Asthma, Occupational ; therapy ; Drainage ; methods ; Humans ; Sputum

Asthma, Occupational ; etiology ; pathology ; Humans ; Inflammation ; pathology ; Neutrophil Infiltration ; Neutrophils ; pathology

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Background Fibrin glue has been utilized to adhere the graft during the pterygium excision with conjunctival autografts.Several relevant clinical randomized controlled trial(RCT) and retrospective studies have been published abroad,but the samples for its effectiveness and safety issue of fibrin glue and suture are still underinvestigation.Objective Current study was to quantificationally assess the efficacy and safety of fibrin glue versus sutures in the application of pterygium excision with conjunctival autografts.Methods Based on established search strategy,a computerized literature search was conducted to identify all citations concerning the RCT for effectiveness and safety evaluation of fibrin glue and suture for the graft fixation during the pterygium excision with conjunctival autografts from MEDLINE ( from 2000 to October,2010 ),EMbase ( from 2000 to October,2010 ),Cochrane Central Register of Controlled Trials ( Issue 4,2010 ),CBMdisc ( 2000 to October 2010 ),CNKI ( 2000 to October 2010 ),and the relevant conference proceedings and references searched by hand was performed as supplement.The included literature was scored with Jadad table.The Cochrane Collaboration' s RevMan 5.0 software was used for the test of heterogeneity or test for overall effect.The effective indexes,such as operative duration,recurrence rate and complication,were evaluated by Meta analysis.Results Six RCTs involving 401 eyes of 377 participants were identified.These literatures were published with English in 2004-2010 from China,New Zealand,Sweden,Israel,Turkey and Malasia and the Jadad scores were 4-5.The quantitatively analysis revealed that fibrin glue appeared to short the operative time compared with suturing method (MD =14.23 ;95％ CI:- 16.18- 12.29;P=0.00) and drop the rate of recurrence ( RR =0.49,95％ CI:0.26 -0.95 ; P =0.03 ).No significant differences were found in the rate of postoperative graft dehiscence or absence (RR =3.41,95 ％ CI:0.85-13.68;P =0.08 ).Conclusions Fibrin glue shows the good effectiveness and easy application during the pterygium excision with conjunctival autografts.Long-term follow-up of multi-central RCTs with a larger number of cases are still needed to support this conclusion.

OBJECTIVETo observe the effect of nourishing Yin, strengthening Qi and activating blood decoction on Fas/FasL in salivary glands of NOD mice with Sjogren's syndrome and their mRNA expression.

METHODThirty-two NOD mice were randomly divided into the model group, the traditional Chinese medicine group (TCM group, orally given 0.4 mL nourishing Yin, strengthening Qi and activating blood decoction as per 100 g x kg(-1) everyday), the hydroxychloroquine group (given 0.4 mL hydroxychloroquine as per 60 mg x kg(-1) everyday), the traditional Chinese medicine and western medicine group (TCM WM group, given nourishing Yin, Strengthening Qi and activating blood decoction 50 g x kg(-1) and hydroxychloroquine 60 mg x kg(-1), 0.4 mL everyday), with eight mice in each group. Eight Balb/C mice were selected as the normal control group (normal group). All of mice were killed after eight weeks, and their submaxillary glands were dissected. The expression levels of Fas/FasL were examined by immunohistochemical method, and the FasL mRNA was detected by RT-PCR.

RESULTThe expression levels of Fas/FasL in salivary glands of the model group were higher than that of other groups (P < 0.05). The expression level of FasL of the normal group was much lower than that in the hydroxychloroquine group (P < 0.05). The relative expression level of Fas mRNA in salivary glands of the model group was higher than that in other groups, but the control group was notably lower than other groups (P < 0.05). The expression level of FasL mRNA in salivary glands of the model group was higher than that in TCM and TCM WM groups (P < 0.05). But the expression level in TCM WM group was notably lower than the hydroxychloroquine group (P < 0.05).

CONCLUSIONThe nourishing Yin, strengthening Qi and activating blood decoction could down-regulate the expression level of Fas/FasL in salivary glands of NOD mice with Sjogren's syndrome and their mRNA expression, and had a better efficacy after being combined with hydroxychloroquine. The nourishing Yin, strengthening Qi and activating blood decoction might treat the Sjogren's Syndrome by reducing apoptosis which is regulated by Fas/FasL

Animals ; Fas Ligand Protein ; genetics ; Female ; Gene Expression Regulation ; Medicine, Chinese Traditional ; methods ; Mice ; Mice, Inbred NOD ; Qi ; RNA, Messenger ; genetics ; metabolism ; Salivary Glands ; metabolism ; Sjogren's Syndrome ; blood ; genetics ; therapy ; Yin-Yang ; fas Receptor ; genetics

OBJECTIVETo analyze the clinical effect and related risk factors of Gartland type II-III supracondylar fractures of humerus in children in the emergency closed reduction and percutaneous Kirschner wire fixation.

METHODSFrom January 2008 to June 2013,112 children of Gartland type II to III supracondylar humeral fractures were treated in children in emergency closed reduction and percutaneous K-wire fixation, including 72 males and 40 females with an average age of 6.2 years old ranging from 2 to 11 years old. Among them,74 cases were in Gartland type II fractures,38 cases were in type III; The duration from injury to surgery time was 2.5 to 8 hours (averaged 4.6 hours). Elbow cast was applied after operation with the elbow extended of 100 degrees for 4 to 6 weeks, then the gypsum and Kirschner wires were removed.

RESULTSAll patients were follow-up from 6 to 60 months (averaged 12 months). All fractures reached clinical healing. The final follow-up was assessed by Flynn criteria, the result was excellent in 86 cases, good in 23 cases, general in 3 cases, excellent and good rate was 97.3%. Three patients had mild cubitus varus deformity without orthopedic treatment. No pin tract infections, iatrogenic ulnar nerve injury, compartment syndrome, and complications such as Volkmann ischemic contracture occurred.

CONCLUSIONClosed reduction and percutaneous Kirschner wire fixation had advantages of exact reduction, firm fixation, fewer complications ,less pain in children undergoing emergency surgery, and.high success rate, so it is a safe and efficient treatment for humeral supracondylar fracture in children.

Bone Wires ; Child ; Child, Preschool ; Female ; Fracture Fixation, Internal ; instrumentation ; methods ; Humans ; Humeral Fractures ; surgery ; Male ; Reconstructive Surgical Procedures

Mutation (substitution, deletion, insertion, etc.) in nucleotide acid causes the maximal sequence lengths of exact match (MALE) between paralogous members from a duplicate event to become shorter during evolution. In this work, MALE changes between members of 26 gene families from four representative species (Arabidopsis thaliana, Oryza sativa, Mus musculus and Homo sapiens) were investigated. Comparative study of paralogous' MALE and amino acid substitution rate (d(A)<0.5) indicated that a close relationship existed between them. The results suggested that MALE could be a sound evolutionary scale for the divergent time for paralogous genes during their early evolution. A reference table between MALE and divergent time for the four species was set up, which would be useful widely, for large-scale genome alignment and comparison. As an example, detection of large-scale duplication events of rice genome based on the table was illustrated.
Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Arabidopsis ; genetics ; Chromosome Mapping ; methods ; Conserved Sequence ; genetics ; Evolution, Molecular ; Humans ; Mice ; Molecular Sequence Data ; Oryza ; genetics ; Proteome ; genetics ; metabolism ; Sequence Alignment ; methods ; Sequence Analysis, Protein ; methods ; Sequence Homology, Amino Acid ; Species Specificity

This study established an HPLC fingerprint of Tibetan medicine Shaji Gao from different habitats and lay a foundation for Shaji Gao varieties identification and preparation process. The chromatographic condition was as follow: Agilent zorbax SB-C18 (4.6 mm x 250 mm, 5 μm) eluted with the mobile phases of acetonitrile and 0.4% phosphoric acid water in gradient mode. The flow rate was 1.0 mL x min(-1), and the detection wavelength was set at 360 nm. The fingerprints of 15 batches Shaji Gao were carried out by similarity comparation, 7 chromatographic peaks were extracted as the common peaks of fingerprint, 3 peaks were identified, which were quercetin, kaempferol and isorhamnetin. The similarity degrees of 14 batches of samples were above 0.9 and 1 batch of samples was below 0.9. This is the first established fingerprint of Shaji Gao by using HPLC. This method has good precision, stability and repeatability that it could provide basis for quality control and evaluation of Shaji Gao.
Chromatography, High Pressure Liquid ; methods ; Medicine, Tibetan Traditional ; Quality Control

This study reported the analysis of plasma phospholipid metabolism of the rats and the pathological biomarkers between the type 2 diabetes model control group (MC) and the normal control group (NC). SD rats were randomly divided into 2 groups: NC and MC. To investigate state of plasma metabolite profiling in normal body, type 2 diabetes mellitus (T2DM) model group using UPLC-Q-TOF/MS which was used as analysis tool in this research. The compounds were identified by UPLC-Q-TOF/MS based on MS/MS fragment ions information, element composition in MassLynx 4.1 and the Lipid Maps database. The sign of two groups of samples in specific markers for screening was through a software package in R software (BioMark software). The results show that the pathological markers were mainly phosphatidylcholine (PC) and triglycerides (TG); the 2-acyl PC in the MC group was less more obviously than that in the NC group; high carbon number and high degree of unsaturation of the TG was reduced under the condition of type 2 diabetes. In the state of type 2 diabetes, metabolic changes occurred in rat plasma phospholipids obviously, which had a close relationship with the occurrence and development of T2DM.
Animals ; Biomarkers ; blood ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; blood ; Diabetes Mellitus, Type 2 ; blood ; Metabolome ; Phospholipids ; blood ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

BackgroundRetinal pigment epithelial(RPE) cells can secrete platelet-derived growth factor (PDGF) and PDGF receptor(PDGFR).Studies have shown that PDGF plays a key role in the formation of proliferative vitreous retinopathy(PVR). ObjectiveThis study was to investigate the proliferation and apoptosis changes of RPE after blockage of the PDGFR-α expression by antisense oligonucleotide ( ASODN ) in vitro. Methods Human RPE cells strain was cultured in low glucose DMEM with 10％ fetal bovine serum.Logarithmic phase cells were collected and incubated in 96-well plate at the density of 5 × 105 cells/hole.PDGFR-α ASODN was transfected into RPE cells at different concentrations for 48 hours.The cells of the blank control group were regularly cultured without any transfection.The changes of PDGFR-α expression were detected by reverse transcription-polymerase chain reaction(RT-PCR),and the proliferation of RPE was detected by MTT as the A490 value.Hoechst 33258 fluorescence staining was used to determine the apoptosis of RPE.Flow cytometry method (FCM) was applied to detect the change of cell cycle and apoptosis rate of RPE cells. ResultsThe A490 values of RPE cells were 1.45±0.12,1.07±0.06,0.65±0.05 in blank control group,1.0 μmol/L Lipo-ASODN group and 2.0 μmol/L Lipo-ASODN group with the significant difference(P=0.00 ),and that of 1.0 μmol/L Lipo-ASODN group and 2.0 μ mol/L Lipo-ASODN group were significantly lower than the blank control group ( P =0.00,0.00).Hoechst 33258 staining showed that the apoptosis cells were obviously more in Lipo-ASODN group compared with blank control group.PDGFR-α ASODN transfection induced an increase of percentage of RPE cells in G0/G1 phase( F =206.70,P =0.00),and the apoptosis rates in 1.0 μmol/L Lipo-ASODN group and 2.0 μmol/L Lipo-ASODN group were significantly enhanced in comparison with blank control group ( 37.8 ± 1.3 vs 10.5 ± 0.1,61.2 ± 1.9 vs 10.5 ± 0.1 ) ( F =1808.90,P =0.00 ).Expression intensity of PDGFR-α mRNA in RPE cells in Lipo-ASODN groups was lower. ConclusionsBlocking the PDGFR-α expression with ASODN technology can suppress proliferation and induce apoptosis of RPE cells.Intensity of PDGFR-α mRNA expression in RPE cells is ASODN dose-dependent.ASODN targeted to PDGFR-α offers an experimental basis of the gene therapy for PVR.