[Status of vaccination and related influencing factors in patients with chronic obstructive pulmonary disease: a real-world cross-sectional study].

Objective: To investigate the influenza and pneumonia vaccination rates in patients with chronic obstructive pulmonary disease (COPD), and analyze the factors affecting vaccination. Methods: Totally 4 016 COPD patients at the initial visit were included in the Respiratory Department of Xiangya Second Hospital of Central South University from December, 2016 to December, 2019. Each patient's vaccination status after the visit for 1 year was reviewed, and finally 3 177 patients were included in the analysis. Relevant factors affecting vaccination were analyzed with logistic regression. Results: The overall vaccination rates of COPD patients with influenza vaccine, pneumonia vaccine and influenza combined pneumonia vaccine were 2.3% (72/3 177), 1.1% (34/3 177) and 1.1% (34/3 177), respectively. The influenza vaccination rate of urban patients (3.3%, 41/1 252) was higher than that of rural patients (1.6%, 31/1 925,P=0.002). The rates of influenza vaccine, pneumonia vaccine and influenza combined pneumonia vaccine in ex-smokers with COPD were 3.3% (33/993), 2.1% (21/993), 2.1% (21/993), respectively and 1.7% (25/1 467), 0.7% (11/1 467), 0.7% (11/1 467), in current smokers with COPD, respectively (P=0.034, P=0.015, P=0.015, respectively). The influenza vaccination rate was higher in patients with COPD assessment test (CAT) scored less than 10 (4%, 27/673) than patients with CAT scored more than 10 (1.8%, 45/2 504,P=0.002). In a multifactor analysis, patients who lived in country side, were current smokers, and had more symptoms were less likely to be vaccinated, with an aOR 1.73(95%CI 1.02-2.93), 2.10(95%CI 1.18-3.76), 2.06(95%CI 1.24-3.43), respectively. 81.2% of COPD patients did not receive the vaccine because they did not know the vaccine. Conclusions: Vaccination rates for influenza vaccine, pneumonia vaccine and both of them in COPD patients were low and the patients lacked knowledge of vaccine. The residence, smoking status and symptoms were related to the vaccination of COPD patients, and these should be taken into account in the vaccination health education.

The role of MIR-186 and ZNF545 in inhibiting the proliferation of multiple myeloma cells.

This study aimed to investigate the mechanism underlying the inhibitory effect of tumor suppressor gene miR-186 and zinc finger protein 545 (ZNF545) on the proliferation of multiple myeloma (MM) cells. CD138 magnetic beads were used to isolate different types of myeloma cell lines (KM3, U266, RPMI-8226, and H929), which were then infected by lentivirus carrying the miR-186 gene. Using uninfected myeloma cells as the control, MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide] assay was performed to calculate the rate of cell proliferation at different time points. In addition, the correlation between the expression of Jagged 1 and miR-186 was analyzed by real-time Polymerase Chain Reaction (PCR). Furthermore, the effect of 5-Aza-2-deoxycytidine and acetylase inhibitor Trichomycin A (TSA) on the expression of ZNF545 and proliferation/apoptosis of MM cells was investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting (WB), MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] cell proliferation assay, and Annexin V-FITC/PI staining. Compared with the control group, the proliferation of miR-186-overexpressing U266 and RPMI-8226 cells was significantly decreased. In cell cloning experiments, miR-186 decreased the number of U266 and RPMI-8226 clones while reducing the protein expression of Jagged 1. The expression level of ZNF545 in myeloma patients was also reduced to some extent. ZNF545 protein also promoted the apoptosis of myeloma cells. By inhibiting the proliferation of myeloma cells, miR-186 gene and ZNF protein may be used as tumor suppressors in the treatment of myeloma.

[Prevalence and quality of spirometry and the impact of spirometry training in Hunan, People's Republic of China].

Objective: To explore quality of spirometry in Hunan province and the impact of education on it. Methods: Cross-sectional study and a prospective randomized cohort study. (1) A total of 460 public hospitals in Hunan province were investigated. Research assistants collected 20 consecutive reports of pulmonary ventilation test reports (PVTRs) and basal information of those hospitals which owned spirometry. (2) To measure the effect of education, 28 randomly selected 2(nd) level hospitals which owned spirometry were randomized to intervention and control group (1∶1). The intervention group received a short-time training which included face-to-face lectures and a hand-by-hand operation training course, while the control group received usual care. PVTRs were investigated 3 months after the intervention. All PVTRs were classified to grade A, B, C, D and E according to the Chinese pulmonary ventilation test (PVT) guidelines. Results: The recovery rate was 100%. The spirometry-equipped ratio was 1.6% (2/129) at 1(st) level hospitals, 39.0% (105/269) at 2(nd) level hospitals, 100% (62/62) at 3(rd) level hospitals in Hunan province. There were 100% (2/2), 91.4% (96/105) and 93.5% (58/62) utilization rate at 1(st), 2(nd) and 3(rd) level hospitals. Common reasons for not owning a spirometer were equipment cost and insufficient insurance. Lack of knowledge about spirometry and inadequate benefits were the top two reasons for low utilization rate. There were 3 120 PVTRs from 156 hospitals which used spirometry, a total of 50.4% (1 574/3 120) PVTRs got grade A, a total of 14.8% (462/3 120) PVTRs were judged as unreliable (grade D, E). There were 560 PVTRs and 28 questionnaires, respectively, before and after intervention. The technicians' knowledge improved after education compared to before (9.8±0.6 vs 8.6±1.1) (P<0.05). And 75.0% (210/280) PVTRs got A grade in the intervention group, which was significantly higher than those in the control group (75.0% vs 37.9%, P<0.05). While none of PVTRs was unreliable, which was lower than that in the control group (0 vs 14.6%, P<0.05). Conclusions: The equipment ratio and the utilization rate of spirometry are still low and imbalanced among three levels hospitals in Hunan. The short-time training is helpful to improve quality of spirometry.

p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer's disease.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aß) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aß and mediates Aß-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aß. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aß deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aß deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing ß-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aß toxicity and would be a novel therapeutic target and biomarker for AD.

Kaempferol Promotes Transplant Tolerance by Sustaining CD4+FoxP3+ Regulatory T Cells in the Presence of Calcineurin Inhibitor.

Calcineurin inhibitor cyclosporine is widely used as an immunosuppressant in clinic. However, mounting evidence has shown that cyclosporine hinders tolerance induction by dampening Tregs. Therefore, it is of paramount importance to overcome this pitfall. Kaempferol was reported to inhibit DC function. Here, we found that kaempferol delayed islet allograft rejection. Combination of kaempferol and low-dose, but not high-dose, of cyclosporine induced allograft tolerance in majority of recipient mice. Although kaempferol plus either dose of cyclosporine largely abrogated proliferation of graft-infiltrating T cells and their CTL activity, both proliferation and CTL activity in mice treated with kaempferol plus low-dose, but not high-dose, cyclosporine reemerged rapidly upon treatment withdrawal. Kaempferol increased CD4+FoxP3+ Tregs both in transplanted mice and in vitro, likely by suppressing DC maturation and their IL-6 expression. Reduction in Tregs by low dose of cyclosporine was reversed by kaempferol. Kaempferol-induced Tregs exhibited both allospecific and non-allospecific suppression. Administering IL-6 abrogated allograft tolerance induced by kaempferol and cyclosporine via diminishing CD4+FoxP3+ Tregs. Thus, for the first time, we demonstrated that kaempferol promotes transplant tolerance in the presence of low dose of cyclosporine, which allows for sufficient Treg generation while minimizing side effects, resulting in much-needed synergy between kaempferol and cyclosporine.

Development of FQ-PCR method to determine the level of ADD1 expression in fatty and lean pigs.

To determine how adipocyte determination and differentiation factor 1 (ADD1), a gene involved in the determination of pork quality, is regulated in Laiwu and Large pigs, we used TaqMan fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) to detect differential expression in the longissimus muscle of Laiwu (fatty) and Large White (lean) pigs. In this study, the ADD1 and GAPDH cDNA sequences were cloned using a T-A cloning assay, and the clone sequences were consistent with those deposited in GenBank. Thus, the target fragment was successfully recombined into the vector, and its integrity was maintained. The standard curve and regression equation were established through the optimized FQ-PCR protocol. The standard curve of porcine ADD1 and GAPDH cDNA was determined, and its linear range extension could reach seven orders of magnitudes. The results showed that this method was used to quantify ADD1 expression in the longissimus muscle of two breeds of pig, and was found to be accurate, sensitive, and convenient. These results provide information regarding porcine ADD1 mRNA expression and the mechanism of adipocyte differentiation, and this study could help in the effort to meet the demands of consumers interested in the maintenance of health and prevention of obesity. Furthermore, it could lead to new approaches in the prevention and clinical treatment of this disease.

Utilizing integrating network pharmacological approaches to investigate the potential mechanism of Ma Xing Shi Gan Decoction in treating COVID-19.

Beginning in December 2019, coronavirus disease 2019 (COVID-19), due to 2019-nCoV infection, emerged in Wuhan and spread rapidly throughout China and even worldwide. Employing combined therapy of modern medicine and traditional Chinese medicine has been proposed, in which Ma Xing Shi Gan Decoction (MXSGD) was recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. We investigated the underlying mechanism of MXSGD in treating COVID-19 utilizing the approaches of integrating network pharmacology. A total of 97 active ingredients of MXSGD were screened out, and 169 targets were predicted. The protein-protein interaction network exhibited hub targets of MXSGD, such as Heat shock protein 90, RAC-alpha serine/threonine-protein kinase, Transcription factor AP-1, Mitogen-activated protein kinase 1, Cellular tumor antigen p53, Vascular endothelial growth factor A, and Tumour necrosis factor. Gene Ontology functional enrichment analysis demonstrated that the biological processes altered within the body after taking MXSGD were closely related to the regulation of such processes as the acute inflammatory response, chemokine production, vascular permeability, response to oxygen radicals, oxidative stress-induced apoptosis, T cell differentiation involved in the immune response, immunoglobulin secretion, and extracellular matrix disassembly. KEGG enrichment analysis indicated that the targets of MXSGD were significantly enriched in inflammation-related pathways, immunomodulation-related pathways, and viral infection-related pathways. The therapeutic mechanisms of MXSGD on COVID-19 may primarily involve the following effects: reducing inflammation, suppressing cytokine storm, protecting the pulmonary alveolar-capillary barrier, alleviating pulmonary edema, regulating the immune response, and decreasing fever.

Investigation of the Booroola (FecB) and Inverdale (FecX(I)) mutations in 21 prolific breeds and strains of sheep sampled in 13 countries.

Twenty-one of the world's prolific sheep breeds and strains were tested for the presence of the FecB mutation of BMPR1B and the FecX(I) mutation of BMP15. The breeds studied were Romanov (2 strains), Finn (2 strains), East Friesian, Teeswater, Blueface Leicester, Hu, Han, D'Man, Chios, Mountain Sheep (three breeds), German Whiteheaded Mutton, Lleyn, Loa, Galician, Barbados Blackbelly (pure and crossbred) and St. Croix. The FecB mutation was found in two breeds, Hu and Han from China, but not in any of the other breeds. The 12 Hu sheep sampled were all homozygous carriers of FecB (FecB(B)/FecB(B)) whereas the sample of 12 Han sheep included all three genotypes (FecB(B)/FecB(B), FecB(B)/FecB+, FecB+/FecB+) at frequencies of 0.33, 0.58 and 0.08, respectively. There was no evidence of FecX(I) in any of the breeds sampled.

Ginkgetin Ameliorates Neuropathological Changes in APP/PS1 Transgenical Mice Model.

The extracellular accumulation of amyloid beta protein (Aß), reactive gliosis and cerebral amyloid angiopathy (CAA) play critical roles in the pathogenesis of Alzheimer's disease (AD). Ginkgetin, a biflavone isolated from Ginkgo biloba leaves, was previously reported to exhibit strong neuroprotection against cytotoxic insults induced by oxidative stress and amyloid beta, but it remains unclear whether ginkgetin has therapeutic effect on Alzheimer's disease (AD) in vivo. In the present study, we investigated 9 months treatment effects of ginkgetin diet in APP/PS1 mice. Our results show that ginkgetin can significantly reduce plasma Aß levels 59% and Aß plaque 51% in the brain of APP/PS1 transgenic mice (P<0.05), effectively inhibits cerebral microhemorrhage 69% (P<0.05), significantly decreases astrogliosis 50% and ameliorate inflammation (P<0.05), exhibits several biological properties for AD.

A staggered-grid finite-difference method with perfectly matched layers for poroelastic wave equations.

A particle velocity-strain, finite-difference (FD) method with a perfectly matched layer (PML) absorbing boundary condition is developed for the simulation of elastic wave propagation in multidimensional heterogeneous poroelastic media. Instead of the widely used second-order differential equations, a first-order hyperbolic leap-frog system is obtained from Biot's equations. To achieve a high accuracy, the first-order hyperbolic system is discretized on a staggered grid both in time and space. The perfectly matched layer is used at the computational edge to absorb the outgoing waves. The performance of the PML is investigated by calculating the reflection from the boundary. The numerical method is validated by analytical solutions. This FD algorithm is used to study the interaction of elastic waves with a buried land mine. Three cases are simulated for a mine-like object buried in "sand," in purely dry "sand" and in "mud." The results show that the wave responses are significantly different in these cases. The target can be detected by using acoustic measurements after processing.