Background Asthma is a complex disease involving genetic and environment interactions.Atopy is a strong risk factor for asthma.The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials.To explore the effects of airway epithelium on asthma,we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier,which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma.Methods Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group:control group,asthma group,ovalbumin (OVA)+OVA group,lipopolysaccharide (LPS) group and LPS+OVA group.In the control group,0.9％ saline was injected intraperitoneally on day 1.Fourteen days later,the rats were exposed to aerosolized 0.9％ saline.In the asthma group,the rats were sensitized with an injection of 10 mg of OVA,followed by an aerosolized 2％ OVA challenge14 days later.The OVA+OVA group was sensitized by an inhalation 2％ OVA,20 minutes a day,from day 1 to day 7,and then OVA challenged in the same way as the asthma group.In the LPS group,LPS (200 μl,1 μg/μl) was given by airway on day 1 and day 3,with a simultaneous aerosol inhalation of 2％ OVA for 20 minutes a day from day 1 to day 7.Fourteen days later,the rats were challenged with saline as in the control group.While in the LPS+OVA group,LPS (200 μl,1 μg/μl) was given by airway on day 1 and day 3,with a simultaneous aerosol inhalation of 2％ OVA for 20 minutes a day from day 1 to day 7.Fourteen days later,the rats were challenged with OVA as in the asthma group.The expression of interleukin (IL)-4,interferon-gamma (IFN-y) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed.The level of IL-4,IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA).Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts.Flow cytometry analysis was also used to count Th1 and Th2 cells.Results The pathological changes in the LPS+OVA group were similar to the asthma group,while in other groups,the pathological changes were not obvious.The ratio of lymphocytes in BALF,IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS+OVA groups were higher than in the control group and the OVA+OVA group (P ＜0.05).The level of IgE was higher in the asthma,LPS and LPS+OVA groups than in the control group and the OVA+OVA group (P ＜0.05).By flow cytometry analysis,the Th1/Th2 ratio was lower in the LPS+OVA and asthma groups than in other groups (P ＜0.05).Conclusions The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses.This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

OBJECTIVETo analyze the clinicopathological features and prognosis of colorectal cancer patients with preoperative cancer-related anemia.

METHODSClinical data of 354 patients with colorectal cancer in the Second Affiliated Hospital of Guangzhou Medical College from January 2003 to July 2009 were analyzed retrospectively. Those with hemoglobin(Hb)<120 g/L before surgery were defined as cancer-related anemia.

RESULTSOf the 354 colorectal cancer cases, 195 were males and 159 were females. The median age was 65(range 22-92) years. Preoperative cancer-related anemia tended to be occurred in female(P<0.01) and those with preoperative albumin ≤35 g/L (P<0.01), right colon cancer(P<0.01) and full-thickness invasion(P<0.05). Cox regression analysis showed preoperative cancer-related anemia was an independent unfavorable factor for overall survival (HR=1.60, 95% CI:1.05-2.44; P<0.05), but not for disease-free survival (HR=1.43, 95% CI:0.97-2.12; P>0.05) in colorectal cancer.

CONCLUSIONSPreoperative cancer-related anemia plays an important role in the development and prognosis of colorectal cancer and great attention should be paid to clinical practice.

Adult ; Aged ; Aged, 80 and over ; Anemia ; etiology ; Colorectal Neoplasms ; complications ; surgery ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

AX15 is a mutein of naturally occurring human ciliary neurophic factor (hCNTF), with improved biological activity, stability and solubility. AX15 is susceptible to protease degradation when expressed in Pichia pastoris. Amino acid sequencing revealed the degradation was occurred behind position 12 and 13 amino acid residues, which constitute a dibasic site, RR. Based on the substrate specificity of KEX2, a KEX2 resistant mutein of AX15-AX15 (R13K) was constructed, in which RR was replaced by RK. It was demonstrated that the stability of AX15 (R13K) improved significantly, as no degradation was detected even after 120 hours of induction. AX15 (R13K) was purified to homogeneity by ultrafiltration and gel filtration. TF-1 cell survival bioassay showed AX15 (R13K) had equivalent specific activity to AX15. The protease resistant mutein of AX15 may have greater in vivo stability and thus have superior therapeutic potential.
Ciliary Neurotrophic Factor ; biosynthesis ; genetics ; Genetic Vectors ; Humans ; Mutant Proteins ; biosynthesis ; genetics ; Mutation ; Peptide Hydrolases ; chemistry ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification

Objective To evaluate the feasibility and safety of a delivery pathway for the performance of percutaneous left atrial appendage (LAA) occlusion in experimental canine models. Methods Transseptal puncture was performed via femoral vein approach under fluoroscopic and angiographic guidance in 12 experimental dogs. A pigtail catheter was advanced into the left atrium (LA), which was followed by LA angiography. The diameters of the neck of LAA were measured on LAA angiogram obtained in appropriate projection. After the delivery sheath was advanced along the wire into LA, a pigtail catheter was inserted into the ostium of the LAA and the sheath was then advanced over the pigtail into the LAA. LAA angiography was then performed through the delivery sheath to confirm the position of the delivery sheath. One hour after the procedure both electrocardiography (ECG) and transthoracic echocardiography (TTE) were carried out in five dogs to check the results, immediately after which the five dogs were sacrificed to macroscopically observe the damages of the puncture site of inter-atrial septum as well as inside the LA and LAA. One hour and 2 weeks after the procedure TTE was conducted in the remaining 7 dogs and these dogs were followed up for one month. Results One dog died of pericardial tamponade during the operation. In 8 dogs the LAA was clearly displayed in the projection position of right anterior oblique (RAO) 30°/cranial (CRA) 20°,while in 3 dogs the LAA was well visualized in the projection position of RAO 30° , and in one dog in the projection position of RAO 30°/caudal (CAU) 20°. The diameter of LAA neck was (13.6 ± 5.2) mm. The delivery sheath was safely advanced into the LAA along the pigtail catheter in all dogs, and no air embolism, thrombus or pericardial tamponade occurred. Hematoma at puncture point of groin occurred in 2 dogs, which was absorbed through pressure dressing. Macroscopic examination of the heart performed immediately after the operation showed that no bloody pericardial effusion was found, and mild hematoma at posterior wall of LA was seen in one dog and mild damage of the upper-margin intima of LAA was noted in 2 dogs. The mean fluoroscopy time was (10.1 ± 2.5) minutes and the mean operation time was (58 ± 12) minutes. TEE showed no pericardial effusion 2 weeks after the procedure. During the follow-up period of one month no sudden death, stroke or infection occurred. Conclusion This method of placing the delivery sheath into the LAA is clinically safe and effective, and it can reliably establish a pathway to advance the LAA occluder into LAA.

Objective To explore the application efficacy of artificial nose in CCU patients with tracheal intubation.Methods Totals of 62 patients with tracheal intubation were randomly divided into the group of artificial nose and group of electrothermal and constant temperature moist,then the sputum viscosity,irritating cough,airway administration hours,average intubation time,consumables costs,and the incidence of ventilator-associated pneumonia in two groups were observed and compared.Results In artificial nose group,the incidence of irritating cough was28.1％,the incidence of ventilator-associated pneumonia was 15.6％,airway administration hours was( 2.3 ± 0.5 ) h,average intubation time was ( 112 ± 6.5 ) h,consumables costs was (44.2±6.7)yuan all better than that of electrothermal and constant temperature moist group,which was 71.9％,37.5％,( 3.5 ± 0.6 ) h,( 133 ± 7.8 ) h,and ( 56.3 ± 1.5 ) yuan,respectively,differences were statistically significant ( x2 =12.25,3.925 0; t =8.660 5,11.699 8,8.212 9,respectively; P ＜ 0.01 or P ＜0.05).Sputum viscosity status of artificial nose group was that Ⅰ grade 12.5％,Ⅱ grade 62.5％,Ⅲ grade 25.0％,whilethat of electrothermal and constant temperature moist group was 46.9％,25.0％,28.1％,respectively,and the differences was statistically significant ( x2 =11.559 0,P ＜ 0.01 ).Conclusions Artificial nose using in patients with endotracheal intubation can achieve the desired efficacy of airway humidification,improve the efficacy of airway administration,save energy and time and significantly reduce the incidence of ventilator-associated pneumonia,which likely to be generally used in clinical.

BACKGROUNDAsthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma.

METHODSThirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group: control group, asthma group, ovalbumin (OVA) + OVA group, lipopolysaccharide (LPS) group and LPS + OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge 14 days later. The OVA + OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS + OVA group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin (IL)-4, interferon-gamma (IFN-γ) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Th1 and Th2 cells.

RESULTSThe pathological changes in the LPS + OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS + OVA groups were higher than in the control group and the OVA + OVA group (P < 0.05). The level of IgE was higher in the asthma, LPS and LPS + OVA groups than in the control group and the OVA + OVA group (P < 0.05). By flow cytometry analysis, the Th1/Th2 ratio was lower in the LPS + OVA and asthma groups than in other groups (P < 0.05).

CONCLUSIONSThe experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

Animals ; Bronchi ; pathology ; Cell Count ; Cytokines ; physiology ; Disease Models, Animal ; Epithelial Cells ; pathology ; Hypersensitivity ; etiology ; Immunoglobulin E ; blood ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Lipopolysaccharides ; toxicity ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Wistar

BACKGROUNDAlthough dopamine transporter (DAT) is essential for addiction, the effect of additive drugs on DAT function is still controversial, especially for opiates. We investigated the functional changes of dopamine transporter in striatum of rhesus monkeys during acute morphine injection and its abstinence.

METHODSFour rhesus monkeys, 6 to 9 years old, two male and two female, were examined for 12 days. Single photon emission computed tomography (SPECT) was performed with (99)T(cm)-TRODAT-1 as the radiopharmaceutical dopamine transporter agent during different stages of acute morphine injection and its abstinence. The ratios of SPECT signal between striatum and cerebellum (ST/CB) were calculated.

RESULTSThe ST/CB ratio declined significantly on the first day of morphine injection and continued declining with more morphine injections. After abstinence, the ratio increased with time, but was still significantly lower on the 5th day of abstinence than the normal level.

CONCLUSIONSIn rhesus monkey, acute morphine injection has both rapid and lasting effects on DAT by downregulating its function. The decline was partially reversible following morphine abstinence. The results suggest that striatum is one effective target of morphine and that the DAT function in striatum is one indicator for morphine addiction.

Acute Disease ; Animals ; Cerebellum ; metabolism ; Corpus Striatum ; drug effects ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; analysis ; physiology ; Female ; Macaca mulatta ; Male ; Morphine Dependence ; physiopathology ; Organotechnetium Compounds ; Tomography, Emission-Computed, Single-Photon ; Tropanes

Human beta defensin 2 (HBD-2) may play an important role in human defense against infection. Its antimicrobial capacity has been fully documented in in vitro study. In order to evaluae its in vivo effects, we developed an HBD-2 transgenic mouse model. The HBD-2 minigene containing CMV promoter, full length of HBD-2 cDNA and BGH polyA tail was generated by PCR amplification and introduced into the fertilized oocytes of C57 X ICR hybridized mouse by microinjection, and offspring were produced. DNA was isolated from the tails of the mouse pups, and the HBD-2 minigene incorporation was analyzed by PCR using HBD-2 specific primers. The HBD-2 gene expression in the multi-tissues of transgenic mice was determined at mRNA level by RT-PCR and at peptide level by immunohistological staining with the use of HBD-2 monoclonal antibody. The results showed that among 17 F0 transgenic mice, HBD-2 positive signal was determined by PCR in 4 mice, suggesting that HBD-2 minigene has been incorporated into the offspring mice. Meanwhile, a widespread expression of HBD-2 mRNA and peptide was detected in the F1 transgenic mice's multi-tissues such as trachea, lung, intestine, esophagus, testis, spleen, skin, endothelium and brain.
Animals ; Anti-Infective Agents ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Transgenic ; Models, Animal ; Polymerase Chain Reaction ; RNA, Messenger ; analysis ; biosynthesis ; genetics ; beta-Defensins ; biosynthesis ; genetics

OBJECTIVETo verify the linkage of the candidate regions identified in a previous study (markers D2S168, D2S151, D2S142 on chromosome 2) with hypertension in Chinese families.

METHODSA genetic linkage study focused on chromosome 2 was performed on 240 Chinese families containing 856 patients with essential hypertension. A total of 1080 individuals were genotyped using 9 highly polymorphic microsatellite markers around the candidate regions on chromosome 2 with an average spacing of 5 cM. Non-parametric linkage (NPL), parametric linkage analysis and transmission-disequilibrium test (TDT) with the GENEHUNTER software were used to assess evidence for linkage.

RESULTSLinkage of a region on chromosome 2 around D2S151 and D2S142 with hypertension was confirmed by different statistical methods (NPL, LOD score and TDT). However, the linkage of D2S168 could not be replicated in this extension study.

CONCLUSIONSThe data suggest that a region on chromosome 2 at or near the loci of D2S142 and D2S151 may harbor genes responsible for the development of essential hypertension in Chinese.

Alleles ; China ; Chromosomes, Human, Pair 2 ; genetics ; Family Health ; Female ; Gene Frequency ; Genetic Linkage ; Humans ; Hypertension ; genetics ; Linkage Disequilibrium ; Male ; Microsatellite Repeats

Objective The application of hinged scaffold in the terrible triad of the elbow has been widely accepted by or-thopedic trauma physicians. We discussed whether to repair the collateral ligament or not of terrible triad of the elbow under hinged ex-ternal fixator in this study. Methods 23 patients with terrible triad of the elbow,who had been admitted in Foshan Hospital of tradi-tional Chinese Medicine from June 2011 to August 2016 were selected. In the surgeries, we firstly repaired and fixed the coronoid and radial head fractures,and the repairments of the lateral collateral ligament complex(LCLC) was based on the severity of injury and the stability of the elbow joint. All the patients were treated with hinged external fixator in flexion 90°,forearm neutral position and the medial collateral ligament complex (MCLC) was not repaired. The patients were followed up from 8 to 26 months with an average of 13.7 months. Elbow flexion and extension amplitude and forearm rotation amplitude were measured at the time of follow-up. The clinical effects were eval-uated according to HSS scoring of elbow joint function. Results Their average elbow range of flexion and extension at the last follow-up is (122.2 ± 11.9)°,LDLC insertion site reconstruction and non-reconstruction has the flexion and extension range of (120.3 ± 13.1)°,(125.6±9.0)°;their average forearm rotation amplitude was(118.7±14.3)°,LDLC insertion site reconstruction and non-re-construction has the forearm rotation amplitude of (116.0±13.1)°,(123.8±16.0)°. HSS score was (82.0±12.6) points.The results were excellent in 7 cases,good in 11. The excellent-good rate was 78.3%. After surgery,1 case developed radial head subluxation,1 case developed nonunion of radial head without recurrent dislocation of elbow joint,6 cases developed ectopic ossification of the elbow joint. Conclusion With the use of hinged external fixator,it is not necessary to repair the MCLC. And the LCLC injury cannot be repaired when it does not cause severe instability of the elbow,with the use of hinged external fixator can get a good effect.