[Correlative factors analysis and predictive model construction of intestinal flora imbalance during acute exacerbation of chronic obstructive pulmonary disease].

Objective: To explore correlative factors and construct predictive model of intestinal flora imbalance in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods: The patients in acute exacerbation stage of COPD (AECOPD) hospitalized in Yixing People's Hospital from January 1 to December 31, 2019 were included. According to the clinical symptoms and results of fecal examination, the subjects were divided into case group (n=45) and control group (n=83). Multivariate logistic regression was used to analyze the correlative factors of intestinal flora imbalance in AECOPD patients. The prediction model of intestinal flora imbalance in patients with AECOPD was constructed according to the results of factor logistic regression analysis, and the effectiveness of the prediction model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The ages of subjects in case group and control group were (76±9) and (74±8) years old, respectively, among which males accounted for 80.0% (36/45) and 69.9% (58/83), respectively. The multivariate logistic regression model analysis showed that serum albumin concentration, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus were correlative factors of intestinal flora imbalance in patients with AECOPD. The OR (95%CI) were 0.98 (0.80-0.97), 3.70 (1.79-11.72), 2.62 (1.46-10.80) and 3.85 (1.17-8.58), respectively. The prediction model of intestinal flora imbalance was logit P=3.858-0.13×serum albumin consentration+1.52×acute exacerbation ≥2 times/year+1.379×chronic cor pulmonale+1.155×diabetes mellitus. The area under the ROC curve of this model was 0.847 and the sensitivity and specificity of the prediction model were 88.9% and 71.1%, respectively. Conclusions: Serum albumin, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus are correlative factors of intestinal flora imbalance in patients with AECOPD. The predictive model shows high clinical value in predicting intestinal flora imbalance in patients with AECOPD.

In vitro and in vivo studies on a Mg-Sr binary alloy system developed as a new kind of biodegradable metal.

Magnesium alloys have shown potential as biodegradable metallic materials for orthopedic applications due to their degradability, resemblance to cortical bone and biocompatible degradation/corrosion products. However, the fast corrosion rate and the potential toxicity of their alloying element limit the clinical application of Mg alloys. From the viewpoint of both metallurgy and biocompatibility, strontium (Sr) was selected to prepare hot rolled Mg-Sr binary alloys (with a Sr content ranging from 1 to 4 wt.%) in the present study. The optimal Sr content was screened with respect to the mechanical and corrosion properties of Mg-Sr binary alloys and the feasibility of the use of Mg-Sr alloys as orthopedic biodegradable metals was investigated by in vitro cell experiments and intramedullary implantation tests. The mechanical properties and corrosion rates of Mg-Sr alloys were dose dependent with respect to the added Sr content. The as-rolled Mg-2Sr alloy exhibited the highest strength and slowest corrosion rate, suggesting that the optimal Sr content was 2 wt.%. The as-rolled Mg-2Sr alloy showed Grade I cytotoxicity and induced higher alkaline phosphatase activity than the other alloys. During the 4 weeks implantation period we saw gradual degradation of the as-rolled Mg-2Sr alloy within a bone tunnel. Micro-computer tomography and histological analysis showed an enhanced mineral density and thicker cortical bone around the experimental implants. Higher levels of Sr were observed in newly formed peri-implant bone compared with the control. In summary, this study shows that the optimal content of added Sr is 2 wt.% for binary Mg-Sr alloys in the rolled state and that the as-rolled Mg-2Sr alloy in vivo produces an acceptable host response.

Microstructure and characteristics of the metal-ceramic composite (MgCa-HA/TCP) fabricated by liquid metal infiltration.

In this article, a novel MgCa alloy-hydroxyapatite-tricalcium phosphate (HA/TCP) composite was fabricated using the liquid alloy infiltration technique. The feasibility of the composite for biomedical applications was studied through mechanical testing, electrochemical testing, immersion testing, and cell culture evaluation. It was shown that the composite had a strength about 200-fold higher than that of the original porous HA/TCP scaffold but retained half of the strength of the bulk MgCa alloy. The corrosion test indicated that the resulting composite exhibited an average corrosion rate of 0.029 mL cm⁻² h⁻¹ in the Hank's solution at 37°C, which was slower than that of the bulk MgCa alloy alone. The indirect cytotoxicity evaluation revealed that 100% concentrated (i.e., undiluted or as-collected) extract of the MgCa-HA/TCP composite showed significant toxicity to L-929 and MG63 cells (p < 0.05). In contrast, the diluted extracts with 50 and 10% concentrations of the MgCa-HA/TCP composite exhibited a similar degree of cell viability (p > 0.05), equivalent to the grade I cytotoxicity of the standard ISO 10993-5: 1999.

Corrosion resistance and surface biocompatibility of a microarc oxidation coating on a Mg-Ca alloy.

The Mg-Ca alloy system has been proposed as a potential new kind of degradable biomaterial with possible application within bone. Here microarc oxidation (MAO) coatings were fabricated on top of a Mg-Ca alloy using different applied voltages and the effect of applied voltage on the surface morphology and phase constitution, hydrogen evolution, pH variation in the immersion solution and in vitro biocompatibility of the MAO coating on the Mg-Ca alloy were extensively studied. It was found that the thickness and pore size of the MAO coating increased with the increasing applied voltage, whereas some micro-pores could be seen inside the 400 V treated MAO coating. The 360 V treated MAO coating gave the best long-term corrosion resistance during a 50 days immersion test. All the MAO coatings could promote MG63 cell adhesion, proliferation and differentiation in comparison with the uncoated Mg-Ca alloy sample, due to significantly reduced Mg ion release and pH value variations in the culture medium. After 5 days culture well-spread and elongated MG63 cells could be seen on the surface of the 360 V and 400 V MAO coatings, in contrast to no cells on the uncoated Mg-Ca alloy sample. In summary, MAO showed beneficial effects on the corrosion resistance of, and thus improved cell adhesion to, the Mg-Ca alloy, and should be a good surface modification method for other biomedical magnesium alloys.

Corrosion fatigue behaviors of two biomedical Mg alloys - AZ91D and WE43 - In simulated body fluid.

Magnesium alloys have been recently developed as biodegradable implant materials, yet there has been no study concerning their corrosion fatigue properties under cyclic loading. In this study the die-cast AZ91D (A for aluminum 9%, Z for zinc 1% and D for a fourth phase) and extruded WE43 (W for yttrium 4%, E for rare earth mischmetal 3%) alloys were chosen to evaluate their fatigue and corrosion fatigue behaviors in simulated body fluid (SBF). The die-cast AZ91D alloy indicated a fatigue limit of 50MPa at 107 cycles in air compared to 20MPa at 106 cycles tested in SBF at 37°C. A fatigue limit of 110MPa at 107 cycles in air was observed for extruded WE43 alloy compared to 40MPa at 107 cycles tested in SBF at 37°C. The fatigue cracks initiated from the micropores when tested in air and from corrosion pits when tested in SBF, respectively. The overload zone of the extruded WE43 alloy exhibited a ductile fracture mode with deep dimples, in comparison to a brittle fracture mode for the die-cast AZ91D. The corrosion rate of the two experimental alloys increased under cyclic loading compared to that in the static immersion test.

Microstructure, biocorrosion and cytotoxicity evaluations of rapid solidified Mg-3Ca alloy ribbons as a biodegradable material.

Rapidly solidified (RS) Mg­3Ca alloy ribbons were prepared by the melt-spinning technique at different wheel rotating speeds (15 m s(-1), 30 m s(-1) and 45 m s(-1) with the as-cast Mg­3Ca alloy ingot as a raw material. The RS45 Mg­3Ca alloy ribbon showed a much more fine grain size feature (approximately 200­500 nm) in comparison to the coarse grain size (50­100 µm)of the original as-cast Mg­3Ca alloy ingot. The corrosion electrochemical tests in simulated body fluid indicated that the corrosion rate of the as-cast Mg­3Ca alloy was strongly reduced by the RS procedure and tended to be further decreased with increasing wheel rotating speeds(1.43 mm yr(-1) for RS15, 0.94 mm yr(-1) for RS30 and 0.36 mm yr(-1) for RS45). The RS Mg­3Ca alloy ribbons showed more uniform corrosion morphology compared with the as-cast Mg­3Ca alloy after polarization. The cytotoxicity evaluation revealed that the three experimental as-spun Mg­3Ca alloy ribbon extracts did not induce toxicity to the L-929 cells,whereas the as-cast Mg­3Ca alloy ingot extract did. The L-929 cells showed more improved adhesion on the surfaces of the three as-spun Mg­3Ca alloy ribbons than that of the as-cast Mg­3Ca alloy ingot.

In vitro degradation and cytotoxicity of Mg/Ca composites produced by powder metallurgy.

Mg/Ca (1 wt.%, 5 wt.%, 10 wt.% Ca) composites were prepared from pure magnesium and calcium powders using the powder metallurgy method, aiming to enlarge the addition of Ca content without the formation of Mg(2)Ca. The microstructures, mechanical properties and cytotoxicities of Mg/Ca composite samples were investigated. The corrosion of Mg/Ca composites in Dulbecco's modified Eagle's medium (DMEM) for various immersion intervals was studied by electrochemical impedance spectroscopy measurements and environmental scanning electron microscope, with the concentrations of released Mg and Ca ions in DMEM for various immersion time intervals being measured. It was shown that the main constitutional phases were Mg and Ca, which were uniformly distributed in the Mg matrix. The ultimate tensile strength (UTS) and elongation of experimental composites decreased with increasing Ca content, and the UTS of Mg/1Ca composite was comparable with that of as-extruded Mg-1Ca alloy. The corrosion potential increased with increasing Ca content, whereas the current density and the impedance decreased. It was found that the protective surface film formed quickly at the initial immersion stage. With increasing immersion time, the surface film became compact, and the corrosion rate of Mg/Ca composites slowed down. The surface film consisted mainly of CaCO(3), MgCO(3)x3H(2)O, HA and Mg(OH)(2) after 72 h immersion in DMEM. Mg/1Ca and Mg/5Ca composite extracts had no significant toxicity (p>0.05) to L-929 cells, whereas Mg/10Ca composite extract induced approximately 40% reduced cell viability.

Influence of artificial biological fluid composition on the biocorrosion of potential orthopedic Mg-Ca, AZ31, AZ91 alloys.

The electrochemical behavior of potential orthopedic Mg-Ca, AZ31 and AZ91 alloys was studied in Hank's solution, Dulbecco's Modified Eagle's Medium (DMEM) and serum-containing medium (DMEM adding 10% fetal bovine serum (DMEM+FBS)) over a 7 day immersion period. The biocorrosion of the above three alloys for various immersion time intervals was investigated by linear polarization and electrochemical impedance spectroscopy (EIS). After 7 day immersion, potentiodynamic polarization tests were carried out and the surface morphologies of experimental samples were examined by scanning electron microscopy (SEM) observation complemented by energy-disperse spectrometer (EDS) analysis. It was shown that the corrosion of magnesium alloys was influenced by the composition of the solution. The results indicated that chloride ion could reduce the corrosion resistance and the hydrocarbonate ions could induce rapid surface passivation. The adsorbed amino acid on the experimental magnesium alloys' surface increased their polarization resistance and reduced current densities. The influence of the serum protein on corrosion was found to be associated with the magnesium alloy compositions. A Mg-Ca alloy exhibited an increased corrosion rate in the presence of serum protein. An AZ31 alloy showed an increased corrosion rate in DMEM+FBS in the initial 3 day immersion and the corrosion rate decreased thereafter. An AZ91 alloy, with high Al content, showed a reduced corrosion rate with the addition of FBS into DMEM.

Surface modification of an Mg-1Ca alloy to slow down its biocorrosion by chitosan.

The surface morphologies before and after immersion corrosion test of various chitosan-coated Mg-1Ca alloy samples were studied to investigate the effect of chitosan dip coating on the slowdown of biocorrosion. It showed that the corrosion resistance of the Mg-Ca alloy increased after coating with chitosan, and depended on both the chitosan molecular weight and layer numbers of coating. The Mg-Ca alloy coated by chitosan with a molecular weight of 2.7 x 10(5) for six layers has smooth and intact surface morphology, and exhibits the highest corrosion resistance in a simulated body fluid.

A study on alkaline heat treated Mg-Ca alloy for the control of the biocorrosion rate.

To reduce the biocorrosion rate by surface modification, Mg-Ca alloy (1.4wt.% Ca content) was soaked in three alkaline solutions (Na(2)HPO(4), Na(2)CO(3) and NaHCO(3)) for 24h, respectively, and subsequently heat treated at 773K for 12h. Scanning electron microscopy and energy-dispersive spectroscopy results revealed that magnesium oxide layers with the thickness of about 13, 9 and 26microm were formed on the surfaces of Mg-Ca alloy after the above different alkaline heat treatments. Atomic force microscopy showed that the surfaces of Mg-Ca alloy samples became rough after three alkaline heat treatments. The in vitro corrosion tests in simulated body fluid indicated that the corrosion rates of Mg-Ca alloy were effectively decreased after alkaline heat treatments, with the following sequence: NaHCO(3) heated

Synaptic integration at a sensory-motor reflex in the leech.

1. In the medicinal leech the distribution of synapses from the pressure sensory (P) neurone to the annulus erector (AE) motoneurone and the site of impulse initiation in the AE cell were determined to understand better the integration of sensory inputs by the motoneurone. 2. The axon of the AE cell bifurcates before leaving the ganglion. Laser photoablation experiments indicated that the axon proximal to the bifurcation is inexcitable. Two techniques, laser photoablation and measurement of impulse timing, each located the site of impulse initiation at the bifurcation. 3. The medial P cell makes a monosynaptic connection with the AE cell, eliciting an excitatory postsynaptic potential (EPSP) of 1-3 mV amplitude recorded in the AE cell soma. 4. Intracellular injection of dyes into separate cells showed that P cell branches appear to contact AE cell branches both ipsilaterally and contralaterally. Laser photoablation of selected portions of the P and AE cells' axons revealed functional contacts on both sides. 5. The primary axon bifurcation of the AE cell is the site of integration of synaptic potentials that spread passively from both sides of the ganglion. These summed synaptic potentials account for the concerted activity of the two AE cells in each ganglion.

Effect of conduction block at axon bifurcations on synaptic transmission to different postsynaptic neurones in the leech.

1. The cutaneous receptive field of the medial pressure (mP) sensory neurone in the leech has been examined. The cell has one major receptive field and an anterior and a posterior minor receptive field, principally on lateral and dorsal skin. The two minor receptive fields are contiguous with the major receptive field and are innervated by fine anterior and posterior axons, but there is no overlap between major and minor receptive fields. 2. At low frequencies of stimulation of the minor receptive fields, conduction block takes place in the mP cell at the central branch point within the leech ganglion. 3. The mP cell synapses directly with many other cells in the leech ganglion, including the anterior pagoda (AP) cell, longitudinal (L) motoneurone and the annulus erector (AE) motoneurone, which were studied as a group of postsynaptic neurones. Conduction block in the mP cell affects its synaptic transmission to all three postsynaptic neurones, but the effect can be different in different postsynaptic neurones. Block at the central branch point for an impulse travelling along the anterior axon reduces transmission to the AE cell much more than to the AP or L cells, while block at the central branch for an impulse travelling along the posterior axon has the reverse effect. 4. The distribution of functional connections of the branches of the mP cell with each postsynaptic cell was studied. For this analysis, branches of the mP cell were selectively silenced either during conduction block or by laser microsurgery. Generally, nearly all of the functional connections with the L and AP cell are made by anterior branches of the mP cell while the connection with the AE cell was primarily made by posterior branches of the mP cell. 5. The possible sites of contact between the mP cell and postsynaptic cells were determined by injecting separate markers into the mP cell and a postsynaptic cell. In confirmation of physiology, the mP cell's posterior branches had few, if any, contacts with the AP cell, while anterior branches had few, if any, contacts upon the AE cell. 6. Conduction block can thus act as a switch in the central nervous system (CNS), altering the mP cell's pattern of synaptic transmission to different postsynaptic neurons depending upon the region of a single sensory neurone's receptive field that is stimulated. This effect, dependent upon inputs to a single neurone, may be expected to influence the performance of the system and its outputs.

Unequal competition between axons for neuronal targets.

Precise wiring of the nervous system depends not only on a matching between neurons and their synaptic targets, but also upon competition between neurons for particular targets. Neurons in adult leeches regenerate synaptic connections with their usual neuronal targets in the central nervous system, selecting only those targets with which they connect during embryogenesis. Thus during development axons of nociceptive (N) sensory cells make contacts on the cell bodies of certain neurons in adjacent ganglia but not upon those same types of cells in their own ganglion. After injury the N cell axons accurately regenerate contacts on the appropriate target cells. An abnormal feature observed after injury is that N cell axons sprout and grow to make contacts upon cell bodies within their own ganglion. This is a consequence of the normal innervation of those cells having been removed, thereby eliminating the source of competition. Similar competition during embryogenesis may guide the formation of selective connections.

Competitive interactions between neurons making axosomatic contacts in the leech.

Axons of lateral nociceptive (N) neurons in leech segmental ganglia wrap certain somata in adjacent ganglia but no somata in their own ganglion. In adults, the N neurons, which accurately regenerate axosomatic wrappings, can be induced to sprout in their own ganglion and wrap target homologues if the ganglion is isolated by cutting the nerve cord. Manipulations that denervate the new targets without injuring the lateral N cell, including focal lesions and protease injections into other N cells, also cause sprouting within 2-4 months. In contrast, cutting the lateral N cell's axons causes little or no sprouting within the ganglion without denervation. Therefore, denervation rather than injury accounts for sprouting within the ganglion. It is concluded that lateral N cells can wrap somata in their own ganglion that are homologues of their usual targets, but they are prevented from doing so by axonal wrappings from N cells in adjacent ganglia.

Laser microbeam axotomy and conduction block show that electrical transmission at a central synapse is distributed at multiple contacts.

Touch (T) sensory neurons in the leech innervate defined regions of skin and synapse on other neurons, including other T cells, within the ganglionic neuropil. The cells' receptive fields in the periphery are comprised of a central region, innervated by thick axons, and adjoining regions (minor fields) innervated by thinner axons. Secondary branches, known to be sites of synapses, emerge from the thinner and thicker axons. Pairs of T cells appear to make up to 200 separate contacts distributed within the neuropil. When the T cell is hyperpolarized, as occurs during natural stimulation of the cell, action potentials generated in the minor field and travelling into the ganglion along the thin axons may fail to conduct at central branch points. Evidence is presented, using axon conduction block and laser axotomy of cells filled with 6-carboxy-fluorescein, that synapses between separate groups of branches can function independently. Thus, selective activation of branches of the thin anterior axon produced a synaptic potential 36 +/- 6% of control amplitude, which was consistent with counts of 39 +/- 6% of contacts made by these branches. Laser axotomy of postsynaptic neurons showed that the anterior contacts indeed made the principal or only contacts activated during anterior conduction block. The results show that conduction block can modulate transmission within the ganglion, and it operates by silencing particular contacts between cells.