The protective mechanism of D-pinitol on advanced glycation end products-induced proliferation and migration in vascular smooth muscle cells / 中华老年医学杂志

Objective To investigate the effect and its mechanism of D-pinitol on advanced glycation end products(AGEs)-induced proliferation and migration in mouse aortic vascular smooth muscle cells (VSMC).Methods VSMCs were isolated from mouse aorta and cultured in vitro.Effects of different concentrations of D-pinitol on proliferation and migration of VSMCs were observed by using the AGEs-induced glycosylation injury model of VSMCs.Cell proliferation and migration were detected by CCK-8 assay and cell scratch,respectively.The protein expression levels of transforming growth factor-β1(TGF-β1),p-smad2,p-smad3 and asporin were determined by Western blot.Results Compared with control group,AGEs group showed the increased protein expression levels of asporin,TGF-β1,p-smad2 and p-smad3 (40.06 ± 4.50 vs.17.47 ± 0.57),(55.25 ± 2.07 vs.14.42± 2.07),(0.97 ± 0.02 vs.0.47 ± 0.02),(0.45±0.01 vs.0.26 ± 0.02),all P＜ 0.01.Compared to AGEs group,D-pinitol group could inhibit the cell proliferation and migration and cause dose-dependent decreases of protein expressions of TGF-β1,p-smad2,p-smad3 and asporin(P ＜ 0.05 or P＜0.01).Conclusions D-pinitol can inhibit AGEs-induced cell proliferation and migration in mouse aortic VSMCs.Asporin may participate in the VSMCs extracellular matrix remodeling via TGF-β/smad pathway.

Association of blood glucose control with carotid plaque and pulse wave velocity in elderly patients with type 2 diabetes mellitus / 中华老年医学杂志

Objective To investigate the correlation of glycosylated hemoglobin(HbA1C)levels with carotid atherosclerotic plaque and pulse wave velocity (PWV) in elderly patients with type 2 diabetes mellitus (T2DM).Methods There were 130 cases of elderly patients with T2DM,aged from 60 to 92 years,of whom there were 59 males.All subjects were divided into 3 groups based on the HbA1Clevels:the low level group (HbA1C＜7％,n=49),the middle level group (77％≤HbA1C＜ 8.5 ％,n =58) and the high level group (HbA1C ≥8.5 ％,n=23).Height,body weight,blood pressure,blood glucose,blood lipids,HbA1C and other indexes were collected and compared among groups.In addition,carotid ultrasound and PWV examinations were performed.Results There were significant difference in levels of systolic blood pressure (SBP),fasting blood glucose (FBG),high density lipoprotein cholesterol (HDL-C),carotid intima-media thickness (IMT),plaque score,plaque stability and PWV among groups (all P＜0.05).Correlation analysis showed that IMT levels were correlated with gender (r=0.389),age (r=0.296),FBG (r=0.203),HbA1C(r=0.405) and HDL-C (r =-0.208),all P ＜ 0.05.Carotid artery plaque score correlated with gender (r =0.321),age (r =0.355),HbA1C(r=0.340) and HDL-C (r=-0.249) (all P＜0.01)and there is a correlation between the stability of carotid plaques with body mass index (BMI) (r =-0.286),SBP (r =-0.188),HbA1C(r=-0.368) and HDL-C (r=0.405) (all P＜0.05);PWV was correlated with age (r=0.516),SBP (r=0.521),diastolic blood pressure (r=0.225),FBG (r=0.181),HbA1C(r=0.229),triglyceride (r =-0.253),total cholesterol (r=-0.311) and LDL-C (r=-0.244),all P＜ 0.05.Moreover,there was a correlation between IMT and PWV (r =0.234,P ＜ 0.01).Logistic regression analysis showed that gender,age and HbA1C were independently associated with IMT;gender,age,BMI and HbA1C were independently associated with carotid atherosclerosis plaque score;age,HbA1C and HDL-C were independently associated with the stability of carotid atherosclerotic plaque;age and SBP were independently associated with PWV.Conclusions HbA1C,SBP,HDL-C and BMI are independent risk factors for arteriosclerosis in elderly diabetics.

Efficacy comparison of interlobar node dissection by video-assisted thoracoscopic surgery and thoracotomy in treatment of non-small cell lung cancer / 肿瘤研究与临床

Objective To investigate the positive detective rate of interlobar node in the operation of non-small cell lung cancer (NSCLC), and to compare the effect of interlobar node dissection by video-assisted thoracoscopic surgery (VATS) with thoracotomy in treatment of lung cancer. Methods 108 patients with NSCLC who received the surgery by the same group of thoracic surgeons were collected from Aug 2012 to Mar 2016 in Guangdong Medical University Affiliated Kaiping Central Hospital. The positive transfer and detective rates of interlobar node in patients with different clinical and pathological stage were analyzed. Then the patients were divided into traditional open thoracotomy group and VATS group according to the operation mode, meanwhile, the number of interlobar nodes dissection in the two groups were compared. Results The positive transfer rates of the interlober nodes in patients with different clinical stage were ⅠA 5.7 % (2/35),ⅠB 5.0 % (1/20), ⅡA 14.3 % (3/21), ⅡB 13.3 % (2/15), ⅢA 29.4 % (5/17); For patients with different pathological T stage were T1A 8.3 % (2/24), T1B 9.1 % (2/22), T2A 12.9 % (4/31), T2B 14.3 % (2/14), T3 21.4 %(3/14), T4 33.3 % (1/3), and over-all transfer rate was 13.0 % (14/108). In pathology stage and pathology T stage, the number of interlober nodes had no statistical difference in traditional open thoracotomy group and VATS group (all P>0.05). Conclusions Even in the early clinical stage, the transfer of interlobar node may be positive. The transfer rate of interlobar node is correlated positively with pathology T stage. VATS can achieve the same effect in interlobar node dissection compared with the traditional approach.

Mediastinal lymph node dissection by video -assisted thoracoscopic surgery versus thoracotomy in the treat-ment of lung cancer / 中国基层医药

Objective To compare the effect of mediastinal lymph node dissection by video -assisted thora-coscopic surgery (VATS)with thoracotomy in the treatment of lung cancer.Methods 96 patients with non -small cell lung cancer were collected.Patients undergoing VATS were matched with those undergoing thoracotomy in terms of gender,age,clinical tumor stage,tumor location and surgical procedure.Results After matching,48 patients in VATS group and 48 patients in open group were eligible for analysis.In the VATS and open groups,the mean total numbers of dissected lymph nodes were (27.2 ±7.4)and (28.8 ±10.6)(P =0.507),the numbers of N1 nodes were (9.4 ±4.0)and (8.3 ±4.6)(P =0.323).And the number of N2 nodes was similar between the VATS and open group [(18.5 ±6.9)vs (21.3 ±9.9),P =0.201].No significant differences were observed between the two groups(all P >0.05 ).But the days of the postoperation and the chest tube indwelling in thoracotomy group were (8.1 ±3.9)and (7.3 ±4.4)days,which in the VATS group were (6.8 ±3.5)and (5.6 ±3.5),the VATS group had more advantages than the thoracotomy group(P <0.05).The intraoperative blood loss more than 400mL and peri-operative blood transfusion rate of the thoracotomy group were 27.38% and 25.00%,those of the VATS group were 7.03% and 8.60% respectively,which in thoracotomy group were higher than the VATS group.Conclusion Under-go our retrospective study,after mature VATS to treat lung cancer,with regard to the number of the dissected lymph nodes,VATS lobectomy can achieve complete mediastinal lymph node dissection compared with the traditional approach.There are more advantages by VATS in the complications.

Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer / 부인종양

OBJECTIVE: To assess the toxicity of delivering extended field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for locally advanced cervical carcinoma. METHODS: Forty-five patients who underwent EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to IIIB cervical cancer were retrospectively reviewed. The clinical target volume included all areas of gross and potentially microscopic disease and regional lymph node regions. All patients underwent high-dose-rate brachytherapy. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: The median follow-up was 28 months (range, 5 to 62 months). Forty-two patients had a complete response, and three had a persistent disease. Of those 42 patients, 15 patients (35.7%) had recurrence. The regions of recurrence were in-field in 2 patients and out-field in 13 patients. Acute grade > or =3 gastrointestinal, genitourinary and hematologic toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%) suffered from late grade 3 toxicities. Seven patients experienced ovarian transposition, 5 of those patients (71%) maintained ovarian function. Thirty-eight patients (84.4%) were alive at the last follow-up. CONCLUSION: Concurrent cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are acceptable. EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

Differences of blood plasma renin activity, angiotensin Ⅱ and aldosterone levels in essential or secondary hypertension / 中华内科杂志

Objective To study on the difference of plasma renin activity ( PRA),angiotensin Ⅱ (Ang Ⅱ ),and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO),and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR).Methods The plasma aldosterone,Ang Ⅱ and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA,n =111 ),aldosterone-producing adenoma (APA,n=l18),PHEO (n=98) and EH (n=86).ARR was calculated.Results Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [ 374 (294,465 ) pmol/L and 629 (449,997) pmol/L] and PA group [471 (346,632) pmol/L and 673(499,825) pmol/L] were higher than those in EH group [ 277 (224,332) pmol/L and 427 (341,501 ) pmol/L ] (P ＜ 0.01 ).They were also higher in APA group [576 (416,731 ) pmol/L and 726 (554,906 )pmol/L ] than those in IHA group [399(313,504) pmol/L and 609(485,776)pmol/L ] (P ＜0.01).Ang Ⅱ levels in both positions were lower in PA group [43.2(26.4,74.4) ng/L and 60.1(38.5,103.6) ng/L] than in EH group [56.7 (43.3,78.9) ng/L and 84.3(61.3,108.4) ng/L] or PHEO group [54.3(29.9,101.5) ng/L and 102.8 (49.9,167.0) ng/L] (all P values ＜ 0.01 ),and there was no difference between IHA and APA group (P ＞ 0.05 ).The PRA level in both positions of each group were PHEO group [ 0.3 (0.2,1.0) μg ·L-1 · h-1 and 1.4(0.6,3.4) μg · L-1 · h-1] ＞EH group [0.2(0.1,0.4)μg · L-1 · h-1 and 0.6(0.4,1.0)μg· L-1 ·h-1] (P＜0.01) ＞PAgroup [0.1(0.1,0.1)μg· L-1 · h-1 and 0.2(0.1,0.3)μg·L-1 · h-1] (P＜0.01),and APA group [0.1(0.1,0.1)μg · L-1 · h-1 and0.1(0.1,0.3)μg · L-1 ·h - 1 ] ＜ IHA group [ 0.1 ( 0.1,0.2 ) μg · L - 1 · h - 1 and 0.2 (0.1,0.3 ) μg · L-1 · h - 1 ] ( supine P ＜0.01 ; upright P ＜ 0.05 ).APA was divided into 2 types with renin-Ang Ⅱ -responsive APA ( n =26) and unresponsive APA (n =92).The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang Ⅱ-responsive APA than in unresponsive APA patients.ARR in upright was higher in PA group ( P ＜ 0.01 ) but lower in PHEO group ( P ＜ 0.05 ) compared with EH.ARR was higher in APA than in IHA (P ＜0.01 ).The sensitivity and specificity of ARR as 40 (aldosterone unit:ng/dl;PRA unit:μg · L-1 · h-1; its value should multiply 27.7 when transferred to pmol/L,simili) were 93％ and 76％,respectively.Conclusion The levels of PRA,Ang Ⅱ and aldosterone from patients with EH,PA and PHEO are significant different.ARR as 40 in upright position could be used for PA screening cutoff point.

Epigenetic aspects in pheochromocytoma / 中华内分泌代谢杂志

Although the mutations in RET,VHL,NF1,SDHB,and SDHD genes have been identified to be　responsible for familial pheochromocytomas, the pathogenesis of most pheochromocytomas remains unknown.Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for the malignancy　are critical problems that require further resolution.Indeed,epigenetic changes are now recognized to be at least as　common as genetic changes in cancer.In recent years,research has been initiated to shed light on epigenetic aspects　such as DNA methylation and microRNA in pheochromocytomas,to explore the molecular mechanism,and might　provide a diagnostic tool and a target for future therapies.

Expression of steroidogenic factor-1 and DAX-1 in human adrenocortical tumours / 中华内分泌代谢杂志

ObjectiveTo detect mRNA and protein expression of steroidogenic factor-1 ( SF-1 ) and DAX-1 in human adrenocortical tumors and normal adrenal cortex,and to investigate the effect of SF-1 and DAX-1 on the steroidogenesis and development of adrenocortical tumors.Methods Total RNA and protein was extracted from angiotensin Ⅱ unresponsive aldoterone-producing adenomas ( A Ⅱ -U-APA,n =12 ),angiotensin Ⅱ responsive aldoterone-producing adenomas ( AⅡ -R-APA,n =5 ),cortisol-producing adenomas ( CPA,n =10 ),adrenal nonfunctional adenomas ( NFA,n =10 ),aldosterone-producing carcinoma ( APC,n =2 ) and normal adrenal cortex ( NAC,n =8).To analyze gene expression of SF-1,DAX-1,ACTH receptor(ACTHR),and β-actin by real-time quantitative PCR in different tissues.The protein expression of SF-1,DAX-1,and β-actin in the same tissues by Western blot.To study the relationship of ACTHR,SF-1,and DAX-1 with clinical data in adrenocortical tumors.ResultsThe expression of SF-1,DAX-1 mRNA and protein was different in NAC,AⅡ -U-APA,A Ⅱ -R- APA,APC,CPA,and NFA tissues [ relative expression of SF-1 mRNA:24.58±2.45,23.89±3.17,21.59±3.00,(38.75,44.16),14.17±2.80,and 36.38±3.50; DAX-1 mRNA:0.57±0.06,0.37±0.05,0.43±0.05,( 1.52,1.21 ),0.39 ±0.04,and 0.83 ±0.08 ; SF-1 protein:0.76 ±0.11,0.76 ±0.10,0.73 ±0.07,(1.24,1.40),0.55±0.04,and0.98±0.10; DAX-1 protein:0.65±0.14,0.39±0.13,0.43±0.14,(1.18,1.02),0.56±0.04,and 1.03±0.13 ; all P＜0.05 or P＜0.01 ].There was negative correlation by higher SF-1/DAX-1 ratio and tumor size in AⅡ -U-APA tissues.The mRNA and protein expression of SF-1 was lower in CPA and there was the positive correlation with tumor size.Conclusion SF-1 and DAX-1 might play a key role in the development of the adrenocortical tumorigenesis and steroidogenic tissues.

Methylation of p16 gene promoter in human pheochromocytomas and paragangliomas / 中华内分泌代谢杂志

Objective To elucidate gene mutation and promoter methylation changes of p16 gene in pheochromocytomas (PHEO) and paragangliomas (PGL) and to assess its relation with tumor clinical characters. Methods A total of 34 tumors (20 PHEO, 14 PG L, 15 benign, 19 malignant) were collected.Direct sequencing of p16 gene after PCR was performed to analyze genetic alterations. Hypermethylation of p16 gene promoter CpG island was analyzed by methylation specific PCR(MSP). In addition, mRNA expression was detected by RT-PCR. Results Homozygous deletion and gene mutation were not observed in 34 PHEO and PGL. Aberrant methylation of p16 gene promoter CpG island was found in 35.3% (12 of 34 tumors, 3 PHEO, 9 PGL). The p16 promoter hypermethylation in PGL was significantly higher than PHEO (P=0. 005). The higher p16 promoter hypermethylation was associated with malignant behavior, tumor number, and younger age at presentation, but no statistical significance, due to the limited number of cases. The p16 mRNA expression in malignant cases was lower than in benign tumors(0.83±0.65 vs 1.12±0.81 ,P=0.278). Conclusion p16 gene homozygous deletion and mutation were not frequent in PHEO and PGL. The promoter hypermethylation is mainly attributed to inactivation of the p16 gene.