BACKGROUND: Lung protective ventilation strategies and positive endexpiratory pressure (PEEP) have been widely used as an effective ventilation pattern in clinical practice of administration of acute respiratory distress syndrome (ARDS) in recent years, but there arestill great arguments on the therapeutic effects.OBJECTIVE: To observe the changes of oxygenation index and inflammatory transmitters in peripheral blood and bronchoalveolar lavage fluid(BALF) of different lung areas [superior area of lung (upper lobe), ventral side of inferior lung (heart lobe), and dorsalis inferior lung (diaphragm lobe)] of ARDS dogs caused by pulmonary and extrapulmonary insults under lung protective ventilation treatment.DESIGN: A randomized control animal study.SETTING: Department of Respiratory Medicine, the General Hospital of Chinese PLA.MATERIALS: Twenty-four adult healthy male mongrel dogs were randomly divided into four groups with 6 dogs in each: pulmonary ARDS experimental group, pulmonary ARDS control group, extrapulmonary ARDS experimental group and extrapulmonary ARDS control group.METHODS: Models of extrapulmonary ARDS were induced by intravenous injection of oleic acid (0.1-0.15 mg/kg), and the pulmonary ARDS models were established by intratracheal administration of diocty sulfosuccinate sodium salt. After lung injury, the experimental groups received lung protective ventilation treatment (tidal volume: 8 mL/kg, PEEP: 0.981 kPa)for 3 hours, and the control groups also received ventilation of large tidal volume (tidal volume: 14-17 mL/kg, PEEP: 0 kPa).MAIN OUTCOME MEASURES: ① changes of oxygenation index in each group; ② dynamically observed the changes of the inflammatory transmitters [tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL1β) and interleukin-6 (IL-6)] in pe. Ripheral blood and BALF of different lung areas (upper lobe, heart lobe and diaphragm lobe) of ARDS dogs under lung protective ventilation treatment.RESULTS: All the 24 dogs were involved in the analysis of results. ①After lung injury, the oxygenation indexes were significantly decreased in all the groups, and the oxygenation indexes after lung protective ventilation in the experimental groups were obviously higher than those in the control groups (P ＜ 0.05). At 2 and 3 hours after lung protective ventilation, the oxygenation indexes in the extrapulmonary ARDS experimental group were markedly higher than those in the pulmonary ARDS experimental group (P＜ 0.05). ② After lung injury, the levels of the inflammatory transmitters in peripheral blood were all obviously increased in all the groups, which were decreased to different extent after the lung protective ventilation treatment,but the therapeutic effect in the pulmonary ARDS experimental group was not as good as that in the extrapulmonary ARDS experimental group. ③The levels of inflammatory transmitters in BALF of lung upper lobe and heart lobe were obviously higher in pulmonary ARDS dogs than in extrapulmonary ARDS dogs.CONCLUSION: The ameliorations of the release of inflammatory transmitters and oxygenation index at different areas are obviously different between ARDS dogs caused by pulmonary and extrapulmonary insults, and lung protective ventilation has good effect on extrapulmonary ARDS dogs,but has bad effect on pulmonary ARDS ones.

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies against self-FGFR-1 were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-1-immunized group than in mouse FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P<0.05), and the survival time was significantly longer in cFR-1-immunized group than in the control groups (P<0.01). MVD was significantly lower in cFR-1-immunized group than in mFR-1-immunized group and NS group (16.8+/-5.6 vs 64.6+/-1.8 and 59.6+/-8.7, P<0.01). Antibodies against self-FGFR-1 were found in mFR-1-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-1-immunized group were significantly increased (P<0.01) These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein (AF) vaccine in a mouse H22 hepatoma model, tumor volume and survival rate of the mice were studied at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining, and anti-FGFR1 antibody-producing B cells (APBCs) were tested by enzyme-linked immunospot (ELISPOT) assay. Compared with the three control groups, the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group (P<0.05). The number of APBCs in AF-immunized mice (129.6+/-10.9) was more than in controls [6.2+/-1.1 (FGFR1), 6.0+/-1.2 (Ag43) and 5.2+/-1.4 (NS), P<0.01]. Moreover, the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice, but not in control groups. MVD in AF-immunized group was significantly lower than in FGFR1-immunized group, Ag43-immunized group and NS group (10.3+/-3.1 vs 39.4+/-8.6 vs 42.3+/-9.8 and 43.6+/-10.6, P<0.01). These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.

OBJECTIVETo evaluate the effectiveness of a helium-oxygen mixture (79%He- 21%O(2)) as an aerosolizing compressed gas for beta(2)-agonist therapy in patients with an asthma exacerbation.

METHODSTwenty-four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled. The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases). The experimental group inhaled Berotec with heliox-driven, and the control group inhaled Berotec with compressed air-driven. Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled. The patients inhaled Berotec with heliox-driven or compressed air-driven in a random order.

RESULTSThe results of spirometric parameters and arterial blood-gas analysis were measured. In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV(1)), and expiratory flow in 50% forced vital capacity (FEF(50)) were presented. But the severe patients showed significant differences between heliox-driven and compressed air-driven for FVC, FEV(1), FEF(50) and partial pressure of oxygen (PaO(2)).

CONCLUSIONSCompared with the traditional inhalation of beta(2)-agonist therapy using compressed air-driven, the method of inhaling beta(2)-agonist with heliox-driven has more obvious benefits for those suffering from severe asthma. This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of beta(2)-agonist in the treatment of exacerbation of severe asthma.

Adrenergic beta-Agonists ; administration & dosage ; Adult ; Asthma ; therapy ; Bronchodilator Agents ; administration & dosage ; Female ; Fenoterol ; administration & dosage ; Helium ; administration & dosage ; Humans ; Male ; Middle Aged ; Oxygen ; administration & dosage

OBJECTIVE: To explore the mechanism of formaldehyde inducing ovarian toxicity in female rats by observing the effect of formaldehyde on the expression of Fas and caspase-8 mRNA, and the activity of caspase-3 and caspase-8 of ovary tissues in female rats. METHODS: Forty female Sprague-Dawley(SD) rats were randomly divided into a control group and 3 formaldehyde groups at different concentrations. The rats in the formaldehyde groups were intraperitoneally injected different doses of formaldehyde (20.0,2.0 and 0.2 mg/kg) continuously for 14 days.After 14 days, all rats were sacrificed and their ovaries were collected for detecting the expression of Fas and caspase-8 mRNA with RT-PCR, the protein expression of Fas with Western blot, and the activities of caspase-8 and caspase-3 with spectrophotometric method. RESULTS: Compared with the control group, the expression of Fas mRNA and its protein and caspase-8 mRNA and the activity of caspase-8 and caspase-3 of ovary tissues in the rats treated with formaldehyde significantly increased with dose (P<0.05). CONCLUSION The increase of Fas gene expression and the activity of caspase-8 and caspase-3 may be the important mechanism of ovarian toxicity induced by formaldehyde in female rats.
Animals ; Apoptosis ; drug effects ; genetics ; Caspase 3 ; genetics ; metabolism ; Caspase 8 ; genetics ; metabolism ; Environmental Pollutants ; toxicity ; Female ; Formaldehyde ; toxicity ; Ovary ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; fas Receptor ; genetics ; metabolism

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day interval,Microvessel density(MVD)was detected by immunohistochemistry.The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining,and anti-FGFR1 antibody-producing B cells(APBCs)were tested by enzyme-linked immunospot(ELISPOT)assay.Compared with the three control groups,the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group(P<0.05).The number of APBCs in AF-immunized mice(129.6±10.9)was more than in controls[6.2±1.1(FGFR1),6.0±1.2(Ag43)and 5.2±1.4(NS),P<0.01].Moreover,the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice,but not in control groups.MVD in AF-immunized group was significantly lower than in FGFR1-immunized group,Ag43-immunized group and NS group(10.3±3.1 vs 39.4±8.6 vs 42.3±9.8 and 43.6±10.6,P<0.01).These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.

Objective To compare the diagnostic accuracies of deep convolutional neural network (CNN) and dermatologists for pigmented nevus and seborrheic keratosis.Methods CNN network ResNet-50 was trained with 5 094 dermoscopic images of pigmented nevus and seborrheic keratosis using transfer learning,so as to establish a CNN two-classification model.Then,this model was applied to the automatic classification of 30 dermoscopic images of pigmented nevus and 30 dermoscopic images of seborrheic keratosis.Meanwhile,in combination with clinical photos of skin lesions,95 experienced dermatologists who had received dermoscopy training gave their diagnosis for the above 60 dermoscopic images.The diagnostic accuracies were compared between the two methods,and misclassified images were further analyzed.Results The CNN automatic classification model had the diagnostic accuracies of 100％ (30/30)and 76.67％ (23/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 88.33％ (53/60).The average diagnostic accuracies of 95 dermatologists were 82.98％ (25.8/30) and 85.96％ (24.9/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 84.47％ (50.7/60).There were no significant differences in the diagnostic accuracies for pigmented nevus or seborrheic keratosis between the CNN automatic classification model and 95 dermatologists (x2 =0.38,P ＞ 0.05).The dermoscopic images misclassified by CNN were divided into 3 categories:special-type lesions with high pigment content and marked keratosis,typical skin lesions with interference factors,and typical skin lesions without definite reasons for misclassification.Conclusions The performance of CNN automatic classification model is similar to that of experienced dermatologists in the two classification of pigmented nevus and seborrheic keratosis.The reasons for misclassification by CNN still need to be explored by dermatologists and professionals in artificial intelligence.

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies against self-FGFR-l were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-l-immunized group than in mouse FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P＜0.05), and the survival time was significantly longer in cFR-l-immunized group than in the control groups (P＜0.01). MVD was significantly lower in cFR-l-immunized group than in mFR-l-immunized group and NS group (16.8 ±5.6 vs 64.6±1.8and 59.6±8.7, P＜0.01). Antibodies against self-FGFR-1 were found in mFR-l-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-l-immunized group were significantly increased (P＜0.01) These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

COVID -19 poses a major threat to safety and health of human life. Vaccination has become an important means to resist and prevent COVID -19. Under the background of limited global supply of COVID -19 vaccine and its initial application, it is extremely necessary to discuss its ethical principles. Based on the bioethics theory and in accordance with relevant laws and regulations on vaccine use in China, this paper put forward the ethical principles of COVID -19 vaccine use, including safety principle, respect principle, fairness and justice principle, optimization principle and humanitarianism principle, which provided reference for scientifically formulating COVID -19 vaccination strategy and forming a group immune barrier to effectively control the epidemic situation in COVID -19.

Porcine epidemic diarrhea virus (PEDV) is one of the major etiologies responsible for the acute, highly contagious disease in the digestive tract of pigs, especially neonatal piglets. Since PEDV was first identified in Europe in the late 1970s, it has resulted in significant economic losses in many Asian swine-raising countries, including China. Recently, reverse genetics techniques including targeted RNA recombination, bacteria artificial chromosome system and in vitro ligation have been successfully used to manipulate the genome of PEDV, which providing new strategies for the clear delineation of the functions of the viral proteins, the mechanisms behind PEDV pathogenesis and the design of novel vaccines against PEDV. Here, we review the progresses of different reverse genetics platforms developed for PEDV and their applications, covering the roles of trypsin in PEDV propagation, functions of S and ORF3 protein and the development of next generation PED vaccines, and the perspectives of reverse genetics for PEDV.