[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.

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.

[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.

[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.

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.

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.

Diagnosis of airway-invasive pulmonary aspergillosis by tree-in-bud sign in an immunocompetent patient: case report and literature review.

Invasive fungal infections are rare in immunocompetent hosts, and diagnosis may be missed or delayed due to our lack of understanding of the particular clinical signs, disease progression, and treatment outcome. Here, we present a case of pulmonary invasive aspergillosis that arose in an immunocompetent and previously healthy patient. The patient presented with a several-week history of remittent high fever, cough, and expectoration. These symptoms were unresponsive to treatments for tuberculosis and pulmonary bacterial infection. Computed tomography images revealed the characteristic bronchiolitis tree-in-bud pattern in the airways. Lung biopsy specimens were culture-positive for Aspergillus fumigatus. Treatment with voriconazole and caspofungin followed by amphotericin B cleared the infection and resolved the symptoms.

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.

[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.

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.

[Determination of catechins in grape seeds by capillary electrophoresis].

A capillary zone electrophoresis (CZE) method has been developed for the determination of four pharmacologically active catechins in grape seed. The components analyzed were (+)-catechin, (-)-epicatechin, epigallocatechin and epicatechin gallate. Separation was achieved by using a mixed buffer of 0.02 mol/L borate and 0.005 mol/L phosphate at pH 10.0 as background electrolyte and an uncoated fused silica capillary with 50 microns i.d. x 375 microns o.d. (effective length 41.5 cm) maintained at 25 degrees C. The applied voltage was 25 kV, and detection was performed by DAD at wavelength of 210 nm. By using proposed CZE method, four catechins were well separated within only 10 minutes with the repeatability of < 1% RSD for migration time and < 5% RSD for peak area. Correlation coefficients better than 0.995 were obtained within the concentration range from 0.005 g/L to 0.5 g/L for the four analytes studied with the detection limit of 3 mg/L-10 mg/L. The contents of these compounds in ten species of grape seeds cultivated in China were successfully determined.

Protective effects of sodium tanshinone IIA sulphonate against adriamycin-induced lipid peroxidation in mice hearts in vivo and in vitro.

Protective effects of sodium tanshinone IIA sulphonate against adriamycin-induced lipid peroxidation were investigated. Data showed that treatment with sodium tanshinone IIA sulphonate could prevent mice from decrease in body weight caused by adriamycin. It was found that myocardial lipid peroxidation in sodium tanshinone IIA sulphonate-treated mice was lower compared with that in adriamycin-treated ones. The activities of some endogenous antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and catalase, were higher in the sodium tanshinone IIA sulphonate group than that in the adriamycin group. In vitro experiments showed that sodium tanshinone IIA sulphonate could inhibit adriamycin-induced mitochondrial lipid peroxidation and swelling. Sodium tanshinone IIA sulphonate could scavenge adriamycin semiquinone free radical in heart homogenate dose-dependently. Thus, protective effects of sodium tanshinone IIA sulphonate may not only be related to its antioxidant activity but also to its regulation of antioxidant enzyme activities in the heart.

Two-peak kinetic curve of the chemiluminescence in phorbol-induced macrophage.

Phorbol-1,2-myristate-1,3-acetate can induce rat macrophage to emit chemiluminescence. The kinetic curve of the chemiluminescence clearly showed two peaks when a proper ratio of phorbol-1,2-myristate-1,3-acetate and macrophage were mixed. It was proved that the first one mainly came from the oxygen free radicals and the second one from NO generated in the phorbol-1,2-myristate-1,3-acetate stimulated cells by using the substitute and inhibitor of NO synthase.

Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury.

Using low temperature electron spin resonance (ESR) technique, we found that Salvia miltiorrhiza injection could scavenge the oxygen free radicals generated from ischemia-reperfusion injury in the myocardium as effectively as SOD. Using ESR spin trapping technique we found that one of its effective components, Danshensu, could scavenge superoxide anion free radicals generated from the reaction system of xanthine and xanthine oxidase, and that lipid free radicals generated from lipid peroxidation of myocardial mitochondrial membranes could be scavenged by another effective component, Tanshinone. The membrane fluidity of the mitochondria isolated from the ischemia-reperfused hearts was studied with the ESR spin labelling technique, and the TBA-method was used to detect the lipid peroxidation. It was found that Danshensu could protect the mitochondrial membrane from the ischemia-reperfusion injury and lipid peroxidation.

Studies on nitric oxide free radicals generated from polymorphonuclear leukocytes (PMN) stimulated by phorbol myristate acetate (PMA).

The interaction of NO and O2- free radicals generated from PMA (phorbol myristate acetate)-stimulated PMN (polymorphonuclear leukocytes) was studied by a nitroxide spin trap, DMPO (5,5-dimethyl-1-pyrroline-1-oxide). It was found that addition of L-arginine to the system would significantly decrease the trapped O2- by DMPO and addition of NG-monomethyl-arginine (NGMA) would significantly increase the trapped O2- by DMPO. It was proved that the formation of ONOO- by the reaction of NO and O2- was the main reason for the decrease of trapped O2- in the experiment with xanthine/xanthine oxidase and irradiation of riboflavin systems. The yield of NO during this process was calculated. The generation dynamic of NO was studied by a luminol-dependent chemiluminescence technique and it was found that after stimulation of PMN by PMA, there would be an immediate, significant chemiluminescence, which came mainly from the active oxygen free radicals generated by PMN. If L-arginine was added to this system, the chemiluminescence would increase about 100-fold, but NGMA inhibited the increase of the chemiluminescence. Ten minutes after addition of L-arginine, this increase did not change, the chemiluminescence peak decreased gradually, but the half life increased. The ESR and chemiluminescence properties of NO and ONOO- synthesized were also studied in model systems.

[Mechanism of scavenging effects of (-)-epigallocatechin gallate on active oxygen free radicals].

The concentration of 50% scavenging ratio (SC50) and the scavenging rate constants (k) and stiochiometric factor (n) were determined when (-)-epigallocatechin gallate [(-)-EGCG] scavenging superoxide anion free radical (O2.-) and hydroxyl radical (.OH). The mechanism of scavenging active free radicals of (-)-EGCG and the promotion of (-)-EGCG free radical and its structure were analyzed in vitro. Our results suggest that the centers of scavenging reaction of (-)-EGCG are B, D, and A cycles, and each (-)-EGCG traps six O2.- or .OH. It is in accord with the value of stiochiometric factor n = 6.