[Research advances on the mechanism of circular RNA in diabetic wound healing].

In recent years, a large number of studies have shown that non-coding RNAs play an important role in wound healing process. Among them, studies on the mechanism of circular RNA (circRNA) have shown that circRNA is closely related to the proliferation of cells related to wound healing, such as endothelial progenitor cells and keratinocytes, and circRNA is also involved in the chronic wound healing process. Based on the introduction of the related concept of circRNA, this paper focuses on the possible regulatory mechanism of circRNA in different stages of diabetic wound healing and summarizes the potential role of circRNA in the process of diabetic peripheral vascular atherosclerosis, aiming to explore the in-depth molecular mechanism and clinical significance of circRNA in diabetic wound healing process, and provide reference for further research.

[Application of exhaled nitric oxide detection in the diagnosis, treatment and management of chronic airway diseases: current status and prospects].

Airway inflammation is the most important pathological basis of chronic airway diseases. The detection and evaluation of airway inflammation is helpful for the diagnosis, treatment and management of airway diseases. Exhaled nitric oxide is the most widely used noninvasive airway inflammation detection technique in recent years, which provides a simple and quick reference for the diagnosis and management of chronic airway diseases, but there are still some controversies and deficiencies. This paper briefly expounds the biological significance of exhaled nitric oxide and detecting technique, summarizes the clinical application and the deficiencies of exhaled nitric oxide detection. In the future, with the further researchers on technology and the accumulation of application experiences, the detection technology of exhaled nitric oxide will play a more significant role in the accurate management of chronic airway diseases.

[Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome].

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.

[Strengthen the management of asthma in the elderly and strive to improve the prognosis of the disease].

Asthma in the elderly is a special type of asthma, with special pathophysiology, clinical characteristics, complications and drug reaction, resulting in its diagnosis and treatment complicated, with higher morbidity and mortality. Combined with the newly published Chinese Expert Consensus on the Diagnosis and Management of Asthma in the Elderly, this paper calls for strengthening the management of asthma in the elderly, promoting relevant research, and perfecting the clinical diagnosis and treatment program suitable for the elderly asthma patients, so as to improve the level of asthma control and improve the prognosis.

[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

[Evaluation of the effectiveness of bronchial thermoplasty in patients with severe asthma in the real world two years after bronchial thermoplasty treatment].

Objective: To assess the effectiveness of bronchial thermoplasty (BT) in "real-world" patients with severe asthma at 2 years post therapy. Method: Outcomes of 70 patients with severe asthma undergoing bronchial thermoplasty from March 2014 to November 2017 in China-Japan Friendship Hospital were retrospectively analyzed two years post therapy. The scores of Asthma Control Test (ACT) and Mini Asthma Quality of Life Questionnaire (mini-AQLQ), the number of severe exacerbations, emergency department visits and hospitalizations for asthma symptoms in the past year, indicators of pulmonary function including forced expiratory volume in one second (FEV(1)), FEV(1) as a percentage of predicted value (FEV(1)%pred) and FEV(1)/forced vital capacity (FEV(1)/FVC), maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment were evaluated and analyzed before and 2 years after BT therapy, and the subjective assessment about effectiveness of BT were given by the patients. Results: Before and 2 years after BT, the numbers of subjects suffering severe exacerbations in the past year were 70 (100%) and 37 (52.9%), and the numbers of total severe exacerbations were 575 and 162 respectively. The numbers of patients having emergency department visits due to asthma exacerbation were 46 (65.7%) and 9 (12.9%), and the numbers of emergency department visits were 186 and 19 respectively. The numbers of patients hospitalized due to asthma exacerbation were 43 (61.4%) and 16 (22.9%), and the numbers of total hospitalizations were 124 and 24, respectively. The rate of severe exacerbation, emergency department visit and hospitalization were significantly reduced two years after the treatment by 71.9%, 88.9% and 83.3% (all P<0.001). The scores of ACT and mini-AQLQ were significantly increased [22 (21, 24) vs 17 (13, 19), (5.57±0.89) vs (3.83±0.92); both P<0.001]. Two years after BT, 4 patients (5.7%) were weaned off inhaled corticosteroids (ICS) and long-acting ß(2)-agonist (LABA), while 14 patients (37.8%) were weaned off oral corticosteroid (OCS), with daily dose of ICS and OCS significantly decreased (both P<0.05). The proportion of patients treated with montelukast sodium and theophylline was also significantly reduced after BT (40.0% vs 81.4%, 27.1% vs 71.4%; both P<0.001). In addition, the indicator of FEV(1), FEV(1)%pred and FEV(1)/FVC ratio were all greatly improved two years after the treatment [2.27 (1.84, 2.82) vs 2.10 (1.70, 2.61) L, (76.8±19.5)% vs (72.5±19.8)%, (66.3±13.6)% vs (63.8±13.0)%; all P<0.05]. The annual cost for asthma drug and asthma treatment after BT were significantly decreased (P<0.001). Fifty-nine patients (84.3%) subjectively assessed the treatment as effective. Conclusion: The bronchial thermoplasty in "real-world" patients with severe asthma could significantly improve the asthma control, lung function and quality of life, and reduce severe exacerbations, emergency department visits and hospitalizations for asthma symptoms, while the maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment are significantly decreased.

[Effects of bronchial thermoplasty on airway remodeling, asthma control and quality of life in patients with severe asthma].

Objective: To investigate the effects of bronchial thermoplasty (BT) on airway remodeling, asthma control and quality of life in patients with severe asthma. Methods: From January to September 2019, 11 patients with severe asthma were recruited from China Japan Friendship Hospital to receive BT treatment. The treatment was performed over three sessions separated by 3-week intervals. The right lower lobe, the left lower lobe and the bilateral upper lobes were treated respectively. In this study, patients' self-control method was used. The timepoint before the first BT treatment was defined as pre-treatment group, and the timepoint before the third treatment was defined as post-treatment group. Histological staining was used to detect the airway remodeling of the left lower lobe in two groups, including the mass of airway smooth muscle (ASM) and collagen in airway wall, and the thickness of basement membrane. The cell classification of bronchoalveolar lavage fluid (BALF) from the left lower lobe and peripheral blood, total serum IgE, asthma control test (ACT), mini asthma quality of life questionnaire (miniAQLQ) and the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred) were evaluated in the two groups. The correlation was analyzed between airway remodeling and asthma control and quality of life. Results: Effects of BT in post-treatment group, compared with pre-treatment group: the mass of ASM and collagen in airway wall was significantly decreased [(9.8±2.5)% vs (25.8±7.7)%, (12.9±4.0)% vs (17.4±5.6)%] (both P<0.05), while basement membrane thickness was not significantly different (P>0.05); the percentage of eosinophils in BALF and peripheral blood, and total serum IgE were not significantly different (all P>0.05); ACT score and miniAQLQ score were significantly increased [(23.1±1.8) vs (13.8±6.2) points, (5.3±1.3) vs (3.6±1.5) points] (both P<0.05), while FEV(1)% pred was not statistically different (P>0.05). The mass of ASM was negatively correlated with ACT score (r=-0.712), miniAQLQ score (r=-0.557) and FEV(1)%pred (r=-0.477), while the mass of collagen was negatively correlated with ACT score (r=-0.549) and miniAQLQ score (r=-0.639) (all P<0.05). Conclusion: BT treatment could improve airway remodeling, asthma control and quality of life in patients with severe asthma; besides, the reduction of remodeling is related to the improvements of asthma control and quality of life.

[The clinical characteristics and airway inflammatory phenotypes in 35 patients with severe asthma].

Objective: To analyze the clinical features and airway inflammatory phenotypes in patients with severe asthma. Methods: Patients with severe asthma were recruited in this cross-sectional study in our center. History of asthma, blood and sputum samples, and respiratory function were tested and recorded. The phenotypes of inflammation in airway were evaluated. Results: A total of 35 asthmatic patients with the mean age 41.4 years were involved in this study from January 2013 to December 2013. The disease duration were (14.3±13.6) years with mostly male in China-Japan Friendship Hospital. Thirteen patients reported the history of smoking. Twenty-one patients had the complications such as allergic rhinitis, followed by chronic rhinosinusitis of 11 cases, nasal polyp of 7 cases, gastroesophageal reflux disease of 5. The forced expiratory volume in one second/predicted value ratio (FEV(1)%pred) in 29 patients was lower than 80%.Twenty-one participants did not react in bronchial reversibility test. Sixteen patients were administrated with oral cortical steroids (OCS). The average annual cost per patient was 22 thousand RMB. Sixteenrefractory asthmatics were diagnosed as eosinophilic asthma. Conclusions: The clinical features associated with severe asthma include male gender, smoking, persistent airway limitation. Systemic use of corticosteroids is common and treatment costs are high. The eosinophilic asthma is the main inflammatory phenotype in patients with severe asthma.

[Distribution of airway inflammation phenotype in patients with bronchial asthma and its correlation with control level].

Objective: To investigate the distribution of airway inflammation phenotypes in patients with bronchial asthma and its correlation with asthma control level. Methods: Patients who met GINA 2017 asthma diagnostic criteria from October 2017 to April 2018 in respiratory outpatient department of China-Japan Friendship Hospital were included. The clinical data of non-acute asthma patients were prospectively collected, including general data, asthma control level, pulmonary function, induced sputum cell classification, serum total IgE, exhaled nitric oxide (FeNO), blood cell classification. The correlation between phenotype distribution of airway inflammation and airway inflammation markers (eosinophils in sputum, FeNO, blood eosinophil, serum IgE) and asthma control was analyzed by correlation analysis. The correlation between sputum eosinophil level and FeNO, blood eosinophil count, serum total IgE, forced expiratory volume in one-second (FEV(1)) predicted (FEV(1)%pred) was analyzed by correlation analysis too. Results: A total of 97 asthmatic patients were enrolled. There were 38 males (39.2%) and 59 females (60.8%), aged (48±14) (range 22 to 80). Control level of asthma:13 cases (13.4%) were controlled, 39 cases(40.2%) were partially controlled and 45 cases (46.4%) were uncontrolled. The phenotypes of airway inflammation were eosinophilic 51 cases (52.6%), neutrophilic 9 cases (9.3%), mixed 35 cases (36.1%) and paucigranulocytic 2 cases (2.1%). There was no significant correlation between airway inflammation phenotype distribution, airway inflammation markers and asthma control level (P>0.05). Sputum eosinophil level was positively correlated with FeNO level in controlled and uncontrolled patients (r=0.420, P=0.008 and r=0.325, P=0.031); sputum eosinophil level was positively correlated with blood eosinophil level in uncontrolled asthma patients (r=0.328, P=0.037). There was no significant correlation between sputum eosinophil level and FEV(1)%pred (P>0.05). Conclusions: Eosinophil type is the dominant type of airway inflammation in asthmatic patients, and there is no significant correlation between airway inflammation and asthma control level. At present, airway inflammation cannot be used to assess asthma control level.

From Antimicrobial to Anticancer Peptides: The Transformation of Peptides.

BACKGROUND: Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and kill various targets, including gram-negative bacteria, gram-positive bacteria, fungi, and tumor cells. OBJECTIVE: An overview of the state of play with regard to the research trend of antimicrobial peptides in recent years and the situation of targeting tumor cells, and to make statistical analysis of the patents related to anticancer peptides published in recent years, is important both from toxicological and medical tumor therapy point of view. METHODS: Based on the Science Citation Index Expanded version, the Derwent Innovation Index and Innography as data sources, the relevant literature and patents concerning antimicrobial peptides and anticancer peptides were analyzed through the Thomson Data Analyzer. Results of toxicologic and pharmacologic studies that brought to the development of patents for methods to novel tumor drugs were analyzed and sub-divided according to the specific synthesis of anticancer peptides. RESULTS: The literature and patent search data show that the research and development of global antimicrobial peptides and anticancer peptides has been in an incremental mode. Growing patent evidence indicate that bioinformatics technology is a valuable strategy to modify, synthesize or recombine existing antimicrobial peptides to obtain tumor drugs with high activity, low toxicity and multiple targets. CONCLUSION: These findings may have important clinical implications for cancer treatment, especially in patients with conditions that are not currently treatable by other drugs, or that are resistant to existing cancer drugs.

[The relationship between smoking status and epidermiology of asthma in people aged over 14 years in China].

Objective: To study the relationship between bronchial asthma and smoking status in Chinese people. Methods: Asthma epidemiological survey and stratified-cluster-random method survey were performed in residents over 14 years in 8 provinces (cities) of China from February 2010 to August 2012. Asthma was diagnosed based upon case history, clinical signs and lung function test. Smoking status was investigated by questionnaire. Results: Sampling population was 180 099 and 164 215 were valid. A total of 2 034 subjects were diagnosed as asthma including 79 692 men and 84 523 women. The overall prevalence rate of asthma was 1.24% (2 034/164 215). Smokers were 23.8% (39 137/164 215) in the whole population. Smokers were 34.5% (702/2 034) in asthmatic patients, compared with 23.7% (38 435/162 181) in no-asthmatic population. The incidence of asthma was 1.79% and 1.06% in smokers and non-smokers respectively (P<0.001), suggesting that OR of smoking was 1.70 (95% CI 1.55-1.86, P<0.001). According to asthma control test (ACT) score, the level of asthma control in non smoking group was higher than that in smoking group(43.2% vs 35.3%). The times of hospitalization due to acute exacerbations(0.51 vs 0.41 events/person/year), total hospitalization rate(27.35% vs 20.12%), annual emergency room visits (0.80 vs 0.60 events/person/year) and emergency room visit rate (31.77% vs 24.47%) were all much higher in smoking asthmatic patients than those in non smoking asthmatic patients, indicating that the level of asthma control in smoking patients was significantly worse than in non smoking patients. Conclusions: The smoking rate in Chinese people over 14 years is still high. The prevalence rate of asthma in smokers is significantly higher than that of non-smokers. The level of asthma control in smokers is significantly worse than that in non smokers.

[A multi-center study for the association between the perception and control of disease among asthmatic patients in Chinese urban areas].

Objective: To investigate the current perception of disease among asthmatic patients in Chinese urban areas, and to address its association with asthma control. Methods: This was a nationwide, multi-center, cross-sectional study covering 30 third-level, grade A hospitals in 30 provinces, municipalities and autonomous regions (not including Tibet) across Chinese mainland. The survey was carried out from October 2015 to May 2016. Asthmatic outpatients were selected to receive face-to-face questionnaire survey on asthma control including Asthma Control Test (ACT) score, classification of asthma control level[according to the Global Initiative for Asthma (GINA) 2015 classification system, as assessed by the physician completing the survey], perception of asthma (including question 1: nature of asthma as a disease; question 2: selection of first-line therapeutic agents to be regularly used daily for asthma; question 3: appropriate timing of the use of short-acting aerosols of ß(2) receptor agonists; and question 4: therapeutic goals for asthma). Results: A total of 3 875 asthmatic outpatients were included; among them, 69.0% (2 660/3 857) were aware that asthma is "an airway inflammatory disorder resulting from the combined effects of heredity and environment" ; 60.2% (2 321/3 857) considered "inhaled glucocorticoids or their compound preparations" to be the first-line therapeutic agents to be regularly used daily for patients with persistent chronic asthma; 85.7% (3 277/3 823) considered it appropriate to use short-acting aerosols of ß(2) receptor agonists "as needed in the event of disease aggravation or acute exacerbation" ; and 75.4% (2 761/3 661) were aware that asthma "can be adequately or completely controlled in the long term" . The ACT score[20 (16, 23) vs 19 (16, 22) points; Z=-3.928, P<0.001]and asthma control rate (29.92% vs 25.31%; χ(2)=8.616, P=0.003) were significantly higher, and the rate of uncontrolled asthma (19.92% vs 23.48%; χ(2)=6.267, P=0.012) was significantly lower among the 2 660 (69.0%) patients correctly answering question 1 than among the 1 197 (31.0%) patients giving incorrect answer. The ACT score[21 (17, 23) vs 19 (15, 22) points; Z=-9.190, P<0.001] and asthma control rate (32.66% vs 22.20%; χ(2)=49.614, P<0.001) were significantly higher, and the rate of uncontrolled asthma (18.40% vs 25.00%; χ(2)=24.267, P<0.001) was significantly lower among the 2 321 (60.2%) patient correctly answering question 2 than among the 1 536 (39.8%) patients giving incorrect answer. Conclusions: Compared to previous surveys, there has been improved perception of disease among asthmatic patients in Chinese urban areas. Correct perception of disease is favorable for improving asthma control level.

[Analysis of short-term respiratory adverse events in 183 bronchial thermoplasty procedures].

Objective: To analyze the short-term (3 weeks) adverse respiratory events after bronchial thermoplasty(BT) in patients with severe asthma. Methods: The China-Japan Friendship Hospital recruited 62 patients with severe asthma for BT treatment from March 2014 to July 2016, with a total of 183 BT procedures. The data of adverse respiratory events within 3 weeks after procedure were collected to analyze the factors that might potentially influence the occurrence of adverse events. Results: Forty-three patients (69.4%) experienced adverse respiratory events within 3 weeks after treatment. Totally 153 adverse respiratory events occurred after 87 procedures(47.5%). The main adverse events were cough (15 events, 8.20%), sputum production (37 events, 20.22%), temporary PEF reduction (37 events, 20.22%), chest distress (12 events, 6.56%), blood in sputum (11 events, 6.01%), asthma exacerbation (10 events, 5.46%), and pneumonia(6 events, 3.28%). Most events were relieved or resolved with standard therapy in 1 week. No severe adverse events including tracheal intubation, malignant arrhythmias or death occurred within 3 weeks after procedure. The baseline eosinophil percentage in induced sputum and blood, operation times, and preoperative FEV(1) (% predicted) might influence the occurrence of adverse events after treatment. Patients with preoperative FEV(1) (% predicted) ≥60% had lower risk of adverse events. Conclusion: BT showed a good security profile in treating patients with severe asthma within 3 weeks after procedure.

32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody.

BACKGROUND: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given. METHODS: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor. RESULTS: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients. CONCLUSIONS: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.

Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC.

The long-term benefits of antiviral treatment are limited by the resistance of hepatitis B virus (HBV). However, the effect of interferon (IFN)α treatment on drug-resistant HBVs is so far unknown. We, therefore, investigated the effects of IFN-α inducer poly-IC on the replication of HBV mutants resistant to drugs such as lamivudine (LAM), adefovir dipivoxil (ADV) and entecavir (ETV) in mice. HBV DNA and HBV DNA intermediate (RI) were employed as markers of the virus replication and 2',5'-oligoadenylate synthase (OAS) mRNA as a marker of IFN-α/ß induction. Poly-IC inhibited wtHBV replication and increased levels of OAS mRNA. Compared to the wt virus, the capacity of virus replication was reduced in most LAMr and ETVr mutants except those with mutations rtM(204V+L180M+V173L), and was similary in the ADVr mutants except rt(A121V+N236T). The virus replication was reduced after poly-IC treatment with LAMr and ADVr mutants similary to the wt virus. In contrast, ETVr mutants were resistant to the poly-IC treatment. In conclusion, the capacity of HBV replication and the sensitivity to IFN therapy are influenced by drug-resistant mutations. The IFN therapy may effectively inhibit HBV replication in particular in patients with LAMr or ADVr mutations but not in patients with ETVr mutations.

Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice.

OBJECTIVE: Mice injected with Bacillus Calmette-Guérin (BCG) were challenged with lipopolysaccharide (LPS) to induce inflammatory liver injury. This study was performed to explore the protective effects of interleukin (IL)-4 against liver injury induced by BCG and LPS in mice. MATERIALS AND METHODS: Mice injected with BCG (125 mg/kg) were challenged with LPS (10 µg/kg) to induce the model of inflammatory liver injury. Half an hour after injection of LPS, mice were subcutaneously administered rmIL-4 at 5 and 0.5 µg/kg, respectively. Liver injury was evaluated by serum transaminase assay and H & E staining. Liver cytokine concentrations were determined by enzyme-linked immunosorbent assay, and intrahepatic cytokine and iNOS mRNA levels by reverse transcriptase polymerase chain reaction. Intrahepatic apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated nick end labeling. NF-κB p65 and ERK signal pathway was detected by Western-blotting. NF-κB signal pathway was also detected by electrophoretic mobility shift assay. RESULTS: IL-4 reduced the serum ALT, AST and LDH, alleviated the inflammatory cells infiltration, down regulated the expression of TNF-α, IL-1ß, IFN-γ, IL-6 and iNOS mRNA in liver, and alleviated hepatic glutathione depletion (GSH). In addition, IL-4 displayed inhibition of extracellular signal-regulated kinase phosphorylation and NF-κB activation. CONCLUSION: IL-4 may protect mice against BCG/LPS-induced immune liver injury, besides ERK and NF-κB signal pathways were involved in the effects.

Cloning, expression, and function of BLAME, a novel member of the CD2 family.

The CD2 family is a growing family of Ig domain-containing cell surface proteins involved in lymphocyte activation. Here we describe the cloning and expression analysis of a novel member of this family, B lymphocyte activator macrophage expressed (BLAME). BLAME shares the structural features of the CD2 family containing an IgV and IgC2 domain and clusters with the other family members on chromosome 1q21. Quantitative PCR and Northern blot analysis show BLAME to be expressed in lymphoid tissue and, more specifically, in some populations of professional APCs, activated monocytes, and DCS: Retroviral forced expression of BLAME in hematopoietic cells of transplanted mice showed an increase in B1 cells in the peripheral blood, spleen, lymph nodes, and, most strikingly, in the peritoneal cavity. These cells do not express CD5 and are CD23(low)Mac1(low), characteristics of the B1b subset. BLAME may therefore play a role in B lineage commitment and/or modulation of signal through the B cell receptor.

alpha7-Containing nicotinic receptors are segregated to the somatodendritic membrane of the cholinergic neurons in the avian nucleus semilunaris.

Segregation of ion channels and neurotransmitter receptors is an important mechanism for determining the functionality of the nervous system. In the case of nicotinic acetylcholine receptors, electrophysiological and anatomical studies have demonstrated that these receptors can be located at the somatodendritic and the axon terminal portions of neurons. Functionally, somatodendritic nicotinic receptors mediate fast excitatory transmission and possibly regulate other cell functions, while presynaptic nicotinic receptors enhance the release of neurotransmitters from axon terminals. Neurons in the mesencephalic lateral spiriform nucleus of the chick do not appear to restrict the localization of nicotinic receptors to specific membrane compartments, since receptors containing alpha5 and/or beta2 subunits are found both on the cell bodies and on the axonal projections of these neurons [Torrao A. S. et al. (1996) Brain Res. 743, 154-161]. We report here that, in contrast to lateral spiriform neurons, neurons in the nucleus semilunaris do appear to compartmentalize nicotinic receptors. The cholinergic nucleus semilunaris neurons express a high density of alpha7-containing nicotinic receptors on their somas [Britto L. R. G. et al. (1992) J. comp. Neurol. 317, 325-340]. However, when we examined the projections of these neurons in the lateral spiriform nucleus, we found no evidence for expression of alpha7-containing receptors on the cholinergic fibers from nucleus semilunaris neurons. Furthermore, patch-clamp electrophysiological recording from lateral spiriform neurons indicated an absence of presynaptic alpha7-containing nicotinic receptors capable of modulating the release of acetylcholine. We conclude that neurons are capable of segregating alpha7-containing nicotinic receptors to specific areas of their plasma membrane. Such targeting of nicotinic receptors would play an important role in determining their functional role in neurons.