Predictive Value of Combined LIPS and ANG-2 Level in Critically Ill Patients with ARDS Risk Factors.

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P < 0.001, P < 0.006, and P < 0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.

Prevention and management of lung cancer in China.

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer.

[Efficacy and Safety of Tiotropium Bromide in the Treatment of Chronic Obstructive Pulmonary Disease--a Multi-center Randomized Clinical Trial].

OBJECTIVE: To investigate the efficacy and safety of domestic tiotropium inhalation capsule in patients with chronic obstructive pulmonary disease (COPD) with multi-center randomized clinical trial. METHODS: Patients with stable slight to moderate COPD were randomized into trial group (n=109) with tiotropium 18 pg Qd or control group (n =111) with ipratropium 40 µg Qid for a treatment of four weeks. The spirometry and scoring questionaire were recorded at different visits during the treatment. Rescue medication consumption and adverse events were recorded. Results Forced expiratory volume in 1 s (FEV1) of both groups increased obviously 30 min and 3 h after first dosing. After four weeks treatments, FEV, and forced vital capacity (FVC) in both groups were improved obviously, and the improvement in tiotropium group was significantly higher than that ipratropium group. COPD symptom scores were significantly reduced in both groups, and the improvement in tiotropium group was significantly better than that in ipratropium group. There was no significant difference in rescue medication consumption between the two groups. The ratios of adverse events were 22. 02% and 15. 32% in tiotropium and ipratropium group, respectively (P=0. 23). CONCLUSION: Domestic tiotropium inhalation capsule is efficient and safe in the treatment of COPD.

Polymorphisms of angiotensin converting enzyme and nitric oxide synthase 3 genes as risk factors of high-altitude pulmonary edema: a case-control study and meta-analysis.

High-altitude pulmonary edema (HAPE) is a non-cardiogenic type of pulmonary edema developing altitudes > 2,500 m. Angiotensin converting enzyme (ACE) and nitric oxide synthase 3 (NOS3) play important roles in regulating pulmonary vascular tone. To assess associations between genetic variants in the ACE and NOS3 genes and HAPE risk, 27 HAPE patients and 108 matched controls were genotyped and analyzed. The indicated HAPE association of the NOS3 G894T (Glu298Asp) single nucleotide polymorphism (SNP), which may change NO production, was further evaluated by a meta-analysis of six studies involving 399 HAPE patients and 495 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined with fixed-effects models. Stratification analyses of ethnicity and geographic location were performed. Significant associations were observed for the dominant model in two ACE tag SNPs influencing serum ACE concentrations (rs8066114 polymorphism: GG+CG vs. CC; rs4461142 polymorphism: TT+CT vs. CC). Furthermore, Single-locus analysis indicated significantly different distributions of G allele frequency between the cases (29.63%) and controls (17.13%) for the ACE rs8066114 polymorphism. The case-control distributions of genotype frequencies and T allele frequency of NOS3 G894T (Glu298Asp) polymorphism were significantly higher in the cases than controls, and the NOS3 G894T (Glu298Asp) SNP showed elevated HAPE risk under the dominant model (TT+GT vs. GG). Meta-analysis showed overall association of NOS3 G894T SNP with HAPE risk under the allele contrast and dominant genetic models, which remained significant for Asians. In conclusion, ACE rs8066114 and rs4461142 and NOS3 rs1799983 (G894T) polymorphisms may be associated with increased HAPE risk in Asians.

[Diagnostic value of computed tomography-guided percutaneous lung biopsy for malignant lung tumors].

OBJECTIVE: To explore the diagnostic efficiency of percutaneous lung biopsy for malignant lung tumors under the guidance of computed tomography (CT). METHODS: The clinical data of 623 patients undergoing CT-guided percutaneous lung biopsy at Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University from January 2010 to November 2012 were analyzed to examine the influencing factors for the occurrences of pneumothorax and hemoptysis, including patient age, gender, site of puncture, tumor location and size, depth and number of puncture, chronic obstructive pulmonary disease (COPD) and doctor's clinical experience. RESULTS: A total of 623 cases were recruited. There were 410 male and 213 female with an average age of 60 ± 11 (15-87) years. Among them, 618 were diagnosed as malignant lung tumors with a positive rate of 99.2%. Pathological classifications were adenocarcinoma (n = 387, 62.1%), squamous carcinoma (n = 166, 26.6%), small cell lung cancer (n = 30, 4.8%), undifferentiated cancer (n = 18, 2.9%) adenosquamous carcinoma (n = 2, 0.3%), sarcomatoid carcinoma (n = 6, 0.9%), leiomyosarcoma (n = 3, 0.5%), neuroendocrine carcinoma (n = 2, 0.3%), low differentiated carcinoid (n = 1, 0.2%), cribriform carcinoma (n = 1, 0.2%), malignant lymphoma (n = 1, 0.2%) and metastatic renal cell carcinoma (n = 1, 0.2%) respectively. Another 5 patients (0.8%) had an initial diagnosis of chronic inflammation according to their pathological features of lung punctures. Their definite diagnoses were lung squamous cell carcinoma (n = 3), adenocarcinoma (n = 1) and small cell carcinoma (n = 1) respectively. The major complications were pneumothorax and hemoptysis. Among 73 cases of pneumothorax (n = 73, 11.7%), 65 cases (n = 65, 10.4%) of mild pneumothorax (lung compression < 20%) were cured by sufficient oxygen inhalation and repose while 8 cases (1.3%) suffered lung compression ≥ 75% recovered via closed thoracic drainage. Eighty-four patients (13.5%) suffered from the complications of slight or self-limited hemoptysis with blood-tinged sputum. The symptoms of hemoptysis disappeared after oral hemostatic or other treatments. Another 5 patients (0.8%) suffered from moderate hemoptysis (100-500 ml) and their symptoms disappeared after rest or an intravenous infusion of haemostatic. None of them died of massive hemoptysis or biopsy. The occurrence of pneumothorax was significantly correlated with the diameter of lesions ( ≤ 2 cm) (P = 0.006), depth of needle (>3 cm) (P = 0.044), number of puncture needles ( ≥ 3 needles) (P = 0.025), inadequate clinical experience of puncturing doctors (P = 0.003) and COPD (P = 0.036); the occurrence of hemoptysis was obviously correlated with the diameter of lesions ( ≤ 2 cm) (P = 0.031), depth of needle (>3 cm) (P = 0.018), number of puncture needles ( ≥ 3 needles) (P = 0.015) and inadequate clinical experience of puncturing doctors (P = 0.014). However, the relationship was unremarkable between the occurrences of pneumothorax and hemoptysis and patient gender, age, sites of puncture and tumor location. CONCLUSION: With a high diagnostic value, CT-guided percutaneous lung biopsy is both safe and effective for malignant lung tumors.

Spatial scale applicability of 4-Scale geometrical optics model canopy reflectance simulation.

Accurately clarifying the applicable spatial scale of 4-Scale model is conducive to improving the accuracy of its application in canopy reflectance simulation of different vegetation types, and to further improving the inversion accuracy of leaf area index, canopy density, and other parameters. Two forest plots (one for broad-leaved forest and one for mixed forest) with each area of 100 m×100 m in Maoershan Experimental Forest Farm, Shangzhi, Heilongjiang, were divided into the spatial scales of 10, 20, 30, 40 and 50 m, respectively. The 4-Scale model was used to simulate forest canopy reflectance. Local mean method, the nearest neighbor method, bilinear interpolation method, and cubic convolution method were used to convert Sentinel-2 images with spatial resolution of 10 m to other scales, with the results being evaluated. The simulated canopy reflectance and remote sensing pixel reflectance were compared and analyzed. The spatial scale of mixed forest and broad-leaved forest suitable for high-precision inversion parameters of 4-Scale model was determined. The results showed that the 4-Scale model underestimated the pixel forest canopy reflectance as a whole. The canopy reflectance of mixed forest and broad-leaved forest had the worst simulation effect at the 20 m scale. Both the root mean square error (RMSE) and the mean absolute error from (MAE) of red and near-infrared band were large. When the scale was >20 m, the simulation effect became better. The applicability of the model was the best when the mixed forest was 40 m and the broad-leaved forest was 30 m. The mean and standard deviation of the reflectance difference between the simulated value and the remote sensing pixel were the minimum in the red and near near-infrared bands, with the minimum RMSE and MAE. The simulation results of mixed forest and broad-leaved forest at 10 m scale were not stable, the rule of mean and standard deviation was inconsistent, and the difference between RMSE and MAE was large under the same band.

[Clinical analysis of external micro-locking plate in the treatment of fifth metatarsal comminuted fractures].

OBJECTIVE: To explore the clinical efficacy of external micro-locking plate combined with closed reduction in the treatment of fifth metatarsal comminuted fracture with severe soft tissue injury. METHODS: From January 2018 to December 2019, 13 patients received micro-locking plate combined with closed reduction treatment due to the fifth metatarsal comminuted fracture with severe soft tissue injury. There were 11 males and 2 females patients, ranging in age from 21 to 69 years. According to the fracture AO fracture classification, 9 cases belonged to type 87(S)-C2.2 and 4 cases belonged to type 87(S)-C2.1. The fifth metatarsal cuneiform articular surface was not involved, and all of them were comminuted fractures of the fifth metatarsal shaft. All soft tissues were damaged to varying degrees. Three patients got small defect of skin and soft tissue, and they were treated with debridement and suture after one-stage emergency surgery. The fracture healing and complications were observed, and the clinical efficacy was evaluated according to the midfoot function score of American Orthopaedic Foot & Ankle Society (AOFAS) at the latest follow-up. RESULTS: All patients were followed up, and the duration ranged from 3 to 12 months. One patient had delayed union. One patient had local skin necrosis and was treated with second-stage skin grafting to repair the wound surface. No external screw breakage or infection was reported, the skin soft tissue healed satisfactorily and reached bony union, with the union time ranging from 8 to 19 weeks. The postoperative functional recovery was rated according to the midfoot score of AOFAS, the score ranged from 49 to 98, and 7 patients got an excellent result, 4 good, 1 fair and 1 poor. CONCLUSION: The external micro-locking plate combined with closed reduction in the treatment of fifth metatarsal comminuted fracture with severe soft tissue injury has the advantages of simple operation, good stability and low infection rate, which is helpful to the repair of soft issue injury, and the fixation can be removed early in outpatient clinic. To sum up, this surgical procedure is suitable for patients with severe soft tissue injury and comminuted fracture to avoid periosteum stripping. The space occupying is smaller than the micro-external fixator, which is convenient for patients with early functional exercise.

[Micro-locking plate external fixation for the treatment of proximal phalanx comminuted fractures].

OBJECTIVE: To explore clinical efficacy of external placement of micro-locking plate combined with small incision reduction in treating proximal phalanx comminuted fractures. METHODS: From January 2018 to December 2019, 17 patients with proximal phalanx comminuted fractures were treated with micro-locking plate combined with small incision open reduction, including 13 males and 4 females, aged from 16 to 64 years old with an average of (37.2±20.1) years old. Two patients were accompanied by soft tissue extrusion and opening injuries, which were treated with fixed treatment after the first-stage emergency debridement. Curative effect was evaluated according to total active flexion scale (TAFS) of American Hand Surgery Association at 6 months after operation;and fracture healing, nailing, local soft tissue healing, complications were observed. RESULTS: All patients were followed up from 6 to 12 months with an avaerge of(9.3±3.6) months. Two patients occurred delayed union, 1 occurred local skin necrosis and was treated with the second-stage skin grafting to repair wound surface. No external screw breakage or infection was reported, skin soft tissue healed favorably and reached bony union, the union time from 12 to 24 weeks with an average of (15.7±2.1) weeks. According to TAFS standard, 9 patients got excellent result, 5 good and 3 poor at 6 months after operation. CONCLUSION: External micro-locking plate combined with small incision reduction in treating proximal phalanx comminuted fracture, which has advantages of good condition of skin and soft tissue, simple operation, early functional exercise, good range of motion of interphalanx joint, and function score of recovery period is high.

[Kirschner wire combined with PEEK anchor for the treatment of Wagstaffeâ ¡fracture].

OBJECTIVE: To explore clinical effect of Kirschner wire combined with PEEK anchor with thread to fix fibula bone block in WagstaffeⅡfracture. METHODS: From January 2018 to December 2020, 29 patients with WagstaffeⅡfracture of ankle joint were treated with Kirschner wire fixation of avulsed fibular bone block, PEEK with thread anchor repair and reinforcement, and plaster external fixation, including 18 males and 11 females, aged from 27 to 69 years old with an average of (46.3±10.2) years old. All of them were unilateral operations, and the time from injury to operation ranged from 3 to 5 days with an average of(4.05±0.63) days. Clinical efficacy was evaluated by using American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot functional scoring system and visual analogue scaleat scoring system before and after operation at 6 months. RESULTS: All patients were followed up from 6 to 12 months with an average of (9.7±2.1) months. Two patients occurred pain of ankle joint during walking, which was relieved after strengthening rehabilitation exercise and anti-nflammatory and analgesic drug treatment. AOFAS score was incrased from(62.16±19.73) preoperativyly to(91.35±6.37) at 6 months after operation (t=5.51, P<0.01);15 patients got excellent results, 12 moderate and 2 good. VAS was decreased (5.91±1.57) preoperativly to (0.41±0.37) at 6 months after operation(t=10.54, P<0.01). CONCLUSION: Kirschner wire combined with PEEK anchor with thread to fix fibula bone block in WagstaffeⅡfracture strengthen repair of inferior tibiofibular syndesmosis ligament and anterior talofibular ligament, and effectively relieved ankle joint pain, obtain good function recovery, the avulsion fracture block was fixed securely, and receive good clinical effect.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

[Three-step sequential method for limb skin and soft tissue defect combined with bone or tendon exposed wound].

OBJECTIVE: To explore clinical effect of VSD technology, coverage of artificial dermis and autograft for the treatment of limb skin soft tissue defect combined with bone or tendon exposed wound. METHODS: Eighteen patients suffered from limb skin soft tissue defect combined with bone or tendon exposed wound treated by three-step sequential method from January 2013 to June 2015. Among them, including 13 males and 5 females aged from 23 to 72 years old with an average of 34.6 years old; the time from injury to operation ranged from 1.5 to 5.0 hours with an average of 2.5 h. The area of skin and soft tissue injury ranged from 4.2 cm×3.1 cm to 7.4 cm×5.2 cm. Wound recovery and taken skin wound recovery were observed to evaluate clinical results. RESULTS: All patients were followed up from 5 to 16 months, with an average of 7.6 months. Deep bone tendon tissue of wounds were effectively recovered, artificial dermis survived, and quality of healed wound was tough and shape was good. Wound transplant flap was survived, no obvious scar tissue formation, appearance was flat, skin color was a little deeper than normal skin, the overall effect was satisfactory. CONCLUSIONS: Three-step sequential method has good curative effect for patients suffered from limb skin soft tissue defect with bone or tendon exposed wound and refused to repair the flap, and has advantage of simple operation, operation risk, less invasive.

[Different mini skin flaps in repairing finger soft tissue with bone defect].

OBJECTIVE: To explore surgical methods and clinical effects of three different types of mini skin flap transplantation for repairing finger soft tissue with bone defect. METHODS: Thirty-three patients with finger soft tissue or bone defect were treated from December 2014 to October 2016, including 24 males and 9 females aged from 21 to 52 years old with an average of (36.42±5.70) years old, and soft tissue defect area ranged from 1.3 cm×1.8 cm to 2.3 cm×4.2 cm. According to damage degree, nature and patients' options, 15 finger of 15 cases were adopted retrograde dorsal metacarpal artery perforators fascia flap, 10 fingers of 9 cases were treated with free foot artery descending branch wrist skin flap, 9 fingers of 9 cases were treated with free the second toe details phalanges compound flap. Survival rate, postoperative complications and finger function assessed by Dargan functional criteria at the latest follow up were observed. RESULTS: All flaps were survived, both of donor site and recipient site were without deep infected. The donor site of one patient occurred necrotic, and the distal donor site of one patient occurred surface necrotic, then healed by active dressing change. All patients were followed up from 6 to 16 months with an average of(8.34±1.28) months. Two points of finger recognition were restored between 8 and 12 mm with an average of (8.84±0.43) mm, and the appearance, texture and sensory functions of skin flap were restored. No obvious complications were observed on the donor site. According to Dargan function evaluation of finger joints, 18 patients got excellent results, 14 moderate and 1 good. CONCLUSIONS: Three kinds of mini skin flap could receive good results in repairing soft tissue of finger or bone defect. Reverse dorsal metacarpal artery perforator fascia flap is not necessary with anastomosing blood vessels and has advantages of safe, simple and high survival rate. Descending branch of superior cutaneous branch of free ulnar artery could cut multiple other perforator flaps simultaneously, and the scar is small and hidden. Dissociated the second toe combined metatarsal phalangeal flap could repair shape and function of finger to the maximum extent and donor site is hidden.

[Transfection of human beta defensin 2 gene into the lung by aerosol inhalation: experiment with rats].

OBJECTIVE: To investigate the feasibility to transfect human beta defensin 2 (hBD2) gene into the lung so as to enhance the endogenous hBD2 expression to defend infectious diseases. METHODS: Recombinant plasmid containing hBD2 gene, pLXSN-hBD2, was mixed with a new cationic liposome prepared by film at different weight ratios. Sixteen Wistar rats were divided into 2 groups: experimental group (n = 11), undergoing aerosol inhalation of liposome/pLXSN-hBD2 complex, and control group (n = 5), undergoing aerosol inhalation of blank vector pLXSN. The tracheae were taken out from 5 rats of the experiment and control groups each 2 days later, and from 2 rats of the experimental group 6, 15, and 21 days later respectively so as to obtain the epithelial cells of trachea. DNA was extracted from the tracheal epithelial cells and PCR was used to examine the transfection and integration of hBD2. Western blotting was used to detect the protein expression of hBD2. RESULTS: Aerosolization impacted obviously the microcapsule structure of liposome/plasmid complexes, and there was the least structural destruction of complex at a ratio of 10:1 that suited for aerosolization best. After the inhalation the relevant plasmids were all successfully integrated into the epithelial cells in both groups. Protein expression of hBD2 was not detected in the control group and the hBD2 protein expression level 2 days after transfection of the experimental group was 4866.9 +/- 148.2, and then decreased gradually, and reached 3.2 +/- 1.5 twenty-one days after the transfection. CONCLUSION: The recombinant plasmid pLXSN-hBD2 can be transfect into the airway epithelial cells via aerosol inhalation and the expression of hBD2 sustains for a period of time.

[Application of drilling columnar autogenous iliac bone graft and clinical analysis of postoperative complications in the donor bone region].

OBJECTIVE: To investigate the clinical effect of drilling columnar autogenous iliac bone graft and analyze the effect of bone grafting on postoperative complications in donor site. METHODS: From March 2014 to October 2016, 68 patients with autogenous iliac bone graft were retrospectively analyzed, and divided into drilling group and osteotomy group, 34 patients in each group. In drilling group, there were 24 males and 10 females with an average age of (40.06±5.60) years old ranging from 23 to 53 years old;in osteotomy group, there were 26 males and 18 females with an average age of (39.32±6.44) ranging from 22 to 56 years old. The operative time of bone extraction, blood loss in donor area, healing time of donor site and postoperative donor site complications were observed and compared between the two groups. VAS score was used to evaluate the pain of donor site in different periods after operation. RESULTS: All patients were followed up for 12 to 24 months, with an average of 16.9 months in drilling group and 17.1 months in osteotomy groups. The bone healing structure was displayed in the recipient area in two groups, the effect of autogenous iliac bone grafting was good. There was no significant difference in operative time between two groups (P>0.05). There was significant difference between two groups in the amount of donor site bleeding and the time of donor site wound healing(P<0.05). Postoperative complications(iliac depression and numbness) were significantly different between two groups (P<0.05). There was no significant difference in VAS score between two groups at 2 weeks after operation(P>0.05). VAS scores of drilling group at 6 months and 1 year after operation were lower than those of osteotomy group (1.85±0.61 vs 2.97±0.67, P=0.000; 1.15±0.56 vs 2.41±0.61, P=0.000). CONCLUSIONS: When bone graft is no need to have large pieces of special shape or more cortical bone iliac, it is simple to operate and less complications postoperative by drilling type columnar autogenous iliac bone graft. What's more, it has the obvious advantages of promote healing, improve patient quality of life compared with traditional osteotomy.

Effects of para-toluenesulfonamide intratumoral injection on non-small cell lung carcinoma with severe central airway obstruction: A multi-center, non-randomized, single-arm, open-label trial.

BACKGROUND: Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). OBJECTIVES: To determine the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. METHODS: Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. RESULTS: In full-analysis set (N=88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%-69.5%), bronchoscopy: 48.9% (95%CI: 38.1%-59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%-54.2%), bronchoscopy: 29.6% (95%CI: 20.3%-40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16-0.53 liters), FEV1 (mean difference: 0.27 liters, 95%CI: 0.07-0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9-74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9-10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). CONCLUSION: PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO.

[Role of Fas and FasL expression in apoptosis of pulmonary artery smooth muscle cells in hypoxia induced by inhibition of Na+/H+ exchanger isoform-1 in rat].

OBJECTIVE: To investigate the role of Fas and FasL expression in apoptosis of pulmonary artery smooth muscle cells (PASMCs) in hypoxia induced by inhibition of Na(+)/H(+) exchanger isoform-1 (NHE-1) in rat. METHODS: The cells were cultured in hypoxia (<1% O(2)) for 2, 6, 12, 24 and 48 hours respectively. Then cell apoptosis was observed with terminal deoxynudeotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The changes in fas and fasl mRNA expression in PASMCs were detected by semi-quantitative reverse transcription-polymerase chain reaction (sqRT-PCR) in vitro. The expression of Fas and FasL protein in cells was determined immunohistochemically. RESULTS: No significant changes in the expression of fas/fasL mRNA and protein between cells transfected with NHE-1 ribozyme gene and cells transfected with pLXSN, or non-transfected control in hypoxia. CONCLUSION: Apoptosis of PASMCs induced by NHE-1 inhibition may occur independently of Fas/FasL death pathway.

[Enhanced expression of signal transducers and activators of transcription in lung tissue of hypoxic pulmonary hypertension rat models].

OBJECTIVE: To investigate the expression levels of signal transducers and activators of transcription (STATs) in the lung tissue of hypoxic pulmonary hypertension (HPH) rat models. METHODS: The Wister rat HPH models were divided into 4 groups: 1 week group (H1), 2 week group (H3), 3 week group (H3), and 4 week group (H4) (n = 12 in each group). The levels of STATsmRNA expression of the lung tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot. The protein expression of STATs and cellular morphologic changes were observed by immunohistochemistry and Tiger image analysis. RESULTS: The RT-PCR showed that the levels of STAT1mRNA expression of the lung tissue in H1 1.25 +/- 0.12, H2 2.28 +/- 0.15 and H3 1.27 +/- 0.12 were significantly higher than that in the healthy control group 0.61 +/- 0.07 (P < 0.01); the levels of STAT2mRNA expression in H1 0.54 +/- 0.06, H2 1.01 +/- 0.08 and H3 1.36 +/- 0.09 were significantly higher than that in control group 0.30 +/- 0.03 (P < 0.01); the mRNA expressions of STAT3 in H1 0.74 +/- 0.11, H2 1.19 +/- 0.13 and H3 0.80 +/- 0.08 were significantly higher than that in control group 0.26 +/- 0.10 (P < 0.01); and the mRNA expressions of STAT5 in H1 0.92 +/- 0.10, H2 1.23 +/- 0.10 and H3 1.03 +/- 0.11 were significantly higher than that in control group 0.60 +/- 0.11 (P < 0.01). The Northern blot assay demonstrated that the expressions of STAT1mRNA in H1 0.49 +/- 0.10 and H3 0.67 +/- 0.07 were significantly different from that in H2 0.91 +/- 0.07 (P < 0.01); the expressions of STAT3mRNA in H1 2.10 +/- 0.21 and H3 2.58 +/- 0.17 were significantly different from that in H1 3.56 +/- 0.29 (P < 0.01); the expressions of STAT5mRNA in H1 0.99 +/- 0.10 and H3 1.45 +/- 0.12 were significantly different from that in H2 1.79 +/- 0.15 (P < 0.01). It is obvious that the mRNA expressions of STATs in the lung tissue of rat HPH models were increased in the 1st week, to the highest in the 2nd week, and decreased in the 3st week, and all higher than that of control group. The granules of STAT3 and STAT5, positively stained, were observed in the cytoplasm of pulmonary alveolar wall, intrapulmonary vascular and bronchial wall in H3. The protein expressions of STAT3 8.16 +/- 0.49 and STAT5 6.03 +/- 0.37 in H3 were markedly higher than those in H1, H4, and control group. CONCLUSION: The up-regulation of the STATs expression in lung tissue of HPH rat models suggested that the STATs were involved in the pathogenesis of HPH formation.

[The effect of Na(+)/H(+) exchanger-1 (NHE-1) antisense expression vector on NHE-1 gene expression in human lung adenocarcinoma cells and its biological significance].

OBJECTIVE: To explore the inhibitory effect of Na(+)/H(+) exchanger-1 (NHE-1) antisense expression vector on NHE-1 gene in human lung neoplasm cells and to observe its biological effect. METHODS: NHE-1 antisense vector (pNHE-1) was introduced into human lung adenocarcinoma cell line A549 cells with cationic liposome transfection methods. Semi-quantification RT-PCR was performed to analyze the expression level of NHE-1 mRNA in A549 cells and transfected A549 cells. Intracellular pH (pHi) values were measured with fluorescence spectrophotometer. The growth characteristics of the cells was observed. Tumor cell apoptosis was observed with in situ apoptosis assessment. RESULTS: PCR verified the integration of antisense vector with the genomic DNA of transfected cells in positive clones. Semi-quantification RT-PCR showed that the NHE-1 gene expression level was significantly lower in transfected A549 cells (0.42 +/- 0.06) than in those untransfected (0.71 +/- 0.08, P < 0.01) and those transfected with pLXSN (0.69 +/- 0.16, P < 0.01). Compared with A549 cells, pHi values decreased significantly in transfected A549 cells at 12 h, 24 h and 48 h (6.990 +/- 0.005, 6.840 +/- 0.005 and 6.750 +/- 0.005 respectively vs 7.150 +/- 0.004, 7.140 +/- 0.007 and 7.120 +/- 0.008 respectively, P < 0.001). The growth of transfected A549 cells was significantly slower (P < 0.01), the double time was longer (3.20 vs 4.97) and the apoptosis rate was markedly higher [(24.50 +/- 3.62)% vs (1.50 +/- 0.55)%, P < 0.01]. CONCLUSION: The antisense vector was successfully transfected to A549 cells with liposome and integrated with transfected cell genome, and the expression of NHE-1 mRNA of A549 cells was inhibited, thereby resulted in a decrease of the pHi value by means of reduction of Na(+)/H(+) exchanging activity, with the inhibition of proliferation and growth of A549 cells and increased of A549 cell apoptosis.

Directed evolution of an LBP/CD14 inhibitory peptide and its anti-endotoxin activity.

BACKGROUND: LPS-binding protein (LBP) and its ligand CD14 are located upstream of the signaling pathway for LPS-induced inflammation. Blocking LBP and CD14 binding might prevent LPS-induced inflammation. In previous studies, we obtained a peptide analog (MP12) for the LBP/CD14 binding site and showed that this peptide analog had anti-endotoxin activity. In this study, we used in vitro directed evolution for this peptide analog to improve its in vivo and in vitro anti-endotoxin activity. METHODS: We used error-prone PCR (ep-PCR) and induced mutations in the C-terminus of LBP and attached the PCR products to T7 phages to establish a mutant phage display library. The positive clones that competed with LBP for CD14 binding was obtained by screening. We used both in vivo and in vitro experiments to compare the anti-endotoxin activities of a polypeptide designated P1 contained in a positive clone and MP12. RESULTS: 11 positive clones were obtained from among target phages. Sequencing showed that 9 positive clones had a threonine (T) to methionine (M) mutation in amino acid 287 of LBP. Compared to polypeptide MP12, polypeptide P1 significantly inhibited LPS-induced TNF-α expression and NF-κB activity in U937 cells (P<0.05). Compared to MP12, P1 significantly improved arterial oxygen pressure, an oxygenation index, and lung pathology scores in LPS-induced ARDS rats (P<0.05). CONCLUSION: By in vitro directed evolution of peptide analogs for the LBP/CD14 binding site, we established a new polypeptide (P1) with a threonine (T)-to-methionine (M) mutation in amino acid 287 of LBP. This polypeptide had high anti-endotoxin activity in vitro and in vivo, which suggested that amino acid 287 in the C-terminus of LBP may play an important role in LBP binding with CD14.