1.Inhibitory effects of autophagy inhibitor 3-MA on high glucose-induced proliferation of human retinal pigment epithelium cells
Wenwen, HOU ; Huanqi, SHI ; Zhen, ZHANG ; Xiaomei, ZHANG
Chinese Journal of Experimental Ophthalmology 2017;35(1):5-9
Background Diabetic retinopathy (DR) is one of the common complications of diabetes.Retinal pigment epithelium (RPE) cells,as important constituent cells of the retina,play important roles in the development and progression of DR.Objective This study was to investigate the suppressive effects of autophagy inhibitor 3-MA on the proliferation of human retinal pigment epithelium cells (hRPECs) following high glucose culture.Methods HRPECs were divided into control group,high-glucose group and 3-MA+high glucose group.The cells were cultured by the DMEM/F12 with 5 mmol/L glucose in the control group,and by the DMEM/F12 with 5 mmol/L glucose in the high glucose group and by the DMEM/F12 with 10 mmol/L 3-MA (for 1 hour firstly) and 30 mmol/L glucose in the 3-MA+high glucose group.The cells were inoculated into 24-well plate with the content of 1 ×105/well,and then the cells were consecutively cultured for 24 hours with DMEM/F12 containing 0.5% fetal bovine serum after achieved attached 80% confluence.The morphology and uhrastructure of the cells were examined by optics microscope and transmission electronic microscope.The proliferative rate of the cells was assayed by CCK-8 kit.The expression of autophagy-related gene microtubule associated protein light chain 3B (LC3B) in the cells was detected by Western blot and LC3B-Ⅱ/LC3B-Ⅰ value was quantitatively evaluated among the groups.Results The cells grew well with uniform size and regulatory arrangement in the control group.The cells in the high glucose group enlarged and the number of cells evidently increased.In the 3-MA+high glucose group,the cells decreased with a disorder arrangement.Under the transmission electron microscope,the cells were normal with the round-or oval-like nucleus and normal organelles in the control group,and autolysosome could be seen in the cells in the high glucose group.In the 3-MA+high glucose group,some autophagic bodies were found.The proliferative rate of the cells was (100.0±2.0) %,(116.9-±5.2)% and (103.7 ±4.7)% in the control group,high glucose group and 3-MA+high glucose group respectively,showing a significant difference among the groups (F =13.526,P =0.006).The proliferative rate was considerably raised in the high glucose group compared with the control group and 3-MA+high glucose group (both at P<0.05),but there was no significant difference in the proliferative rate of the cells between the control group and 3-MA+high glucose group (P>0.05).Compared with the control group,the expressing intensity of LC3B-Ⅰ protein was weakened and that of LC3-Ⅱ protein was enhanced,and the expression intensity of LC3B-Ⅰ and LC3B-Ⅱ proteins in the 3-MA+high glucose group was similar to that in the control group.The LC3-Ⅱ/LC3-Ⅰ ratio was 0.131 ±0.065,2.504±0.097 and 0.274±0.007 in the control group,high glucose group and 3-MA+high glucose group,respectively,with significant differences among the groups (F =1 694.676,P =0.000),and the LC3-Ⅱ/LC3-Ⅰ ratio was increased in the high glucose group in comparison with the control group and the 3-MA+high glucose group (all at P<0.05).No significant difference was found in the LC3B-Ⅱ/LC3B-Ⅰ ratio between the control group and 3-MA + high glucose group (P > 0.05).Conclusions High glucose culture of hRPECs can activate autophagy process and promote cell proliferation.3-MA,an autophagy inhibitor,suppresses the high glucoseinduced growth of HRPECs by inhibiting autophagy process.
2.Therapeutic effects of extended-field and involved-field irradiation in three-dimensional radiotherapy in patients with esophageal cancer: a meta-analysis
Wenwen BAI ; Zhiguo ZHOU ; Ruohui ZHANG ; Yuzhi SONG ; Chanjun ZHEN ; Xueying QIAO
Chinese Journal of Radiation Oncology 2016;25(9):923-928
Objective To investigate the therapeutic effects,adverse effects,and patterns of failure of elective irradiation of lymphatic drainage area (extended-field) and involved-field irradiation in three-dimensional radiotherapy (3DRT) in patients with esophageal cancer via a Meta-analysis.Methods The databases Wanfang Data,CNKI,VIP,CBM,PubMed,Embase,and Cochrane Library were searched to collect the controlled clinical trials on extended-field irradiation and involved-field irradiation in 3DRT in patients with esophageal cancer.Stata 11.0 was used for data analysis.The odds ratio (OR) with 95% confidence interval was used to describe the differences between two groups.Results According to the inclusion and exclusion criteria,a total of 12 controlled clinical trials involving 1 095 patients with esophageal cancer were included in this meta-analysis.The results of the meta-analysis showed that compared with the involved-field irradiation group,the extended-field irradiation group had a significantly reduced rate of out-field failure in patients with esophageal cancer who received 3DRT (OR=3.727,P=0.007),but showed significantly higher rates of grade ≥ 3 acute radiation pneumonitis and radiation esophagitis (acute radiation pneumonitis:OR =0.348,P =0.001;radiation esophagitis:OR =0.385,P =0.000).The two groups had similar 1-,2-,and 3-year local control rate and overall survival rate (local control rate:OR=0.966/0.946/0.732,P=0.837/0.781/0.098;overall survival rate:OR=0.952/1.149/0.768,P=0.756/0.422/0.120),as well as a similar distant metastasis rate (OR=0.986,P=0.937).Conclusions Compared with involved-field irradiation,extended-field irradiation can reduce the rate of out-field failure in patients with esophageal cancer who receive 3DRT.However,it does not have significant advantages in local control rate and overall survival rate and has an increased incidence rate of adverse effects.
3.A clinical study of salvage radiotherapy for supraclavicular lymph node metastasis in patients with esophageal cancer
Zhiguo ZHOU ; Chanjun ZHEN ; Ping ZHANG ; Junli LIANG ; Xueying QIAO ; Wenwen BAI ; Xin LIU ; Shuoshuo WANG ; Xianshu GAO
Chinese Journal of Radiation Oncology 2016;25(8):813-817
Objective To evaluate the efficacy of salvage radiotherapy for supraclavicular lymph node metastasis ( SLNM) after initial treatment in patients with esophageal cancer. Methods A total of 117 patients with SLNM after radical resection for esophageal cancer were enrolled as subjects from 2006 to 2012. All patients received three?dimensional radiotherapy with 1. 8?2. 0 Gy per cycle, 5 cycles a week. The survival rates were calculated using the Kaplan?Meier method and analyzed using the log?rank test. The Cox model was used for multivariate analysis. Results The follow?up rate was 100%. In all the patients, the 1?and 3?year overall survival (OS) rates were 38. 5% and 14. 1%, respectively. The 1?and 3?year OS rates were significantly higher in patients treated with salvage radiotherapy or radiochemotherapy ( n=100) than in patients without any salvage treatment (n=17)(42% vs. 18%,P=0. 008;17% vs. 0%, P=0. 008). The patients treated with radiochemotherapy ( n=32) had significantly higher 1?and 3?year OS rates than those treated with radiotherapy alone (n=68)(59% vs. 34%, 36% vs. 11%, P=0. 002) or without any salvage treatment (n=17)(59% vs. 18%, 36% vs. 0%, P=0. 002). Patients without visceral metastasis (n=80) had significantly higher 1?and 3?year OS rates than those with visceral metastasis ( n=37) ( 44% vs. 27%, P=0. 002;22% vs. 0%,P=0. 002) . Patients with supraclavicular doses of ≥60 Gy in salvage radiotherapy ( n=75) had significantly higher 1?and 3?year OS rates than those with supraclavicular doses of<60 Gy in salvage radiotherapy ( n=25) ( 75% vs. 25%,P=0. 000;24% vs. 8%,P=0. 000) . The multivariate analysis using the Cox model showed that supraclavicular doses of ≥60 Gy, mediastinal metastasis, visceral metastasis, and salvage treatment method were independent factors for survival ( P=0. 001,0. 015,0. 009, 0. 025) . Conclusions Salvage radiotherapy can improve the survival of patients with SLNM in esophageal cancer. Salvage radiotherapy or radiochemotherapy is highly recommended for patients with SLNM alone. A radiation dose of ≥60 Gy in salvage radiotherapy improves survival in patients.
4.Clinical efficacy and prognostic factors of simultaneous integrated boost intensity-modulated radiation therapy for esophageal squamous cell carcinoma
Wenwen BAI ; Yuzhi SONG ; Yongzhi QIAO ; Liyuan FU ; Ruohui ZHANG ; Chanjun ZHEN ; Xueying QIAO
Chinese Journal of Radiation Oncology 2018;27(6):570-575
Objective To evaluate the clinical efficacy and analyze relevant prognostic factors of simultaneous integrated boost intensity-modulated radiation therapy ( SIB-IMRT ) for esophageal squamous cell carcinoma. Methods A total of 101 patients diagnosed with esophageal squamous cell carcinoma received SIB-IMRT from 2009 to 2015. The prescribed dose of PTV was 5040 cGy/28 times ( 180 cGy/time) and the dose for planning gross tumor volume (PGTV) was 6020 cGy/28 times (215 cGy/time) or 6160 cGy/28 times ( 220 cGy/time) simultaneously. The total treatment time was 5. 5 weeks ( once a day, 5 times a week).The adverse events, mode of treatment failure,l-,3-and 5-year local control (LC) and overall survival ( OS) rates were observed. Results The quantity of patients who completed the 1-,3-and 5-year follow-up was 101, 84 and 45, respectively. The 1-,3-and 5-year LC rates were 81. 6%,70. 4% and 68. 4%, respectively. The 1-, 3-and 5-year OS rates were 72. 3%, 49. 4% and 45. 2%, respectively. The median survival time was 36 months. Univariate and multivariate analyses showed that clinical staging ( stageⅠ/Ⅱ/Ⅲ) and tumor response ( complete remission/ partial remission/no remission ) were the prognostic factors of OS (P=0. 016,0. 000,0. 005,0. 000).There were no significant differences in the LC and OS between the two groups of 215 cGy and 220 cGy (P=0. 283,0. 951).The incidence rates of grade 1,2,3 acute pneumonitis were 10. 9%(11/101),2. 0%(2/101) and 2. 0%(2/101), respectively. The incidence rates of grade 1, 2, 3 acute esophagitis were 63. 4%( 64/101 ) , 10. 9%( 11/101 ) and 4. 0%( 4/101 ) , respectively. No acute esophageal perforation or hemorrhage occurred. Five patients experienced late pneumonitis ( two died) . One case developed late lemostenosis, two cases developed esophageal perforation and hemorrhage, and two patients experienced esophageal hemorrhage. The patients treated with a fractionated dose of 220 cGy had a higher incidence rate of acute pneumonitis and upper gastrointestinal adverse reactions than those receiving 215 cGy ( P= 0. 062, 0. 024 ) . The local failure and recurrence accounted for 62. 5% of all treatment-related failures. Conclusions SIB-IMRT yields high long-term clinical efficacy and tolerable adverse events in the treatment of esophageal squamous cell carcinoma. Compared with the dose of 215 cGy, the fractionated dose of 220 cGy fails to improve LC and OS rates, whereas enhances the risk of adverse events. The clinical staging and short-term clinical efficacy are the prognostic factors of survival rate.
5.Clinical anatomical study of the adult lateral skull base.
Dezhi YU ; Jianxin QIU ; Jie WANG ; Wenwen ZHEN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(10):449-453
OBJECTIVE:
Through the observation and the measurements of the significant anatomical landmark the lateral skull base, to provide anatomical data of clinical location and navigation for surgery at the lateral skull base.
METHOD:
Significant anatomical landmarks of twenty adult cadaveric heads (40 sides) fixed in 10% formaldehyde and 20 operation cases (20 sides) had been observed and measured. Lateral skull bases of cadaveric heads were numbered from 1st to 40th, while the operation cases were numbered from 1st to 20th.
RESULT:
The anatomical data was achieved by measuring related anatomical landmark as follows: the distances between the significant landmark of the lateral skull base and the pars neuraxis, vein of the jugular foramen; the areas of trautmann triangle; post labyrinths triangle and the superficial triangle of processus mastoideus; the maximal distance of initiative displacement of facial nerve in the lateral skull base operations.
CONCLUSION
The data measured at lateral skull base could effectively help operators not only to enlarge the field of vision in operations with security and to avoid the damagement of the important blood vessel and nerves, but also to retain the function of the facial nerve to the utmost.
Adult
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Female
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Humans
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Male
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Mastoid
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anatomy & histology
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Skull Base
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anatomy & histology
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Temporal Bone
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anatomy & histology
6.Effect of adrenocorticotropic hormone stimulation during adrenal vein sampling
Zhipeng DU ; Qingfeng CHENG ; Ying SONG ; Wenwen HE ; Kanran WANG ; Fuqin PENG ; Zhiping LIU ; Jinbo HU ; Yifan HE ; Qianna ZHEN ; Qifu LI ; Shumin YANG
Chinese Journal of Endocrinology and Metabolism 2021;37(2):129-134
Objective:Aimed to investigate the value of adrenocorticotropic hormone (ACTH) stimulation in adrenal venous blood sampling (AVS).Methods:Patients who diagnosed as primary aldosteronism (PA) and completed successful bilateral cannulation judged by selection index (SI) for routine and(or) ACTH stimulation AVS were enrolled. The lateralization index(LI) was calculated to compare the effect of ACTH stimulation on AVS cannulation success rate and lateralization judgment.Results:A total of 73 patients with PA were enrolled in the study, of whom 28 were confirmed as aldosterone producing adenoma (APA) after unilateral adrenalectomy. Cortisol and aldosterone in peripheral and adrenal veins were significantly increased after ACTH stimulation. The left SI was increased from 6.5(3.0-13.6) to 26.8 (16.9-40.3) ( P<0.01) and the right SI from 20.8(4.8-34.8) to 57.6(35.7-80.9) ( P<0.01) after ACTH stimulation. There was no significant difference on LI before and after ACTH stimulation [7.7(2.3-19.6) vs 5.6(1.9-14.6), P=0.14]. The success rates of left and right adrenal cannulation were increased by 15% and 10% respectively after ACTH stimulation. For 57 patients who were determined in successful cannulation by both routine and ACTH stimulation AVS, 27 patients were determined to have lateralization by both AVS methods, 21 patients were determined to have bilateralization, and the consistency of lateralization by both AVS methods was 84%(48/57). Among the 28 patients who were confirmed to be APA after unilateral adrenalectomy, the correct rate of lateralization by both AVS methods was 89% (25/28). Conclusion:ACTH stimulation is able to improve the success rate of bilateral adrenal vein cannulation, and is helpful to judge AVS results. For patients with successful cannulation, there is no significant difference in lateralization judgment for routine and ACTH stimulation AVS.
7.Re-evaluation of the optimal cutoff of saline infusion test in the diagnosis of primary aldosteronism
Xiuyong YANG ; Ying SONG ; Wenwen HE ; Mei MEI ; Qingfeng CHENG ; Shumin YANG ; Jinbo HU ; Zhipeng DU ; Jian LONG ; Qianna ZHEN ; Qifu LI
Chinese Journal of Endocrinology and Metabolism 2018;34(6):460-465
Objective To assess the diagnostic value of saline infusion test ( SIT) and its optimal cutoff in the diagnosis of primary aldosteronism ( PA ), and to analyze whether the dietary salt intake affects the SIT accuracy. Methods This is a prospective study. All 236 patients with a high risk for PA underwent the screening test, SIT and the fludrocortisone suppression test (FST) in separate days. The diagnosis of PA was established according to the FST criteria. According to the 24 h urinary sodium level, the patients were divided into low salt, normal salt, and high salt groups respectively, and the effect of salt intake on SIT was analyzed. Receiver operating characteristic (ROC) analysis was performed to compare the diagnostic accuracies. Results Finally, in 236 patients with high risk for PA, 134 patients with PA and 102 patients with essential hypertension ( EH) were diagnosed. Using post-test plasma aldosterone concentration (PAC) for diagnosis, the area under the ROC curve (AUCROC) of the SIT was 0.974 (0.957, 0.991), which was significantly higher than that of the post-test plasma aldosterone to renin ratio (ARR) [0.900 ( 0. 862, 0. 938)] and that of the PAC suppression percentage [ 0. 752 ( 0. 690, 0. 813)] ( both P<0.01). Considering both sensitivity and specificity, an optimal cutoff of PAC post-SIT was set at 8 ng/dl, resulting in a sensitivity of 88. 1% and a specificity of 95. 1%. The PAC post-SIT, whether in PA or EH patients, had no statistically significant differences among low salt, normal salt, and high salt groups (P>0.05). Conclusion SIT is reliable for the diagnosis of PA. PAC post-SIT more than 8.0 ng/dl is recommended to confirm PA.
8.Comparison of simultaneous integrated boost and late course boost intensity-modulated radiation therapy in the treatment of esophageal carcinoma
Wenwen BAI ; Liyuan FU ; Jing LI ; Ruohui ZHANG ; Chanjun ZHEN ; Rui ZHANG ; Shuoshuo WANG ; Ming LIU ; Xueying QIAO
Chinese Journal of Radiological Medicine and Protection 2018;38(4):258-264
Objective To analyze and compare the outcomes of esophageal carcinoma treated with simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) and late course boost intensity-modulated radiation therapy (LCB-IMRT).Methods We retrospectively analyzed 128 patients with esophageal squamous cell carcinoma who were treated with SIB-IMRT or LCB-IMRT at the fifth department of radiation oncology in our hospital,from January 2009 to August 2015.Propensity score matching analysis was used to balance the variables differences in the two groups.Survival,failure patterns and toxicities were observed and compared between the two groups.Results one hundred and eleven patients were finally included after propensity scores matching.The 1-,3-and 5-year local control rates and survival rates were 83.6% vs.81.7%,70.8% vs.46.3% and 66.0% vs.38.2% in the whole group,respectively.The 1-,3-and 5-year local control rates of SIB-IMRT and LCB-IMRT group were 81.6% vs.88.0%,72.3% vs.67.6% and68.5% vs.60.8%,respectively (P>0.05).The 1-,3-and 5-year survival rates of SIB-IMRT and LCB-IMRT group were 81.3% vs.82.4%,51.7% vs.36.7% and 45.8% vs.26.7%,respectively (P > 0.05).There was no statistical difference between the two group in ≥ grade 3 toxicities (P > 0.05).There were 40 (36.0%) patients result in treatment failure in all.The treatment failure rates in SIB-IMRT and LCB-IMRT group were 33.8% (26/77) vs.41.2% (14/34),respectively (P > 0.05).The local failure accounted for 65.0% (26/40) of all treatment-related failures.Conclusions The toxicities of esophageal squamous cell carcinoma treated with SIB-IMRT and LCB-IMRT have no significant differences and were well tolerated.There were no significant differences in local control rates and survival rates between the two groups.However,SIB-IMRT had better trend than LCB-IMRT.Given SIB-IMRT's convenient manipulation,it could be a better choice in the treatment of advanced esophageal carcinoma.
9.Efficacy and safety of salvage radiotherapy for recurrent esophageal cancer after chemoradiotherapy: a Meta-analysis
Wenhui YU ; Ping ZHANG ; Chanjun ZHEN ; Wenwen BAI ; Sihan LIU ; Mingyue CHEN ; Zhiguo ZHOU
Chinese Journal of Radiation Oncology 2021;30(9):892-897
Objective:To compare the efficacy and adverse events of salvage radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy in this Meta-analysis.Methods:Databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang data were searched from the inception to April 2020 to collect the clinical trials which comparatively analyzed the efficacy and safety between radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy. Meta-analysis was performed using RevMan 5.1 software. RR and 95% CI were used to describe the differences among different groups. Results:According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 842 patients were included. Meta-analysis showed that the overall survival in the salvage radiotherapy group was significantly lower than that in the salvage esophagectomy group ( RR=0.40, 95% CI: 0.27-0.61, P<0.001), whereas significantly higher than that in the chemotherapy group ( RR=2.91, 95% CI: 1.43-5.95, P=0.003). There was no significant difference in the treatment-related mortality between the salvage radiotherapy and salvage esophagectomy groups ( RR=0.53, 95% CI: 0.14-1.98, P=0.350), but the incidence was significantly higher in the salvage esophagectomy group (1.7%-11.4% vs. 1.9%-2.8%). Conclusion:Salvage radiotherapy is an effective treatment for recurrent esophageal cancer after chemoradiotherapy, which can be regarded as one choice for clinical patients.
10.Pathological types and clinical features of unilateral primary aldosteronism
Jiayu LI ; Yi YANG ; Linqiang MA ; Junlong LI ; Wenwen HE ; Ying SONG ; Jinbo HU ; Shumin YANG ; Qifu LI ; Qianna ZHEN
Chinese Journal of Endocrinology and Metabolism 2024;40(2):139-144
Objective:To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods:A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results:According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion:The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.