Hyperplasia of smooth muscle cells is a major aspect of airway remodeling in asthma .In recent years.It is found that the epigenetic regulation plays an important role on the proliferation of airway smooth muscle cells and the secretion of inflammatory cytokines , including DNA methyltransferase inhibitors to inhibit the phenotype trans-formation;histone acetylation related with hypertrophy .In addition , the microRNA is potentially related with the regulation of a variety of physiological functions of airway smooth muscle cells of asthma model , including inhibition of proliferation and release of inflammatory factors .Hope that epigenetics can become a new target for the treatment of asthma .

In recent years, with the rapid development of antibody drugs, the antibody-based therapies have gradually expanded from the cancer and autoimmune diseases to metabolic and infectious diseases and so on. However, the development of antibody-based anti-infective drugs is much slower as there are only two kinds of drugs in the market. This is due to the complex infective mechanism of viruses, bacteria and other pathogens, and the monovalent character of monoclonal antibodies that greatly limit the anti-infection effect of antibody drugs. The development and application of novel technologies, such as recombinant polyclonal antibody technology, will greatly accelerate the development of antibody-based anti-infection drugs. This article will introduce the application and trends in the development of antibody-based drugs in the field of anti-infection therapy.
Anti-Infective Agents ; pharmacology ; Antibodies, Monoclonal ; pharmacology ; Drug Design ; Humans

Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Purpura, Thrombotic Thrombocytopenic ; etiology ; Transplantation, Autologous

Objective:To observe the clinical effects of acupuncture plus external medicine application for cervical radiculopathy.Methods:A total of 98 patients with cervical radiculopathy were randomly divided into an observation group and a control group based on the random digital table.The observation group (50 cases) was treated by acupuncture plus external medicine application and the control group (48 cases) was treated by acupuncture alone.The patients received the treatment every day.Ten sessions made a course.Cervical spondylosis symptom scale was used to assess the cases before and after the treatment.The clinical efficacy was compared between the two groups after the treatment.Results:The total effective rate was 98.1％ in the observation group versus 87.6％ in the control group with a statistically significant difference between the two groups (P＜0.05).The cure rate was 52.0％ in the observation group versus 18.8％ in the control group with a significant difference between the two groups (P＜0.05).There was no significant difference in the score of cervical spondylosis symptom scale between the two groups before the treatment (P＞0.05).It increased with a significant difference in both groups after the treatment (both P＜0.05),while a significant difference was found in the results between the two groups after the treatment (P＜0.05).Conclusion:Acupuncture plus external medicine application is more effective than acupuncture alone for treating cervical radiculopathy.The method also effectively improves the clinical symptoms.

Objective To isolate and cultivate mouse hepatic progenitor cells (mHPCs) from E14.5 mouse fetal liver in vitro and induce mHPCs differentiation into cholangiocytes.Methods Isolation of mHPCs from mouse fetal liver was based on the cell surface antigen delta-like protein 1/preadipocyte factor 1 (Dlk/Pref-1) by a fluorescence-activated cell sorter (FACS).Then mHPCs isolated were co-cultured with/without mouse embryonic fibroblasts (MEFs) by using Transwell.The cell antigen alpha-fetoprotein (AFP), albumin (ALB) and cytokeratin19 (CK19) expression in freshly isolated DLK1+cells or co-cultured for 4 days and 6 days were observed with immunocytochemical method.Results When co-cultured with MEFs, the division and proliferation were observed in most of DLK1+ cells and grape-like aggregation was formed.Cells began to adhere to growth and began to become spindle-shaped on 4th day.The DLK1+cells isolated freshly by FACS were expressed AFP and low levels of ALB but not expressed CK19.But, these cells expressed CK 19 and weak expression of ALB on 4th day.In addition, the expression of CK19 increased and the expression of ALB almost not detected on 6th day.Conclusions Most of DLK1+ cells, isolated from E14.5 fetal livers by FACS, are proved to be mHPCs.Furthermore, these cells can proliferate quickly and differentiate into cholangiocytes by co-culture with MEFs.

Will-powered technique training in the lower resistant state is an important therapy method of TCM psychology. The therapy refers to five aspects of improving cognitive and emotional function by using TIP technique, making imaginary training in the lowered resistant state, strengthening will-power training with situation and image technique, adopting information module imprinted technique and developing training technique. The content includes cultivating abilities in independence, resolution, firmness, and self-control. The technique has application value in clinic.

Objective To investigate the character and location of a novel gene R049 and its expressed protein in uropathogenic Escherichia coli(UPEC) strain 132 isolated in China. MethodsThe chromosome library of UPEC132 was constructed by a shotgun strategy and the sequence analysis was carried out by a high-throughput pyrophosphate sequencing. Sequence reads were assembled with the Newbler program.The characters of R049-associated specific fragment were analyzed using the bioinformatics methods. Outer and inner membrane proteins of UPEC132 were extracted and then detected by SDS-PAGE and Western blot analysis together with the whole-cell lysates. ResultsThe 169 022 bp contig containing gene R049 was obtained and its sequence was very similar to the chromosome associated sequence of UPEC strain 536. It showed that a 20 773 bp fragment including R049 replaced the pathogenicity island PAI Ⅲ536 of UPEC536 in above 169 022 bp contig. The fragment had a lower GC content (46.97％) and 16 bp direct repeats in two ends. Significantly it also was adjacented to thrW tRNA, insertion element and genes coding integrase. Thus the 20 773 bp fragment was named R049 genome island(R049-GI). There were 25 ORFs in R049-GI, and gene R049 was located in the thirteenth ORF. The results of SDS-PAGE and Western blot revealed gene R049 encoded an outer membrane protein in the size of 47.0× 103. ConclusionGene R049, encoding an outer membrane protein, was a component part of the genome island in UPEC 132 chromosome acquired by horizontal gene transfer.

Objective To assess the diagnostic value of CT-gnided pereutaneous fine-needle aspiration biopsy (FANB) for the space-occupying lesions of the pancreas. Methods The authors retrospectively reviewed the medical records of 68 patients with pancreatic lesions who underwent CT-guided percutaneous fine-needle aspiration biopsy. The lesions were located at the pancreatic head (n = 49), body (n = 12) or tail (n = 7). The maximum diameter of the 68 lesions ranged from 2 cm to 7 cm. The lesion's diameter was < 3 cm in 10 cases and was ≥ 3 cm in 58 cases. A 20-gauge fine-needle was used to puncture and to make the aspiration in all patients. Both plain and contrast-enhanced abdominal CT scanning were performed before the biopsy procedure. The technical key points of aspiration biopsy included selection of the appropriate cross-section, the entry of the needle, and multiple insertions in fan-like fashion with fast manipulation of puncture and aspiration. All biopsy specimens were sent for pathologic evaluation. Results All the lesions were safely and successfully punctured through the anterior approach without major complications. The technical success of needle puncturing was 100%. Of 68 patients, the pathological results obtained from the biopsy included malignant tumor in 46, benign lesion in 17 and no abnormal finding in 5, of which follow-up observation found no abnormality in 2 and malignant process was eventually confirmed in remaining three. The overall accuracy, specificity and sensitivity of the biopsy were 96%, 95% and 100%, respectively. The accuracy of CT-guided biopsy for malignant and benign lesions was 94% and 100% respectively (P > 0.05). The diagnostic accuracy for lesions larger than 3.0 cm (97%) or located at the pancreatic tail (100%) was a little higher than that for lesions smaller than 3.0 cm (90%) or located at the pancreatic head (96%) or body (92%), although the difference was not statistically significant (P > 0.05). No serious complications occurred in our series. Conclusion CT-guided percutaneous fine-needle aspiration biopsy is a safe and effective technique for the diagnosis and differentiation of the space-occupying lesions of the pancreas.

Objective To investigate the effect of angiotenisn ⅡI (Ang Ⅱ) on RIN-m β-cell,and to explore the mechanism of β-cell function impairment caused by Ang Ⅱ.Methods RIN-m cells were cultured with various concentrations of AngⅡ (0.1,1,10,100 nmol/L).After incubation for 24 hours,the basal(3.3 mmol/L) and glucose-stimulated(16.7 mmol/L) insulin secretion(GSIS)were detected by radioimmunoassay,mRNA and protein expressions of uncoupling protein 2(UCP2)were determined by RT-PCR and Western blot,respectively.The intracellular ATP content was measured by luciferase bioluminescence.The mitochondrial membrane potential and cellular Ca~(2+) concentration were detected by flow cytometry.Results (1) Various concentrations of Ang Ⅱ had no significant influence on the basal insulin secrection of RIN-m cell(F=0.644,P = 0.634).Except for 0.1 nmol/L AngⅡ,the other concentrations of Ang Ⅱ markedly reduced GSIS of RIN-m cells(F= 118.528,P = 0.000).(2) Compared with the control group,Ang Ⅱ significantly increased mRNA and protein expression of UCP2(F= 1 370,P = 0.000;F=675.175,P = 0.000).(3)Except for 0.1 nmol/L Ang Ⅱ,the other concentrations of Ang Ⅱ significantly decreased the mitochondrial membrane potential,cellular ATP content,and cellular Ca2+ concentration of RIN-m cell(F=4.035,P=0.008;F=3.353,P = 0.013;F=5.867,P = 0.001).Conclusion Ang Ⅱ impairs GSIS of p-cell,the mechanism of impairment may be interpreted that Ang Ⅱ can increase the expression of UCP2,furthermore,it can reduce mitochondrial membrane potential,decrease the content of cellular ATP and the concentration of cellular Ca~(2+),can finally impair the function of β-cell.

Objective To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) pathway in the protective effect of remifentanil or ischemic preconditioning (IPC) against hepatic ischemia-reperfusion (I/R) injury in rats.Methods One hundred and forty-four male SD rats,weighing 200-250 g,were randomly assigned into 6 group ( n =24 each):sham operation group (group S),I/R group,remifentanil group (group R),IPC group,SB203580 (a specific p38MAPK inhibitor) + remifentanil group (group SB + R),and SB + IPC group.The animals were anesthetized with intraperitoneal 20％ urethane 1 mg/kg.Partial liver ischemia was produced by clamping the hepatic pedicle supplying left lobe and middle lobe for 30 min,followed by 120 min reperfusion.In group R,remifentanil was infused intravenously at 2μg· kg- 1 · min- 1 starting from 30 min before ischemia until the end of reperfusion.In IPC group,the rats were subjected to 3 episodes of 5 min ischemia at 5 min intervals before I/R.SB203580 0.2 mg/kg was injected intravenously at 5 min before remifentanil infusion or IPC in groups SB + R and SB + IPC,and the equal volume of normal saline was given in the other groups.Six rats in each group were selected at 30,60,90 and 120 min of reperfusion and venous blood samples were taken from inferior vena cava for measurement of serum ALT and AST activities and concentrations of TNF-a and 1L-1β.The rats were then sacrificed and liver tissues were taken for microscopic examination and determination of phosphor-p38MAPK expression by Western blot.Results Compared with group S,serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased at each time point (P ＜ 0.05) and pathological injury was aggravated in group I/R.Compared with group I/R,serum AST and ALT activities and serum levels of TNF-a and IL-lβ were significantly decreased and phosphor-p38MAPK expression was up-regulated at 90 min of reperfusion in groups R and IPC ( P ＜ 0.05).The serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased,phosphor-p38MAPK expression was down-regulated at 90 min of reperfusion ( P ＜ 0.05),and pathological injury was aggravated in group SB + R compared with group R,and in group SB + IPC compared with group IPC.Conclusion Activation of p38MAPK pathway and inhibition of inflammatory response may be involved in the mechanism by which remifentanil or IPC reduces the hepatic I/R injury in rats.