Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) plays the pivotal role in tumor development and metastasis, so it is a promising drug target in malignancy. To acquire MT1-MMP specific binding peptides, we first analyzed MMPs sequences to find the divergent and specific sequence of MT1-MMP by bioinformatics approach, then set the specific sequence as the sense peptide target and designed antisense peptide library. Finally, by means of molecular docking, molecular dynamics simulation and in vitro cell assays, we screened the antisense peptide library against MT1-MMP and further studied the obtained specific peptides. Here, we identified the divergent and specific sequence of AYIREGHE (Named MT1-loop) located in MT1-MMP loop by multiple sequence alignment and established the antisense peptides library with capacity of 1 536 sequences. After two rounds of virtual screening, we obtained five antisense peptides with Rerankscores in the top for further screening. They all interacted with MT1-MMP, and docked well at the active site composed of MT1-loop sequence. Analysis of the affinities of these five antisense peptides to other MMPs (MMP1-3, MMP7-13, MMP14 HPX, MMP16) revealed that the peptide FVTFPYIR was more specific to MT1-MMP. Molecular dynamics simulation showed that the peptide FVTFPYIR might affect the stability of MT1-MMP and thus have effects on its activities. Meanwhile, the peptide FVTFPYIR could specifically inhibit the growth of MG63 and MDA-MB-231 tumor cells both of which expressed MT1-MMP. The work provides a new insight and way for the development of antitumor lead peptides targeting MT1-MMP.
Amino Acid Sequence ; Humans ; Matrix Metalloproteinase 14 ; chemistry ; Molecular Dynamics Simulation ; Neoplasms ; Peptide Library ; Peptides ; chemistry

Objective To investigate the application and effect of aerobic exercise of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD).Methods Ninety-four hospitalized patients with COPD from June 2011 to June 2012 were enrolled.The clinical curative effect and safety of aerobic exercise of pulmonary rehabilitation in patients with COPD were observed and compared.Results After 3 months treatment,first second forced expiratory volume (FEV1) and forced vital capacity (FVC) were increased compared with those before treatment [(3.25 ± 0.49) L vs.(2.59 ± 0.55) L,(1.95 ± 0.41) L vs.(1.44 ± 0.48) L],and there were significant differences (P ＜ 0.05).There was no significant difference in FEV1/FVC before and after treatment (P ＞ 0.05).After 3 months treatment,arterial partial pressure of oxygen and arterial oxygen saturation were increased compared with those before treatment [(87.61 ± 8.56) mm Hg(1 mm Hg =0.133 kPa) vs.(63.88 ± 8.79) mm Hg,0.9648 ±0.0449 vs.0.7632 ± 0.0477],partial pressure of arterial carbon dioxide was decreased compared with that before treatment [(30.57 ± 9.47) mm Hg vs.(49.23 ± 9.54) mm Hg],and there were significant differences (P ＜ 0.05).There was no signifi.cant difference in blood pressure and heart rate before and after treatment (P＞ 0.05).No obvious adverse reactions were observed.Conclusions The aerobic exercise of pulmonary rehabilitation can improve significantly lung function.It is safe and rehable,and has less adverse reaction in patients with COPD.It is worthy of promotion and use.

BACKGROUND:The experimental animal models can be used to in-depth investigate the effect of ultrasound and contrast-enhanced ultrasound in the diagnosis and treatment of ischemic biliary lesions. But there is no report on the phase timing standard of rabbit model contrast-enhanced ultrasound that used in various hepatobiliary diseases. OBJECTIVE:To investigate the ultrasonic appearance of normal rabbit biliary ducts with conventional ultrasonography and contrast-enhanced ultrasonography, and the criterion of contrast-enhanced ultrasonography phase timing of rabbit liver. METHODS:The conventional ultrasonography of hepatobiliary system was performed on 10 healthy New Zealand rabbits, and contrast-enhanced ultrasonography was performed on duct wal s that displayed in conventional ultrasonography, then the features were analyzed. RESULTS AND CONCLUSION:(1) The bile duct of normal New Zealand rabbits showed a portal to biliary caliber ratio of 3.59±0.54. (2) The detection rates of common and middle lobe bile ducts were significantly higher than that of lateral lobe bile ducts on both conventional ultrasonography and contrast-enhanced ultrasonography. (3) The phases of contrast-enhanced ultrasonography of normal rabbit liver were divided into arterial phase (10-20 seconds), portal phase (21-30 seconds) and late phase (31-180 seconds). The normal duct wal presented hyper-enhancing at arterial phase and persistent iso-enhancing at portal and late phases. The establishment of these parameters of normal New Zealand rabbits not only lays a foundation for the application of contrast-enhanced ultrasonography on biliary ischemia but also expands to other hepatobiliary models.

Cytology in China developed from nothing and underwent a long journey from gynecologic cytology to that of all organs, laying a solid foundation for new developments in the 21st century. Thyroid fine-needle aspiration (FNA) was primarily developed in an endocrinology department and then in the clinical laboratory department or pathology department in the 1970–80s. Wrights staining is popular in endocrine and clinical laboratory departments, while hematoxylin and eosin staining is common in pathology. Liquid based cytology is not common in thyroid FNA cytology, while BRAF(V600E) mutation analysis has been the most popular molecular test. The history and practice of thyroid FNA practice in China were reviewed based on retrospective study of the practice in Qilu Hospital of Shandong University.
Biopsy, Fine-Needle* ; China* ; Endocrinology ; Eosine Yellowish-(YS) ; Hematoxylin ; Pathology ; Retrospective Studies* ; Thyroid Gland*

OBJECTIVETo compare the abilities of transient elastography (TE) versus real-time tissue elastography (RTE) for assessing liver fibrosis in patients with chronic liver disease.

METHODSNinetytwo patients with chronic liver disease were enrolled in the study, and included 77 cases of chronic hepatitis B, 4 cases of chronic hepatitis C, 4 cases of autoimmune liver disease, 2 cases of primary biliary cirrhosis, I case of abnormal bile duct development, and 4 cases of unknown etiology.All patients were assessed by both TE and RTE in a single day.The correlation coefficient of liver fibrosis level and the receiver operating characteristic (ROC) curve of S more than 2 and =4 of TE and RTE were determined.The values were compared using findings fiom pathological analysis as reference.

RESULTSThe correlation coefficient of liver fibrosis level was significantly higher for TE (r =0.755, 95% CI:0.651-0.831, P =0.000) than for RTE (r=0.481, 95% CI:0.306-0.624, P =0.000) (Z=3.07, P =0.002).The areas under the ROC curves for S more than 2 and =4 were 0.903 and 0.740 for TE and 0.915 and 0.786 for RTE, respectively, indicating that the performance of TE was superior to that of RTE.

CONCLUSIONTE was superior to RTE for assessment of liver fibrosis.

Autoimmune Diseases ; Elasticity Imaging Techniques ; Hepatitis B, Chronic ; diagnostic imaging ; Hepatitis C, Chronic ; diagnostic imaging ; Humans ; Liver Cirrhosis, Biliary ; diagnostic imaging ; ROC Curve

Objective:To explore the value of bedside chest radiograph in the diagnosis and follow-up of severe and critical COVID-19.Methods:Twenty-nine patients with severe or critical COVID-19 were collected from January 23 to February 23, 2020，from four COVID-19 designated hospitals in Guangdong Province. Bedside radiography was taken in all the 29 patients, ranged from 1 to 16 times for each patient. Twenty-seven patients underwent follow-up, and the number of re-examination ranged 1 to 15 times, and the interval of review is 1 to 8 days.The imaging findings of bedside chest radiography and the imaging changes on follow-up chest radiography were analyzed retrospectively.Results:Twenty-nine patients were collected. The radiography showed the lesions involved all more than 3 lung fields. The films showed consolidation shadow in 19 cases, multiple patches of shadow in 23 cases, reticular pattern in 12 cases, strips shadow in 14 cases, interlobar fissure thickening in 18 cases, and "white lung" in 4 cases.The complications included pleural effusion in 4 cases, pneumothorax in 2 cases, mediastinal and subcutaneous emphysema in 1 case. The radiography showed the lesions progressed in 15 cases, with expanded involvement of the lung.The increase of lesion density was found in 6 cases, new lesions were noted in 5 cases, while both of them were found in 4 cases. Nine cases showed improvement, with reduced range and decreased density. Patchy or consolidation shadow turned to strips shadow or articular pattern shadow in 8 cases.There was no significant change in 3 cases with large consolidation shadow.Conclusions:Bedside chest radiography has a good value in the follow-up of severely and critically ill patients with COVID-19, and can provide great help for clinicians to evaluate their condition.

Objective:To explore the ingredients, targets, and mechanisms of Hanchuan Zupa Granules in the treatiment of Influenza A virus.Methods:By using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGkb), Therapeutic target database (TTD) and DrugBank database to obtain relevant components and targets of Hanchuan Zupa Granules in the treatment of Influenza A virus; R software was used for the obtain of Hanchuan Zupa Granules -Influenza A virus intersection targets; Cytoscape software was applied for the construction of "Hanchuan Zupa Granules-component-target" network; Protein-protein interaction network (PPI) and topological analysis were constructed by STRING database and Cytoscape software. Intersection targets for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by R software; Auto Dock Tools were used for molecular docking.Results:All together 111 potential active ingredients, with corresponding 131 targetswere identified from Hanchuan Zupa Granules in the treatment of Influenza A virus. Quercetin, apigenin, luteolin, kaempferol, wogonin, etc. are included as core ingredients. STAT3, MAPK1, MAPK3, AKT1, JUN, etc. are included as core targets. Intersection targets were mainly enriched in 178 signal pathways such as IL-17 signal pathway, influenza A signal pathway, TNF signal pathway, etc; Molecular docking showed that core component had a good affinity with the target.Conclusion:Hanchuan Zupa Granules could play the role of anti-Influenza A virus with multi-component-multi-target-multi-pathway,characteristics, and this syudy provide a basis for future experimental research on its mechanism.

BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P＜0.01 or P＜0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P＜0.01),the expression of interleukin 10 was decreased(P＜0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P＜0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P＜0.01 or P＜0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P＜0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P＜0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.

Objective:To detect the common pathogenic bacteria in rat wounds using electronic nose so as to explore the feasibility of electronic nose for rapid screening of pathogenic bacteria in clinic.Methods:The wound was cutted from the left and right side of the psoas muscle of 45 SD rats. The type of standard bacterial fluids applied to the wound was divided into Staphylococcus aureus group, Escherichia coli group, Pseudomonas aeruginosa group, Acinetobacter baumannii group and Klebsiella pneumoniae group according to the random number table, with 9 mice per group. Three days later, the wound pus was sent to culture. Five standard bacterial fluids were detected by electronic nose, and the overall recognition rate and individual recognition rate of standard bacterial fluids were calculated by neural network (BP). The wound pus in each group was detected by electronic nose to visually compare the overlap degree of the radar map of the wound pus with the standard bacterial fluid characteristic radar map. The detection rate of wound pus in each group by electronic nose was compared. The wound pus in each group was submitted for examination, and the clinical detection rate of wound pus in each group was compared. The consistency was compared between electronic nose test and clinical test.Results:The overall BP identification rate of five standard bacteria liquid was 93.2%. The BP single identification rate of the Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae reached over 99.0%, and was more than 88.0% for Pseudomonas aeruginosa and Acinetobacter baumannii. The radar pattern of wound pus was highly overlapped with the characteristics of radar pattern of standard bacterial fluid. The detection rate of wound pus by electronic nose was the highest (100.0%) in Pseudomonas aeruginosa group and Escherichia coli group, followed by 88.9% in Klebsiella pneumoniae group and 72.2% in Pseudomonas aeruginosa group and Acinetobacter baumannii group. Using electronic nose, the detection rate in Pseudomonas aeruginosa group and Acinetobacter baumannii group was significantly different from that in Staphylococcus aureus group and Escherichia coli group ( P<0.05). The clinical detection rate of wound pus was 100.0% in Staphylococcus aureus group, Escherichia coli group and Klebsiella pneumoniae group, 94.4% in Pseudomonas aeruginosa group and 66.7% in Acinetobacter baumannii group. The clinical detection rate in Acinetobacter baumannii group differed significantly compared to that in Staphylococcus aureus group, Escherichia coli group and Klebsiella pneumoniae group ( P<0.05), while there was no significant difference between Acinetobacter baumannii group and Pseudomonas aeruginosa group ( P>0.05). Comparison of detection rate of wound pus between electronic nose and clinic examination showed a Kappa coefficient of 0.475. Conclusions:The animal wound pus detected by electronic nose can obtain a feature map with high repeatability compared to the standard bacterial fluid. The electronic nose detection has a medium degree of consistency with clinical detection, providing an experimental basis for the feasibility of using electronic nose to rapidly screen types of pathogenic bacteria.