N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

Protective effects of CY-09 and astaxanthin on NaIO_(3)-induced photoreceptor inflammation via the NLRP3/autophagy pathway

AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST groups.Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western blotting.Retinal pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST successively.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay.Apoptosis was analyzed by flow cytometry.Changes in autophagosome morphology were observed by transmission electron microscopy.Quantitative polymerase chain reaction(qPCR)was used to detect NLRP3 and caspase-1.NLRP3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western blotting.IL-1βand IL-18 were measured by ELISA.RESULTS:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited autophagy.Compared with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo.CY-09 and AST may protect retina from inflammatory injury.

Role of tumor necrosis factor alpha-induced protein 6(TNFAIP6)in tumors:a pan-cancer analysis

Background:There is growing evidence that the gene named tumor necrosis factorα–induced protein 6(TNFAIP6)has an important role in various tumors.However,a systematic pan-cancer analysis of TNFAIP6 is lacking.Here we aimed to analyze the expression of TNFAIP6 across multiple cancers and verify its expression during the progression of colon cancer.Methods:We performed a comprehensive bioinformatics analysis to examine the expression of TNFAIP6 across 27 tumor types.GEPIA2 was used to evaluate the effect of TNFAIP6 on clinical cancer prognosis.cBioportal was used to assess TNFAIP6 mutations.The correlation between TNFAIP6 and cancer immune infiltrates was explored using TIMER2.0.The CancerSEA database was used to perform functional analysis of TNFAIP6.Metascape was used to identify TNFAIP6-related gene enrichment pathways.Immunohistochemistry was performed to detect TNFAIP6 protein expression in the colon cancer.In addition,the Comparative Toxicogenomics Database was searched for known and possible antitumor drugs that may be associated with TNFAIP6.Results:We found that,in most of the cancers included in this analysis,TNFAIP6 was highly expressed,and there is a distinct relationship between TNFAIP6 expression and cancer prognosis.TNFAIP6 expression is associated with cancer-associated fibroblasts,neutrophils,and endothelial cells.TNFAIP6 and similar genes may also be involved in the PID_VEGF_VEGFR_pathway.Immunohistochemistry revealed an increasing trend of TNFAIP6 protein expression in normal,adenoma,and colon cancer tissues.Several known and possible antitumor drugs that may be associated with TNFAIP6 were identified in the Comparative Toxicogenomics Database.These results suggest that a number of drugsmay target TNFAIP6 during cancer treatment,including cisplatin,irinotecan,resveratrol,U 0126,NSC689534,genistein,NSC668394,oxaliplatin,plerixafor,topotecan,vincristine,flutamide,doxorubicin,MRK 003,folic acid,demecolcine,tunicamycin,zoledronic acid,and schizandrin B.Conclusions:TNFAIP6 may function as an oncogene in certain cancers.Furthermore,this study provides evidence that TNFAIP6 is an important factor in colon cancer progression.

复杂地形风电场微观选址优化算法研究

我国拥有丰富、分布广泛的风能资源,其中复杂地形的风能开发正成为新的焦点。在风能开发中微观选址极为重要。由于传统风电场微观选址优化在复杂地形中效率低下,难以充分利用风资源,本文提出两种更高效的优化方法。其一,采用灰狼优化算法对风电场选址进行优化,优化主要以单个风力机容量系数为个体,总发电量的提高为目标,多优化个体共同构成电场整体排布方案。这种针对复杂地形下风电场微观选址优化的方式,能显著提升优化效率,有效实现选址优化目的。其二,采用作图法,分析风电场内特定高度的容量系数和风向分布,提出多种排布方案,基于发电量最大化原则选定方案实现优化,这种方法直接锁定最优结果,减少计算资源消耗。

原发性急性闭角型青光眼患者房水中CXCR2和bFGF表达与小梁切除术后预后的关系

目的:探讨原发性急性闭角型青光眼(APACG)患者的房水中趋化因子受体2(CXCR2)、碱性成纤维细胞生长因子(bFGF)水平与小梁切除术后预后的关系。方法:收集2020-06/2022-01期间本院收治的80例80眼行小梁切除术的APACG患者纳入病例组,依据术后疗效分为成功组60例60眼和失败组20例20眼;收集同期本院行白内障超声乳化术且眼压正常的白内障患者86例86眼纳入对照组。采用酶联免疫吸附法检测房水中CXCR2、bFGF水平;采用ROC曲线分析房水中CXCR2、bFGF水平预测APACG患者小梁切除术失败的价值;APACG患者小梁切除术失败的影响因素采用多因素Logistic回归分析。结果:病例组房水中CXCR2、bFGF水平显著高于对照组(P<0.05)。失败组房水中CXCR2、bFGF水平及术后浅前房发生患者比例显著高于成功组(P<0.05)。房水中CXCR2、bFGF水平单独及联合预测APACG患者小梁切除术后失败的AUC分别为0.885、0.883、0.953。CXCR2、bFGF是APACG患者小梁切除术后失败的危险因素(P<0.05)。结论:APACG患者房水中CXCR2、bFGF水平显著升高,且二者均是小梁切除术后失败的危险因素。

Lossless embedding: A visually meaningful image encryption algorithm based on hyperchaos and compressive sensing

A novel visually meaningful image encryption algorithm is proposed based on a hyperchaotic system and compressive sensing(CS), which aims to improve the visual security of steganographic image and decrypted quality. First, a dynamic spiral block scrambling is designed to encrypt the sparse matrix generated by performing discrete wavelet transform(DWT)on the plain image. Then, the encrypted image is compressed and quantified to obtain the noise-like cipher image. Then the cipher image is embedded into the alpha channel of the carrier image in portable network graphics(PNG) format to generate the visually meaningful steganographic image. In our scheme, the hyperchaotic Lorenz system controlled by the hash value of plain image is utilized to construct the scrambling matrix, the measurement matrix and the embedding matrix to achieve higher security. In addition, compared with other existing encryption algorithms, the proposed PNG-based embedding method can blindly extract the cipher image, thus effectively reducing the transmission cost and storage space. Finally, the experimental results indicate that the proposed encryption algorithm has very high visual security.

A 3-month comparison study of subjective and objective visual quality of small incision lenticule extraction and transepithelial photorefractive keratectomy in patients with low and moderate myopia

AIM:To compare the subjective and objective visual quality between small incision lenticule extraction(SMILE)and transepithelial photorefractive keratectomy(t PRK)in patients with low and moderate myopia.METHODS:Patients undertaking SMILE or t PRK for the correction of low and moderate myopia were consecutively recruited in this prospective cohort study with a 3-month follow-up period.Objective evaluation[visual acuity test,manifest refraction,wavefront aberrations,the total cut-off value of the total modulation transfer function(MTFcut-off),and Strehl ratio(SR)]and subjective evaluation of visual quality(quality-of-life questionnaire)were conducted before surgery and at days 1,7,30,and 90 after surgery.RESULTS:A total of 47 patients(94 eyes)with SMILE and 22 patients(22 eyes)with t PRK were enrolled.The uncorrected visual acuity(UCVA)was better in SMILE patients on day 7 after surgery(1.13±0.13 vs 0.99±0.17,t=4.85,P<0.001)but was comparable at days 30 and 90.At day 90,the SMILE group had a lower spherical equivalent(SE)than the t PRK group(0.04±0.31 vs 0.19±0.43,t=2.08,P=0.042).Total higher order aberrations(HOAs)were induced in both surgical types,which were more evident in the t PRK group with 3-mm pupil diameter(0.16±0.07 vs0.11±0.05,t=4.27,P<0.001)and 5-mm pupil diameter(0.39±0.17 vs 0.36±0.11,t=2.33,P=0.022).The MTFcut-offand SR showed a trend of improvement in both SMILE and t PRK patients but were statistically better in the SMILE group with both pupil diameters.There was a significant improvement of contrast sensitivity(CS)over baseline levels at the spatial frequency of 18 cycles/degree(c/d)in the SMILE group(F=2.72,P=0.033)and at 3 c/d(F=3.03,P=0.031),12 c/d(F=3.72,P=0.013),and 18 c/d(F=4.62,P=0.004)in the t PRK group.The subjective quality of life questionnaire showed a steady improvement in the SMILE group(F=8.31,P<0.001)but not the t PRK group.CONCLUSION:SMILE and t PRK are both safe and effective ways to correct low and moderate myopia.A generally better and quicker recovery of visual quality favors the application of SMILE in qualified patients.

外周血HMGB1、sTLR4表达与亚临床绒毛膜羊膜炎相关胎膜早破及早发型败血症的关系

目的探讨母体外周血高迁移率族蛋白B1(HMGB1)和可溶性Toll样受体4(sTLR4)表达与亚临床绒毛膜羊膜炎(HCA)相关胎膜早破及新生儿早发型败血症(EOS)的关系。方法收集2017年5月—2018年4月在成都市第二人民医院产科足月分娩的胎膜早破(>12 h)产妇314例。根据分娩后胎盘病理检查结果,分为HCA组135例和非HCA组179例;另外根据新生儿随访情况,将受试对象分为EOS组21例和非EOS组293例。采集受试对象第一产程静脉血,比较各组产妇外周血HMGB1、sTLR4水平,并绘制受试者工作特征(ROC)曲线。结果HCA组WBC、HMGB1及sTLR4水平高于非HCA组(P<0.05)。HMGB1、sTLR4、WBC联合诊断HCA的曲线下面积(AUC)为0.864(95%CI:0.826,0.895),敏感性和特异性分别为0.686(95%CI:0.623,0.694)和0.901(95%CI:0.871,0.925)。经多因素Logistic回归模型分析,产妇临产外周血HMGB1[OR=5.899(95%CI:2.413,15.386)]是发生HCA的独立危险因素,而sTLR4[OR=0.771(95%CI:0.624,0.914)]是发生HCA的独立保护因素。EOS组孕妇HMGB1、sTLR4水平高于非EOS组,合并HCA例数多于非EOS组(P<0.05)。HMGB1、sTLR4联合预测EOS的AUC为0.888(95%CI:0.840,0.926),敏感性和特异性分别为0.861(95%CI:0.837,0.882)和0.768(95%CI:0.717,0.804)。结论母体血清HMGB1及其受体sTLR4水平与HCA及EOS的发生密切相关,对于HCA的早期诊断及新生儿EOS的早期预警都有一定临床意义。

超声乳化联合EX-PRESS引流钉植入治疗难治性开角型青光眼合并白内障

目的:观察超声乳化联合EX-PRESS引流钉植入治疗难治性开角型青光眼合并白内障的疗效。方法:选取难治性开角型青光眼合并白内障患者共66例67眼。试验组采用超声乳化吸除联合EX-PRESS引流钉植入术,对照组采用超声乳化吸除联合小梁切除术。术前进行BCVA、IOP检查;观察并发症、手术时间,术后观察视力、眼压、滤过泡改变;随访时间为术后1d,1wk,1、6mo,1a。结果:试验组手术时间为23.26±2.00min,对照组手术时间为31.73±2.17min,两组间有差异(t=16.68,P<0.01)。试验组术后发生浅前房和滤过泡瘢痕化者各1眼;对照组术后发生低眼压3眼,前房出血和脉络膜脱离各1眼,滤过泡瘢痕化者5眼。滤过泡Kronfeld分型无差异(Z=-0.775,P=0.438)。两组干预因素及时间对患者术后眼压均有影响(F组间=8.67,P组间<0.01;F时间=127.58,P时间<0.01;F组间×时间=7.5,P组间×时间<0.01)。干预因素对患者术后视力无影响,两组术后视力同术前相比均有差异(F组间=0.35,P组间=0.55;F时间=34.92,P时间<0.01;F组间×时间=0.38,P组间×时间=0.86)。结论:超声乳化联合EX-PRESS引流钉植入治疗难治性开角型青光眼合并白内障安全有效、手术时间短,可作为一种常规青白联合手术方式。

区域折射型多焦点与非球面单焦点IOL植入术后视力及视觉质量分析

目的:对比区域折射型多焦点人工晶状体(IOL)和非球面单焦点IOL植入术后患者的全程视力及视觉质量。方法:前瞻性选取2017-01/2019-08于我院眼科接受白内障超声乳化吸除联合IOL植入术的年龄相关性白内障患者82例96眼,根据术中植入的IOL类型分为观察组(46例53眼,植入Oculentis MF30区域折射型多焦点IOL)和对照组(36例43眼,植入ADAPT AO非球面单焦点IOL)。比较两组患者术后3mo的全程视力和视觉质量。结果:术后3mo,与对照组相比,观察组近、中视力显著改善,对比敏感度显著提高,调制传递函数截止频率、斯特列尔比、客观调节幅度以及模拟视力显著增加,VF-12-CN评分显著降低(38.16±4.05分vs 45.72±4.69分),脱镜率评分(11.38±1.04分vs 9.23±0.87分)和手术满意度评分(3.57±0.36分vs 3.32±0.31分)显著升高(P<0.05)。年龄>65岁、文盲、好眼裸眼远视力≥0.1(LogMAR)、植入非球面单焦点IOL是导致白内障患者生活质量下降的影响因素。结论:与非球面单焦点IOL相比,区域折射型多焦点IOL术后短期可提供良好的全程视力,对比敏感度、视觉质量、生活质量、脱镜率以及满意度均显著提高。

Development and validation of a risk prediction model for repeated indwelling urinary catheterization in patients with cervical cancer after surgery

Objective:To study the factors influencing secondary indwelling catheterisation after cervical cancer surgery and to develop a predictive risk model.Methods:A total of 260 patients in a tertiary hospital in Chongqing were selected from January 2020 to December 2021 via convenience sampling.Relevant information of patients was recorded,including age;body mass index;history of hypertension and diabetes,bladder dysfunction,postoperative urinary retention,and postoperative urinary tract infection;Histology;staging;surgical approach;Operation time;Time of first remove of catheter;indwelling catheter days;Hospitalization days.Least absolute shrinkage and selection operator was used to reduce dimensionality and select patient characteristics,and multivariate analysis was performed based on the selected variables.Based on the outcome of analysis,a line chart model was developed for predicting the risk of secondary catheterization in patients with indwelling catheterization after radical cervical cancer surgery.The coefficient of conformity index(C-index)and calibration curves were used to evaluate the accuracy and fit.The model was internally validated via bootstrapping(1000 random samples),and the clinical utility of the model was assessed via decision curve analysis(DCA).Results:Four characteristic variables were selected,including preoperative bladder function,postoperative urinary tract infection,surgical approach,and Time of first remove of catheter.They are independent risk factors affecting urinary tract.The risk prediction model exhibited good discrimination performance with a C-index of 0.722(95%CI,0.661-0.783)and was well calibrated.The C-index was 0.708 in internal validation analysis.DCA showed that the risk model was clinically useful for predicting secondary catheterization,and clinical benefits were observed at the decision threshold of≥11%.Conclusion:A novel model was developed to predict the risk of secondary catheterization.The model was based on preoperative bladder dysfunction,postoperative urinary tract infection,surgical approach,and number of days since the removal of the primary catheter.

Traditional Chinese medicine for the treatment of endometriosis: a comprehensive-review of treatment mechanisms

The study aims to reveal the mechanism of traditional Chinese medicine in the treatment of endometriosis and provide support for further research on traditional Chinese medicine and its active ingredients.The literature survey was conducted using PubMed,Web of Science,CNKI and other databases with“endometriosis”,“Chinese medicine”,“Chinese herbal medicine”and“natural plants”as the main keywords.Traditional Chinese medicine can exert their therapeutic effects on endometriosis by inhibiting inflammation through multiple pathways and multiple targets,regulating cell proliferation and apoptosis,angiogenesis,cell adhesion and oxidative stress.Traditional Chinese medicine can intervene in endometriosis in multiple ways and with multiple targets.In-depth study of Chinese medicine for endometriosis can provide new ideas for exploring the pathogenesis of endometriosis and developing new drugs.

获得性免疫缺陷综合征患者白内障超声乳化摘除手术后的临床观察

目的:观察获得性免疫缺陷综合征患者白内障超声乳化摘除术后视力变化及早期术后并发症情况。方法:收集2016-05/2019-04在我院行白内障超声乳化摘除联合人工晶状体植入术的获得性免疫缺陷综合征合并白内障患者33例47眼,记录术后1d,1wk,1、3mo的裸眼视力、最佳矫正视力、眼压、前房细胞计数及术后并发症发生情况。结果:获得性免疫缺陷综合征合并白内障患者术后裸眼视力及最佳矫正视力均较术前明显改善(P<0.05)。术后1d房水细胞计数较术前增加,但术后1wk起房水细胞计数较术前无明显变化。术后3mo内所有术眼无严重术后眼部并发症发生。结论:获得性免疫缺陷综合征合并白内障患者行白内障超声乳化摘除联合人工晶状体植入手术安全有效。

Assessment of radiofrequency ablation margin by MRI-MRI image fusion in hepatocellular carcinoma

AIM:To investigate the feasibility and clinical value of magnetic resonance imaging(MRI)-MRI image fusion in assessing the ablative margin(AM) for hepatocellular carcinoma(HCC).METHODS:A newly developed ultrasound workstation for MRI-MRI image fusion was used to evaluate the AM of 62 tumors in 52 HCC patients after radiofrequency ablation(RFA).The lesions were divided into two groups:group A,in which the tumor was completely ablated and 5 mm AM was achieved(n = 32);and group B,in which the tumor was completely ablated but 5 mm AM was not achieved(n = 29).To detect local tumor progression(LTP),all patients were followed every two months by contrast-enhanced ultrasound,contrast-enhanced MRI or computed tomography(CT) in the first year after RFA.Then,the follow-up interval was prolonged to every three months after the first year.RESULTS:Of the 62 tumors,MRI-MRI image fusion was successful in 61(98.4%);the remaining case had significant deformation of the liver and massive ascites after RFA.The time required for creating image fusion and AM evaluation was 15.5 ± 5.5 min(range:8-22 min) and 9.6 ± 3.2 min(range:6-14 min),respectively.The follow-up period ranged from 1-23 mo(14.2 ± 5.4 mo).In group A,no LTP was detected in 32 lesions,whereas in group B,LTP was detected in 4 of 29 tumors,which occurred at 2,7,9,and 15 mo after RFA.The frequency of LTP in group B(13.8%;4/29) was significantly higher than that in group A(0/32,P = 0.046).All of the LTPs occurred in the area in which the 5 mm AM was not achieved.CONCLUSION:The MRI-MRI image fusion using an ultrasound workstation is feasible and useful for evaluating the AM after RFA for HCC.

Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found. CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.

绝经后女性2型糖尿病患者的DKK1蛋白表达水平及其临床意义

目的探讨Wnt信号通路中DKK1蛋白在绝经后2型糖尿病(T2DM)女性患者中的表达及其与胰岛素抵抗和胰岛β细胞功能的关系。方法选取2015年10月-2017年10月于石河子大学第一附属医院和新疆维吾尔自治区石河子市第十五社区卫生服务中心住院的绝经后女性T2DM患者。收集患者临床资料并检测常规生化指标、空腹胰岛素(FINS)、空腹C肽(FCP)及DKK1蛋白表达水平,计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR)及胰岛素β细胞功能指数(HOMA-β)。采用SPSS 20.0统计软件进行数据分析。结果与NGT组相比,T2DM组FPG、果糖胺、HbA1c、TC及HOMA-IR水平提高,FCP、ISI及HOMA-β水平降低(P<0.05)。T2DM组DKK1蛋白表达水平升高(P<0.05)。DKK1蛋白表达水平与FCP呈负相关,与HOMA-IR呈正相关(P<0.05)。FPG、DKK1蛋白是影响FCP及HOMAIR水平的因素(P<0.05)。结论 Wnt信号通路中DKK1蛋白水平的高表达可能参与绝经后女性T2DM患者胰岛素抵抗、胰岛β细胞功能减退的发生发展过程,进而导致绝经后女性T2DM的糖代谢及脂代谢紊乱。

Lijiang 2.4-meter Telescope and its instruments

The Lijiang 2.4-meter Telescope(LJT), the largest common-purpose optical telescope in China,has been available to the worldwide astronomical community since 2008. It is located at the Gaomeigu site,Lijiang Observatory(LJO), in the southwest of China. The site has very good observational conditions.During its 10-year operation, several instruments have been equipped on the LJT. Astronomers can perform both photometric and spectral observations. The main scientific goals of LJT include recording photometric and spectral evolution of supernovae, reverberation mapping of active galactic nuclei, investigating the physical properties of binary stars and near-earth objects(comets and asteroids), and identification of exoplanets and all kinds of transients. Until now, the masses of 41 high accretion rate black holes have been measured, and more than 168 supernovae have been identified by the LJT. More than 190 papers related to the LJT have been published. In this paper, the general observation conditions of the Gaomeigu site is introduced at first. Then, the structure of the LJT is described in detail, including the optical, mechanical, motion and control system. The specification of all the instruments and some detailed parameters of the YFOSC is also presented. Finally, some important scientific results and future expectations are summarized.

HER2-Specific T Lymphocytes Kill both Trastuzumab-Resistant and Trastuzumab-Sensitive Breast Cell Lines In Vitro

Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells （DCs） modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells. Methods： The peripheral blood mononuclear cells （PBMCs） from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus （rhAAV/HER2） to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase （LDH） releasing assay. Results： Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [（69.86±13.41）%] and MDA-MB-453 [（78.36±10.68）%] at 40：1 （effector：target ratio, E：T）, but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 （less than 10%）. Conclusion： The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.

Circulating Tumor Cells in Metastatic Breast Cancer:Monitoring Response to Chemotherapy and Predicting Progression-Free Survival

Objective:The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC) in peripheral blood from metastatic breast cancer patients.The primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival(PFS).Methods:The breast cancer cell line MCF-7 was serially diluted into the peripheral blood from 45 healthy donors to set up the sensitivity of RT-PCR assay.The expression of CK19 mRNA was amplified from both 49 patients and 45 healthy donors respectively.The CK19 protein quantity from plasma was measured by competitive inhibition ELISA assay.Results:The sensitivity of RT-PCR could reach 1/106?107 white blood cells with specificity of 95.6%.The objective response rate(ORR) of patients with CK19 mRNA-negative undertaken one cycle chemotherapy was significantly higher than those with positive(P0.0001).PFS among CK19 mRNA-negative patients was also increased,although there was no significance(P=0.098).The results of ELISA assay showed that CK19 protein was decreased significantly after one cycle chemotherapy,which gave rise to a little higher ORR(P=0.015) and increased PFS(P=0.016).Conclusion:Patients with unamplified CK19 mRNA after one cycle chemotherapy could achieve better radiographic evaluation and increased PFS,which was showed to be of consistency with the CK19 protein assay among the patients treated.

Sub-threshold micro-pulse diode laser treatment in diabetic macular edema： a Meta-analysis of randomized controlled trials

AIM：To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation（SDM） and traditional modified Early Treatment Diabetic Retinopathy Study（mETDRS）treatment protocol in diabetic macuiar edema（DME）.METHODS：A comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for DME.The participants were type Ⅰ or type Ⅱ diabetes mellitus with clinically significant macuiar edema treated by SDM from previously reported randomized controlled trials（RCTs）.The primary outcome measures were the changes in the best corrected visual acuity（BCVA） and the central macuiar thickness（CMT） as measured by optical coherence tomography（OCT）.The secondary outcomes were the contrast sensitivity and the damages of the retina.RESULTS：Seven studies were identified and analyzed for comparing SDM（215 eyes） with mETDRS（210 eyes）for DME.There were no statistical differences in the BCVA after treatment between the SDM and mETDRS based on the follow-up：3mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.77）,6mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.75）,12mo（MD,-0.05;95% Cl,-0.17 to 0.07;P=0.40）.Likewise,there were no statistical differences in the CMT after treatment between the SDM and mETDRS in 3mo（MD,-9.92;95% Cl,-28.69 to 8.85;P=0.30）,6mo（MD,-11.37;95% Cl,-29.65 to 6.91;P=0.22）,12mo（MD,8.44;95% Cl,-29.89 to 46.77;P=0.67）.Three RCTs suggested that SDM laser results in good preservation of contrast sensitivity as mETDRS,in two different followup evaluations：3mo（MD,0.05;95% Cl,0 to 0.09;P=0.04） and 6mo（MD,0.02;95% Cl,-0.10 to 0.14;P=0.78）.Two RCTs showed that the SDM laser treatment did less retinal damage than that mETDRS did（OR,0.05;95% Cl,0.02 to 0.13;P〈0.01）.CONCLUSION：SDM laser photocoagulation shows an equally good effect on visual acuity,contrast sensitivity,and reduction of DME as compared to conventional mETDRS protocol with less retinal damage.