Bacteria ; isolation & purification ; Community-Acquired Infections ; etiology ; microbiology ; virology ; Humans ; Pneumonia ; etiology ; microbiology ; virology

Cell Movement ; Cilia ; physiology ; Epithelial Cells ; physiology ; ultrastructure ; Humans ; Hypermastigia ; ultrastructure ; Protozoan Infections ; diagnosis

China ; epidemiology ; Coronavirus Infections ; epidemiology ; prevention & control ; transmission ; Humans ; International Cooperation

Adenosine Deaminase ; metabolism ; Adult ; Aged ; Female ; Humans ; Interferon-gamma ; analysis ; Interleukin-12 ; analysis ; Isoenzymes ; metabolism ; Male ; Middle Aged ; Pleural Effusion ; chemistry ; Tuberculosis, Pleural ; diagnosis ; metabolism

Adult ; China ; Communicable Disease Control ; Communicable Diseases, Emerging ; prevention & control ; Coronavirus Infections ; Humans ; Male

Objective To analyze the potential factors facilitating post-pyloric placement of spiral naso-jejunum tube in critically ill patients.Methods A retrospective study was carried out in patients requiring enteral nutrition (EN) from Apr 2005 through Dec 2011 in Intensive Care Unit (ICU).Severity of illness was assessed with APACHE Ⅱ score (acute physiology and chronic health evaluation Ⅱ).A selfpropelled spiral naso-jejunum tube was placed and observed for 24 hours.The forward movement and place of the tube tip was checked by bedside X-ray.The APACHE Ⅱ score,therapeutic measures,agents administered within 24 hours after tube insertion were recorded.The patients were divided into the success group and the failure group identified by bedside X-ray whether the tube tip entered into jejunum or not.Univariate analysis and multivariate Logistic regression analysis were used to find out the potential factors impacting on the success or failure in post-pyloric placement of naso-jejunum tube.Results A total of 508 patients composed of 337 male and 171 female,and aged (62.0 ± 19.2) years with APACHE Ⅱ score of (21.9 ± 7.3) were enrolled for study.The placement was successful in 205 (40.4％) of 508 patients.Univariate analysis showed that APACHE Ⅱ score ≥ 20,sedatives and analgesics,catecholamines,prokinetics,artificial airway and mechanical ventilation were potential factors facilitating the post-pyloric placement of naso-jejunum tube.Multivariate logistic regression identified that APACHE Ⅱ score ≥ 20,sedatives and analgesics and prokinetics were independent factors facilitating the post-pyloric placement of naso-jejunum tube.Conclusions The success rate of self-propelled spiral nasojejunal tubes insertion was relatively low.The prokinetics contributed higher success rate of naso-jejunum tube placement than factors of APACHE Ⅱ score ≥ 20,sedative and analgesic,catecholamine drugs,artificial airway and mechanical ventilation.There were no effects of age and gender on the placement of naso-jejunum tube.

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

BACKGROUNDAirway hyperresponsiveness (AHR) is one of the most important characteristics of asthma. This study investigated the parameters, by which assess the airway responsiveness under tidal ventilation.

METHODSFemale BALB/c mice were sensitized and challenged with ovalbumin (OVA) (group A), and part of them were treated with budesonide aerosol (group B). All the mice were anaesthetized and mechanically ventilated. The values of tidal volume (Vt), airway pressure (PA), airway flow (F), expiratory lung resistance (RL) and dynamic compliance of the thorax and lung (CT-L) were recorded by the AniRes2003 animal lung function system. In addition, the expiratory volume in the first 0.1 second after the start of expiration (EV0.1) was obtained according to the flow-volume (F-V) curve. The maximal or minimal values of EV0.1, RL and CT-L were documented after each dose of methacholine (MCH) and compared with values from negative control group (group C).

RESULTS(1) When the dose of MCH reached 100 ng/g or 200 ng/g, the decrease of Vt in group A was much more significant than group C (P = 0.001, < 0.001 respectively), but not so between groups B and group C (P = 0.974, 0.362 respectively). (2) With the dose of 25, 50, 100 or 200 ng/g MCH, the decrease in percentage of EV0.1 in group A was much higher than group C (P = 0.012, 0.025, 0.001, 0.003 respectively), while that in group B showed no significant difference as compared with group C (P = 0.507, 0.896, 0.972, 0.785). (3) RL and CT-L: with the dose of 200 ng/g MCH, there was a statistically significant increase of RL in group A compared to group B or group C (P < 0.001, < 0.001 respectively), but no significant difference between groups B and C (P = 0.266). With doses of 100 ng/g and 200 ng/g MCH, there was a statistically significant decrease of CT-L in group A compared to group B (P = 0.001, = 0.001) and group C (P < 0.001, < 0.001 respectively), but no significant difference between groups B and C (P = 0.775, 0.310). (4) Histopathology: there were eosinophilic predominant peribronchial and perivascular inflammatory influx in murine lungs after OVA sensitizing and challenging, which could be counteracted by inhalation of budesonide in group B.

CONCLUSIONSThe decline in EV0.1 in response to MCH challenge correlated with simultaneous changes in Vt, RL and CT-L, but more sensitively than all the other parameters. The decline in EV0.1 and inflammation in murine lung could be significantly alleviated by inhalation of nebulized budesonide solution, which indicated that EV0.1 to MCH is a valid measure of AHR in mice.

Airway Resistance ; drug effects ; Animals ; Bronchial Hyperreactivity ; drug therapy ; Budesonide ; therapeutic use ; Female ; Lung Compliance ; drug effects ; Methacholine Chloride ; pharmacology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; immunology

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests