[Radiological assessment of interstitial lung disease: what can lung ultrasound do?]

The use of lung ultrasound in the screening, diagnosis, and evaluation of interstitial lung disease has been relatively well studied, but has not been widely accepted and applied in clinical practice. There are also some differences in the examination methods applied in these studies. This paper summarized the application, advantages, and disadvantages of lung ultrasound in the diagnosis and follow-up of interstitial lung disease by comprehensively reviewing the examination methods, research results and progress of new technologies of lung ultrasound in interstitial lung disease.

[Prognosis and related risk factors of acute respiratory distress syndrome in elder patients].

Objective: To study the risk factors associated with the hospital survival rate of elder patients with acute respiratory distress syndrome (ARDS) in Medical/Respiratory Intensive Care Units (MICUs/RICUs) by evaluating the prognosis, and therefore to provide insight into patient treatment strategy. Methods: Twenty MICUs/RICUs of 19 general hospitals in mainland China participated in the multicenter prospective cohort study carried out from Mar 1st, 2016 to Feb 28th, 2018. Patients who met the criteria of Berlin ARDS and older than 65 years were recruited. Baseline data, risk factors of ARDS, ventilator setup and prognosis data were collected from all patients. Univariant and multivariant regression analysis were conducted to analyze the factors associated with the prognosis. Results: 170 elder ARDS patients (age≥65 years) met the Berlin ARDS criteria, among whom 8.8% (15/170), 42.9% (73/170) and 48.2% (82/170) patients had mild, moderate and severe ARDS, respectively. The most common predisposing factor for elder ARDS was pneumonia, which was present in 134 patients (78.8%). 37.6% (64/170) patients were treated with noninvasive mechanical ventilation (NIV), but 43.8% (28/64) cases experienced treatment failure. 76.5% (130/170) patients were treated with invasive mechanical ventilation. All patients 80 years or older were given invasive mechanical ventilation. 51.8% (88/170) cases had complications of non-pulmonary organ failure. 61.8% (105/170) patients deceased during hospital stay. Multivariant logistic analysis showed that the independent risk factors for hospital survival rate in elder patients with ARDS were SOFA score (P=0.030, RR=0.725, 95% CI 0.543-0.969), oxygen index after 24 hours of ARDS diagnosis (P=0.030, RR=0.196, 95% CI 0.045-0.853), accumulated fluid balance within 7 days after diagnosis of ARDS (P=0.026, RR=1.000, 95% CI 1.000-1.000) and shock (P=0.034, RR=0.140, 95% CI 0.023-0.863). Conclusion: Among 20 ICUs, the high mortality rate of elder patients with ARDS was correlated with higher 24 hour SOFA score, lower 24 hour oxygen index after ARDS diagnosis, more positive fluid balance within 7 days and concomitant shock. The conservative fluid strategy within 7 days of ARDS diagnosis may benefit the elder ARDS patients.

Knockdown of MMP11 inhibits proliferation and invasion of gastric cancer cells.

Matrix metalloproteinase 11 (MMP11 or stromelysin-3) has recently been reported to play a crucial role in the development and progression of multiple malignancies. The aim of this study was to investigate the function of MMP11 expression in human gastric adenocarcinoma (GAC). Using immunohistochemistry assay, we studied the expression level of MMP11 in GAC and adjacent non-cancerous tissues (ANCT). The association between MMP11 expression and tumor size and pathological grade, as well as metastatic potential was analyzed. Through small hairpin RNA (shRNA)-mediated MMP11 knockdown in SGC-7901 GAC cells, we observed the changes of the biological behaviors of GAC cells. Our results indicated that the rate of positive expression of MMP11 was higher in GAC tissues than in ANCT (55.0 vs 30.0 percent, P=0.025). MMP11 expression had no association with the factors of age or gender of the GAC patients, or the size, pathological staging and lymph node metastases of the tumors (each P greater than 0.05). Furthermore, MMP11 knockdown inhibited the proliferative activities and invasive potential of SGC-7901 GAC cells with decreased expression of IGF-1, PCNA and VEGF. Taken together, our findings demonstrated that MMP11 expression was increased in GAC tissues, but did not correlate with the clinicopathologic features. Knockdown of MMP11 expression could inhibit the proliferation and invasion of GAC cells probably through down-regulation of the IGF-1 signaling pathway, suggesting that MMP11 might be a potential therapeutic target for the treatment of gastric cancer.

Development and validation of a nomogram for predicting the risk of nursing home-acquired pneumonia.

OBJECTIVE: Nursing home-acquired pneumonia (NHAP) is one of the most frequent infections in nursing homes, with a difficult diagnosis, poor prognosis, and high mortality. The present study was performed to develop and validate a nomogram to predict the risk of NHAP in nursing homes. MATERIALS AND METHODS: Based on a literature review and clinician's recommendations, we identified and collected the possible factors affecting the occurrence of NHAP. Based on the above factors, a retrospective observational study of 620 nursing home residents' medical records was performed from September 2016 to September 2021. Significant risk factors for NHAP were identified by univariate and multivariate analysis successively. A nomogram was constructed based on the binary logistic regression models to visualize the prediction model. The model's performance was determined by the concordance index (C-index), and the prediction accuracy was evaluated using a calibration curve. Clinical effectiveness was evaluated by decision curve analysis (DCA). RESULTS: Finally, 12 independent risk factors were identified and assembled into the nomogram. The nomogram had a C-index of 0.958 (95% confidence interval: 0.943-0.972). The area under the receiver operating characteristic curve (AUC-ROC) value of the nomogram was 0.958 (p<0.05), and the calibration plot showed good goodness of fit. The decision curve analysis and clinical impact curve showed good clinical usefulness of the nomogram. CONCLUSIONS: A nomogram for the early prediction of NHAP, which is easy for nurses to perform in nursing homes, was successfully constructed and validated, and it had a good predictive performance.

Critical prognostic factors for poststroke dysphagia: a meta-analysis.

OBJECTIVE: Poststroke dysphagia (PSD) is one of the most significant problems after stroke. The prognosis of dysphagia is closely related to the outcomes of stroke. This meta-analysis aimed at identifying and evaluating critical predictors of prognosis for PSD. MATERIALS AND METHODS: Electronic databases were searched for relevant case-control and cohort studies in which the prognostic factors of PSD were reported. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Review Manager 5.3 was used to calculate odds ratios (OR) and their 95% confidence intervals (CI) of the included factors and to perform heterogeneity and sensitivity analyses. Stata 15.1 was used to evaluate publication bias. RESULTS: Eighteen of 3132 total studies were finally included in this meta-analysis. Ten predictors of PSD were identified, including 2 protective factors and 8 risk factors. Early intervention (OR=0.75, 95% CI=0.61-0.93) and an MRS (modified Rankin scale) score of 0 before onset (OR=0.58, 95% CI=0.47-0.71) were related to a better prognosis of PSD. The risk factors ranked by pooled OR values were aspiration (OR=7.64, 95% CI=5.94-9.82), brainstem injury (OR=4.82, 95% CI=3.01-7.72), severity of stroke (OR= 3.06, 95% CI=1.69-5.53), bihemispheric injury (OR=3.0, 95% CI=1.67-5.40), older age (OR=1.75, 95% CI=1.50-2.04), malnutrition (OR=1.36, 95% CI=1.22-1.53), severe dysphagia on admission (OR=1.16, 95% CI=1.03-1.29), and reduced level of consciousness (OR=1.03, 95% CI=1.00-1.07). CONCLUSIONS: Prognostic factors for a good outcome of PSD included early intervention and an MRS score of 0 before onset. Aspiration, brainstem injury, severe stroke and bihemispheric injury are the four most significant predictors of poor prognosis in PSD. Identifying these prognostic factors should help clinicians to better detect patients at risk and provide effective interventions for PSD.

[The differentiation and vicissitude of variety of Aucklandiae Radix].

Aucklandiae Radix is a commonly used Chinese herbal medicine. Historically, the varieties of Aucklandiae Radix for its medicinal use are complicated. Early Radix Aucklandiae was produced domestically, and it began to be imported since the Northern and Southern Dynasties. The two families, four genera, including Saussure Aucklandiae Radix of Compositae, Inula Inulae Radix, Vladimiria Vladimiriae Radix, dali Aucklandiae Radix and Aristolochiaceae Aristolochic aristolochia debilis, are all applied for medicinal purposes. In modern time, there are 3 major classes of crude drugs of Aucklandiae Radix, namely, Aucklandiae Radix, Inulae Radix, root of common Vladimiriae Radix.

Chinonin, a novel drug against cardiomyocyte apoptosis induced by hypoxia and reoxygenation.

The inhibitory effects of Chinonin, a natural antioxidant extracted from a Chinese medicine, on apoptotic and necrotic cell death of cardiomyocytes in hypoxia-reoxygenation process were observed in this study. The possible mechanisms of Chinonin on scavenging reactive oxygen species and regulating apoptotic related genes bcl-2 and p53 were also investigated. Neonatal rat cardiomyocytes were subjected to 24-h hypoxia and 4-h reoxygenation. Cell death was evaluated by DNA electrophoresis on agarose gel, cell death ELISA and annexin-V-FLUOS/propidium iodide (PI) double staining cytometry. Hypoxia caused the increase of apoptotic rates and the release of lactate dehydrogenase (LDH), while reoxygenation not only further increased the apoptotic rates and leakage of LDH, but also induced necrosis of cardiomyocytes. In addition, hypoxia increased the levels of NO(2)(-)/NO(3)(-) and thiobarbituric acid reacted substances (TBARS), while reoxygenation decreased NO(2)(-)/NO(3)(-), but further increased TBARS in the cultured media. Moreover, hypoxia up-regulated the expression levels of bcl-2 and p53 proteins, while reoxygenation down-regulated bcl-2 and further up-regulated p53. Chinonin significantly decreased the rates of apoptotic and necrotic cardiomyocytes, and inhibited the leakage of LDH. It also diminished NO(2)(-)/NO(3)(-) and TBARS, down-regulated the expression level of p53 protein, and up-regulated bcl-2 protein, respectively. The results suggest that Chinonin has preventive effects against apoptotic and necrotic cell death and its protective mechanisms are related to the antioxidant properties of scavenging nitric oxide and oxygen free radicals, and the modulating effects on the expression levels of bcl-2 and p53 proteins.

Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron.

Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases.

Flagellin-PAc Fusion Protein Inhibits Progression of Established Caries.

Dental caries remains one of the most common infectious diseases of humankind, which develops slowly throughout life, affecting children, adolescents, and adults. A vaccine against caries is urgently needed. We previously developed recombinant flagellin as a mucosal adjuvant for anti-Streptococcus mutans vaccines by nasal immunization. Furthermore, we demonstrated a fusion protein strategy that combined flagellin and the target surface adhesion protein (PAc) in a single construct. This construct enhanced specific IgA responses in oral fluids and provided improved prophylactic protection against caries. In the present study, we observed prolonged progression of dental caries in rats after S. mutans Ingbritt challenge. In addition, we observed a therapeutic effect of the flagellin-PAc fusion protein (KF-rPAc) against dental caries as a mucosal vaccine with a new immunization protocol. The present study demonstrated that KF-rPAc by nasal immunization can promote PAc-specific systemic and mucosal antibody responses and inhibit dental caries progression efficiently after the implant of S. mutans into the oral cavity of the rats. The rats immunized with KF-rPAc exhibited 53.9% caries reduction compared with the sham-immunized rats. Our data support the concept of administration of KF-rPAc to humans after infection and even caries that has begun to alleviate caries progression. In conclusion, our study demonstrated that KF-rPAc could be used as an anticaries therapeutic mucosal vaccine.

Scavenging effects on active oxygen radicals by schizandrins with different structures and configurations.

We have studied the scavenging effects of different structures and configurations of schizandrins isolated from Fructus Schizandrae, a traditional Chinese herb, on active oxygen radicals with the method of spin-trapping technique. The active oxygen radicals were produced from human polymorphonuclear leukocytes (PMN) stimulated with phorbol myristate acetate (PMA). In addition, the scavenging effects of schizandrins on hydroxyl radicals (.OH) in Fenton's reaction and the scavenging effects on superoxide anions (O2-.) in both riboflavin/EDTA and xanthine/xanthine oxidase systems have also been studied. They are compared with the scavenging effects of both Vitamin C (Vc) and Vitamin E (VE). The experimental results have shown that the scavenging effect of schizandrin B (Sin B) on the active oxygen radicals is stronger than that of S(-) Sin B and R(+) Sin B. For schizandrins of the same molecular structures with different stereoconfigurations the scavenging effects of S type of the benzene ring on active oxygen radicals are stronger than those of R type and for schizandrins of the same stereoconfigurations with different structures the scavenging effects of schizandrin C (Sin C) on the active oxygen radicals are stronger than those of Sin B.

Scavenging effect of berbamine on active oxygen radicals in phorbol ester-stimulated human polymorphonuclear leukocytes.

The scavenging effect of berbamine (Ber) on active oxygen radicals was studied, using a spin-trapping technique and a chemiluminescence (CL) method in phorbol myristate acetate (PMA) stimulated polymorphonuclear leukocytes (PMN) and in four cell-free superoxide (O2-.) or hydroxyl radical (OH.) generating systems. Ber (0.1 to 0.3 mM) effectively reduced active oxygen radicals in PMN stimulated with PMA, but had no obvious effect on oxygen consumption during the respiratory burst of PMN, measured with spin probe oxymetry. Ber (0.3 mM) prominently inhibited the CL response of PMA-stimulated PMN. The agent remarkably quenched O2-. in xanthine/xanthine oxidase and irradiation riboflavin systems and OH. in the Fenton reaction. Its scavenging action on O2-. was stronger than that of Vitamin E in the xanthine/xanthine oxidase system but the same as Vitamin E in the riboflavin system, and its action on OH. was similar to that of Vitamin E.

Different effects of five catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells.

Five catechins [(-)-epigallocatechins gallate (EGCG), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC), (-)-epicatechin (EC), and (+)-catechin (C)] were compared with regard to their effects on 6-hydroxydopamine (OHDA)-induced apoptosis in PC12 cells--the vitro model of Parkinson's disease. Measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 6-OHDA inhibited cell viability in a time- and concentration-dependent manner. When PC12 cells were pretreated with the five catechins for 30 min before exposure to 250 microM 6-OHDA, MTT results showed that the five catechins had different effects: EGCG and ECG had obvious concentration-dependent protective effects at 50-400 microM; EC and (+)-C had almost no effects; and EGC especially decreased cell viability. Catechins also had different effects on apoptotic morphology. Only 200-400 microM EGCG and ECG kept cells adhering well. When pretreated with other catechins at any concentration, PC12 cells became round and some of them were detached as when treated with 6-OHDA. In addition, typical apoptotic characteristics of PC12 cells were determined by fluorescence microscopy, flow cytometry, and DNA fragment electrophoresis after the cells were treated with 250 microM 6-OHDA for 24 h or pretreated with catechins before it. Preincubation with 200-400 microM EGCG and ECG led to significant inhibitory effects against PC12 cell apoptosis, as shown by flow cytometry. The other catechins have little protective effect. Therefore, at 200-400 microM, the classified protective effects of the five catechins were in the order ECG > EGCG >> EC > (+)-C > EGC. The data also indicated that EGCG and ECG might be potent neuroprotective agents for Parkinson's disease. The results of fluorescence microscopy and DNA fragment analysis supported the conclusion.

ESR spin trapping studies on the free radicals in gasphase of cigarette smoking.

Free radicals in the gasphase of cigarette smoke were determined by spin trapping agent PBN (N-tert-butyl-2-phenyl nitrone) and DMPO (5,5-dimethyl-1-pyrroline-oxide) on electron spin resonance spectrometer. They were identified according to the spectrum parameters calculated from the spectra. The free radicals mainly consist of alkoxyl and alkyl free radicals, of which alkoxyl free radicals make up 60-70% of the total spectral components. These free radicals are very active and reactive. They can damage cells and lead to some diseases. This work points out the importance of scavenging the free radicals of cigarette smoke to prevent diseases caused by them.

Active oxygen radicals produced by leukocytes of malignant lymphoma.

The electron spin resonance (ESR) spectra of active oxygen radicals produced during the respiratory burst of PMA-stimulated leukocytes and oxygen consumption are studied by ESR spin trapping and spin probe oxymetry for 31 times in 17 cases of malignant lymphoma. The results showed that the spectra produced from PMA-stimulated patients' leukocytes were predominantly spin adducts of DMPO-hydroxyl radicals (DMPO-OH). The decrease in oxygen consumption during respiratory burst suggested that respiratory burst function was inhibited. Kinetic observations of patient condition showed that respiratory burst and oxygen consumption were improved and even approached normal, when the patient was in remission or the condition was ameliorated. This paper is the first of its type and helps clarify the mechanism of malignant proliferation and metastasis.

[The biochemical properties of L-arginine/nitric oxide pathway in rat brain mitochondria].

Biochemical property of L-arginine (L-Arg)/nitric oxide synthase (NOS)/nitric oxide (NO) system was observed in rat brain mitochondria. The results showed that there existed L-Arg transporters of high-affinity, low-transport and saturability in mitochondria membrane of normal rat brain. The maximum transport velocity (V(max)) and Michaelis constant (Km) were 5.87+/ -0.46 nmol/mg pro x min(-1) and 7.8+/- 0.56 micromol/L respectively. In normal condition, endothelium-type NOS was expressed in the mitochondria of rat brain, with its V(max) and Km being 2.7+/-0.3 nmol/mg pro x min(- 1) and 20.85+/-3.27 micromol/L, respectively. NO production was increased in a time-dependent manner and reached a maximum value at 60 min. These results suggest that the L-Arg transporters in MT membrane of normal rat brain were similar with Y(+) type amino acid transporters in cellullar membrane. Furthermore the NOS of mitochondria belongs to eNOS, whereas the L-Arg/NOS/NO system may be a source of NO.

[Effects of glycyrrhiza flavonoid on lipid peroxidation and active oxygen radicals].

The antiperoxidant activity of glycyrrhiza flavonoid (FG) was studied by using colorimetric estimation of lipid peroxide (MDA) formation. The scavenging effects of FG on O2-. and OH. was investigated by using chemiluminescence method and spin trapping technique in different systems. The results were as follows: FG 2.8-25 micrograms/ml effectively inhibited MDA formation induced by incubating mice liver homogenate at 37 degrees C for 1 h; FG 0.265-26.5 micrograms/ml or 2.58-258 micrograms/ml was shown to markedly scavenge O2-. in alkaline/DMSO or xanthine/xanthine oxidase systems, respectively in a concentration-dependent manner. FG 144 micrograms/ml or 258 micrograms/ml also significantly scavenged the active oxygen radicals produced by PMN stimulation with PMA or OH. produced in Fenton's reaction respectively. The results suggest that FG may be used as an antioxidant.

[A study on the protective effect of metallic chelators on ischemia-reperfusion injury of isolated rat heart].

A Langendorff isolated rat heart preparation was used to determine the effect of the metallic chelators, deferoxamine and penicillamine on the extent of myocardial ischemia reperfusion injury. Each heart was subjected to 15-60 minutes of total ischemia at 37 degrees C followed by 15-60 minutes of reperfusion with either saline, deferoxamine (0.61 mmol/L), or penicillamine (30 mmol/L) treated perfusate. Reperfusion injury was assessed by the production of free radicals with electronic spin resonance spectroscopy and spin trap PBN, by the amount of creatine phospholipase released into the perfusate, by the changes in the myocardial vascular resistance, and by pathologic examination of myocardium. The results showed that the drug treated groups released significantly less radical adducts of PBN (P < 0.01) and creatine phosphokinase into the perfusate than the saline treated group (P < 0.01). The mean vascular resistance significantly increased in the saline treated group than in the drug treated groups (P < 0.01). Ultrastructural examination showed prominent attenuation of mitochondrial swelling in drug treated groups in comparison with the saline one. These findings indicated that both deferoxamine and penicillamine can protect the isolated rat heart from ischemia reperfusion injury. The possible mechanism of which is that metallic chelators block the transitional metal-catalyzed fenton reaction, and subsequently decrease the production of hydroxyl radical.

[Direct detection of oxygen free radicals produced by myocardial reperfusion using electron spin resonance spectroscopy].

There is a growing evidence for the role of oxygen free radicals (OFR) in mediating myocardial tissue injury during myocardial ischemia and particularly during reperfusion. But almost all of the evidence was indirect, using electron spin resonance (ESR) spectroscopy, we have directly measured OFR generated in ischemic and reperfused isolated rabbit hearts. 17 hearts were rapidly frozen in liquid nitrogen after their arrest by cardioplegic solution and sampled after 150 min of sustained hypothermic global ischemia or after reperfusion. The ESR spectra obtained from experiment have directly demonstrated that OFR is produced in significant amounts in the isolated rabbit hearts during early stage of reperfusion but only small amount during ischemia. The mitochondrial electron transport chain appeared to be the main source of OFR. We found that superoxide dismutase scavenged OFR generated during reperfusion efficiently, but catalase did not. We believe that superoxide anion, not hydroxyl radical, is the main OFR which is responsible for myocardial reperfusion injury. We also found that Salvia, a traditional Chinese medicine, a very efficient OFR scavenger, had the similar effect as superoxide dismutase.