were analyzed. Oropharyngeal, nasal, sputum and stool specimens were collected to detect RT-PCR for SARS-CoV-2 over COVID-19 period. RESULTS: Among the 11 patients, 6 (54.5%) were female, and the median age was 51 (IQR, 36-62) years. Seven patients (63.6%) experienced sinonasal symptoms, with 6 (54.5%) exhibiting sinonasal symptoms on the onset day. Seven patients (63.6%) demonstrated nasal obstruction, 5 (45.5%) had rhinorrhea, and 4 (36.4%) exhibited olfactory dysfunction. All six patients with sinonasal symptoms on the onset day had non-severe infections. Most patients (85.7%) with sinonasal symptoms had non-severe infections. Sinonasal symptoms commonly appeared early. The positive RT-PCR rate for SARS-CoV-2 in various specimens was highest in the first week (73.3%), then gradually decreased over the disease course, but 3 patients (27.3%) had experienced a long-lasting fluctuated positive RT-PCR results since 29 days of illness in both groups, especially for two patients with airway comorbidities. CONCLUSIONS: Sinonasal symptoms were more prevalent in patients with mild or moderate COVID-19 and usually appeared early. In addition, regular nucleic acid testing for SARS-CoV-2 should be considered for COVID-19 patients with certain airway comorbidities.

No study has evaluated the diagnostic value of SpyGlass by comparing SpyGlass results and non-SpyGlass results. In this retrospective study, we aimed to compare the diagnostic value of EUS-guided fine-needle aspiration (EUS-FNA) and EUS-FNA combined with SpyGlass to evaluate whether SpyGlass is valuable for increasing the diagnostic yield of EUS-FNA. From April 2015 to April 2020, 251 patients suspected of having pancreatic cystic lesions (PCLs) by imaging techniques who then underwent EUS-FNA were retrospectively enrolled. Only 98 patients who underwent surgical resection with a pathological diagnosis of pancreatic cystic lesion (PCL) were studied. The diagnostic performance outcomes were compared between the EUS-FNA group (EUS-FNA alone, n = 40) and the SpyGlass group (EUS-FNA combined with SpyGlass, n = 58) to assess the value of SpyGlass in diagnosing PCLs. There were 71 females and 27 males with an overall mean age of 47.6 years. The median diameter of the PCLs was 42.2 mm (range, 11.4–100.0 mm). Approximately 37 cysts were localized in the head/neck of the pancreas, while 61 in the body/tail. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of the EUS-FNA group were 96.4% (27/28), 83.3% (10/12), 93.1% (27/29), 90.9% (10/11) and 92.5% (37/40), while those in the SpyGlass group were 100% (54/54), 75% (3/4), 98.2% (54/55), 100% (3/3) and 98.3% (57/58), respectively. The diagnostic accuracy rate in the SpyGlass group was higher than that in the EUS-FNA group; however, no significant difference was found between the two groups (P = 0.368). The diagnostic accuracy of evaluating specific cyst types in the EUS-FNA group was 85% (34/40), similar to that in the SpyGlass group (85.0% vs 84.5%, P = 0.944). SpyGlass seems less valuable for the diagnosis of PCLs when EUS and EUS-FNA have been performed by experienced endoscopists.

Background In this study we compared intraoperative bleeding and regional cerebral oxygenation in patients with different degrees of the reverse Trendelenburg position (RTP) during endoscopic sinus surgery (ESS). Methods In total, 120 patients with chronic rhinosinusitis treated by ESS were randomly assigned to the following 4 groups: a horizontal position (HP) group, and 5°, 10°, and 15° RTP (5-RTP, 10-RTP, and 15-RTP, respectively) groups. The primary outcome was the Boezaart grading scale (BS). The cerebral oxygen saturation (ScO2 ), total blood loss, numerical rating scale (NRS) scores, and complications were also recorded. Results The median BS values in the HP, 5-RTP, 10-RTP, and 15-RTP groups were 2.0, 2.0, 2.1, and 1.7, respectively. Multiple pairwise comparisons of the BS showed significant differences between the 15-RTP group and the other 3 groups (HP, 5-RTP, and 10-RTP). Regarding the NRS and bleeding rate, significant differences were found between the HP and 15-RTP groups. No difference was found in ScO2 among the 4 groups, and no cerebral desaturation events occurred in any group. No complications, including vital organ (heart, brain, and kidney) dysfunction problems, were reported in this study during hospitalization. Conclusion Compared with HP, 5-RTP, and 10-RTP, 15-RTP can improve visual clarity during ESS, and ScO2 is not affected by the degree of RTP. No cerebral deoxygenation or vital organ dysfunction was observed in this study. Therefore, we recommend 15-RTP with moderate deliberate hypotension for ESS.

Background Endoscopic drainage of walled-off necrosis (WON) is still a challenge due to stent-associated problems. We explored endoscopic gastric fenestration (EGF) as an innovative alternative intervention. Aim To assess the feasibility, efficacy and safety of EGF for WON. Methods Between March 2019 and March 2020, five patients with symptomatic WON in close contact with the stomach wall were treated by EGF. Endoscopic ultrasound (EUS) was used to select appropriate sites for gastric fenestration, which then proceeded layer by layer as in endoscopic submucosal dissection. Both the stomach muscularis propria and pseudocyst capsule were penetrated. Fenestrations were expanded up to 1.5-3 cm for drainage or subsequent necrosectomy. Results EGF failed in Case 1 due to nonadherence of WON to the gastric wall. EGF was successfully implemented in the other four cases by further refinement of fenestration site selection according to computed tomography, endoscopy and EUS features. The average procedure time for EGF was 124 min (EUS assessment, 32.3 min; initial fenestration, 28.8 min; expanded fenestration, 33 min), and tended to decrease as experience gradually increased. The diameter of the fenestration site was 1.5-3 cm, beyond the caliber of a lumen-apposing metal stent (LAMS), to ensure effective drainage or subsequent necrosectomy. Fenestration sites showed surprising capacity for postoperative self-healing within 1-3 wk. No EGF-related complications were seen. WON disappeared within 3 wk after EGF. In Case 3, another separate WON, treated by endoscopic LAMS drainage, recurred within 4 d after LAMS removal due to stent-related hemorrhage, and resolved slowly over almost 3 mo. No recurrences were observed in the five patients. Conclusion EGF is an innovative and promising alternative intervention for WON adherent to the gastric wall. The challenge resides in the gauging of actual adherence and in selecting appropriate fenestration sites.

Gliomas grow and invade along white matter fiber tracts. This study assessed the effects of motor cortex gliomas on the cerebral white matter fiber bundle skeleton. The motor cortex glioma group included 21 patients, and the control group comprised 14 healthy volunteers. Both groups underwent magnetic resonance imaging-based 3.0 T diffusion tensor imaging. We used tract-based spatial statistics to analyze the characteristics of white matter fiber bundles. The left and right motor cortex glioma groups were analyzed separately from the control group. Results were statistically corrected by the family-wise error rate. Compared with the controls, patients with left motor cortex gliomas exhibited significantly reduced fractional anisotropy and an increased radial diffusivity in the corpus callosum. The alterations in mean diffusivity (MD) and the axial diffusivity (AD) were widely distributed throughout the brain. Furthermore, atlas-based analysis showed elevated MD and AD in the contralateral superior fronto-occipital fasciculus. Motor cortex gliomas significantly affect white matter fiber microstructure proximal to the tumor. The range of affected white matter fibers may extend beyond the tumor-affected area. These changes are primarily related to early stage tumor invasion.

BackgroundMucus hypersecretion and goblet cell upregulation are common features of chronic rhinosinusitis with nasal polyps (CRSwNP). Although epidermal growth factor (EGF) has been reported to stimulate the expression of MUC5AC, the major macro-molecular constituent of airway mucus, the precise mechanisms underlying the regulation of MUC5AC expression are still not fully understood. The aim of this study therefore was to investigate the role of EGF in regulation of mucin MUC5AC expression and define the involvement of transmembrane protein 16A (TMEM16A) in mediating the EGF-induced mucus overexpression.MethodsHuman nasal epithelial cells (HNECs) derived from tissue of patients with CRSwNP and control subjects were established as air–liquid interface (ALI) cultures. Differentiated cultures were treated with different concentrations of EGF for 4–24 h, and assessed for the expression of TMEM16A and MUC5AC by real-time RT-PCR, Western blotting, ELISA and immunofluorescence. Cultures pretreated for 30 min with T16Ainh-A01 (a specific TMEM16A inhibitor) or LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor) were also assessed similarly following EGF treatment.ResultsEGF treatment (10–100 ng/ml for 4–24 h) significantly increased the expression of both TMEM16A and MUC5AC mRNA and protein, as well as the percentage of TMEM16A-positive cells, MUC5AC-positive cells and cells coexpressing TMEM16A and MUC5AC in HNECs compared to control non-EGF-treated HNECs. Pretreatment of the HNECs with T16Ainh-A01 and LY294002 attenuated these EGF-induced effects.ConclusionsThis study demonstrated that EGF upregulates the expression of MUC5AC in HNECs from CRSwNP patients. Furthermore, the EGF-mediated regulation of MUC5AC expression is likely to involve a PI3K-TMEM16A signalling pathway in CRSwNP.

Flexible stress/strain sensors have widespread applications including healthy monitoring systems, smart robotics, and wearable devices. Graphene, a promising carbon material with several excellent properties, is widely used in flexible stress/strain sensors. Creating a graphene-based pressure sensor with improved sensitivity remains highly challenging owing to the difficulty in widening the band gap of graphene. Herein, a novel heterostructural enhanced-sensitivity stress/strain sensor composed of two-dimensional (2D) graphene and one-dimensional (1D) lead zirconate titanate (PZT) nanowires as the sensitivity material, was fabricated. The polarized charges generated by the piezoelectric nanowires under mechanical stress acted as ionized impurities to increase the scattering carriers of graphene, thereby changing its conductivity; additionally, the high piezoelectric property of nanowires provided numerous polarized charges, resulting in increased scattering carriers. Therefore, the as-fabricated device has an enhanced sensitivity of 2.95 × 10−2 kPa−1, which is higher than that of the pure graphene-based pressure sensor. In particular, the fabricated sensor can detect bending strain, such as the bending and straightening of a finger, and the angle of opening a book. Furthermore, the device can record handwritten signals that can be used as indicators of biometric information. Thus, the fabricated device provides a viable and convenient approach for application in multi-functional electronic wearable devices.

The application of precision medicine concept in clinical work needs a period of practice and experience accumulation. The present article introduced an example of functioning approach named “multidisciplinary therapy strategy of precision medicine” (MDTS‐PM), clinical practice and process, decision‐making, and therapies. The MDTS‐PM integrates multidisciplinary experts and develops real‐time therapeutic strategy based on clinical phenomes and gene sequencing of tissue DNA and circulating DNA. The strength of MDTS‐PM is the combination of dynamical clinical phenomes, genetic information, diagnosis, and treatment to make the therapy more targeted and specific. MDTS‐PM provides comprehensive, whole‐process, and personalized diagnosis and treatment services for patients with complex cancer or complex drug resistance progression; provides guidance for further adjustment of drug use; and establishes a multidisciplinary cooperative team, improves the quality of clinical diagnosis and treatment, and optimizes the process of medical services.

During the 2020 Spring Festival in China, the outbreak of a novel coronavirus, named COVID‐19 by WHO, brought on a worldwide panic. According to the clinical data of infected patients, radiologic evidence of lung edema is common and deserves clinical attention. Lung edema is a manifestation of acute lung injury (ALI) and may progress to hypoxemia and potentially acute respiratory distress syndrome (ARDS). Patients diagnosed with ARDS have poorer prognosis and potentially higher mortality. Although no effective treatment is formally approved for COVID‐19 infection, support of ventilation with oxygen therapy and sometimes mechanical ventilation is often required. Treatment with systemic and/or local glucocorticoids might be helpful to alleviate the pulmonary inflammation and edema, which may decrease the development and/or consequences of ARDS. In this article, we focus on the lung edema and ALI of patients with this widely transmitted COVID‐19 infection in order to provide clinical indications and potential therapeutic targets for clinicians and researchers.

Background Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces reactive oxygen species (ROS) involved in oxidative stress and signal transduction. Recent studies have suggested that NADPH oxidase is associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of this study was to detect the expression of NADPH oxidase subunits and 4-hydroxynonenal (4-HNE) in nasal polyp tissue and normal nasal mucosa, in order to explore the possible role played by NADPH oxidase in the pathogenesis of CRSwNP. Methods Thirteen patients with CRSwNP and 9 normal control subjects were selected to participate in this study, in which we evaluated the expression of different NADPH oxidase subunits (gp91phox , p67phox , p47phox , and p22phox ) in nasal polyp (NP) tissue and control mucosa by Western blotting and real-time polymerase chain reaction (PCR). Immunohistochemistry and immunofluorescence staining were used to detect expression of the p67phox subunit and 4-HNE in NP tissue and normal nasal mucosa. Results Western blot and real-time PCR results showed that p67phox expression was significantly increased in NP tissue when compared with its expression in control mucosa (p = 0.004). p67phox was expressed in the eosinophils and neutrophils found in NP tissue, but not in the macrophages. Additionally, the levels of 4-HNE expression were also significantly increased in NP tissue when compared with control mucosa (p = 0.001). Conclusion The levels of p67phox messenger RNA (mRNA) and protein as well as 4-HNE were both upregulated in NP tissue, suggesting that p67phox and oxidative stress play roles in the pathogenesis of CRSwNP.

Background Eosinophilic (Eos) and non-eosinophilic (non-Eos) chronic rhinosinusitis with nasal polyps (CRSwNP) react differently to clinical treatment, with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) being more likely to recur after surgery. Objective To explore the clinical value of the visual analog scale (VAS), nasal endoscopy score (Lund–Kennedy, L–K), computed tomography (CT) score (Lund–Mackay scoring system, L–M), and blood Eos percentage in the differential diagnosis of Eos CRSwNP and non-Eos CRSwNP. Methods Ninety-nine patients with CRSwNP were enrolled in this study and assigned to 2 groups (Eos CRSwNP and non-Eos CRSwNP). The blood Eos percentage and VAS, L–K, and L–M scores in the 2 groups of patients were compared. A receiver operating characteristic (ROC) was used to assess the usefulness of VAS, L–K, and L–M scores for differentiating Eos CRSwNP and non-Eos CRSwNP. Results There were significantly differences between the Eos CRSwNP group and non-Eos CRSwNP group in the following scores: blood Eos percentage, mean VAS score, olfaction/VAS, general discomfort/L–K, edema score/L–K, olfactory cleft (OC) score via endoscopy, mean L–M score, anteriorethmoid sinus score, posterior ethmoid sinus score, sphenoid sinus score, frontal sinus score, and OC score via CT. An ROC analysis showed that blood Eos percentage had the highest area under the ROC curve (AUC) value (0.749); however, several other scores (olfaction score/VAS, edema score/L–K, and mean L–M score) also had high AUC values. The combination of olfaction score/VAS and blood Eos percentage had the highest clinical convenience score as well as high sensitivity and specificity. A combination of cutoff values for the 2 predictors (blood Eos percentage ≥3.85%, olfaction score/VAS score ≥3) showed a sensitivity of 75.5% and a specificity of 78.0%. Conclusion The olfaction score/VAS score and the blood Eos percentage can be combined to differentiate Eos CRSwNP from non-Eos CRSwNP in a Chinese population.

In this article, a highly integrated $S$ -band prototype multifunction chip (MFC) featuring high integration level, bidirectional operation, reduced number of pads, and optimized power consumption is demonstrated with a GaAs 0.15- $\mu \text{m}$ pHEMT technology. In order to pursue a high integration level, the MFC utilizes four amplifiers, two bidirectional mixers, and compact integrated passive filters. For the sake of power supply pads, the self-biasing technique is adopted with the on-chip power-combining technique. As for the power consumption minimization, when the system voltage is constant, the current reuse technique is selected with optimized transistor size without degradation of the key specifications. The main function for the MFC is to provide double-conversion and gain amplification both in the transmission path and the receiving path on one chip. In transmit mode, the MFC achieves 0-dB gain and 7-dBm $P_{-1\,\mathrm {dB}}$ from 2.6 to 3.2 GHz. The obtained local oscillator (LO)-radio frequency (RF) isolation is better than 50 dB, and the intermediate frequency (IF)-RF isolation is 85 dB. In receive mode, it achieves −5-dB gain with $V_{\mathrm {DD}}$ of the MFC is 5 V. The fabricated MFC occupied 5 mm $\times 5$ mm, which is the largest record area that the process can withstand.

When attempting to analyze and understand large-scale video datasets, choosing training videos using active learning can significantly reduce the annotation costs associated with supervised learning without sacrificing the accuracy of classifiers. However, to further reduce the computational overhead of exhaustive comparisons between low-level visual feature with high dimensions, we have developed a novel video hashing coding model based on an active learning framework. The model optimizes mean average precision in a straightforward way by explicitly considering the structure information in video clips when learning the optimal hash functions. The structure information considered includes the temporal consistency between successive frames and the local visual patterns shared by videos with same semantic labels. Rather than relying on the similarity between paired videos, we use a ranking-based loss function to directly optimize mean average precision. Then, combined with the active learning component, we jointly evaluate the unlabeled training videos according to the uncertainty and average precision values with an efficient algorithm based on structured SVM. Extensive experimental results over several benchmark datasets demonstrate that our approach produces significantly higher search accuracy than traditional query refinement schemes.

With the advent of immune checkpoint inhibitors (ICIs) therapies, a major breakthrough has been made in cancer treatment. However, instead of good results, some patients experienced a deterioration of their disease. This unexpected result is termed as hyper-progressive disease (HPD). The biology of HPD is currently not fully understood. Isolation of CD3+ cells from peripheral blood mononuclear cells (PBMC) in healthy control, tumor patients receiving immunotherapy with or without immunotherapy-induced HPD, then conducted single-cell RNA sequencing (scRNA-seq). By analyzing scRNA-seq data, we identified 15 cell clusters. We observed developed-exhausted CD4+ T cells and regulatory T cells (Tregs) increasingly enriched in HPD group. Meanwhile, some effector T cells were decreased in HPD. The imbalance potentially contributes to the occurrence of HPD and poor clinical prognosis. In addition, we analyzed ligand-receptor interactions between subsets. The ligand-receptor interaction “CD74-MIF” was absent in HPD. However, in vitro experiment, we found that CD74 regulated effector function of effector CD8+ T cells. Overall, the article provides a primary study of immune profile in HPD.

Cardiac voltage‐gated ion channels (VGICs) play critical roles in mediating cardiac electrophysiological signals, such as action potentials, to maintain normal heart excitability and contraction. Inherited or acquired alterations in the structure, expression, or function of VGICs, as well as VGIC‐related side effects of pharmaceutical drug delivery can result in abnormal cellular electrophysiological processes that induce life‐threatening cardiac arrhythmias or even sudden cardiac death. Hence, to reduce possible heart‐related risks, VGICs must be acknowledged as important targets in drug discovery and safety studies related to cardiac disease. In this review, we first summarize the development and application of electrophysiological techniques that are employed in cardiac VGIC studies alone or in combination with other techniques such as cryoelectron microscopy, optical imaging and optogenetics. Subsequently, we describe the characteristics, structure, mechanisms, and functions of various well‐studied VGICs in ventricular myocytes and analyze their roles in and contributions to both physiological cardiac excitability and inherited cardiac diseases. Finally, we address the implications of the structure and function of ventricular VGICs for drug safety evaluation. In summary, multidisciplinary studies on VGICs help researchers discover potential targets of VGICs and novel VGICs in heart, enrich their knowledge of the properties and functions, determine the operation mechanisms of pathological VGICs, and introduce groundbreaking trends in drug therapy strategies, and drug safety evaluation., The structure, distribution, interaction and function of voltage‐gated ion channels (VGICs) maintains a physiological balance of the ionic currents, normal action potential (AP), excitation‐contraction coupling, and synchronization in cardiomyocytes.Various genetic mutations and molecular dysregulation of the VGICs could result in ionic imbalance, abnormal AP waveform, and even cardiac arrhythmia.

In deepwater gas well testing, the high-pressure and low-temperature environment in the wellbore provides conditions for hydrate formation. When the thermodynamic inhibitor is used, it needs a large amount and is difficult to inject. Low-dose hydrate inhibitors such as kinetic inhibitors are rarely used in high supercooling and natural gas–dominated environments. The mixed use of thermodynamic inhibitors and kinetic inhibitors provides a new way. By simulating the wellbore temperature and pressure conditions during the deepwater gas well testing, the inhibiting effect of the mixtures of PVCap and methanol with various concentrations was experimentally tested by using rocking cells with a step-cooling method at 21MPa. The effect of PVCap and its mixture with methanol on hydrate plugging was evaluated by monitoring the movement of slider in the rocking cell. The results showed that 5 wt%, 16 wt%, and 20 wt% methanol mixed with 0.5 wt% PVCap could prolong the induction time, and the higher the methanol concentration, the longer the hydrate induction time. Among them, the best combination of 20wt% methanol and 0.5wt% PVCap can inhibit the hydrate for 379 min. The hydrate was formed but did not block the rocking cell, indicating that the combination of PVCap and methanol could not only prolong the hydrate formation time but also avoid the blockage after hydrate formation. The hydrate formation rate with various inhibitor concentrations was calculated; it may provide some guidance for making a shut-in plan for on-site wells.

We study whether Google search behavior for “mortgage assistance” and “foreclosure help” aggregated in the mortgage default risk indicator (MDRI) of Chauvet et al. (2016) helps predict future house prices and foreclosures in local residential markets. Using a long-run equilibrium model, we disaggregate house prices into their fundamental and bubble components, and we find that MDRI dampens both components of house prices. This negative relationship is robust to various model specifications and time horizons. A higher intensity of search online, however, is associated with lower future foreclosure rates. We also find that foreclosure rates increase after a decline in the fundamental component of home values, but are not sensitive to their transitory (bubble) component. Foreclosure rates are higher in metropolitan areas located in non-recourse states. We interpret these findings as evidence for strategic household behavior. Our paper sheds new light on the predictive power of household sentiment derived from Google searches on prices and foreclosure rates in local housing markets.

Background As a typical “united airway” disease, asthma-chronic rhinosinusitis (CRS) overlap has recently drawn more attention. Bronchiectasis is a heterogeneous disease related to a variety of diseases. Whether bronchiectasis exists and correlates with asthma-CRS patients has not been fully elucidated. The purpose of the study was to explore the presence and characteristics of bronchiectasis in patients with overlapping asthma and CRS. Methods This report describes a prospective study with consecutive asthma-CRS patients. The diagnosis and severity of bronchiectasis were obtained by thorax high-resolution computed tomography (HRCT), the Smith radiology scale and the Bhalla scoring system. CRS severity was evaluated by paranasal sinus CT and the Lund-Mackay (LM) scoring system. The correlations between bronchiectasis and clinical data, fraction of exhaled nitric oxide, peripheral blood eosinophil counts and lung function were analyzed. Results Seventy-two (40.91%) of 176 asthma-CRS patients were diagnosed with bronchiectasis. Asthma-CRS patients with overlapping bronchiectasis had a higher incidence rate of nasal polyps (NPs) (P = 0.004), higher LM scores (P = 0.044), higher proportion of ≥ 1 severe exacerbation of asthma in the last 12 months (P = 0.003), lower postbronchodilator forced expiratory volume in one second (FEV1) % predicted (P = 0.006), and elevated peripheral blood eosinophil counts (P = 0.022). Smith and Bhalla scores were shown to correlate positively with NPs and negatively with FEV1% predicted and body mass index. Cutoff values of FEV1% predicted ≤ 71.40%, peripheral blood eosinophil counts > 0.60 × 109/L, presence of NPs, and ≥ 1 severe exacerbation of asthma in the last 12 months were shown to differentiate bronchiectasis in asthma-CRS patients. Conclusions Bronchiectasis commonly overlaps in asthma-CRS patients. The coexistence of bronchiectasis predicts a more severe disease subset in terms of asthma and CRS. We suggest that asthma-CRS patients with NPs, severe airflow obstruction, eosinophilic inflammation, and poor asthma control should receive HRCT for the early diagnosis of bronchiectasis.

Background Lung cancer is still the main cause of death in patients with cancer, due to poor understanding of intracellular regulations. Of those, osteopontin (OPN) may induce the epithelial‐to‐mesenchymal transition (EMT) to promote tumor cell metastasis. The present study aims to evaluate the regulatory mechanism of internal and external OPN in the development of lung cancer. Methods We evaluated genetic variations and different bioinformatics of genes in chromosome 4 among subtypes of lung cancer using global databases. We validated the expression of OPN and EMT‐related proteins (e.g., E‐cadherin, vimentin) in 208 non‐small‐cell lung cancer (NSCLC) tumors and the adjacent nontumorous tissues, further to explore the function of OPN in the progression of lung cancer, with a focus on a potential communication between OPN and EMT in the lung cancer. Results We found that OPN might act as a target molecule in lung cancer, which is associated with lymph node metastasis, postresection recurrence/metastasis, and prognosis of patients with lung cancer. Biological behaviors and pathological responses of OPN varied among diseases, challenges, and severities. Overexpression of OPN was correlated with the existence of EMT in lung cancer tissues. Internal and external OPN plays the decisive roles in lung cancer cell movement, proliferation, and EMT formation, through the upregulation of OPN‐PI3K and OPN‐MEK pathways. PI3K and MEK inhibitors downregulated the process of EMT and biological behaviors of lung cancer cells, probably through altering vimentin‐associated cytoskeletons. Conclusion OPN can be a metastasis‐associated or specific biomarker for lung cancer and a potential target for antimetastatic treatment., OPN can be a metastasis‐associated or specific biomarker for lung cancer.OPN over‐expressed in lung cancer was correlated with cell movement, proliferation and the existence of EMT.OPN plays the decisive roles in lung cancer biological behaviors and EMT formation, through PI3K/Akt and MAPK/Erk1/2 pathways.

Single-cell biomedicine, a new merging discipline of cell biology and medicine to improve the life quality of patients, gains high priority in cell biology and toxicology. Single-cell nuclear elements are specially focused and headlined to understand regulatory mechanisms by which transcriptional factors, DNA elements, and genome organization interact with each other and contribute to the developmental evolution and dynamic formation of genotoxicity. Cell molecular phenomics, clonal genotypes, and structural metamorphoses during the cell cycle at single-cell level provide deep insights to understanding mechanism-based bridges between cell biology and toxicology, between cell sensitive and resistance, and between chronic diseases and cancer.

Rationale: Particulate matter with an aerodynamic diameter equal or less than 2.5 µm (PM2.5) represents a main constituent of polluted air with a potential detrimental impact on human health. Objec...

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. TH2- and TH17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP. Objective We sought to investigate the interregulation of TH2 and TH17 pathways in Chinese patients with CRSwNP. Methods Levels of key TH2- and TH17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of TH2 and TH17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between TH2- and TH17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored. Results Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive TH2- and TH17-related factors. The TH2 cytokines IL-4 and IL-13 inhibited expression of TH17-related factors, whereas the TH17 cytokines IL-17 and TGF-β1 enhanced expression of TH2-related factors. Dexamethasone treatment inhibited both the TH2 and TH17 pathways. A patient's atopic status was related to their TH2 immune response. Edema scores were positively correlated with the TH2 pathway and negatively correlated with the TH17 pathway. Conclusion The TH2 and TH17 pathways are mutually exclusive and regulate each other, favoring the development of a TH2 immune response in Chinese patients with CRSwNP.

In this paper, we consider a wireless-powered dual-relay network consisting of one multi-antenna source, two single-antenna energy-constrained relays and one single-antenna destination without direct source to destination link. In order to establish the communication flow, the energy-constrained relays harvest energy from the radio frequency transmitted by the source firstly, then exploit the harvested energy to forward the source information to the destination based on distributed space time coding (DSTC). Under this network architecture, three decode-and-forward (DF) technique-based relaying protocols, i.e., time switching-based relaying (TSR) protocol, power splitting-based relaying (PSR) protocol, and hybrid relaying (HR) protocol, are considered to drive the energy transfer and information transmission. To maximize the network throughput, the joint design for the optimal energy and information beamforming vectors employed at the source, the optimal time switching, and power splitting ratios under these three protocols are investigated and solved efficiently by employing simple sequential optimization approach or alternating optimization approach. Simulations are conducted to show the superior performance achieved by our proposed scheme. Moreover, we find that the TSR protocol outperforms the PSR protocol in the low signal-to-noise ratio (SNR) region, while the latter outperforms the former in the high SNR region. And the HR protocol achieves the best performance in any SNR region. At the same time, the effect of the relays’ locations on the throughput performance of these three protocols is also investigated.

Background The location of the origin of the posterior inferior cerebellar artery (PICA) is highly variable. An extracranial origin PICA from the vertebral artery (VA) is not rare. But the PICA originated extradurally where the VA ascends between the transverse foramina of C-2 and C-1, a rare anatomic variant. Double-origin PICA is another rare anatomic variant observed in 1%–4% of patients in whom 2 PICA branches converge distally. Case Description We present a rare cadaveric anatomy case in which both PICAs originated extradurally between the vertebrae C1 and C2, a simultaneously existing right double-origin PICA. For this case, the right PICA was a double-origin PICA, including 1 extradural origin in which the VA ascends between the transverse foramina of C-2 and C-1 and another being intradural and intracranial. Conclusions To our knowledge, this is the first report of a cadaveric anatomy case of bilateral PICA that originated extradurally between the vertebrae C-1 and C-2, and simultaneously there existed a right double-origin PICA. Such a case is rare, but understanding of the anatomic variation is important. To avoid complications during surgery at the craniovertebral junction, these potential variations should be correctly identified preoperatively.

For some professional sports, it is highly required to supervise and analyze the athletics pose in training of athletes. Key frame extraction from training videos plays a key role to facilitate the browse of sport training videos. In this paper, we propose a deep key frame extraction method for analyzing weightlifting sport training videos. To alleviate the bias from complex background, Fully Convolutional Networks (FCN) is employed firstly to extract the region of interest (ROI) which contains mainly the athlete and barbell for a more precise pose estimation of frames. Then over the extracted ROI, Convolutional Neural Networks (CNN) are leveraged to estimate the pose probability of each frame. Finally, a variation aware key frame extraction is constructed to extract the key frames considering neighboring probability difference of frames. The experimental results demonstrate that the proposed method achieves good performance in key frame extraction of sport videos, and significantly outperforms the comparisons.

Urban geological information management systems based on a B/S structures are an inevitable trend in the development of smart geology and big data. Such systems are important platforms for promoting the sharing of data and services among different city entities. It is necessary to overcome the limitations of C/S or partial B/S structures and establish an urban geological information management system based on a comprehensive B/S structure, which is currently rare. According to the above questions, this paper focuses on three types of technical tasks to construct an urban geological information management system based on a B/S structure. In terms of data management, we leave many functions to the server, and group data by type. In terms of data application and sharing, we quickly query and graphically display the data from massive data sets, and perform collaborative analyses of different professional data. In terms of 3D geological modelling and analysis, in order to efficiently provide large-scale 3D geological model analysis in the browser, we explore a new data structure and algorithm for optimization modelling to reduce the amount of model and the number of calculations. Using the above technical methods, we develop a geological information management system for a city in eastern China. The system realizes the “One Map” function for land and resources, creates a platform for the sharing of geological data and services among different entities, and provides technical support for the construction of “smart cities”.

Background We aimed to assess the recurrence risk of sinonasal inverted papillomas (SNIPs), based on a staging system developed according to the originating site of SNIP. Methods A total of 200 patients with SNIP were enrolled, and a staging system was developed based on the originating sites and corresponding recurrence rates of tumor in the patients. In the verification phase, 675 patients with SNIPs were enrolled as above, and the originating sites of the SNIPs were confirmed by an endoscopic sinus surgery. Cluster analysis was performed to determine the stage for each SNIP. Results Overall, 608 patients completed the study. SNIP recurrence rates for stages 1‐4 were 0 (n = 43), 4.0% (n = 420), 13.4% (n = 134), 36.4% (n = 11), respectively (total = 6.4%). Conclusions The origin site‐based classification of SNIP may aid surgeons in selecting appropriate endoscopic surgical approaches to minimize the risk of recurrence.

Although mature podocytes lack tight junctions (TJs) and form slit diaphragms between opposing foot processes, TJ integral membrane protein CLDN5 is predominantly expressed throughout the plasma membrane of podocytes under normal conditions. Here using podocyte specific Cldn5 knockout mice as a model, we identify CLDN5 as a crucial regulator of podocyte function and reveal Cldn5 deletion exacerbates podocyte injury and proteinuria in diabetic nephropathy (DN) mouse model. Mechanistically, CLDN5 absence reduces ZO1 expression and induces the nuclear translocation of ZONAB, followed by transcriptional downregulation of WIF1, which leads to activation of WNT signaling pathway. Knockout Wif1 in podocytes result in the development of proteinuria and typical glomerular ultrastructure change occurring in Cldn5 knockout mice, while targeted delivery of Wif1 to podocytes prevents the development of glomerular nephropathy in Cldn5 knockout diabetic mice. Podocyte-derived WIF1 also plays a paracrine role on tubular epithelial cells, evidenced by animals with podocyte deletion of Cldn5 or Wif1 have worse kidney fibrosis after unilateral ureteral obstruction when compared with littermate controls with intact podocyte WIF1 expression. These findings establish a novel function of podocyte CLDN5 in restricting WNT activity in the kidney.

Huijun Qiu,1,* Rui Zheng,1,* Xinyue Wang,1,* Zhuanggui Chen,2,3 Peiying Feng,2,4 Xuekun Huang,1,2 Yuqi Zhou,2,5 Jin Tao,2,6 Min Dai,2,7 Lianxiong Yuan,8 Xiangdong Wang,9 Luo Zhang,9 Qintai Yang1,2 1Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 4Department of Dermatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 6Department of Gastroenterol, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 7Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 8Department of Science and Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 9Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qintai YangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaTel +86-20-85252252Fax +86-20-85253336Email yangqint@mail.sysu.edu.cnLuo ZhangDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 16 Hougou Hutong, Chongnei Street, Donghuamen Street, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86-10-65141136Fax +86-10-85115988Email dr.luozhang@139.comBackground: To explore the epidemiological characteristics of allergic rhinitis (AR) and allergic conjunctivitis (AC) based on the Internet big data.Methods: The Baidu index (BDI) of keywords “allergic rhinitis” and “allergic conjunctivitis” in Mandarin, the daily pollen concentration (PC) released by the Beijing Meteorological Bureau and the volumes of outpatient visits (OV) of the Beijing Tongren Hospital (Beijing) and the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou) from 2017 to 2020 were obtained. The temporal and spatial changes of AR and AC were discussed. The correlations between BDI and PC/OV were analyzed by Spearman correlation analysis.Results: The trends of BDI of “AR”/“AC” in Beijing showed obvious seasonal variations, but not in Guangzhou. The BDI of “AR” and “AC” was consistent with the OV in both cities (r1AR-BJ=0.580, P< 0.001; r1AR-GZ=0.360, P=0.031; r1AC-BJ=0.885, P< 0.001; r1AC-GZ=0.694, P< 0.001). The BDI of “AR” and “AC” was highly consistent with the change of the PC in Beijing (r AR-Pollen=0.826, P< 0.001; r AC-Pollen=0.564, P< 0.001). The OV of AR in Beijing and Guangzhou decreased significantly in the first half of 2020, but there was no significant change in AC. In the first half of 2020, the OV of AC in Beijing was significantly higher than that of AR, while that of AC in Guangzhou was slightly higher than that of AR.Conclusion: The BDI could reflect the real-world situation to some extent and has the potential to predict the epidemiological characteristics of AR and AC. The BDI and OV of AR decreased significantly, but those of AC were still at a high level, during the COVID-19 pandemic, in the environment where most people in Beijing and Guangzhou wore masks without eye protection.Keywords: allergic rhinitis, allergic conjunctivitis, Internet, Baidu, big data, COVID-19

Background Clear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown. Methods Differentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1). Results A total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)–receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance. Conclusion PCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

Tian Tian,1 Cheng Wang,2– 4 Yuan Xu,5 Yuzhi Bai,1 Jing Wang,1 Zhou Long,2,3 Xiangdong Wang,6,7 Lichun Zhou8 1General Practice Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Institute of Digital Economy Industry, ICT, Hangzhou, People’s Republic of China; 3Luoyang Institute of Information Technology Industries, Luoyang, People’s Republic of China; 4Ningbo Institute of Information Technology Application, CAS, Ningbo, People’s Republic of China; 5Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Institute of Computing Technology (ICT), Chinese Academy of Sciences (CAS), Beijing, People’s Republic of China; 7Beijing Key Laboratory of Mobile Computing and Pervasive Device, Beijing, People’s Republic of China; 8Department of Neurosurgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yuan Xu Email xuyuan3200@sina.comBackground: Previous studies have shown that the gait of patients with type-2 diabetes mellitus is abnormal compared with the healthy group. Currently, a three-dimensional motion analyzer system is commonly used for gait analysis. However, it is challenging to collect data and use in clinical study due to extensive experimental conditions and high price. In this study, we used a wearable gait analysis system (Gaitboter) to investigate the spatial and temporal parameters, and kinematic data of gait in diabetic patients, especially those with peripheral neuropathy. The aim of the study is to evaluate the wearable gait analysis system in diabetic study.Materials and Methods: We conducted a case–control study to analyze the gait of type 2 diabetes mellitus. Gaitboter was used to detect and collect gait data in the ward of Beijing Chao-yang Hospital, Capital Medical University from June 2018 to October 2018. We collected the gait data of participants (N= 146; 73 patients with type 2 diabetes, 16 with peripheral neuropathy and 57 without peripheral neuropathy, and 73 matched controls). The gait data (stance phase, swing phase, double-foot stance phase, single-foot stance phase, walking cadence, stride length, walking speed, off-ground angle, landing angle, maximum swing angle, minimum swing angle, and foot progression angle) in diabetic patients were recorded and compared with controls. SPSS 22.0 statistical software was used to analyzed the gait parameter data.Results: We found that the landing angle and the maximum swing angle of diabetes patients with or without peripheral neuropathy were significantly less than those of the control group (P < 0.05). The walking speed of diabetes patients with peripheral neuropathy is significantly less than those of the control group (P < 0.05).Conclusion: This study confirms that the wearable gait analysis system (Gaitboter) is an ideal system to identify abnormal gait in patients with type 2 diabetes and provides a new device and method for diabetes-related gait research.Keywords: gaitboter, gait analysis, diabetes mellitus, peripheral neuropathy, swing phase

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease with limited treatment options of corticosteroids, sinus surgery, or both. CRSwNP is frequently associated with allergic rhinitis and asthma, but the molecular mechanisms underlying CRSwNP inflammation are not completely understood. We obtained four gene expression profiles (GSE136825, GSE36830, GSE23552, and GSE72713) from four Gene Expression Omnibus (GEO), which collectively included 65 nasal polyp samples from CRSwNP patients and 54 nasal mucosal samples from healthy controls. Using an integrated analysis approach, we identified 76 co-differentially expressed genes (co-DEGs, including 45 upregulated and 31 downregulated) in CRSwNP patients compared with the healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified the terms including immune effector process, leukocyte migration, regulation of the inflammatory response, Staphylococcus aureus infection, and cytokine-cytokine receptor interaction. protein-protein interaction (PPI) network analysis and real-time quantitative PCR (RT-qPCR) showed that 7 genes might be crucial in CRSwNP pathogenesis. Repurposing drug candidates (Alfadolone, Hydralazine, SC-560, Iopamidol, Iloprost, etc) for CRSwNP treatment were identified from the Connectivity Map (CMap) database. Our results suggest multiple molecular mechanisms, diagnostic biomarkers, potential therapeutic targets, and new repurposing drug candidates for CRSwNP treatment.

Background and Objectives We initially reported EUS-guided lauromacrogol ablation (EUS-LA) to treat pancreatic cystic neoplasms (PCNs); however, its long-term effectiveness remains unknown. This study was performed to further determine the effectiveness of EUS-LA in a larger population with a long-term follow-up based on 5 years of experience with EUS-LA. Materials and Methods From April 2015 to April 2020, 279 patients suspected of having PCNs were prospectively enrolled, and seventy patients underwent EUS-guided ablation using lauromacrogol alone. Fifty-five patients underwent follow-up, 35 of whom had a follow-up duration of at least 12 months. The effectiveness of ablation was determined based on volume changes. Results Among the fifty female and twenty male patients with an overall mean age of 50.3 years, cysts were located in the head/neck of the pancreas in 37 patients (52.9%) and in the body/tail of the pancreas in 33 patients (47.1%). The adverse events rate was 3.6% (3/84), with 14 patients undergoing a second ablation. Among the 55 patients who underwent follow-up, the median cystic volume sharply decreased from 11,494.0 mm3 to 523.6 mm3 (P < 0.001), and the mean diameter decreased from 32.0 mm to 11.0 mm (P < 0.001). Postoperative imaging showed complete resolution (CR) in 26 patients (47.3%) and partial resolution (PR) in 15 (27.3%) patients. CR was observed in 18 (51.4%), and PR was observed in 9 (25.7%) patients among the 35 patients followed for at least 12 months. Conclusions EUS-LA was effective and safe for the treatment of PCNs with stable effectiveness based on at least 12 months of follow-up.

Colonoscopy tissue slides examination can find cells of early-stage colon tumor, which is important to clinical diagnosis. DigestPath2019 in MICCAI is a recent challenge to automatically segment colonoscopy lesion regions and classify the whole slide image WSI into benign or malignant. To obtain high accuracy and refined boundary information for lesion segmentation, this paper proposes an end-to-end segmentation and classification framework CoUNet, which combines a segmentation model D-ResUNet and CRFasRNN. Our D-ResUNet combines Deformable ResNet and UNet structure, which modifies the last two residual blocks of ResNet into deformable residual blocks. This strategy can ensure extracting high-level semantic information and retaining low-level cell morphologic information to improve the edge and shape predictions. The connected CRFasRNN formulates the CRF as RNN to reduce noise prediction of segmentation model and refine final segmentation performance. We also propose WSI-level color normalization strategy to normalize each patch in WSI to relieve various staining problem and balanced dice loss for solving data-imbalanced problem. Experimental results on DigestPath2019 show the efficiency and robustness of our proposed framework.

Background The preoperative prediction of the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) remains difficult in clinical practice. Objective We aimed to develop a nomogram that combined peripheral risk factors to clinically predict the recurrence of CRSwNP. Methods Data from 158 CRSwNP patients who underwent endoscopic sinus surgery (ESS) from January 2012 to December 2016 were collected, and the patients were followed up for 3 years. Of these, 96 patients who underwent ESS in an earlier period formed the training cohort for nomogram development, and 62 patients who underwent ESS thereafter formed the validation cohort to confirm the model’s performance. Risk factors for recurrence identified by univariate and multivariate logistic regression were used to create a nomogram. Results The recurrence rate was 29.2% (28/96) for the training cohort and 35.5% (22/62) for the validation cohort. Univariate analysis identified blood eosinophils (Eos), serum IgE level, asthma comorbidity, and the number of previous ESSs as risk factors for recurrence. Among those four parameters, serum IgE level and a previous ESS surgery were identified as two independent risk factors. A nomogram consisting of blood Eos, total serum IgE level, asthma comorbidity, and the number of previous ESSs was constructed, demonstrating a C index of 0.81 (95% CI, 0.79-0.83) and 0.80 (95% CI, 0.77-0.83) for predicting recurrence in the training and validation cohorts, respectively. The nomogram had well-fitted calibration curves. Conclusion The nomogram might be able to preoperatively predict the recurrence of CRSwNP by using currently available and objective parameters. Further studies are required to validate its reliability and effectiveness.

Background Tissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of these two ECM proteins in the expression of MMPs in nasal polyps. Methods The concentrations of MMP‐2, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐12, MMP‐13, TIMP‐1, TIMP‐2, TIMP‐3, TIMP‐4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and were analyzed by adjusted logistic regression and spearman correlation test. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real‐time PCR. Results The protein levels of MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐1, TIMP‐2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. The adjusted logistic regression analyses showed that MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐2, periostin, and tenascin C were related to the occurrence of CRSwNP. Spearman correlation test showed periostin was positively correlated with MMP‐3 and TIMP‐2, and tenascin C was positively correlated with MMP‐3, MMP‐7, MMP‐8, MMP‐9, and TIMP‐2. Periostin stimulated the gene expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in fibroblasts and MMP‐9 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in epithelial cells. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C. Conclusions Periostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.

Background This study aims to explore the information chain management model of large instrument and equipment inter-working in the operating room (OR) led by information nurses. Methods Through the chain management process of large instruments and equipment in the OR, which was based on information nurses, the management model of inter-working and integrating information chain was established, the key links were controlled, and the whole life cycle management of instruments and equipment from expected procurement to scrapping treatment was realized. Using the cluster sampling method, 1562 surgical patients were selected. Among these patients, 749 patients were assigned to the control group before the running mode, and 813 patients were assigned to the observation group after the running mode. The related indexes for large instrument and equipment management in the department before and after the running mode were compared. Results In the observation group, the average time of equipment registration was (22.05 ± 2.36), the cost was reduced by 2220 yuan/year, and the satisfaction rate of the nursing staff was 97.62%. These were significantly better, when compared to the control group (P P Conclusion The integrated management model of large instrument and equipment interworking in the OR based on chain flow realizes the whole life cycle management of instruments and equipment, which is essential to improve management efficiency.

Lung cancer has high mortality, often accompanied with systemic metabolic disorders. The present study aimed at defining values of trans‐nodules cross‐clinical phenomic and lipidomic network layers in patients with adenocarcinoma (ADC), squamous cell carcinomas, or small cell lung cancer (SCLC). We measured plasma lipidomic profiles of lung cancer patients and found that altered lipid panels and concentrations varied among lung cancer subtypes, genders, ages, stages, metastatic status, nutritional status, and clinical phenome severity. It was shown that phosphatidylethanolamine elements (36:2, 18:0/18:2, and 18:1/18:1) were SCLC specific, whereas lysophosphatidylcholine (20:1 and 22:0 sn‐position‐1) and phosphatidylcholine (19:0/19:0 and 19:0/21:2) were ADC specific. There were statistically more lipids declined in male

Acute lung injury is a serious form and major cause of patient death and still needs efficient therapies. The present study evidenced that co‐transplantation of mesenchymal stem cells (MSCs) and telocytes (TCs) improved the severity of experimental lung tissue inflammation, edema, and injury, where TCs increased MSCs migration into the lung and the capacity of MSCs proliferation and movement. Of molecular mechanisms, Osteopontin‐dominant networks were active in MSCs and TCs, and might play supportive and nutrimental roles in the interaction between MSCs and TCs, especially activated TCs by lipopolysaccharide. The interaction between epidermal growth factor and its receptor from MSCs and TCs could play critical roles in communications between MSCs and TCs, responsible for MSCs proliferation and movement, especially after inflammatory activation. Our studies provide the evidence that TCs possess nutrimental and supportive roles in implanted MSCs, and co‐transplantation of MSCs and TCs can be a new alternative in the therapy of acute lung injury., TCs can accelerate the migration of MSCs from the intraperitoneal space into injured lung tissues through intercellular signals and/or cell‐cell interaction.Pre‐activated MSCs and TCs with LPS show more efficient in cell‐cell communication by OPN‐ or EGFR‐dominated signal pathways