[show abstract][hide abstract] ABSTRACT: Epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib have been widely used in patients with non-small-cell lung cancer. Unfortunately, the efficacy of EGFR-TKIs is limited because of natural and acquired resistance. As a novel cytoprotective mechanism for tumor cell to survive under unfavorable conditions, autophagy has been proposed to play a role in drug resistance of tumor cells. Whether autophagy can be activated by gefitinib or erlotinib and thereby impair the sensitivity of targeted therapy to lung cancer cells remains unknown. Here, we first report that gefitinib or erlotinib can induce a high level of autophagy, which was accompanied by the inhibition of the PI3K/Akt/mTOR signaling pathway. Moreover, cytotoxicity induced by gefitinib or erlotinib was greatly enhanced after autophagy inhibition by the pharmacological inhibitor chloroquine (CQ) and siRNAs targeting ATG5 and ATG7, the most important components for the formation of autophagosome. Interestingly, EGFR-TKIs can still induce cell autophagy even after EGFR expression was reduced by EGFR specific siRNAs. In conclusion, we found that autophagy can be activated by EGFR-TKIs in lung cancer cells and inhibition of autophagy augmented the growth inhibitory effect of EGFR-TKIs. Autophagy inhibition thus represents a promising approach to improve the efficacy of EGFR-TKIs in the treatment of patients with advanced non-small-cell lung cancer.
PLoS ONE 01/2011; 6(6):e18691. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: to summarize the complications of posterior vertebral column resection (pVCR) and pedicle screw fixation for the treatment of rigid thoracic and lumber spinal deformity.
fifty four patients from a single center from February 2000 to February 2009 were included in this study. There were 23 males and 31 females with an average age of 28.3 years (range, 16-58 years). Patients were divided into 4 diagnostic categories: severe scoliosis (n = 9, mean Cobb angle, 91.7°), kyphoscoliosis (n = 22, mean scoliosis, 101.5°, and mean kyphosis, 69.4°), angular kyphosis (n = 21, mean kyphosis, 72.2°), global kyphosis (n = 2, mean kyphosis, 93.6°). All of the patients received one stage pVCR combined correction with pedicle screws and circumferential fusion. Radiographs and hospital charts were reviewed to analyze the outcomes of correction.
a mean of 1.4 vertebral levels were resected, the mean operative time was 470 min, and the mean blood loss was 4180 ml. All the patients were followed-up for an average time of 26 months (range, 12 - 66 months). At the latest follow-up, the major curve correction averaged: severe scoliosis 61.4° (67%), kyphoscoliosis 59.7° (56%)/kyphosis 42.3° (59%), angular kyphosis 48.5° (71%), global kyphosis 62.7° (67%). A total of 21 complications (38.9%) occurred in 17 patients, including 5 (9.3%) neurological complications happened in early stage and one case of delayed complete paraplegic. There were 11 (20.4%) non-neurological complications happened in early stage and 5 (9.3%) cases in late stage.
one stage posterior-only vertebral column resection can achieve satisfactory correction of severe deformities with limited flexibility. Given its technically demanding and exhausting features, its potential risk of significant complications should be paid more attention.
Zhonghua wai ke za zhi [Chinese journal of surgery] 11/2010; 48(22):1709-13.
[show abstract][hide abstract] ABSTRACT: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. To date, the molecular mechanisms of DN remain largely unclear. The present study aimed to identify and characterize novel proteins involved in the development of DN by a proteomic approach. Proteomic analysis revealed that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2), the key enzyme in ketogenesis, was increased fourfold in the kidneys of type 2 diabetic db/db mice. Consistently, the activity of HMGCS2 in kidneys and 24-h urinary excretion of the ketone body β-hydroxybutyrate (β-HB) were significantly increased in db/db mice. Immunohistochemistry, immunofluorescence, and real-time PCR studies further demonstrated that HMGCS2 was highly expressed in renal glomeruli of db/db mice, with weak expression in the kidneys of control mice. Because filtered ketone bodies are mainly reabsorbed in the proximal tubules, we used RPTC cells, a rat proximal tubule cell line, to examine the effect of the increased level of ketone bodies. Treating cultured RPTC cells with 1 mM β-HB significantly induced transforming growth factor-β1 expression, with a marked increase in collagen I expression. β-HB treatment also resulted in a marked increase in vimentin protein expression and a significant reduction in E-cadherin protein levels, suggesting an enhanced epithelial-to-mesenchymal transition in RPTCs. Collectively, these findings demonstrate that diabetic kidneys exhibit excess ketogenic activity resulting from increased HMGCS2 expression. Enhanced ketone body production in the diabetic kidney may represent a novel mechanism involved in the pathogenesis of DN.
AJP Endocrinology and Metabolism 10/2010; 300(2):E287-95. · 4.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cervical kyphosis is an uncommon but potentially debilitating and challenging condition. We reviewed the etiology, presentation, clinical and radiological evaluation, and treatment of cervical kyphosis. Based on the current controversy as to the ideal mode of surgical management, we paid particular attention to the available surgical strategies. There are three approaches for cervical kyphosis: the anterior, posterior or combined procedures. The principal indication for the posterior strategy is a flexible kyphosis or kyphosis caused by ankylosing spondylitis. The main point of debate is between the choice of the anterior or the combined strategy. The two strategies were compared with regard to clinical outcome, correction of deformity, rate of fusion, complications, revision surgery, and mortality. The combined strategy appears to result in a greater degree of correction than the anterior-alone strategy, and it is more likely to improve the cervical alignment to achieve a lordosis. However, the procedure carries a higher rate of postoperative neurological deterioration, complications, revision surgery, and mortality. Although the anterior-alone strategy achieves a smaller reduction of cervical kyphosis, it has a lower rate of postoperative neurological deterioration, complications, revision surgery, and mortality. We recommend that the surgical treatment of cervical kyphosis should be planned on an individual basis. A multicenter, prospective, randomized controlled study would be necessary to determine the ideal mode of treatment for complex cervical kyphosis.
European Spine Journal 10/2010; 20(4):523-36. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: To observe the eyes' refractive status without cycloplegia in 2046 pupils. METHODS: The cross-sectional study was conducted in 2046 pupils of 4092 eyes in Xi'an city primary schools. The objective ophthalmic examinations were done on all participants,which included non-cycloplegic objective refraction, visual acuity, ocular pressure, fundus evaluation by special trained ophthalmologists and nurses. The special designed inventory scale was filled in and input special computer program, then the data were statistically analyzed with SPSS10.0. RESULTS: In the primary school of 2046 pupils of 4092 eyes, the detective rate of emmetropia was 32.0% of 1309 eyes, hypermetropia was 4.2% of 170 eyes, myopia was 63.8% of 2613 eyes, low myopia was 51.4% of 2102 eye, moderate myopia was 11.3% of 464 eyes, and high myopia was 1.1% of 47 eyes in total. In both eyes, the detective rate was 61.2%of 1348 eyes in 2204 boys, 67% of 1265 in 1888 girls. Among 6 grades, the constituent ratio of moderate and high myopia groups were significantly increased with the age's growing, including emmetropia 45.5% of 343 eyes out of 754 in 1st grade and 19.2% of 122 eyes out of 634 in 6th grade.The average refractive error of spherical equivalent refraction was (-1.32+/-1.60)D.Among 6 grades,the 1st grade' was (0.82+/-1.42)D,and the 6th grade's was (-1.82+/-1.68)D, there were significant differencesamong 6 grades(p<0.01).There was a significant difference between girls and boys(p<0.01). The average myopizing rate was -0.2 D at per year, -1.0 D in the total of the progression in 6 years.CONCLUSIONS: Poor condition of myopizing was showed in Chinese pupils. It should be taking seriously and making early intervention.
Yan ke xue bao = Eye science / "Yan ke xue bao" bian ji bu 08/2010; 25(1):16-19.
[show abstract][hide abstract] ABSTRACT: To explore an effective and reasonable surgical strategy for active spinal tuberculosis with severe kyphotic deformity (kyphotic angle >or= 45 degrees).
From January 2004 to January 2008, 30 consecutive patients of active spinal tuberculosis complicated with significant angulation were enrolled in this study, including 8 male and 22 female. The average age was 35 years (range, 7 - 60 years), with average angle of kyphosis of 58 degrees (range, 45 degrees - 70 degrees). There were 28 patients complicated with intraspinal abscess, of which 10 patients presented with incomplete paraplegia. According to the Frankel's scoring system, there were 2 patients with Frankel Grade B, 6 with Grade C, 2 with Grade D. After antituberculous chemotherapy (HREZ) for at least 2 weeks, all patients underwent posterior multiple-level pedicle screw instrumentation and kyphotic correction, and then received anterior debridement, decompression and supportive bone grafting, all of which were completed in the same day. The postoperative standardized chemotherapy was 6HREZ/6-12HRE. The angle of kyphosis, curve correction after surgery, and recovery of paraplegia were analyzed. Fusion status and erythrocyte sedimentation rate were recorded to determine the presence of active disease.
Operative time was 4 to 6 hours (average 5.2 h), blood loss was 600 to 900 ml (average 760 ml). No perioperative severe complications occurred. The kyphotic angle was corrected to 0 degrees - 10 degrees, and the maximum corrected angle was 65 degrees . The average follow-up duration was 18 months (range, 12 - 48 m). All patients showed evidence of solid fusion and healing of the active disease at 6 months follow-up. Neurologic deficits were improved: 2 patients from B to D, 6 patients from C to E, 2 patients from D to E. No recurrence of the tuberculosis infection or instrumentation failure happened at final follow-up.
Combined posterior instrumentation and anterior debridement, fusion surgery in one stage is proved to be successful in treating spinal tuberculosis, correcting the kyphosis, and providing solid fusion.
Zhonghua wai ke za zhi [Chinese journal of surgery] 04/2010; 48(8):597-600.
[show abstract][hide abstract] ABSTRACT: Ghrelin, the only identified circulating orexigenic signal, is unique in structure in which a specific acyl-modification of its third serine occurs. This acylation is necessary for ghrelin to bind to its receptor and to exert its biologic activity, which is catalyzed by ghrelin O-acyltransferase (GOAT). Although ghrelin is mainly secreted from gastric X/A like endocrine cells, it is also expressed in pancreatic islet cells and regulates insulin secretion. In this study, we examined the expression and regulation of GOAT in pancreas.
GOAT mRNA and immunoreactivity were examined in pancreatic islets and INS-1 cells by RT-PCR and immunofluorescent staining or Western blotting.
Insulin inhibits the expression of GOAT mRNA and GOAT promoter activity in a dose and time-dependent manner. The mammalian target of rapamycin (mTOR) is activated by insulin. Blocking mTOR signaling by either rapamycin or overexpression of its negative regulator tuberous sclerosis complex 1 (TSC1) or TSC2 attenuates the inhibitory effect of insulin on the transcription and translation of GOAT.
Our study suggests that GOAT is present in pancreatic islet cells and that insulin inhibits the expression of GOAT via the mediation of mTOR signaling.
Cellular Physiology and Biochemistry 01/2010; 26(4-5):707-16. · 3.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vascular smooth muscle cells (VSMCs) switching from a contractile/differentiated to a synthetic/dedifferentiated phenotype has an essential role in atherosclerosis, postangioplastic restenosis and hypertension. However, how normal VSMCs maintain the differentiated state is less understood.
We aimed to indentify the effect of cartilage oligomeric matrix protein (COMP), a normal vascular extracellular matrix, on modulation of VSMCs phenotype.
We demonstrated that COMP was associated positively with the expression of VSMC differentiation marker genes during phenotype transition. Knockdown of COMP by small interfering (si)RNA favored dedifferentiation. Conversely, adenoviral overexpression of COMP markedly suppressed platelet-derived growth factor-BB-elicited VSMC dedifferentiation, characterized by altered VSMC morphology, actin fiber organization, focal adhesion assembly, and the expression of phenotype-dependent markers. Whereas alpha(7) integrin coimmunoprecipitated with COMP in normal rat VSMCs and vessels, neutralizing antibody or siRNA against alpha(7) integrin inhibited VSMC adhesion to COMP, which indicated that alpha(7)beta(1) integrin is a potential receptor for COMP. As well, blocking or interference by siRNA of alpha(7) integrin completely abolished the effect of COMP on conserving the contractile phenotype. In accordance, ectopic adenoviral overexpression of COMP greatly retarded VSMC phenotype switching, rescued contractility of carotid artery ring, and inhibited neointima formation in balloon-injured rats.
Our data suggest that COMP is essential for maintaining a VSMC contractile phenotype and the protective effects of COMP are mainly mediated through interaction with alpha(7)beta(1) integrin. Investigations to identify the factors affecting the expression and integrity of COMP may provide a novel therapeutic target for vascular disorders.
Circulation Research 12/2009; 106(3):514-25. · 11.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the clinical effects of thoracoscopy-assisted mini-open surgery for anterior column reconstruction in thoracic spinal tuberculosis.
Fifty-eight patients, 35 men and 23 women, aged 39.2 (range, 19-60) years with thoracic spinal tuberculosis with an average kyphotic angle of 29.2° (range, 18°-42°) underwent thoracoscopy-assisted mini-open surgeries, including thorough debridement and anterior spinal reconstruction. According to the Frankel Grading system, preoperative neurological function was judged as Grade B in 3 cases, Grade C in 7, Grade D in 28, and Grade E in 20. All patients were followed up for an average of 4.6 years. Outcomes were evaluated retrospectively.
Surgery was accomplished successfully in all cases. The average operation time was 230 min (range, 180-320 min), the average intraoperative blood loss 570 ml (range, 350-1200 ml), and the mean drainage duration 3.6 days (3-5 days). Complications occurred in 19 patients (32.8%). Neurological improvement of one to three grades had occurred in 29 patients by final follow-up. The average correction rate of the kyphotic angle was 36.4%, and no obvious correction loss was detected during follow-up. No recurrent tuberculosis was found in the group.
Thoracoscopy-assisted mini-open surgery provides a simple, safe, effective, and practical technology with minimal invasiveness for the treatment of thoracic spinal tuberculosis.
[show abstract][hide abstract] ABSTRACT: This work characterizes the mitochondrial proteomic profile in the failing heart and elucidates the molecular basis of mitochondria in heart failure. Heart failure was induced in rats by myocardial infarction, and mitochondria were isolated from hearts by differential centrifugation. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, a system biology approach was employed to investigate differences in mitochondrial proteins between normal and failing hearts. Mass spectrometry identified 27 proteins differentially expressed that involved in energy metabolism. Among those, the up-regulated proteins included tricarboxylic acid cycle enzymes and pyruvate dehydrogenase complex subunits while the down-regulated proteins were involved in fatty acid oxidation and the OXPHOS complex. These results suggest a substantial metabolic switch from free fatty acid oxidation to glycolysis in heart failure and provide molecular evidence for alterations in the structural and functional parameters of mitochondria that may contribute to cardiac dysfunction during ischemic injury.
Science in China Series C Life Sciences 11/2009; 52(11):1003-10. · 1.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: To analyze the etiology and prevention of complications related to the pedicle screw technique in the treatment of thoracic scoliosis.
There were 183 thoracic deformity patients 110 idiopathic scoliosis, 32 adult scoliosis, 28 congenital kyphoscoliosis, 8 Marfan syndrome with scoliosis, and 6 others. All patients' Cobb angles were evaluated preoperatively, intraoperatively, and postoperatively by roentgenograms. The deformity correction rate was calculated. All radiographic evaluations were carried out in a double-blind fashion. The complication rate was analyzed perioperatively and postoperatively.
The deformity correction rate was 72%, better than others treated with hook-rod system. The perioperation complication rate was 8.4% (pedicle fracture 1.5%, infection 3.8%, pneumothorax and plural effusion 1.6%, transitory neurological damage 0.5%, and over-bleeding shock 1%). The complication rate at follow-up was 3.6% (infection 0.5%, fatigue fracture 1%, loss of deformity correction 1.6%, and transitory neurological damage 0.5%). Compared with those treated with hook-rod system, the perioperation complication rate, loss of deformity correction, permanent damage, and complications related to the internal fixation were all low.
The complication rate of pedicle screw fixation system was low in the treatment of thoracic deformity. When surgeons are thoroughly familiar with the technique and related pathoanatomy, and with the spinal cord function wardship by SEP, complications related to the pedicle screw technique in the treatment of thoracic scoliosis will be well controlled.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 09/2009; 34(8):820-4.
[show abstract][hide abstract] ABSTRACT: PANDER is a cytokine co-secreted with insulin from islet beta-cells. To date, the physiological function of PANDER remains largely unknown. Here we show that PANDER binds to the liver membrane by (125)I-PANDER saturation and competitive binding assays. In HepG2 cells, pre-treatment with PANDER ranging from 4 pM to 4 nM for 8h resulted in a maximal inhibition of insulin-stimulated activation of insulin receptor and insulin receptor substrate 1 by 52% and 63%, respectively. Moreover, PANDER treatment also reduced insulin-stimulated PI3K and pAkt levels by 55% and 48%, respectively. In summary, we have identified the liver as a novel target for PANDER, and PANDER may be involved in the progression of diabetes by regulating hepatic insulin signaling pathways.
[show abstract][hide abstract] ABSTRACT: To investigate the surgical treatment for cervical dumbbell tumors.
Clinical manifestation, surgical type and stage, and surgical method of 36 consecutive patients with cervical dumbbell tumor were retrospectively studied.
The tumors in 35 patients were completely resected once, and the other one patient underwent subtotal resection. Signs and symptoms of all patients were recovered to different degrees, without significant complications and tumor recurrence.
According to the type and stage of dumbbell tumors, we could adopt surgical methods through posterior or posterior combined with anterior approach, together with instruments and fusion, which could completely resect tumors and prevent complications.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 09/2009; 34(9):898-901.
[show abstract][hide abstract] ABSTRACT: To study the role of the carbohydrate response element binding protein (ChREBP) in excessive lipid deposition in the liver of db/db mouse.
The deposition of neutral lipids in the liver was evaluated by Oil Red O staining. Immunohistochemical assay was utilized to determine the localization of ChREBP protein expression in mouse liver. The expressions of ChREBP and its target genes including acetyl-coenzyme A carboxylase 1 (Acc-1), fatty acid synthase (Fas), glycerol-3-phosphate acyltransferase (Gpat) were analyzed by Real-time PCR and Western blot.
Significant lipid droplet deposition was detected in the livers of db/db mice. ChREBP was diffusely expressed in heptocytes with relative higher expression levels around portal and central veins. ChREBP was predominantly located in the cytosol in non-diabetic db/m mice, but was translocated to the nucleus in db/db mice. Nuclear ChREBP protein levels were 8.2-fold higher in db/db mice than in db/m mice(P<0.01). In contrast, another lipogenic transcription factor, sterol regulatory element binding protein-1(SREBP-1), remained unchanged. Consistent with increased nuclear ChREBP levels, expressions of ChREBP target genes involved in lipogenesis including Acc-1, Fas and Gpat were upregulated by 2-fold(P<0.05),1.7-fold (P<0.05) and 4.2-fold(P<0.05), respectively, in db/db mice.
The db/db mouse exhibits significantly higher liver ChREBP activity, which may be associated with the development of hepatic steatosis frequently occurring in type 2 diabetes. Targeting ChREBP might represent a new intervention strategy for fatty liver.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 06/2009; 41(3):307-12.
[show abstract][hide abstract] ABSTRACT: To analyze the accuracy and safety of thoracic pedicle screws placement with interlaminar fenestration technique in severe kyphoscoliosis treatment.
Twenty-three cases of severe kyphoscoliosis between June 1996 and December 2007 underwent pedicle screw placement of thoracic vertebrae by interlaminar fenestration technique. Postoperative CT scan was performed in all cases; there were 9 males and 14 females with the averaging age 17.8 years old. The preoperative Cobb angle of the main thoracic curve was 97.3 degrees in average. The average kyphotic angle in main curve was 67.4 degrees . Patients who underwent screw placement by closing technique and postoperative CT scan in the same stage with severe kyphoscoliosis were selected as control group (B): there were 22 patients with the averaging age 17.2 years old. The preoperative Cobb angle of the main thoracic curve was 96.6 degrees in average. The average kyphotic angle in main curve was 62.1 degrees . The screw-related complications were analyzed and online measure and analyze the degree of screw penetration according to CT by statistics.
There were 209 thoracic pedicle screws being inserted in group A, no spinal cord and large blood vessel injury occurred, 5 patients occurred intraoperative pedicle fracture, dura lesion had 4 patients. Screws misplacement ratio was 8.6%, there were 11 screws located in the thoracic pedicle laterally, 6 screws located in medially, 1 screw presented a moderate anterior cortical perforation. The number of screws misplacement in upper and mild thoracic vertebrae were 15, occupied 83.3%; the number of screws misplacement in lower thoracic vertebrae were 3, occupied 16.7%. There was statistics difference (P < 0.05). Of the total 116 thoracic pedicle screws inserted on the convex side, the ratio of screw misplacement was 5.2%; 93 screws on the concave side, the ratio of screw misplacement was 12.9%, there was statistics difference (P < 0.05). There were 201 thoracic pedicle screws being inserted in group B, no spinal cord and large blood vessel injury occurred, 16 patients occurred intraoperative pedicle fracture, dura lesion had 7 patients. The ratio of screw misplacement was 22.4%, there were 24 screws located in the thoracic pedicle laterally, 11 screws located in medially, 10 screw presented a moderate anterior cortical perforation. The ratio of screw misplacement in Group B was higher than Group A (P < 0.05). All cases received 3.2 years and 3.4 years follow-up. There was no obvious loss of correction in coronal and sagittal plane at the latest follow-up.
It is technically demanding for placement of thoracic screw in the severe kyphoscoliosis treatment. The interlaminar fenestration technique can increase the accuracy and safety of thoracic pedicle screw placement.
Zhonghua wai ke za zhi [Chinese journal of surgery] 06/2009; 47(10):770-3.
[show abstract][hide abstract] ABSTRACT: To analyze the accuracy of free-hand thoracic pedicle screw placement in severe idiopathic scoliosis via CT scan.
Twenty patients with complete CT data were chosen out of 58 patients of severe idiopathic scoliosis from June 1996 to December 2006. The Cobb angle of the main thoracic curve was from 82 degree to 142 degree (96.3 degree +/- 14.3 degree). The kyphotic angle in the main curve was 66.2 degree +/- 12.4 degree. The placement of thoracic pedicle screw was completed free-handedly, and the accuracy of screws placement was evaluated with CT thin-slice scan postoperatively.
Altogether 174 thoracic pedicle screws were inserted, 157 (90.2%) of which were fully contained within the cortical boundaries of the pedicle.The other 17 screws (9.8%) were misplaced in 9 patients: 11 screws (6.8%) were lateral, 9 of which had a breach <or= 2 mm, and the other 2 were between 2 and 4 mm; 6 screws (3.5%) were medial, 3 screws had a breach <or= 2 mm, and the other 3 were between 2 and 4 mm. Of the total 94 thoracic pedicle screws inserted on the convex side,6 were misplaced,with the accuracy rate of 96.3%. Eighty screws were inserted on the concave side, 11 of which screws were misplaced, with the accuracy rate of 86.3%. There was no statistical difference between the convex and concave side as to the accuracy rate of screw implantation (P > 0.05). There was no neural complication in all patients.
It is fairly accurate place thoracic pedicle screw in severe idiopathic scoliosis free-handedly, with some misplacements.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 03/2009; 34(3):226-9.