Liquid biopsy for ALK-positive early non-small-cell lung cancer predicts disease relapse.

Background: We aimed to determine whether circulating tumor cells (CTCs) and cell-free DNA (cfDNA) aids in prognosis of relapse-free survival (RFS). Methods: Non-small cell lung cancer patients with ALK mutations were recruited prospectively. CTCs and cfDNA were quantified at different time points. RFS was estimated and correlated. Results: Baseline median CTCs and cfDNA were 16 cells and 57 ng/mL and declined to nine cells and 30 ng/mL, respectively, postsurgery in 150 patients. Interestingly, patients without detectable CTCs postsurgery fared better for RFS. cfDNA monitoring showed deviations within 7 months of surgery that were significant predictors for RFS. Conclusion: Short-term monitoring of CTCs and cfDNA variations shows promise for early risk detection and may aid in better disease control.

Cloning, expression and stress-respondent transcription of long-chain acyl-coenzyme A synthetase cDNA gene of Nannochloropsis gaditana and its involvement in the biosynthesis of eicosapentaenoic and decosahexaenoic acids.

A novel cDNA gene, NgLACS, that encodes a long-chain acyl-CoA sythetase (LACS), was cloned from Nannochloropsis gaditana and characterized. The cDNA was 2,360 bp in length, consisting of an ORF of 1,950 bp, a 5'-untranslated region of 88 bp and a 3'-untranslated region of 322 bp. The deduced amino acid sequence of LACS was 649 amino acid residues in length with a predicted molecular weight of 71 kDa and an isoelectric point of pH 7.8. When the alga was treated with excessive nitrogen and iron, and at 15 °C, the proportion of long-chain polyunsaturated acyl-CoAs in the total acyl-CoAs and the abundance of NgLACS cDNA gene transcript were up-regulated. Over-expression of NgLACS in Saccharomyces cerevisiae caused the accumulation of eicosapentaenoic acid and docosahexaenoic acid.

Overexpression of NgAUREO1, the gene coding for aurechrome 1 from Nannochloropsis gaditana, into Saccharomyces cerevisiae leads to a 1.6-fold increase in lipid accumulation.

Aureochrome-1 (AUREO1) is a transcription factor that is induced by blue light and controls branching of Vaucheria frigida. We have cloned the gene, NgAUREO1, coding for AUREO1 from Nannochloropsis gaditana, and report that the lipid content in recombinant Saccharomyces cerevisiae was 1.6-fold more than in wild-type S. cerevisiae (6.3 % lipid increased to 10 %). Over-expression of AUREO1 in S. cerevisiae up-regulated the expression of acetyl-CoA carboxylase and acyl-CoA:diacylglycerol acyl-transferase but down-regulated the expression of long-chain-acyl CoA synthetase. This enhanced the accumulation of lipid. This study highlights a novel function of AUREO1 and allows a better understanding of the regulation mechanism of fatty acid metabolism.

LncRNA OIP5­AS1 aggravates house dust mite­induced inflammatory responses in human bronchial epithelial cells via the miR­143­3p/HMGB1 axis.

Bronchial asthma poses a serious threat to human health. Previous studies have documented the role of long non­coding RNAs (lncRNAs) in asthma. However, the molecular mechanism underlying bronchial asthma remains unclear. The aim of the present study was to evaluate the role of the lncRNA Opa­interacting protein 5 antisense RNA1 (OIP5­AS1) in the house dust mite­induced inflammatory response in human bronchial epithelial cells. BEAS­2B cells were treated with Dermatophagoides pteronyssinus peptidase 1 (Der p1) to establish an in vitro model of asthma. OIP5­AS1 expression levels increased in BEAS­2B cells following Der p1 treatment, while microRNA (miR)­143­3p was downregulated. Additionally, the levels of the pro­inflammatory factors tumor necrosis factor­α, interleukin (IL)­6 and IL­8 were measured, and apoptosis was evaluated following OIP5 silencing. OIP5­AS1 knockdown reduced the inflammatory response and apoptosis in BEAS­2B cells. Furthermore, using dual luciferase reporter assays and co­transfection experiments, it was demonstrated that the function of OIP5­AS1 was mediated by miR­143­3p. miR­143­3p overexpression attenuated the Der p1­induced inflammatory response and apoptosis of BEAS­2B cells by targeting high mobility group box 1 (HMGB1). In summary, OIP5­AS1 exacerbated Der p1­induced inflammation and apoptosis in BEAS­2B cells by targeting miR­143­3p via HMGB1.

Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD. METHODS: We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio (FEV(1)/FVC) of less than 0.7 and an FEV(1) between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry (http://umin.ac.jp/ctr/index/htm) number UMIN-CRT C000000233. FINDINGS: 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1.01 [SE 0.06] vs 1.35 [SE 0.06]), risk ratio 0.75 (95% CI 0.62-0.92, p=0.004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated. INTERPRETATION: Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD.

[Percutaneous short segment pedicle screw fixation with vertebral augmentation for the treatment of single level thoracolumbar osteoporosis fracture].

OBJECTIVE: To explore the safety and clinical effects of percutaneous vertebroplasty and pedicle screw fixation in treating osteoporotic thoracolumbar burst fracture. METHODS: From April 2011 to April 2014, 32 patients with osteoporotic thoracolumbar burst fracture were treated with percutaneous vertebroplasty and pedicle screw fixation. There were 13 males and 19 females, aged in ranging from 60 to 73 years old(averaged 65.6 years). All fractures were single thoracolumbar fracture and 4 cases located on T11, 9 on T12, 16 on L3; and 3 on L2. Cobb angle, vertebral anterior compression rate, vertebral posterior compression rate, spinal canal occupying ratio were compared, visual analogue scale (VAS) and Oswestry Disability Index(ODI) were analyzed before and after operation. RESULTS: The mean operation time was 65.7 min(ranged, 60 to 120 min) and blood loss was 25.2 ml (ranged, 20 to 50 ml). The operative incisions obtained primary healing. All patients were followed up from 12 to 48 months with an average of 20.6 months. Vertebral anterior compression rate and vertebral posterior compression rate were respectively corrected from preoperative (49.70±5.89)%, (17.36±4.11)% to (6.00±2.10)%, (5.48±1.65)% at 2 d after operation, and (6.06±1.57)%, (5.68±1.82)% at last follow up. Cobb angle and spinal canal occupying ratio were respectively corrected from preoperative (13.34±3.56)°, (22.77±5.83)% to(2.86±0.95)°, (5.02±1.93)% at 2 d after operation, and (3.04±0.94)°, (5.15±1.93)% at last follow up. VAS and ODI were respectively decreased from preoperative (6.84±0.88)points, (77.50±5.10)% to(1.94±0.72) points, (17.94±4.82)% at 2 d after operation, and (1.63±0.83) points, (15.63±5.19)% at last follow up. Cement leakage occurred in 3 cases. No internal fixation failure and intractable lower back pain were found. CONCLUSIONS: Percutaneous vertebroplasty and pedicle screw fixation could restore vertebral body height, improve spinal canal occupying, correct kyphosis, relieve pain, improve life quality, and it is a safe and effective method in treating osteoporotic thoracolumbar burst fracture.

[Clinical apprehension on application of Tri-lock BPS total hip arthroplasty].

OBJECTIVE: To study short-term results and clinical application of Tri-lock BPS in total hip arthoplasty. METHODS: From May 2010 to July 2011, 32 hips in 31 patients (18 males and 13 females, ranging in age from 50 to 77 years old, with an average of 60.5 years old) were treated by total hip arthroplasty with Tri-lock BPS, including 8 patients with osteonecrosis (ON), 13 patients with fresh femoral neck fracture, 10 patients with developmental dysplasia of the hip (DDH). The therapeutic effects were evaluated by self assessment form, preoperative and postoperative Harris hip score, radiographs, Engh score and bone in growth of femoral side described by Gruen. Based on the short-term results,its design characteristic and clinical properties were analyzed. RESULTS: All the incisions healed well and there were no complications such as femoral fracture, infection, dislocation and neurovascular injuries. All the patients were followed up with an average time of 12.2 months (ranged, 10 to 14 months). All the joints had good or excellent clinical results. The Harris score increased from preoperative 38.3 +/- 4.9 to 92.5 +/- 11.2 at the latest follow-up (t = 27.53, P < 0.01). Radiographically, the positions of the prostheses were normal,the average limbs length and femoral eccentricity recovered to normal. X-ray of the hips showed that the femoral stem prosthesis was in line with good initial fixed standard. At 3 months after surgery, X-ray of the hips showed that bone in growth in Gruen II and VI of femoral side. CONCLUSION: Short-term results show that the design of Tri-lock BPS is more in line with human anatomy, and has the advantages in rapid recovery of hip function and retains more bone mass. It offers a newly valuable technology for the treatment of osteonecrosis, femoral neck fracture and DDH and so on.

[Suture anchor for acute injuries of medial collateral ligament of knee at degree III].

OBJECTIVE: To evaluate clinical efficacy of suture anchors in treating acute injuries of medial collateral ligament (MCL) of knee at degree III. METHODS: Twenty-seven patients with degree III acute MCL injuries of knee were treated with suture anchors from January 2007 to June 2011. There were 15 males and 12 females, aged from 19 to 56 (averaged 32.6) years old. The time from injury to operation was 3 to 10 days, averaged 6 days. Symptoms and physical signs before and after treatment were observed, Lysholm scoring were used to evluated clinical efficacy. RESULTS: All patients were followed up from 16 to 30 months with an average of 21.6 months. The stability of knee joints was good in all patients. Abduction stress test was negative when the knee joint was straightened at 0 degrees and flexed at 30 degrees. The average degree of flexed knee (67.00 +/- 5.80) degrees preoperatively was lower than that of postoperatively (136.50 +/- 6.30) degrees at 1 year. According to Lysholm scoring, preoperative scores ranged from 30 to 43 points, averaged 36.46 +/- 1.48; 1 year after operation ranged from 87 to 100 with an average of 91.50 +/- 3.80 and higher than postoperative. Twenty patients got an excellent results, 5 good and 2 fair. CONCLUSION: Suture anchors in treating acute injuries of medial collateral ligament of knee at degree III has following advantages: small range of tissue dissection, easy to operate, reliable fixation and less complications.

Biomechanical study of the funnel technique applied in thoracic pedicle screw replacement.

BACKGROUND: Funnel technique is a method used for the insertion of screw into thoracic pedicle. AIM: To evaluate the biomechanical characteristics of thoracic pedicle screw placement using the Funnel technique, trying to provide biomechanical basis for clinical application of this technology. METHODS: 14 functional spinal units (T6 to T10) were selected from thoracic spine specimens of 14 fresh adult cadavers, and randomly divided into two groups, including Funnel technique group (n = 7) and Magerl technique group (n = 7). The displacement-stiffness and pull-out strength in all kinds of position were tested and compared. RESULTS: Two fixed groups were significantly higher than that of the intact state (P < 0.05) in the spinal central axial direction, compression, anterior flexion, posterior bending, lateral bending, axial torsion, but there were no significant differences between two fixed groups (P > 0.05). The mean pull-out strength in Funnel technique group (789.09 ± 27.33) was lower than that in Magerl technique group (P < 0.05). CONCLUSIONS: The Funnel technique for the insertion point of posterior bone is a safe and accurate technique for pedicle screw placement. It exhibited no effects on the stiffness of spinal column, but decreased the pull-out strength of pedicle screw. Therefore, the funnel technique in the thoracic spine affords an alternative for the standard screw placement.

[Treatment of Hoffa fracture using hollow lag screw].

OBJECTIVE: To investigate the operation techniques and clinical effects of hollow lag screws for the treatment of Hoffa fractures. METHODS: From February 2001 to May 2009, 13 patients with Hoffa fractures were treated with hollow lag screws, including 8 males and 5 females, ranging in age from 23 to 45 years, with a mean age of 34.2 years. Six patients had the fractures on the left, 7 patients on the right. According to the Letenneuer type, femur lateral condyle: type I in 3 cases, type III in 2 cases; femur medial condyle: type I in 3 cases, type II in 2 cases, type III in 3 cases. According to the type of fracture, hollow lag screws were used to treat the fracture with different approach. RESULTS: All the patients were followed up, and the duration ranged from 12 to 23 months,with a mean of 16.5 months. All the patients had no complications such as popliteal artery, tibial nerve or peroneal nerve injuries. According to Letenneur knee function score: 10 patients got an excellent result, 3 good. At the half year after operation, the X-ray showed all the fractures had bone union. There were no hollow lag screw loosening, broken or nonunion. CONCLUSION: The clinical effect of hollow lag screw for the treatment of Hoffa fractures is satisfactory. The surgical approach and fixation should be determined by the type of fracture, the location of the fracture line and the size of fracture fragments.

[Treatment of adolescent clavicular fracture with titanium elastic nails].

OBJECTIVE: To investigate the feasibility and clinical effects of titanium elastic nails (TEN) for adolescent clavicular fracture. METHODS: From October 2008 to November 2009, 17 adolescent patients with clavicular fracture were treated with internal fixation, including 11 males and 5 females who ranged in age from 12 to 18 years (mean 15.3 years). The mean time from injury to surgery was 3.5 days (2-7 days). Constant function score before surgery and that 3 months after surgery and shoulder ROM before surgery and that 2 months after surgery were compared. Fracture reduction and healing were followed up by X-rays to analyze internal fixation with the TEN technique. RESULTS: All patients were followed up for a mean of 6.5 months (range 3-8 months), during which no infection, TEN fracture or skin bursting was observed. The Constant score rose from preoperative (45.3 +/- 6.1) to (85.6 +/- 4.3) at 3-month follow up (t = 22.164, P < 0.01),and the shoulder activity degree at 2-week follow up was improved obviosly from preoperative (P < 0.01). X-ray at 12-16 weeks after surgery showed good bone healing and recovery of shoulder function. CONCLUSION: Internal fixation with TEN in the treatment of adolescent clavicular fracture is safe, minimally invasive,reliable and cosmetic. This technique provides a liable ption for the treatment of adolescent clavicular fractire

[Pedicle screw at the fracture level and vertebroplasty via paraspinal approach for the treatment of old thoracolumbar fractures].

OBJECTIVE: To investigate the feasibility and safety of the treatment for thoracolumbar fractures with pedicle screw at the fracture level and vertebroplasty via paraspinal approach. METHODS: From August 2007 to August 2010, 22 old patients with thoracolumbar fractures were treated with pedicle screw at the fracture level and vertebroplasty via paraspinal approach. There were 14 males and 8 females, ranging in age from 60 to 71 years (mean, 64.6 years). The time from injury to surgery varied from 1 to 4 d (mean,2.7 d). All the patients suffered from single thoracolumbar fractures and located at T11 in 2 cases, at T12 in 5 cases, at L1 in 11 cases and at L2 in 4 cases. According to the Denis fracture classification, there were 6 compression fractures and 16 burst fractures. The mean preoperative load-sharing classification of spine fractures was 5.4 score. The mean preoperative thoracolumbar injury classification and scoring was 5.2. Based on the ASIA neurologic grading system, preoperative neurological function was grade B in 2 cases,grade C in 3 cases, grade D in 7 cases and grade E in 10 cases. The neurological function, vertebral central and anterior height, kyphotic angle of the vertebral fractures by radiographs and visual analog scale were calculated pre-operatively, post-operatively and at the last follow-up. RESULTS: Median operating time was 60.8 min (ranged from 50 to 95 min) and median blood loss was 84 ml (ranged from 50 to 130 ml). The operative incisions were healed well. The duration of follow-up averaged 21.6 months (ranged from 12 to 48 months). The anterior vertebral body height was corrected from preoperative (52.3 +/- 10.3) % to postoperative (6.1 +/- 4.2) % and (6.8 +/- 5.4) % at the last follow-up. The central vertebral body height was corrected from preoperative (38.9 +/- 11.2) % to postoperative (8.3 +/- 4.7) % and (9.4 +/- 4.5)% at the last follow-up. The Cobbs angle of the injured vertebral segment was corrected from preoperative (19.5 +/- 9.5) degrees to postoperative (4.3 +/- 4.1) degrees and (6.2 +/- 4.7) degrees at the last follow-up. The VAS scores reduced from preoperative 8.56 +/- 0.88 to post-operative 3.48 +/- 0.91 and 3.20 +/- 0.92 at the last follow-up. The postoperative neurologic function of all 22 patients improved 1 to 2 degrees except 10 patients of grade E. There were no instances of instrumentation failure and no patient had persistent postoperative back pain. CONCLUSION: The pedicle screw at the fracture level and vertebroplasty via paraspinal approach has the advantages of less invasive and blood loss, and could prevent the development of kyphosis and offers improvement of the spinal cord function. Furthermore, it could decrease the risks of postoperative back pain and the failure of instrumentation.

[Clinical study on the effects of the femoral attachment site of grafts and the tunnel angle on the function of knee joint after anterior cruciate ligament reconstruction].

OBJECTIVE: To investigate the effects of the attachment site of grafts and the tunnel angle on the function of knee joint after anterior cruciate ligament reconstruction. METHODS: From January 2006 to May 2009, 47 patients(32 males and 15 females, ranging in age from 19 to 51 years old, with an average of 35.3 years old) were treated with single-bundle reconstruction of anterior cruciate ligament. Several indexes were measured at the latest follow-up as follow: attachment sites of graft on the femoral condyle were recorded, the femoral tunnel angles on coronal and sagittal planes were measured on postoperative X-ray films. According to the IKDC score, these patients were divided into two groups. In the first group, 38 patients were found the IKDC score more than 90 at the latest follow-up, and in the second group 9 patients were found IKDC score less than 90. By comparing the two groups, the relation of the indexes and postoperative function of knee was analyzed. RESULTS: The IKDC which was more than 90 at the latest follow-up was found in 38 patients, whose femoral attachments site of ACL was positioned at (29.73 +/- 4.31)% (ranged from 16.21% to 53.82%) from the posterior end of Blumensaat's line. IKDC which was less than 90 was found in 9 patients, whose femoral attachments site of ACL was positioned at (46.61 +/- 3.43)% (ranged from 27.18% to 72.34%). There was significant difference between the two groups (P = -0.000 7). The IKDC more than 90 at the latest follow-up was found in 38 patients,whose femoral tunnel angle on coronal plane was (49.5 +/- 4.72) degrees (ranged from 33 degrees to 67 degrees) and on sagittal plane was (31.3 +/- 5.12) degrees (ranged from 11 degrees to 45 degrees) were significantly less than those whose IKDC less than 90 at the latest follow-up on coronal plane was (67.6 +/- 3.09) degrees (ranged from 41 degrees to 81 degrees) and on sagittal plane was (41.2 +/- 5.69) degrees (ranged from 23 degrees to 56 degrees) (P = 0.000 7, P = -0.000 8). CONCLUSION: There is close relation between the attachment site of grafts and the tunnel angle with the function of knee, so in anterior cruciate ligament should be anatomic reconstructed with the anterior medial approach.

[Surgical treatment of thoracolumbar fractures using reduction and short-segment pedicle screw at the fracture level with the approach through para-vertebral muscles].

OBJECTIVE: To evaluate the efficacy and clinical outcome of reduction and pedicle screws fixation at the fracture level with the approach through para-vertebral muscles in treating thoraeolumbar fractures. METHODS: From January 2007 to March 2010,27 patients with thoracolumbar fractures were treated with posterior open reduction and internal fixation with the approach through para-vertebral muscles. There were 19 males and 8 females with the mean age of 36.3 years old (ranged,21 to 57). According to Magerl type, type A2 was in 5 cases, A3 in 14, B1 in 3, B2 in 5. According to Frankel classification of spinal cord injury: grade D was in 6 cases and grade E in 21 cases. X-rays and CT scans were performed after operation. Cobb angle of the injured vertebral segment,the percentage of vertebral compression,and sagittal diameter stenosis rate of the injured spinal canal were observed by radiographic data. Neurological function was evaluated by the Frankel grade. RESULTS: All patients were followed up from 12 to 28 months with an average of 19.6 months. The percentage of vertebral compression, Cobb angle of the injured vertebral segment, spinal canal sagittal diameter stenosis rate were respectively corrected from (46.6 +/- 10.5)%, (18.3 +/- 7.2) degrees, (30.2 +/- 7.2)% to postoperative (5.2 +/- 3.7)%, (5.3 +/- 5.1) degrees, (6.3 +/- 4.2)% and (6.7 +/- 4.6)%, (7.1 +/- 3.1), (7.2 +/- 4.5)% at last follow-up. There were significant difference in above items between preoperation and postoperation (P < 0.05); and there was no significant difference in above items between postoperation and last follow-up (P > 0.05). In aspect of nerve function, 3 cases with Frankel grade D recovered to grade E. CONCLUSION: Using reduction and short-segment pedicle screws fixation at the fracture level through para-vertebral muscles approach is an effective method in treating thoracolumbar fractures. The method has advantages of simple operation,easy establishing screw, short operative time, less blood loss, which can obtain good reduction and stable, reliable fixation after operation.

[Clinical application and advancement of artificial intervertebral discs for lumbar degenerative disease].

Degenerative disc disease is not only a common disease in the area of spinal surgery, but also one of the main reasons for the low back pain of the adults and disability. Conventionally it was considered be affirmative for the effect of the lumbar spinal fusion. But the way retained the physiological motor function. The lumbar motion segment fusion accelerated degeneration of adjacent segment disc and facet joint. Further study of lumbar functional anatomy and biomechanics made development of modern artificial disc device of different structures and materials possible. Besides the lumbar fusion, artificial lumbar disc replacement has become another choice in treating the lumbar degenerative diseases. The purpose is to release the pain which caused by the degenerative disc for a long period and to reconstruct the height of intervertebral disc in order to protect the nerve tissue. Retaining the spinal movement was in order to avoid degeneration of facet joints and adjacent segments, then, restore the spinal characteristic of kinematics and load at last. This review aims to explain the type of artificial lumbar intervertebral disc, the field of research and its clinical application advancement and prospects.

Possible key role of immune system in Schmorl's nodes.

Schmorl's nodes (SNs) are common abnormalities in the human spine, which represent herniation of the nucleus pulposus of the intervertebral disc into the adjacent cartilaginous endplate of the vertebra. However, the principle mechanism of SNs is still not fully understood. And the relationship of SNs in the spine and their clinical significance as a source of low back pain in the general population remains unknown. It is therefore important to get better understanding of this. Here, we review the clinical and experiment evidence on inducing of the SNs and correlative back pain, and propose a possible mechanism. Studies showed that once the nucleus pulposus enters into vascular tissue, the immune system could recognize it as a foreign body, and induces the immunological reaction. Then, there would be osteoimmunology action, a crosstalk between the immune system and bone, leading to bone loss by dysregulating T-lymphocyte function, and resulting to the bone absorption. Furthermore, the cytokines are involved in the development of immunological reactions and could be responsible for the significant pathology of symptomatic SNs. Given the above background, we hypothesize that immune system could be a key role in SNs and result in the pain.