BACKGROUND: Immature dendritic cells have strong antigen uptake and processing ability, but the lack of a variety of costimulatory molecules cannot activate and proliferate initial T cells to produce immune response, which can lead to T cell anergy, thus inducing low immune response or antigen immune specific tolerance. Simultaneously, immature dendritic cells can induce hyporeactivity of allogeneic antigen-specific T cells, thus prolonging the survival time of transplanted organs. OBJECTIVE: To investigate the effect of immature dendritic cells on liver rejection after orthotopic liver transplantation in rats and its mechanism. METHODS: According to the weight of DA and Lewis rats, the rats were randomly divided into three groups, and the liver transplantation model of DA-Lewis rats was established by “two-cuff” method. The rats of control group received no measures. The rats of cyclosporine group were treated with 10 mg/kg cyclosporine from the second day after operation, once a day, for 7 days. The rats of the immature dendritic cell group were injected with 1×106 immature dendritic cells from bone marrow of DA rats one day before operation through dorsal penile vein; the injection was repeated twice with an interval of 10 minutes. The livers of all these rats were removed 7 days after operation. Hematoxylin-eosin staining was used to observe the pathological changes. The mRNA and protein expressions of SHIP, AKT, IKK and IKβ in these three groups were detected by qRT-PCR and western blot assay. RESULTS AND CONCLUSION: (1) Compared with the control group, the survival time of cyclosporine group and immature dendritic cell group was significantly longer (P < 0.05). (2) In cyclosporine group and immature dendritic cell group, the number of infiltrating mononuclear cells and lymphocytes in the portal area of liver tissue was less, the structure of hepatic lobule was not significantly damaged, and the inflammatory cells in hepatic artery, portal vein and bile duct were significantly less than those in control group, which did not reach the level of severe acute rejection. (3) Compared with the control group, the mRNA expression of IKβ in the cyclosporine group and immature dendritic cell group was increased, while the mRNA expression of SHIP, AKT and IKK significantly decreased (P < 0.05). (4) Compared with the control group, the expression of SHIP and IKβ protein significantly increased, IKK and AKT protein significantly decreased in the immature dendritic cell group (P < 0.05). Compared with the control group, the expression of SHIP and IKK protein significantly decreased, AKT and IKβ protein expression significantly increased in the cyclosporine group (P < 0.05). (5) Results confirm that immature dendritic cells can slow down the severe acute rejection, delay the survival time of liver and reduce the T cell immune response ability of allogeneic liver transplantation.

Background Di(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) are representative environmental endocrine disruptors of phthalate esters (PAEs). Some studies have shown that PAEs exposure may have an impact on lipid metabolism. Objective To investigate the effects of DEHP and/or DBP on lipid metabolism in rats and their possible mechanisms of action. Methods Thirty-six weaned healthy SD male rats, 3 weeks old, weighing 50-70 g, were divided into four groups, i.e., a corn oil control group, a DEHP (750 mg·kg⁻¹) group, a DBP (500 mg·kg⁻¹) group, and a DEHP+DBP (750 mg·kg⁻¹+500 mg·kg⁻¹) group. The rats were exposed to DEHP and/or DBP by oral gavage for 8 weeks, and weighed once a week. The rats were anesthetized 24 h after the last dose, and blood was taken from the apical part of the heart. Serum high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) were detected. Liver tissues and perigenital adipose tissues were collected, weighed, and one portion of the tissues was fixed in 10% neutral formalin for pathomorphological observation, and another portion was used for mRNA detection of lipid metabolism-related genes such as Janus kinase 3 (JAK3), signal transducer and activator of transcription 5b (STAT5b), and peroxisome proliferator-activated receptor γ (PPARγ). Results During the DEHP and/or DBP exposure period, the rats in all groups were free to eat and drink without death or injury observed. Compared with the control group: The body weight gain in the DEHP+DBP group was lower at all time points from the 2nd week onwards (P<0.05); the liver organ coefficients of the DEHP and the DEHP+DBP groups were higher (P<0.05); the serum LDL-C levels in the DEHP and the DBP groups were higher (P<0.05). Compared with the DEHP+DBP group: The body weight gains in the DEHP group at the 2nd, 4th, 5th, and 8th weeks were higher (P<0.05), and the body weight gains in the DBP group were higher at all time points except the 1st week (P<0.05); the liver organ coefficients in the DEHP group and the DBP group were lower (P<0.05); the serum TG level in the DEHP group was higher(P<0.05), and the serum LDL-C levels in the DEHP and the DBP groups were higher (P<0.05). The pathomorphological results of liver tissues showed that the hepatocytes in the DEHP, DBP, and DEHP+DBP groups were disordered with loss of cord-like arrangement, swelling (suggesting change of cell proliferation), and presented bilirubin pigmentation. The pathomorphological results of rat perigenital adipose tissues showed had irregular alignment, sizes, and arrangement of adipocyte in the DEHP, DBP, and DEHP+DBP groups. The results of rat liver lipid metabolism-related gene mRNA levels showed that the liver JAK3, STAT5b, and PPARγ mRNA levels in the DEHP, DBP, and DEHP+DBP groups were lower than those in the control group (P<0.05); the rat liver PPARγ mRNA levels in the DEHP and DBP groups were lower than those in the DEHP+DBP group (P<0.05). Conclusion DEHP and/or DBP can inhibit the increase of body weight to varying degrees, induce inflammatory damage to liver tissues, and cause abnormal lipid metabolism in rats, and the associated mechanism may be related to inhibiting the activation of JAK3/STAT5b/PPARγ signaling pathway in rat liver tissues.

A series of laws and regulations are the essential legal requirement in the field of clinical trial of medical device currently in China, especially the Provision for Clinical Trial of Medical Device. On the basis of current situation of medical device clinical trial, systemic analysis on the hot spot topics in the regulations was conducted to explore the way of improving the control system of clinical trial of medical device in China, which will provide the reference for medical device industry and the investigators of the clinical trial of medical device.
China ; Device Approval ; legislation & jurisprudence

Seminar is an effcient teaching method in cultivation of independent thinking and research ability of residents of obstetric and gynecology.On the basis of introducing the concept of seminar,this paper discusses the application and significance of seminar in standardized training of residents.Seminar teaching can develop the capabilities of each resident to probe into and study some new things by themselves.The wide applications of this method also help to improve the abilities of the residents to understand the theoretical knowledge of gynecology and to elevate their comprehensive competence.

The importance of information resources organization under E-Learning environment was analyzed ac-cording to the new features and technologies of E-Learning environment with the development trends in information resources organization summarized .

Objective Analysis of the results through nine kinds of Immunoglobulin M (IgM) in children with respiratory tract infection test ,and then investigate infant′s characteristics about gender ,geographical and seasonal ,provide a reference for clinical di‐agnosis .Methods Firstly ,collection the 2 736 children′s blood in our hospital and centrifuged serum ,use indirect immunofluores‐cence (ILF) method and IgM antibody reagents to detect Legionella pneumophlia 1(LP1) ,Mycoplasma pneumoniae(MP) ,Coxiella burnetii(COX) ,Chlamydia pneumoniae(CP) ,Adenovirus(ADV) ,Respiratory syncytial virus(RSV) ,Influenza A virus(IFA) ,Influ‐enza B virus(IFB) ,Parainfluenza virus(PIV) and record the children′s information ever months ,and use the card square test to a‐nalysis .Results A total of 2 736 cases of children were detected in 918 cases (33 .5% ) with IgM antibodies ,the detection rate in descending order MP ,FluB ,PIV ,ADV ,RSV ,COX ,FluX ,CP and LP1 ,124 cases of mixed infection ,it′s 13 .51% of the total num‐ber of infections .The total number of infections in men positive 21 .02% ,12 .54% for women ,with statistical significance (P<0 . 05) ,between different sexes .The highest in age groups was the 13 years old group detection rate was 13 .49% ,followed by 35 years old group(7 .79% ) ,and there was a significant difference(P<0 .05) between the groups .The analyzed about seasonal viral infection in children ,the winter(14 .07% ) and spring(7 .79% ) higher incidence ,and prevalence of each season statistically significant (P<0 .05) .Conclusion Children in the region are mostly M P pathogen infection ,and exist differences in seasonal ,gender and age .

Objective: To investigate the effect of NaCl stress on growth and physiological-biochemical characteristics of Stellaria dichotoma amdits mechanism. Methods: In this study, one-year-old S. dichotoma was cultivated in pot at four NaCl levels (0.2%, 0.3%, 0.4%, and 0.5%) and the plant growth parameters and physiological-biochemical characteristics were determined. Results: NaCl stress had no significant effect on S. dichotoma growth at 0.3% NaCl. However, NaCl stress significantly inhibited the growth of S. dichotoma at 0.4% NaCl or above, and this inhibition was greater at higher concentration. The activities of SOD, POD, and CAT increased first and then decreased as NaCl concentration increased; The content of MDA and proline significantly increased as NaCl concentration increased, while membrane permeability and soluble protein content significantly decreased as NaCl concentration increased. Conclusion: S. dichotoma has osmotic stress resistance ability and reactive oxygen scavenging capacity at light NaCl stress, which causes S. dichotoma growth no inhibited at a certain extent NaCl stress.

Objective To evaluate the role of modified microneedle roller in promoting permeation of triamcinolone acetonide across human hyperplastic scar skin. Methods The morphology of human hyperplastic scar skin was visualized by methylene blue staining and H-E staining after the insertion by microneedles of different lengths. The content of triamcinolone acetonide was determined by high performance liquid chromatography (HPLC). The in vivo absorption characteristics across human hyperplastic scar skin were investigated by elution method and the homogenization method at 1 h and 12 h after drug application. Skin irritation was assessed by transepidermal water-loss (TEWL) measurement and laser Doppler flowmetry. Results The preferred microneedle length of 500 µm effectively penetrated through the stratum corneum,and the distribution of the microchannels was homogeneous. It was found that 27. 42% and 60. 64% of the drug administered entered the skin at 1 h and 12 h, respectively. The drug accumulation in the skin at 12 h decreased to 45. 98% of that at 1 h after intracutaneous injection, while the accumulation increased to 2. 73-fold and 4. 18-fold in the microneedle group and direct application of triamcinolone acetonide cream group,respectively,with the content of microneedle group being 3. 56-fold that of the direct cream application group (P<0. 05). Triamcinolone acetonide distribution was not homogeneous at 12 h after intracutaneous injection, with the level being (4. 83 ± 5. 51) µg, while the distribution in the microneedle group was homogenous, with the level being (0.93 ± 0. 14) µg. TEWL results showed no significant difference in skin irritation between microneedle and intracutaneous injection group; however, laser Doppler flowmetry showed that the skin irritation of intracutaneous injection group was 8. 40- fold that of microneedle treatment group. Conclusion Modified microneedle roller treatment followed by cream application, compared with intracutaneous injection, can yield more homogeneous distribution and less skin irritation in human hyperplastic scar skin, but its efficacy for scar treatment remains to be further verified.

As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.
Single-Domain Antibodies

Mycoplasma pneumoniae is the most common pathogen of respiratory tract infection in children and adults. Clinical observation shows that M. pneumoniae infection can cause massive mucus secretion in the respiratory tract, which makes the breathing of patients difficult. Studies have shown that M. pneumoniae infection can cause massive secretion of mucin 5AC (MUC5AC). Adhesin P1 plays an important role in the pathogenesis of M. pneumoniae infection by mediating the adhesion of pathogens to host cells, and the C-terminal residues of P1 (P1-C) are immunogenic. This study investigated the molecular mechanism of Wnt/β-catenin signaling pathway inhibitor Dickkopf-1 (DKK1) in the secretion of MUC5AC in mouse airway epithelial cells (MAECs) induced by P1-C. Scanning electron microscope and hematoxylin-eosin staining were used to observe the effect of P1-C on mucus secretion of MAECs. Protein chip was used to detect the secretion of cytokines and analyse the enrichment of related signaling pathways induced by P1-C in MAECs. Periodic acid schiff stain (PAS) staining, Tunel staining and Masson staining were used to detect the damage of the lungs of mouse exposed to P1-C. Immunohistochemistry was used to detect the secretion of MUC5AC expression, and Western blotting was used to reveal the molecular mechanism of DKK1-regulated secretion of MUC5AC induced by P1-C protein in MACES. The results showed that P1-C induced the massive secretion of mucus and inflammatory factors in MAECs. During P1-C infection, DKK1 down-regulated janus kinase 2 (JAK2), phosphorylation signaling and transcription activator 1 (p-STAT1) and phosphorylation signaling and activator of transcription 3 (p-STAT3) expression. Overexpression of DKK1 significantly up-regulated the expression of MUC5AC repressor transcription factor fork-head box protein A2 (FOXA2). At the same time, the expression of MUC5AC induced by P1-C was inhibited significantly. It is speculated that DKK1 can effectively reduce the secretion of MUC5AC in MAECs induced by P1-C by inhibiting the JAK/STAT1-STAT3 signaling pathway and up-regulating the expression of FOXA2.
Animals ; Mice ; Epithelial Cells ; Lung ; Mucin 5AC/metabolism* ; Mycoplasma pneumoniae/metabolism* ; Signal Transduction