Objective:Toprepare poly-DL-lactide-poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase-1 (TIMP-1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods: The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP-1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP-1 mRNA in HepG2 cells was examined by semi-quantitative RT-PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results: The microsphere encapsulating recombinant TIMP-1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×10~8/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP-1 PELA microsphere efficiently induced TIMP-1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion: PELA microsphere encapsulating recombinant TIMP-1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.

Objective To explore the clinical features and diagnosis of primary immunodeifciency disease caused byTyk2 gene mutations.Methods Clinical data from the ifrst case in China diagnosed of primary immunodeifciency disease caused by Tyk2 gene mutation were retrospectively analyzed, and related literature was reviewed.Results One year and 3 month old boy suffered with repeated pulmonary infection, chronic otitis media, intractable eczema like rash, repeated skin abscess, HSV infection, intracellular bacterial infection, and remarkedly increased total IgE. It was detected that compound heterozygous mutations of c.2269C>G in No. 16 exon and c.149delC in No. 3 exon inTyk2 gene. Literature searching found other 8 cases (5 males and 3 females) of immune deifciency patients caused byTyk2 gene defects, all of which hadTyk2 gene homozygous mutations and presented with repeated infection of paranasal sinus and lung. In the 8 cases 6 cases were combined with mycobacterium tuverculosis infection, 4 cases had repeated virus infection, 4 cases had meningonecephalitis, 3 cases had intractable eczema like rash, 2 cases had salmonella enteritis, 1 case had remarkedly increased total IgE, one case had elevated eosinophils, 5 cases were born in intermarriage family and 1 case died of meningitis caused by unknown etiology.Conclusions When patients have repeated paranasal sinus infection and lung infection, combined with intracellular bacterial infection (including mycobacterium tuberculosis infection), and repeated virus infection or intractable eczema like rash, with or without increased total IgE, immunodeifciency disease caused by Tyk2 gene defection should be considered. Gene sequence analysis can assist in early diagnosis.

Objective To investigate the efficacy of autologous peripheral hematopoietic stem cell transplantation in the treatment of adult dermatomyositis. Methods A 21-year-old patient with dermatomyositis received autologous peripheral hematopoietic stem cell transplantation and was followed up for 6 years. Autologous peripheral hematopoietic stem cells were mobilized by recombinant human granulocyte colony stimulating factor (rhG-CSF) before the transplantation, and the conditioning regimens consisted of cyclophosphamide,methylprednisolone and cyclosporin. Rabbit anti-human T lymphocyte immunoglobulin began to be applied on day 3 after retransfer of stem cells. The improvement in symptoms, physical signs and biochemical indicators was observed, and hematopoietic restructuration and immunity resurrection were evaluated after the transplantation. Results After the transplantation, skin eruption greatly improved and gradually subsided. The muscle force of extremities restored from level Ⅳ before transplantation to level Ⅴ. The level of creatine kinase declined sharply after transplantation, but gradually returned to previous level. Leucocyte count began to decrease on the day of retransfer, and returned to the normal level on day 8. Immune function remained normal before and after the transplantation. Conclusion Autologous peripheral hematopoietic stem cell transplantation is an alternative treatment for severe and refractory dermatomyositis.

Objective To investigate the effects of hyperbaric oxygenation(HBO)therapy on serum con- centrations of soluble intercellular adhesion molecule-1(slCAM-1),soluble vascular cell adhesion molecule-1(sV- CAM-1),soluble E-selectin(sE-selectin)and matrix metalloproteinase-9(MMP-9)in patients with aeute cerebral infarction and their clinical implications.Methods One hundred and twelve cases of cerehral infarction in the ca- rotid artery system were assigned into two groups.Patients in the routine treatment group(RT group,n=62)were treated with routine clinical treatment regime,whereas those in the HBO group(n=50)were treated with H BO ther- apy in additioo to routine clinical treatment.Thirty age- and sex-matched normal subjects were recruited and served as controls.The serum concentrations of sICAM-1,sVCAM-1,sE-selectin and MMP-9 were measured hy using ELISA method before and 10 days after treatment.The assessment of neurological deficits using National Institutes of Health Stroke Scale(NIHSS)score was conducted before treatment,and at 10 and 30 days after treatment,and the therapeutic efficacy was evaluated.Results The concentrations of sICAM-1,sVCAM-1,sE-selectin and MMP-9 of the patients were significantly higher than those of the control subjects.These parameters were all decreased signifi- cantly after treatment in the two patient groups.Moreover,these parameters were lower in the HBO group than those in the RT group after treatment.The NIHSS scores of HBO group were significantly lower than that of the RT group at the 30th clay post-treatment.The effective rate of HBO group was higher than that of RT group.Conclusion HBO therapy can decrease the serum levels of sICAM-1,sVCAM-1,sE-seleetin and MMP-9,which might be one of the mechanisms of HBO in the treatment of cerebral infarction.

Objective To detect the routine coagulation indicators in breast cancer patients receiving the trastuzumab treatment and to analyze the influence of the coagulation indicators on clinical treatment response .Methods Totally 67 hospitalized breast cancer patients receiving the trastuzumab treatment in 401 Hospital of PLA from Jan .2006 to Dec .2012 were collected and divided into the effective group(47 cases) and ineffective group(20 cases) according to the curative effect .The levels of PT ,APTT ,TT ,Fib and D‐D were statistically analyzed .The differences of coagulation indicators were compared between the two groups .The correla‐tion between the coagulation indicators with the curative effect was analyzed .Results Compared with the effective group ,PT , APTT and TT in the ineffective group were slightly extended ,while the D‐D level was slightly increased ,the differences were not statistically significant(P> 0 .05);but the Fib level was significantly increased with statistical difference(P< 0 .05) .Conclusion The breast cancer patients with ineffectiveness in the trastuzumab treatment are easily appear the high Fib status .Determining its plas‐ma concentration is conducive to judge the prognosis of the trastuzumab treatment in breast cancer patients .

ObjectiveTo investigate the effects of early inhaled budesonide on the expression of nuclear factor-kappa B(NF-κB) and intercellular adhesion molecule(ICAM-1) in airway epithelial cells of asthma rats.Methods30 rats were randomly divided into three groups:control group, asthma group and therapeutic group with inhaled budesonide.The expression of NF-κB and ICAM-1 in bronchial epithelium were observed with immunohistochemical staining and computer image analysis system.ResultsThe expression of NF-κB, ICAM-1 and subepithelial collagen deposition were significantly highly in asthma group than those of control group and of therapeutic group (P<0.01 respectively). There was a close correlation between the expression of NF-κB and ICAM-1 in asthma rats (r=0.61,P<0.01), as well as between the expression of ICAM-1 and supepithelial collagen(r=0.47,P<0.01).ConclusionThe excessive expression of NF-κB and ICAM-1 play an important role in the pathogenesis of airway remodeling in asthma.Budesonide can influence airway remodeling by downregulating the expression of NF-κB and ICAM-1.

OBJECTIVE To observe the type of nosocomial infections in our comprehensive ICU,the prevalence and the vicissitude characteristic of infection strains,and the change of antibiotic-resistance.METHODS To summarize the 10 year results of the monitoring which were divided into three stages to compare the changes with time.RESULTS Gram-negative bacilli were 987(76.4%),Gram-positive cocci 216(16.7%) strains,and 89 strains were fungi(6.9%).The top six strains were in turn:Pseudomonas aeruginosa,Acinetobacter baumannii,Staphylococcus aureus,Klebsiella pneumoniae,Escherichia coli,and Stenotrophomonas maltophilia.Distribution of infection sites: 92.3% infection was in lungs,5.2% in urinary tract infection,2.5% in other sites included lungs,abdomene,CSF,blood etc.CONCLUSIONS The main nosocomial infective pathogens in our ICU are Gram-negative bacilli(75.0%),Gram-positive bacterial infection shows a slight increasing,whereas fungi infection decreasing.In addition to S.maltophilia,the great majority of Gram-negative bacilli,ESBL-producing K.pneumoniae and E.coli maintain a higher sensitivity to carbapenem antibiotic.All Gram-positive cocci to vancomycin and teicoplanin maintain a good sensitivity.In the fungal infection,Candida albicans infection ratio is decreased,while non-C.albicans increases.

Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

Aged ; Bronchoscopy ; Esophageal Neoplasms ; complications ; Female ; Humans ; Male ; Middle Aged ; Stents ; Thyroid Neoplasms ; complications ; Tracheal Stenosis ; etiology ; therapy

Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.