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High-speed railway tunnels in various countries have continuously reported accidents of vault falling concrete blocks. Once the concrete block falling occurs, serious consequences follow, and traffic safety may be endangered. The aerodynamic shockwave evolves from the initial compression wave may be an important inducement causing the tunnel lining cracks to grow and form falling concrete blocks. A joint calculation framework is established based on ANSYS Fluent, ABAQUS, and FRANC3D for calculating the crack tip field under the aerodynamic shockwave. The intensification effect of aerodynamic shockwaves in the crack is revealed, and the evolution characteristics of the crack tip field and the influence factors of stress intensity factor (SIF) are analyzed. Results show that (1) the aerodynamic shockwave intensifies after entering the crack, resulting in more significant pressure in the crack than the input pressure. The maximum pressure of the inclined and longitudinal cracks is higher than the corresponding values of the circumferential crack, respectively. (2) The maximum SIF of the circumferential, inclined, and longitudinal crack appears at 0.5, 0.68, and 0.78 times the crack front length. The maximum SIF of the circumferential crack is higher than that of the inclined and longitudinal crack. The possibility of crack growth of the circumferential crack is the highest under aerodynamic shockwaves. (3) The influence of train speed on the SIF of the circumferential crack is more than 40%. When the train speed, crack depth, and crack length change, the change of pressure in the crack is the direct cause of the change of SIF.

Summary: The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and

Objective To develop and validate an ultrasonic radiomics model for predicting the recurrence and differentiation of hepatocellular carcinoma (HCC). Convolutional neural network (CNN) ResNet 18 and Pyradiomics were used to analyze gray-scale-ultrasonic images to predict the prognosis and degree of differentiation of HCC.Methods This retrospective study enrolled 513 patients with HCC who underwent preoperative grayscale-ultrasonic imaging, and their clinical characteristics were observed. Patients were randomly divided into training (n = 413) and validation (n = 100) cohorts. CNN ResNet 18 and Pyradiomics were used to analyze ultrasonic images of HCC and peritumoral images to develop a prognostic and differentiation model. Clinical characteristics were integrated into the radiomics model and patients were stratified into high- and low-risk groups. The predictive effect was evaluated using the C-index and receiver operating characteristic (ROC) curve.Results The model combined with ResNet 18 and clinical characteristics achieved a good predictive ability. The C-indices of early recurrence (ER), late recurrence (LR), and recurrence-free survival (RFS) were 0.695 (0.561–0.789), 0.715 (0.623–0.800) and 0.721 (0.647–0.795), respectively, in the validation cohort, which was superior to the clinical model and ultrasonic semantic model. The model could stratify patients into high- and low-risk groups, which showed significant differences (p

BackgroundChronic pain is often accompanied by emotional dysfunction. Transcranial direct current stimulation (tDCS) has been used for reducing pain, depressive and anxiety symptoms in chronic pain patients, but its therapeutic effect remains unknown.ObjectivesTo ascertain the treatment effect of tDCS on pain, depression, and anxiety symptoms of patients suffering from chronic pain, and potential factors that modulate the effectiveness of tDCS.MethodsLiterature search was performed on PubMed, Embase, Web of Science, and Cochrane Library from inception to July 2022. Randomized controlled trials that reported the effects of tDCS on pain and depression and anxiety symptoms in patients with chronic pain were included.ResultsTwenty-two studies were included in this review. Overall pooled results indicated that the use of tDCS can effectively alleviate short-term pain intensity [standard mean difference (SMD): −0.43, 95% confidence interval (CI): −0.75 to −0.12, P = 0.007] and depressive symptoms (SMD: −0.31, 95% CI, −0.47 to −0.14, P < 0.001), middle-term depressive symptoms (SMD: −0.35, 95% CI: −0.58 to −0.11, P = 0.004), long-term depressive symptoms (ES: −0.38, 95% CI: −0.64 to −0.13, P = 0.003) and anxiety symptoms (SMD: −0.26, 95% CI: −0.51 to −0.02, P = 0.03) compared with the control group.ConclusiontDCS may be an effective short-term treatment for the improvement of pain intensity and concomitant depression and anxiety symptoms in chronic pain patients. Stimulation site, stimulation frequency, and type of chronic pain were significant influence factors for the therapeutic effect of tDCS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=297693, identifier: CRD42022297693.

Abstract While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16− natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.

The dynamic properties of the flow induced by a dielectric barrier discharge (DBD) plasma actuator array are investigated from the Lagrangian perspective. First, numerical simulations based on a body force model are performed to obtain the flow field induced by unsteady plasma actuation in the burst mode. The numerical simulations capture the flow characteristics of plasma actuation well. Subsequently, the ridges of the finite-time Lyapunov exponent field are employed to identify the Lagrangian coherent structures (LCSs). Both the attracting and repelling LCSs organize the plasma-induced flow’s dynamic behaviors. The attracting LCSs visualize the plasma-induced vortices. The vortex formation, development, and merging processes in the unsteady plasma actuation are resolved well by the LCSs. The material transport in the plasma-induced flow is analyzed by tracing the fluid particle motions. Then, the influences of the actuation parameters, duty cycle, and burst frequency on the flow structures are explored via the attracting LCSs. The presented results enhance the understanding of plasma actuation flow physics and promote the optimal use of DBD plasma actuator arrays.

BackgroundThere were limited studies that directly compare the outcomes of various mind-body exercise (MBE) therapies on chronic non-specific low back pain (CNLBP).ObjectivesTo compare the efficacy of the four most popular MBE modes [Pilates, Yoga, Tai Chi (TC), and Qigong] in clinically CNLBP patients, we conducted a systematic review and network meta-analysis (NMA).MethodsWe searched databases for eligible randomized controlled trials (RCTs) (from origin to July 2022). RCTs were eligible if they included adults with CNLBP, and implemented one or more MBE intervention arms using Pilates, yoga, TC, and qigong. In addition, pain intensity and physical function were evaluated using validated questionnaires.ResultsNMA was carried out on 36 eligible RCTs involving 3,050 participants. The effect of exercise therapy on pain was in the following rankings: Pilates [Surface under cumulative ranking (SUCRA) = 86.6%], TC (SUCRA = 77.2%), yoga (SUCRA = 67.6%), and qigong (SUCRA = 64.6%). The effect of exercise therapy on function: Pilates (SUCRA = 98.4%), qigong (SUCRA = 61.6%,), TC (SUCRA = 59.5%) and yoga (SUCRA = 59.0%).ConclusionOur NMA shows that Pilates might be the best MBE therapy for CNLBP in pain intensity and physical function. TC is second only to Pilates in improving pain in patients with CNLBP and has the value of promotion. In the future, we need more high-quality, long-term follow-up RCTs to confirm our findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306905, identifier: CRD42022306905.

Abstract Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC.

BackgroundAging is a significant risk factor in chronic pain development with extensive disability and greater health care costs. Mind-body exercise (MBE) has been scientifically proven to affect the pain intensity and physical health.ObjectivesTo assess the effects of MBE modes (Tai Chi, yoga, and qigong) for treating chronic pain among middle-aged and old people, compared with nonactive and active treatment, as well as function, quality of life, and adverse events.MethodsWe searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Full-Text Database (VIP) till March 2022. No restrictions were chartered within the year and language of publication. We included randomized controlled trials of MBE treatment in middle-aged and elderly people with chronic pain. The overall certainty of evidence was evaluated by using the GRADE approach.ResultsA total of 17 studies (n = 1,332) were included in this review. There was low-certainty evidence indicating that MBE had a moderate effect on reducing pain compared with the nonactive and active control group (standard mean difference (SMD): −0.64, 95% confidence interval (CI): −0.86 to −0.42, P < 0.001). Very-low-certainty evidence showed that the pooled SMD for the functional improvement was −0.75 (95% CI: −1.13 to −0.37, P < 0.001). Low-certainty evidence presented that no influence was observed in physical component summary (SMD: 0.23, 95% CI: −0.16 to 0.62, P = 0.24) and mental component summary (SMD: −0.01, 95% CI −0.39 to 0.36, P = 0.95).ConclusionOur results indicated that MBE was an effective treatment for reducing symptoms of middle-aged and elderly people with chronic pain compared with nonactive and active control groups. TC and qigong had obvious benefits for knee osteoarthritis in self-reported function, but the efficacy of chronic low back pain was uncertain. No significant benefit of MBE on quality of life in older adults with chronic pain was found. More high-quality RCTs should be conducted to explore the efficacy and mechanism of MBE on chronic pain in middle-aged and elderly people from various dimensions, such as affective and cognitive dimensions.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316591, identifier CRD42022316591.

Abstract Background Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. Methods 153 blood spot samples from Bioko malaria patients were collected during 2016–2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. Results A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN–dS (6.2231, p 0.15, p 1) indicated a destabilization of protein structure. Conclusions Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

Abstract Background Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression. Methods Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. Results Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus. Conclusions NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.

Background: Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines.Design: A systematic review and expert consensus.Methods: A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine.Results: Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga).Conclusions: Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five–ten years.

Background: Atrial fibrillation (AF) might lead to adverse cardiac consequences. The association between AF burden and cardiac prognosis is unknown.Methods and Results: This retrospective cohort study enrolled 204 patients (117 males; age 74.5 ± 11.5 years) who underwent dual-chamber pacemaker implantation in our center from October 2003 to May 2017. During a median follow-up of 66.5 months, AF could be detected in 153 (75%) of the 204 pacemaker patients. Primary endpoint events (composite cardiac readmission, stroke or systemic embolism, and all-cause death) occurred in 83 cases (40.7%). In logistic regression analysis, AF detection was associated with increased risks of composite endpoints [odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.3–6.2, p = 0.007], and the hazard was mainly driven by increased cardiac readmission (OR = 2.2, 95% CI: 1.1–4.7, p = 0.034). No significantly elevated risk for new-onset stroke, systemic embolism, or deaths were found in patients with AF detected than those without AF recorded. AF duration grade of more than 6 min suggested progressively increased composite endpoints (OR = 1.8, 95% CI: 1.2–2.7, p for trend = 0.005), cardiac readmission (OR = 1.8, 95% CI: 1.2–2.7, p for trend = 0.005), especially heart failure or acute coronary syndrome-associated readmission (OR = 1.8, 95% CI: 1.2–2.9, p for trend = 0.010), than those with shorter (

Abstract Background Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine. However, antigenic variation and diversity of PfAMA-1 are still major problems to design a universal malaria vaccine based on this antigen, especially against domain I (DI). Detail understanding of the PfAMA-1 gene polymorphism can provide useful information on this potential vaccine component. Here, general characteristics of genetic structure and the effect of natural selection of DIs among Bioko P. falciparum isolates were analysed. Methods 214 blood samples were collected from Bioko Island patients with P. falciparum malaria between 2011 and 2017. A fragment spanning DI of PfAMA-1 was amplified by nested polymerase chain reaction and sequenced. Polymorphic characteristics and the effect of natural selection were analysed using MEGA 5.0, DnaSP 6.0 and Popart programs. Genetic diversity in 576 global PfAMA-1 DIs were also analysed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 program. Results 131 different haplotypes of PfAMA-1 were identified in 214 Bioko Island P. falciparum isolates. Most amino acid changes identified on Bioko Island were found in C1L. 32 amino acid changes identified in PfAMA-1 sequences from Bioko Island were found in predicted RBC-binding sites, B cell epitopes or IUR regions. Overall patterns of amino acid changes of Bioko PfAMA-1 DIs were similar to those in global PfAMA-1 isolates. Differential amino acid substitution frequencies were observed for samples from different geographical regions. Eight new amino acid changes of Bioko island isolates were also identified and their three-dimensional protein structural consequences were predicted. Evidence for natural selection and recombination event were observed in global isolates. Conclusions Patterns of nucleotide diversity and amino acid polymorphisms of Bioko Island isolates were similar to those of global PfAMA-1 DIs. Balancing natural selection across DIs might play a major role in generating genetic diversity in global isolates. Most amino acid changes in DIs occurred in predicted B-cell epitopes. Novel sites mapped on a three dimensional structure of PfAMA-1 showed that these regions were located at the corner. These results may provide significant value in the design of a malaria vaccine based on this antigen.

Objective: To observe the dermoscopic features of psoriasis vulgaris in order to provide evidence basis for differential diagnosis of psoriasis. Methods: From January 2016 to February 2018, 86 cases of psoriasis, 11 of which confirmed by histopathology, were enrolled in this study. Common lesions included papule, erythema, plaque, scalp rash, palmoplantar rash, nail psoriasis and post-treatment lesions. The background color, scale color, scale distribution, vascular morphology, vascular arrangement and vascular orientation were observed using a dermoscope. Results: Typical dermoscopic features of psoriasis included bright red background, silver scales, scattered distribution of dotted vessels and small glomerular vessels arranged in a uniform pattern. These features varied with the types of lesions. Conclusions: Psoriasis displays typical dermoscopic features. Specific dermoscopic features of each type of lesion can facilitate clinical diagnosis of psoriasis.

Abstract. Background:. Primary pulmonary malignancies (PPMs) and non-pulmonary malignancies (PNPMs) may result in airway stenosis requiring stenting. This study aimed to compare and evaluate the clinical features and stent placement outcomes of airway stenosis caused by PPMs and PNPMs. Methods:. A total of 141 patients with malignant airway stenosis who underwent Micro-Tech stent placements between January 2004 and October 2017 at Department of Respiratory Medicine, Beijing Tian Tan Hospital, Capital Medical University were divided into PPM (n = 100) and PNPM groups (n = 41). Patients’ clinical features and stent placement outcomes were collected and analyzed. Chi-square test was used to compare the categorical variables, while independent- or paired-sample t test was used to compare the continuous variables. Results:. There were no significant differences in age, sex, treatment history, respiratory symptoms, and incidence of obstructive pneumonia between groups. Multiple airway involvement (63.0% vs. 31.7%; χ2 = 11.459, P = 0.001) and atelectasis (17.0% vs. 2.4%; χ2 = 5.536, P = 0.019) were more common in the PPM group, while extraluminal obstruction (24.4% vs. 6.0%; χ2 = 8.033, P = 0.005) was more common in the PNPM group. Before stenting, the American Thoracic Society Dyspnea Index (ADI) and Karnofsky Performance Scale (KPS) scores showed no significant differences between groups (all P > 0.05). After stenting, a satisfactory rate of symptom improvement was achieved in both groups (98.0% and 100.0% in the PPM and PNPM groups, respectively; χ2 = 0.016, P = 0.898); ADI and KPS scores, which showed no significant differences between groups (all P > 0.05), were significantly improved in each group (all P

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen causing severe economic loss. However, the molecular mechanism of silkworm resistance to BmNPV and the interactions of this virus with the host during infection remain largely unclear. To explore the virus-binding proteins of silkworms, the midgut subcellular component proteins that may interact with BmNPV were analyzed in vitro based on one- and two-dimensional electrophoresis and far-western blotting combined with mass spectrometry (MS). A total of 24 proteins were determined to be specifically bound to budded viruses (BVs) in two subcellular fractions (mitochondria and microsomes). These proteins were involved in viral transportation, energy metabolism, apoptosis and viral propagation, and they responded to BmNPV infection with different expression profiles in different resistant strains. In particular, almost all the identified proteins were downregulated in the A35 strain following BmNPV infection. Interestingly, there were no virus-binding proteins identified in the cytosolic fraction of the silkworm midgut. Two candidate proteins, RACK1 and VDAC2, interacted with BVs, as determined with far-western blotting and reverse far-western blotting. We speculated that the proteins interacting with the virus could either enhance or inhibit the infection of the virus. The data provide comprehensive useful information for further research on the interaction of the host with BmNPV.

Background: Scarring airway stenosis is commonly seen in China as compared to other developed countries, due to the high prevalence of tuberculosis. Nowadays, interventional bronchoscopy treatment has been widely used to treat this disease in China. This study demonstrated the characteristics of scarring airway stenosis in Chinese adults and retrospectively evaluated the efficacy of interventional bronchoscopy treatment of this disease. Methods: Patients with scarring airway stenosis from 18 tertiary hospitals were enrolled between January 2013 and June 2016. The causes, site, and length of scarring airway stenosis were analyzed, and the efficacy of the interventional bronchoscopy treatment was evaluated. Results: The final study cohort consisted of 392 patients. Endotracheobronchial tuberculosis (EBTB) was the most common cause of scarring airway stenosis (305/392, 77.8%) in Chinese adults with a high rate of incidence in young women. The left main bronchus was most susceptible to EBTB, and most posttuberculosis airway scarring stenosis length was 1.1–2.0 cm. The average clinical success rate of interventional bronchoscopy treatment for scarring airway stenosis in Chinese patients is 60.5%. The stent was inserted in 8.7% scarring airway stenosis in China. Conclusions: Scarring airway stenosis exhibits specific characteristics in Chinese patients. Interventional bronchoscopy is a useful and safe treatment method for the disease.

Choledochal cysts rarely present with acute pancreatitis. We report a patient with type I choledochal cyst(s) who had concomitant acute frank hemorrhagic pancreatitis. A 14-year-old male noted with a history of recurrent abdominal pain, fever and jaundice. Ultrasonography (US) of abdomen at the Emergency Department depicted distended gall bladder with wall thickening. Apparently dilated intrahepatic ducts (IHDs) and fusiform dilatation of the common bile duct (CBD), and mild dilatation of the pancreatic duct were also noted, suggesting a type I choledochal cyst( ). Computed tomography (CT) demonstrated calcifications in the uncinate process of the pancreas in addition to the similar findings on US. He subsequently underwent choledochal cyst excision with a Roux-en-Y hepaticojejunostomy. After surgical treatment, he has been doing well for 3 years.

β-1,3-glucan recognition proteins (βGRPs) as pattern recognition receptors (PRRs) play an important role in recognizing various pathogens and trigger complicated signaling pathways in insects. In this study, we identified a Bombyx mori β-1,3-glucan recognition protein gene named BmβGRP4, which showed differential expression, from a previous transcriptome database. The full-length cDNA sequence was 1244 bp, containing an open reading frame (ORF) of 1128 bp encoding 375 amino acids. BmβGRP4 was strongly expressed in the larval stages and highly expressed in the midgut of B. mori larvae in particular. After BmNPV infection, the expression of BmβGRP4 was reduced significantly in the midgut. Furthermore, a significant increase in the copy number of BmNPV was observed after the knockdown of BmβGRP4 in 5th instar larvae, while the overexpression of BmβGRP4 suppressed the proliferation of BmNPV in BmN cells. Subsequently, the expression analysis of several apoptosis-related genes and observation of the apoptosis morphology demonstrated that overexpression of BmβGRP4 facilitated apoptosis induced by BmNPV in BmN cells. Moreover, BmβGRP4 positively regulated the phosphatase and tensin homolog gene (BmPTEN), while expression of the inhibitor of apoptosis gene (BmIAP) was negatively regulated by BmβGRP4. Hence, we hypothesize that BmNPV infection might suppress BmPTEN and facilitate BmIAP to inhibit cell apoptosis by downregulating the expression of BmβGRP4 to escape host antiviral defense. Taken together, these results show that BmβGRP4 may play a role in B. mori response to BmNPV infection and lay a foundation for studying its functions.

Background: Tracheobronchial mucoepidermoid carcinoma (MEC) is a rare airway tumor in adults for which surgery is considered a first-line treatment. However, some patients already lost the best opportunity of a surgical intervention when diagnoses are confirmed, and surgery causes considerable trauma resulting in partial loss of pulmonary function. Moreover, the tumor is resistant to radiotherapy and chemotherapy. These factors make the treatment of tracheobronchial MEC challenging. This study aimed to evaluate the safety and efficacy of interventional bronchoscopic therapy in adult patients with tracheobronchial MEC. Methods: We retrospectively analyzed the clinical manifestations, bronchoscopic interventions, complications, and outcomes of 11 adult patients with tracheobronchial MEC. Paired t-test was used to analyze the parameters of the American Thoracic Society Dyspnea Index and the Karnofsky Score before and after the first interventional bronchoscopic therapy. Results: All tumors occurred in the main bronchus and were easily visualized by bronchoscopy. After interventional bronchoscopic therapy, the symptoms of all patients showed significant improvement. The American Thoracic Society Dyspnea Index decreased from 1.91 ± 1.22 to 0.27 ± 0.47 (t = 6.708, P < 0.001) and the Karnofsky Score increased from 78.18 ± 16.62 to 95.46 ± 8.20 (t = −5.190, P < 0.001). Bronchoscopic intervention did not result in serious complications or mortality. During the follow-up period between 3 and 96 months after the first therapy, the following results were noted: (1) among the eight patients with low-grade tracheobronchial MEC, only one patient had a relapse and agreed to surgical treatment; (2) among the three patients with high-grade tracheobronchial MEC, one patient required repeated bronchoscopic interventions, one patient died of pulmonary infection, and one patient died of systemic failure owing to tumor metastasis. Conclusions: Interventional bronchoscopic therapy, as an alternative treatment, shows promise in some adult patients with low-grade tracheobronchial MEC confined to the bronchus. However, for adult patients with high-grade tracheobronchial MEC, early diagnosis and surgical treatment are still strongly recommended.

Background: Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. Methods: Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. Results: Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. Conclusions: The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.

Previous studies have revealed that some proteins in Bombyx mori larvae digestive juice show antiviral activity. Here, based on the label-free proteomics data, BmLipase member H-A (BmLHA) was identified as being involved in the response to BmNPV infection in B. mori larvae digestive juice. In the present study, a gene encoding the BmLHA protein in B. mori was characterized. The protein has an open reading fragment of 999 bp, encoding a predicted 332 amino acid residue-protein with a molecular weight of approximately 35.9 kDa. The phylogenetic analysis revealed that BmLHA shares a close genetic distance with Papilio xuthus Lipase member H-A. BmLHA was highly expressed in the middle part of the B. mori gut, and the expression level increased with instar rising in larvae. There was higher expression of BmLHA in A35 than in P50 strains, and it was upregulated in both A35 and P50 strains, following BmNPV infection. The expression level of VP39 decreased significantly in appropriate recombinant-BmLHA-treated groups compared with the PBS-treated group in B. mori larvae and BmN cells. Meanwhile, overexpression of BmLHA significantly reduced the infectivity of BmNPV in BmN cells. These results indicated that BmLHA did not have digestive function but had anti-BmNPV activity. Taken together, our work provides valuable data for the clarification of the molecular characterization BmLHA and supplements research on proteins of anti-BmNPV activity in B. mori.

With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany), Washington University (USA), and Nantong University (China). The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

A method for the analysis of flavonoids in Astragali Radix by high-performance liquid chromatography (HPLC) combined with photodiode-array detection (DAD) and an electrospray ionization (ESI) - mass spectrometry (MS) was developed. After the samples were extracted with ethanol, the optimum separation conditions for these analytes were achieved using a gradient elution system and a 2.0 × 150 mm Shimadzu VP-ODS column. Eight flavonoids were identified to exist in Astragali Radix based on their characteristic UV data and mass spectra. The concentrations of three major components in this herb—ononin, calycosin and formononetin—were determined by LC/ESI-MS in positive selective ion monitoring (SIM) mode. The calibration curves were linear in the range of 0.9~180.0 μg·mL−1 for ononin, 1.8~360.0 μg·mL−1 for calycosin and 1.4~280 μg·mL−1 for formononetin, respectively. The limits of quantification (LOQ) and detection (LOD) were 0.9 μg· mL−1 and 0.2 μg mL−1 for ononin, 1.8 μg mL−1 and 0.5 μg·mL−1 for calycosin, 1.4 μg mL−1 and 0.5 μg·mL−1 for formononetin, respectively. The standard recoveries were between 95.4~104.7%. The developed method was proven to be useful for the quantitative and qualitative analysis of flavonoid constituents in various resources of Astragali Radix.

With the help of chemometric resolution methods, a technique for qualitative and quantitative determination of the volatile chemical constituents in Radix Flemingiae Philippinensis by chromatography-mass spectrometry was developed. After the overlapping chromatographic peaks were resolved into pure chromatograms and spectra using a heuristic evolving latent projections (HELP) method, qualitative analysis was performed by similarity search of the obtained pure mass spectrum of each component in the NIST library and the quantitative results were obtained by calculating the total two-way response volume. A total of 63 components were separated and 55 components were identified, accounting for 90.62% of the total content. The main components were farnesol isomer and β-caryophyllene, accounting for 31.33% and 12.60% of the total content, respectively. The obtained results can provide useful information for further study and development of Radix Flemingiae Philippinensis.

BACKGROUND: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. PATIENTS AND METHODS: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. RESULTS: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. CONCLUSIONS: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

A series of new substituted 3-[4-(phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives bearing groups methoxy, tert-butyl, and atoms of halogens at the para-position of the A-ring were synthesized and in vitro biological activities were evaluated as nonsugar α-glucosidase inhibitors. Most of the test compounds demonstrated significant α-glucosidase inhibitory activity relative to that of Acarbose (IC50 = 29.26 μM). The para-substitution with a methoxy group or halogens could notably increase the potency. Compounds 17, 18, and 23, with IC50 values of 0.025 μM, 0.014 μM, and 0.018 μM, respectively, may be of significance for the further development of new nonsugar α-glucosidase inhibitors.

Humans produce exhaled breath particles (EBPs) during various breath activities, such as normal breathing, coughing, talking, and sneezing. Airborne transmission risk exists when EBPs have attached pathogens. Until recently, few investigations had evaluated the size and concentration distributions of EBPs from mechanically ventilated patients with different ventilation mode settings. This study thus broke new ground by not only evaluating the size concentration distributions of EBPs in mechanically ventilated patients, but also investigating the relationship between EBP level and positive expiratory end airway pressure (PEEP), tidal volume, and pneumonia. This investigation recruited mechanically ventilated patients, with and without pneumonia, aged 20 years old and above, from the respiratory intensive care unit of a medical center. Concentration distributions of EBPs from mechanically ventilated patients were analyzed with an optical particle analyzer. This study finds that EBP concentrations from mechanically ventilated patients during normal breathing were in the range 0.47-2,554.04 particles/breath (0.001-4.644 particles/mL). EBP concentrations did not differ significantly between the volume control and pressure control modes of the ventilation settings in the mechanically ventilated patients. The patient EBPs were sized below 5 µm, and 80% of them ranged from 0.3 to 1.0 µm. The EBPs concentrations in patients with high PEEP (> 5 cmH₂O) clearly exceeded those in patients with low PEEP (≤ 5 cmH₂O). Additionally, a significant negative association existed between pneumonia duration and EBPs concentration. However, tidal volume was not related to EBPs concentration.

Oxysterols are oxidation products of cholesterol. Cholestane-3β, 5α, 6β-triol (abbreviated as triol) is one of the most abundant and active oxysterols. Here, we report that triol exhibits anti-cancer activity against human prostate cancer cells. Treatment of cells with triol dose-dependently suppressed proliferation of LNCaP CDXR-3, DU-145, and PC-3 human prostate cancer cells and reduced colony formation in soft agar. Oral administration of triol at 20 mg/kg daily for three weeks significantly retarded the growth of PC-3 xenografts in nude mice. Flow cytometric analysis revealed that triol treatment at 10-40 µM caused G1 cell cycle arrest while the TUNEL assay indicated that triol treatment at 20-40 µM induced apoptosis in all three cell lines. Micro-Western Arrays and traditional Western blotting methods indicated that triol treatment resulted in reduced expression of Akt1, phospho-Akt Ser473, phospho-Akt Thr308, PDK1, c-Myc, and Skp2 protein levels as well as accumulation of the cell cycle inhibitor p27(Kip). Triol treatment also resulted in reduced Akt1 protein expression in PC-3 xenografts. Overexpression of Skp2 in PC-3 cells partially rescued the growth inhibition caused by triol. Triol treatment suppressed migration and invasion of DU-145, PC-3, and CDXR-3 cells. The expression levels of proteins associated with epithelial-mesenchymal transition as well as focal adhesion kinase were affected by triol treatment in these cells. Triol treatment caused increased expression of E-cadherin protein levels but decreased expression of N-cadherin, vimentin, Slug, FAK, phospho-FAK Ser722, and phospho-FAK Tyr861 protein levels. Confocal laser microscopy revealed redistribution of β-actin and α-tubulin at the periphery of the CDXR-3 and DU-145 cells. Our observations suggest that triol may represent a promising therapeutic agent for advanced metastatic prostate cancer.

EphrinA5, a member of Eph/Ephrin family, possesses two alternative isoforms, large ephrinA5 isoform (ephrinA5L) and small ephrinA5 isoform (ephrinA5S). EphrinA5L is a putative tumor suppressor in several types of human cancers. However, the role of ephrinA5S in hepato-carcinogenesis remains unclear. In this study, we evaluate the role of ephrinA5 isoforms in human hepatocellular carcinomas (HCC).A total of 142 paired HCCs and peritumoral liver tissue was examined for relative expression of ephrinA5L and ephrinA5S by using quantitative real-time polymerase chain reaction. We analyzed their expression in relation to clinical parameters, disease-free survival and overall survival. Functional assays were performed to dissect the possible underlying mechanisms. Both ephrinA5L and ephrinA5S were significantly downregulated in HCCs, as compared to those in peritumoral tissue (p = 0.013 and 0.001). Univariate analysis demonstrated that ephrinA5S was positively correlated with old age and histological grade. In multivariate analysis, high ephrinA5S expression in peritumoral tissue had better disease-free survival (p = 0.002) and overall survival (p = 0.045) in patients with HCC after surgical resection. Functional analysis in HCC cell lines revealed that ephrinA5S had a more potent suppressive effect than ephrinA5L on cell proliferation (p