Stent migration is one of the common complications following transcatheter valve implantation. This study aims to design a "drum-shaped" balloon-expandable aortic valve stent to address this issue and conduct a mechanical analysis. The implantation process of the stent was evaluated using a method that combines numerical simulation and in vitro experiments. Furthermore, the fatigue process of the stent under pulsatile cyclic loading was simulated, and its fatigue performance was assessed using a Goodman diagram. The process of the stent migrating toward the left ventricular side was simulated, and the force-displacement curve of the stent was extracted to evaluate its anti- migration performance. The results showed that all five stent models could be crimped into a 14F sheath and enabled uniform expansion of the native valve leaflets. The stress in each stent was below the ultimate stress, so no fatigue fracture occurred. As the cell height ratio decreased, the contact area fraction between the stent and the aortic root gradually decreased. However, the mean contact force and the maximum anti-migration force first decreased and then increased. Specifically, model S5 had the smallest contact area fraction but the largest mean contact force and maximum anti-migration force, reaching approximately 0.16 MPa and 10.73 N, respectively. The designed stent achieves a "drum-shaped" change after expansion and has good anti-migration performance.
Stents ; Prosthesis Design ; Heart Valve Prosthesis ; Humans ; Aortic Valve/surgery* ; Stress, Mechanical ; Transcatheter Aortic Valve Replacement/instrumentation*

Objective Air pollution is a leading public health issue.This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai. Methods The study monitored 27 asthma outpatients for a year,collecting data on weather,patient self-management[daily asthma diary,peak expiratory flow(PEF)monitoring,medication usage],spirometry and serum markers.To explore the potential mechanisms of any effects,asthmatic mice induced by ovalbumin(OVA)were exposed to PM2.5. Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma.Acute exposure showed a correlation between PEF and levels of ozone(O3)and nitrogen dioxide(NO2).Chronic exposure indicated that interleukin-5(IL-5)and interleukin-13(IL-13)levels correlated with PM2.5 and PM10 concentrations.In asthmatic mouse models,exposure to PM2.5 increased cytokine levels and worsened lung function.Additionally,PM2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways. Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation.Specifically,PM2.5 significantly contributes to these adverse effects.Further research is needed to elucidate the mechanisms by which PM2.5 impacts asthma.

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged

ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology. MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language. ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on. ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.

Background: Arctic-like (AL) lineages of rabies viruses (RABVs) remains endemic in some Arctic and Asia countries. However, their evolutionary dynamics are largely unappreciated. Objectives: We attempted to estimate the evolutionary history, geographic origin and spread of the Arctic-related RABVs. Methods: Full length or partial sequences of the N and G genes were used to infer the evolutionary aspects of AL RABVs by Bayesian evolutionary analysis. Results: The most recent common ancestor (tMRCA) of the current Arctic and AL RABVs emerged in the 1830s and evolved independently after diversification. Population demographic analysis indicated that the viruses experienced gradual growth followed by a sudden decrease in its population size from the mid-1980s to approximately 2000.Genetic flow patterns among the regions reveal a high geographic correlation in AL RABVs transmission. Discrete phylogeography suggests that the geographic origin of the AL RABVs was in east Russia in approximately the 1830s. The ancestral AL RABV then diversified and immigrated to the countries in Northeast Asia, while the viruses in South Asia were dispersed to the neighboring regions from India. The N and G genes of RABVs in both clades sustained high levels of purifying selection, and the positive selection sites were mainly found on the C-terminus of the G gene. Conclusions The current AL RABVs circulating in South and North Asia evolved and dispersed independently.

Forty-one patients with COVID-19 (22 males and 19 females with the age of 24~94 years) from February to March 2020 were enrolled in the study, including 15 severe or critically ill cases (severe group) and 26 moderate cases (non-severe group). The CT findings of intrapulmonary lesions at admission were evaluated and compared between severe and non-severe groups. There were significant difference between severe and non-severe groups in the aspects of the presence or absence of pure ground-glass opacity (GGO) (χ 2=10.791), GGO with focal consolidation (χ 2=5.512), sheet consolidation (χ 2=27.359), crazy paving sign (χ 2=8.343), thickening of the bronchial wall (χ 2=14.473), air bronchogram sign (χ 2=4.977), and pleural effusion (χ 2=6.561), all P<0.05. Multivariate logistic regression analysis showed that range of lesion involvement was a relevant factor for severe cases( OR=0.029,95 %CI:0.001-0.647, P=0.026). The study indicates that CT features are diverse in COVID-19 patients; there is lack of pure GGO, but more GGO with focal consolidation. The appearance of sheet consolidation and crazy paving sign and wide-range of lesion involvement and pleural effusion in CT findings may be indications for severe COVID-19.

Background: High concentrations of particulate matter less than 2.5 μm in diameter (PM2.5) in poultry houses is an important cause of respiratory disease in animals and humans. Pseudomonas aeruginosa is an opportunistic pathogen that can induce severe respiratory disease in animals under stress or with abnormal immune functions. When excessively high concentrations of PM2.5 in poultry houses damage the respiratory system and impair host immunity, secondary infections with P. aeruginosa can occur and produce a more intense inflammatory response, resulting in more severe lung injury. Objectives: In this study, we focused on the synergistic induction of inflammatory injury in the respiratory system and the related molecular mechanisms induced by PM2.5 and P. aeruginosa in poultry houses. Methods: High-throughput 16S rDNA sequence analysis was used for characterizing the bacterial diversity and relative abundance of the PM2.5 samples, and the effects of PM2.5 and P. aeruginosa stimulation on inflammation were detected by in vitro and in vivo. Results: Sequencing results indicated that the PM2.5 in poultry houses contained a high abundance of potentially pathogenic genera, such as Pseudomonas (2.94%). The lung tissues of mice had more significant pathological damage when co-stimulated by PM2.5 and P. aeruginosa, and it can increase the expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α through nuclear factor (NF)-κB pathway in vivo and in vitro. Conclusions The results confirmed that poultry house PM2.5 in combination with P. aeruginosa could aggravate the inflammatory response and cause more severe respiratory system injuries through a process closely related to the activation of the NF-κB pathway.

Objective To explore the clinical value of nodal metastatic characteristics in predicting the distant metastasis of papillary thyroid carcinoma (PTC).Methods A total of 1 408 PTC patients who met the inclusion criteria and received initial thyroidectomy at our department from January 2006 to December 2011 were enrolled in this study.Results After a median follow-up time of 7.8 years,distant metastases developed in 46 patients.Patients with lateral neck lymph node metastasis ≥7,individual size of lateral neck lymph node metastasis ≥ 1.15 cm and the total number of cervical lymph node metastasis ≥9 were prone to higher risk of distant metastasis;the high risk group had a lower 10-year distant metastasisfree survival (78.7％ vs.98％,x2 =122.941,P ＜0.01) and a shorter distant metastasis-free survival time (99.2 M vs.122.5 M,x2 =122.941,P ＜ 0.01).Conclusions Lateral lymph node metastasis is an independent risk factor for distant metastasis in PTC patients.

Herpesvirus infections in Cervidae are a serious threat affecting some deer species worldwide. In our attempt to identify malignant catarrhal fever-associated herpesviruses in deer herds, ten gammaherpesviral DNA fragments were identified in five species of deer in herds in China by using a pan-herpesvirus polymerase chain reaction assay targeting viral DNA polymerase. Notably, in sambar (Rusa unicolor), a novel gamma-2 herpesvirus was identified that showed a close relationship with fallow deer lymphotropic herpesvirus (LHV), while the other fragments were phylogenetically grouped together with Elk-LHV. Determination of whether these viruses have any clinical implication in these deer species should be undertaken urgently.
Animals ; Cattle ; China ; Deer ; DNA ; DNA, Viral ; Herpesviridae Infections ; Herpesviridae ; Malignant Catarrh ; Polymerase Chain Reaction