AIM: To observe the influence of lentiviral vectors expressing siRNA for survivin gene knockdown in A549 cells,sequentially as tools to explore the molecule pathogenesis and new gene therapy of lung adenocarcinoma.METHODS: The lentiviral vectors,which express survivin siRNA,were constructed and transfected into A549 cell strain.The titers of the lentiviruses were determined by 293T cells.The expressions of survivin and caspase-3 were detected by Western blotting and RT-PCR.The cell cycle and cell growth of A549 cells were examined by MTT and FCM.RESULTS: The expression of survivin was suppressed effectively by siRNA targeting survivin.The expression of survivin mRNA decreased by 97%.The expression of survivin protein decreased by 94%.The rate of cell growth was decreased.The G1 phase cells were increased,whereas S phase cells were decreased.CONCLUSION: The lentivirus vectors expressing siRNA for survivin can significantly inhibit gene expression and the cell growth,and markedly induce the apoptosis.It is hopeful to be a new gene therapy of lung adenocarcinoma.

OBJECTIVE: To search the features and the treatment of vascular compressive syndrome caused by the facial, acoustic nerves. METHOD: Ten cases of vascular compressive syndrome caused by the facial, acoustic nerves were included in the group,which were treated by microvascular decompression(MVD). Besides, the microanatomic relationship between the nerve and their adjacent vessel at the root exit zone (REZ) were observed under microscope or nasoendoscopy in MVD. RESULT: Tinnitus, vertigo and facial spasm disappeared after MVD in 7 cases (70%), improved in 2 cases (20%), and relapse in 1 case (10%). All cases were found out vessels compressing at the root zone of the facial nerve and the auditory nerve. CONCLUSION The Clinical features of vascular compressive syndrome caused by the facial, acoustic nerves are facial spasm, tinnitus, and vertigo, for which microvascular decompression has a positive therapeutic effect as long as the diagnosis is correct.
Adult ; Cochlear Nerve ; Decompression, Surgical ; Facial Nerve ; Female ; Follow-Up Studies ; Humans ; Male ; Microsurgery ; Middle Aged ; Nerve Compression Syndromes ; diagnosis ; physiopathology ; surgery

Objective To analyze of the effect of artificial lengthening femoral head replacement in elderly patients with stage Ⅰ of unstable femoral intertrochanteric fracture.Methods 203 patients with stage Ⅰ of unstable femoral intertrochanteric fracture were selected as the research object,and they were taken artificial lengthening femoral head replacement,among which 65caese were male,female in 138 cases.The Harris scoring,SF-36,VAS pain scores on admission,2 weeks after operation,postoperative follow-up limb were counted,and the pain of the affected limb and the hip scores were compared amond 3 time periods.Results All 203 cases of senile patients with follow-up,average operation time was 83.64 minutes,the intraoperative blood loss was 355.41mL.The curative effect was evaluated according to the Harris score,SF-36 and VAS pain scoring criteria,and the Harris scores of the affected limbs at admission,at 2 weeks after the operation and after the follow-up were (28.26 ± 5.50) points,(68.26 ±5.50) points,(93.13 ± 5.31) points,respectively,the differences were statistically significant (t =-71.27,-1 397.55,-46.07,all P ＜ 0.01);The VAS pain scores were (8.19 ± 0.48) points,(3.53 ± 0.71) points,(0.23 ± 0.42) points,respectively,the differences were statistically significant (t =88.06,324.17,60.84,all P ＜ 0.01).The sf-36 scores:physiological [(8.35 ± 1.24) points,(15.23 ± 2.17) points,(19.21 ± 2.12) points],social/family [(7.01 ±1.13) points,(14.12 ± 2.12) points,(19.85 ± 2.24) points],emotional [(4.83 ± 1.01) points,(10.12 ±1.22)points,(14.87 ± 1.32) points],function [(6.35 ± 1.21) points,(13.67 ± 1.87) points,(16.81 ±2.12) points],additional focus [(8.85 ± 1.45) points,(16.38 ± 2.12) points,(20.21 ± 2.42) points],total quality of life [(47.35 ± 4.76) points,(74.69 ± 5.87) points,(89.21 ± 6.12) points],the differences were statistically significant(-39.77,-62.92,-20.21,-44.87,-71.89,-26.79,-45.04,-89.01,-38.25,-45.79,-63.41,-15.29,-45.20,-60.39,-17.54,-52.12,-76.49,-22.58,all P＜0.O1).Conclusion Artificial lengthening femoral head replacement in elderly patients with stage Ⅰ of unstable femoral intertrochanteric fracture has good clinical effect,intraoperative high safety,less postoperative complications,postoperative limb functional recovery is good,and it is worthy of clinical promotion and application.

OBJECTIVETo detect potential mutations in two neonates suspected for Cornelia de Lange syndrome (CdLS).

METHODSPeripheral blood samples from the neonates and their parents were collected and analyzed for CdLS-related genes using targeted sequence capture and next-generation sequencing. Suspected mutations were confirmed by direct Sanger sequencing.

RESULTSThe neonates were found to respectively carry mutations c.7219C to T and p.D2339Lfs*4 of the NIPBL gene, among which the p.D2339Lfs*4 mutation has not been reported previously. No pathogenic mutation was found in other CdLS-related genes including NIPBL, SMC1A, SMC3, RAD21 and HDAC8.

CONCLUSIONThe c.7219C to T and p.D2339Lfs*4 mutations of the NIPBL gene probably account for the disease in both patients.

Objective:To establish a metaheuristics-based automatic radiotherapy treatment planning method (ATP-STAR) and verify its effectiveness.Methods:The main process of the ATP-STAR method was as follows. First, the optimization parameters were vectorized for encoding and corrected using Gaussian convolution. Then, the candidate optimization parameter vector set was selected through simulated annealing. Finally, the optimal combination of optimization parameters was determined by combining the field fluence optimization to achieve automatic trial-and-error. Twenty cases with large individual differences in tumors were selected for testing. Clinical physicists with more than five years of experience were invited to perform manual planning. Both the manual and ATP-STAR plans were made utilizing the matRad open source software for radiation treatment planning, with the fields and prescribed doses consistent with those of the clinical treatment plans. The dosimetric differences of target volumes and organs at risk between the ATP-STAR and manual plans for different diseases were analyzed.Results:For the target volumes, the ATP-STAR plans showed superior homogeneity compared with the manual plans (brain tumors: z = 2.28, P = 0.022; lung cancers: z = 2.29, P = 0.022; liver cancers: z = 2.11, P = 0.035). The conformability of the ATP-STAR plans was comparable to that of the manual plans for brain tumors and liver cancer and was slightly lower than that of the manual plans for lung cancer ( z = 2.29, P = 0.022). The comparison result of doses to organs at risk (OARs) between the manual plans and STAR plans were as follows. For OARs of brain tumors, the ATP-STAR plans decreased the mean left lens Dmean from 2.19 Gy to 1.76 Gy ( z = 2.28, P = 0.022), decreased left optic nerve Dmean from 11.36 Gy to 10.22 Gy ( z = 2.28, P = 0.022), decreased right optic nerve Dmax from 32.92 Gy to 29.97 Gy ( z = 2.10, P = 0.036), and decreased pituitary Dmax from 39.53 Gy to 35.21 Gy ( z = 2.29, P = 0.022). For OARs of lung cancer, the ATP-STAR plans decreased the mean spinal cord Dmax from 38.00 Gy to 31.17 Gy ( z = 2.12, P = 0.034), decreased the bilateral lungs Dmean from 8.51 Gy to 8.07 Gy ( z = 2.29, P = 0.022), and decreased cardiac Dmean from 3.21 Gy to 2.69 Gy ( z =2.29, P = 0.022). For OARs of liver cancer, the ATP-STAR plans decreased spinal cord Dmax from 18.19 Gy to 14.76 Gy ( z = 2.11, P = 0.035), decreased liver Dmean from 15.61 Gy to 14.45 Gy ( z = 2.11, P = 0.035), and decreased kidneys Dmean from 4.76 Gy to 4.04 Gy ( z = 2.10, P = 0.036). Conclusions:The proposed ATP-STAR method relies little on the experience of manual planning and thus is easy to be widely applied. This method is expected to improve the quality and consistency of IMRT plans and save clinical labor and time costs.

Objective:To investigate the effects of off-target isocenter plans with different off-target distances on the plan quality and delivery accuracy of stereotactic body radiotherapy (SBRT) for lung cancer, aiming to provide a reference for the clinical plan design of SBRT for lung cancer.Methods:For 10 lung cancer patients treated with SBRT, isocenter reference plans were designed by setting the plan isocenters at the mass centers of tumors and 60 off-target isocenter plans by setting the isocenters at distances of 1, 3, 5, 8, and 10 cm from the mass centers of tumors. The dosimetric differences between the off-target isocenter plans and the reference plans. Subsequently was analyzed, under different positional errors (0-5 mm). The gamma pass rates (GPRs) of these plans were measured using the Octavius 4D high-resolution dose verification system, and 240 verifications of these plans were completed. The robustness of the delivery accuracy of the reference plans and off-target isocenter plans were analyzed under different positional errors.Results:The off-target isocenter plans yielded slightly worse dose gradient indices than the isocenter reference plans, but there was no statistically significant differences. With an increase in the off-target distance, the mean lung dose (MLD), V20 of normal lungs, as well as the Dmax of bronchi, showed slight upward trends. Compared with the isocenter reference plans, the MLD of the off-target isocenter plans increased by 0.8%, 0.8%, and 1.9% at off-target distances of 1, 3, and 10 cm, respectively, with statistically significant differences ( z = -2.34 to -1.99, P < 0.05), and the V20 of the off-target isocenter plans increased by 2.0%, 2.5%, and 3.7% at off-target distances of 1, 5, and 10 cm, respectively, with statistically significant differences ( z =-2.11 to -1.99, P < 0.05). In the case of a positional error of up to 5 mm, the GPRs of plans with off-target distances of 5 cm and above decreased by more than 1.0% on average and up to a maximum of 3.5%, showing statistically significant differences ( z = 2.13-2.75, P < 0.05). Conclusions:Compared to the reference plans, the off-target isocenter plans showed slightly lower dosimetric quality and less robust delivery accuracy under different positional errors. Therefore, it is necessary to avoid the plans and treatment with too large off-target distances (≥ 5 cm) as far as possible for SBRT of lung cancer.

The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity. However, the transformation of current genetic variant-obesity associations into biological knowledge has been proven challenging. Genomics and proteomics are complementary fields, as proteomics extends functional analyses. Integrating genomic and proteomic data can help to bridge a gap in knowledge regarding genetic variant-obesity associations and to identify new drug targets for the treatment of obesity. We provide an overview of the published papers on the integrated analysis of proteomic and genomic data in obesity and summarize four mainstream strategies: overlap, colocalization, Mendelian randomization, and proteome-wide association studies. The integrated analyses identified many obesity-associated proteins, such as leptin, follistatin, and adenylate cyclase 3. Despite great progress, integrative studies focusing on obesity are still limited. There is an increased demand for large prospective cohort studies to identify and validate findings, and further apply these findings to the prevention, intervention, and treatment of obesity. In addition, we also discuss several other potential integration methods.
Humans ; Proteome/metabolism* ; Proteomics ; Prospective Studies ; Obesity/genetics* ; Genomics ; Genome-Wide Association Study