Downregulation of AATK mediates microRNA-558-induced resistance of A549 cells to radiotherapy.

The deregulation of microRNAs (miRNAs) is often implicated in the control of sensitivity to radiotherapy. The objective of the present study was to identify the association between miR­558 and apoptosis­associated tyrosine kinase (AATK), and their importance in regulating the development of resistance to radiotherapy. The current study demonstrated that AATK, a radiosensitization-associated gene, is a target of miR­558 in lung cancer cells, using in silico analysis and a luciferase reporter system. Furthermore, it was determined that transfection of 30 or 50 nM miR­558 mimics and AATK specific siRNA markedly suppressed the mRNA and protein expression of AATK. To determine whether miR­558 was required for lung cancer cell radioresistance, A549 cells were treated with different doses of ionizing radiation, from 0 to 10 Gy, following transfection with miR­558 mimics or AATK specific siRNA. It was determined that the administration of miR­558 mimics or AATK specific siRNA alone did not significantly alter the survival rate of the cells. By contrast, in the cells exposed to 4, 6 or 8 Gy, the administration of miR­558 mimics or AATK specific siRNA significantly promoted cell survival rate and overexpression of AATK reversed this effect. In conclusion, these data demonstrate that the miR­558/AATK cascade is important for the radiosensitization of lung cancer cells and may be a potential radiotherapy target.

Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening.

Lung cancer, predominantly by non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths over the world. Late diagnosis is one of important reasons for high mortality rate in lung cancer. Current diagnostic approaches have disadvantages such as low accuracy, high cost, invasive procedure, etc. MicroRNAs were previously proposed as promising novel biomarkers in cancer screening. In this study, we evaluated the predictive power of four candidate miRNAs in NSCLC detection. Our study involved 152 NSCLC patients and 300 healthy controls. Blood samples were obtained from the total 452 subjects. After miRNA extraction from serum, the expression of miRNAs in cases and controls were quantified by qRT-PCR and normalized to the level of U6 small RNA. Statistical analyses were performed to compare miRNA levels between cases and controls. Stratified analyses were employed to compare miRNA levels in NSCLC patients with different clinical characteristics. Serum miR-148a, miR-148b, and miR-152 were significantly downregulated in NSCLC patients. However, overexpression of serum miR-21 was observed in NSCLC patients. The combination of four candidate miRNAs exhibited the highest predictive accuracy in NSCLC screening compared with individual miRNAs (AUC = 0.97). Low level of miRNA-148/152 members may associate with advanced stage, large tumor size, malignant cell differentiation, and metastasis. High expression of miR-21 was possibly correlated with large size tumor and advanced cancer stage. Our results showed the dysregulation of miR-148/152 family and miR-21 in NSCLC patients. Hence, the four candidate miRNAs have great potential to serve as promising novel biomarkers in NSCLC screening. Further large-scale studies are needed to validate our results.

[The therapeutic effect analysis of three kinds of methods for the management of post traumatic knee stiffness].

OBJECTIVES: To investigate the therapeutic effect of rehabilitation, arthroscopy and "hybrid technique" for posttraumatic knee stiffness (PTKS), and to make the best choice for the treatment. METHODS: From February 2004 to November 2009, 66 patients suffered from PTKS were treated, and the clinical data were studied retrospectively, 36 male and 30 female patients with an average age of 41 years were analyzed, knee stiffness time averaged 15 months (0.5 - 108.0 months), 21 cases of patients were treated with rehabilitation (rehabilitation group), 22 cases of patients with arthroscopy + rehabilitation (arthroscopy group) and 23 cases of patients with mini-invasive "hybrid technique" + rehabilitation (hybrid technique group). For each case, the difference of range of motion (ROM) and hospital for special surgery (HSS) score of the knee before and after the treatment were analyzed statistically. The characters of PTKS including the course of the disease, the degree of extensor mechanism involving, physical examination and other ancillary data were also analyzed. The management methods for PTKS were summarized. RESULTS: Total 66 cases were followed up ranging from 24.0-72.5 months and the mean time was 34.2 months. The average ROM was improved obviously: rehabilitation group increased from 45° ± 22° to 95° ± 24° (t = -11.2, P < 0.05), arthroscopy group from 47° ± 26° to 118° ± 11° (t = -11.0, P < 0.05) and hybrid technique group from 36° ± 22° to 110° ± 14° (t = -13.4, P < 0.05). Both ROM and HSS score of the knee before and after the treatment for each group showed significant difference statistically (t = -9.1, -6.0, -5.2, P < 0.05). Wound necrosis, tearing, re-fracture and extension lag were not found. According to Judet standard at final follow-up, 15 cases were excellent, 3 cases good and 3 cases normal in rehabilitation group; 15 cases were excellent, 5 cases good and 2 cases normal in arthroscopy group; 14 cases were excellent, 8 cases good and 1 case bad. CONCLUSIONS: Pathology of PTKS is complex, satisfactory result could be obtained through individualized treatment program, which were established depend on the course of the disease, the degree of extensor mechanism involving, physical examination and ancillary data. The timely and effective surgical interference followed by a comprehensive rehabilitation program is the key point for satisfied outcome.

[The treatment of dorsally displaced intra-articular fractures of the distal radius via palmar approach].

OBJECTIVE: To treat dorsally displaced intra-articular fractures of the distal radius, and to assess the integrity of radiocarpal joint and the reliability of stable fixation fracture. METHODS: Sixty-three cases (65 sides) patients with dorsally displaced intra-articular fractures of the distal radius were performed operatively with the open reduction and internal fixation via palmar approach between August 2003 and May 2008. The series included 20 males (21 sides) and 43 females (44 sides). The mean age of patients was 52.4 years ranging from 18 to 82 years. According to the Frykman classification, 6 sides were of type III, 8 of type IV, 5 of type V, 4 of type VI, 13 of type VII and 29 of type VIII. With the exception of the radiocarpal arthrography and the standard antero-posterior and lateral views of the wrist joint, two new tangential antero-posterior and lateral views of the wrist joint were intraoperatively described so as to observe the relation of the distal screws with the articular surface. RESULTS: The 53 cases (54 sides) of the 63 cases (65 sides) were followed up, and the follow-up time was averagely 16.4 months ranging from 4 to 47 months. According to Gartland and Werley criteria, 32 sides were rated as excellent (59.3%), 14 sides as good (25.9%), 7 fair (13.0%) and 1 poor (1.8%), and the excellent-good rate was 85.2%. Observing the new tangential antero-posterior and lateral views of the wrist joint, it showed that screws appeared penetrating into the radiocarpal joint in 26 of the 42 sides by standard antero-posterior view and in 31 of the 42 sides by standard lateral view. CONCLUSION: This palmar approach represents a simple and valuable treatment methodology for the most frequent types of unstable fractures of the distal radius in young and elderly patients.

[Trend of bone development of adolescent at 14 years old].

OBJECTIVE: To describe characteristic of hand-wrist bone development in adolescents of 14 years old in China, and to estimate trend of bone development of them. METHODS: A total of 109 adolescents of 14 years was selected as subjects (males: 53, females: 56). X-rays examination of their left hand-wrist bone were performed and analyzed. The development characteristics of each position in accordance with Gu's mapping of skeletal age were compared with Gu's results and ours. RESULTS: Compared with Gu's, osteoepiphysis of distal radius, the first metacarpal bone, the fourth proximal phalanx were more advanced in boys, osteoepiphysis of distal radius, the second-fifth metacarpal bones, the first-fifth proximal phalanxs, and the second-fifth middle phalanxs were more advanced in girls. CONCLUSION: The results suggested that a forward trend of 14 years old adolescents bone development currently exists in our country, especially in girls. As an important age of criminal responsibility, this forward trend of development of bones among adolescents currently should be kept in mind when estimating bone age of criminals.

Damage control of multiple injuries headed by cervical spinal cord injury.

OBJECTIVE: To explore the strategy of damage control in clinical treatment of multiple injuries headed by cervical spinal cord injury. METHODS: A retrospective analysis was performed in 32 patients. Cervical fractures associated with tetraplegia occurred in 18 patients, traumatic intervertebral disk hernia associated with tetraplegia in 2 patients, and cervical fractures and dislocation associated with tetraplegia in 12 patients. Seventeen cases were combined with craniocerebral injury, 7 combined with pulmonary contusion, multi-fractures of rib or hemopneumothorax, 2 combined with pelvic fracture and other 8 combined with fracture of limbs. The neural function was assessed by the American Spinal Injury Association (ASIA) scale. RESULTS: Thirty-one patients were followed up for an average of 14 months. Of them, 10 got complete recovery, 13 obtained improvement of more than one ASIA grade, 8 did not improve, and 1 died. CONCLUSIONS: For the emergency treatment of multiple injuries headed by cervical spinal cord injury, the damage control strategy is the principle to follow. The final operations are preferably performed within 5 to 10 days after injury so as to raise the successful rate of remedy.

Application of injury severity score to multiple injuries headed by spinal cord injury.

OBJECTIVE: To evaluate the application of injury severity score ( ISS) to multiple injuries headed by spinal cord injury. METHODS: The data of 55 cases (40 males and 15 females, aged 17-69 years, mean equal to 41 years) of multiple injuries headed by spinal cord injury treated in our hospital from January 2000 to December 2004 were reviewed and analyzed with ISS (Version of AIS-2005) to explore their relationship. RESULTS: The ISS values increased with the number of injured regions, so did the complications. The recovery rate was negatively related to ISS values. During the period of immunity observation, the patients with ISS larger than 25 could undergo planned operations safely. CONCLUSIONS: Treatment for multiple injuries headed by spinal cord injury closely depends on the general and local conditions of the patients. ISS may provide useful data for the choice of treatment methods.

[Apoptosis and gene FasL expression induced by carbon disulfide in rat sertoli cells].

OBJECTIVE: To study apoptosis and gene FasL expression induced by carbon disulfide in sertoli cells of male rats. METHODS: Sertoli cells were exposed to different concentrations of CS(2) (0, 0.36, 0.72, 1.44 micromol/ml) for 24 hours. Survival rate, apoptosis rate, expression level of gene FasL were measured using MTT, FCM, and RT-PCR methods respectively. RESULTS: Sertoli cell survival rate decreased as the concentration of CS(2) increased. The survival rate (73.34% +/- 1.39%) was significantly lower than the control group (99.98% +/- 5.48%) when the concentration of CS(2) > or = 1.44 micromol/ml (P < 0.05). Apoptosis rate increased as the CS(2) concentration increased. Apoptosis rate (7.93% +/- 0.43%) was significantly higher when the concentration of CS(2) > or = 1.44 micromol/ml (P < 0.05). Expression level of the FasL significantly increased as the concentrations of CS(2) (P < 0.05). CONCLUSION: CS(2) is cytotoxic to sertoli cells. It could cause apoptosis of sertoli cells.