Background:Non-small cell lung cancer (NSCLC) involves complex alterations in the epidermal growth factor receptor (EGFR) signaling pathway. This study aims to integrate multimodal omics analyses to evaluate and enhance EGFR-targeted therapies. Methods:We reviewed and synthesized omics data-including genomics, transcriptomics, proteomics, epigenomics, and metabolomics data-related to the EGFR pathway in NSCLC, examined the clinical outcomes of current therapies and proposed new treatment strategies. Results:Integrated omics analyses revealed the multifaceted role of EGFR in NSCLC. Transcriptomic analysis revealed gene expression alterations due to EGFR mutations, with upregulation of oncogenes and downregulation of tumor suppressors. Proteomics revealed complex interactions within the EGFR network, revealing cross-talk with other receptors. Epigenomics highlighted the impact of DNA methylation and histone modifications on EGFR and its downstream genes, whereas metabolomics demonstrated shifts in metabolic patterns essential for tumor growth. Conclusion:This study highlights the critical role of multimodal omics in understanding the molecular landscape of NSCLC, offering insights into more effective, personalized therapies. Future advancements in omic technologies and analysis are expected to significantly enhance NSCLC diagnosis and treatment.

目的探讨卵巢-附件影像报告和数据系统(O-RADS)模型及其联合糖类抗原125(CA125)对卵巢肿瘤的诊断价值.资料与方法回顾性分析2014年1月—2016年12月623例在华中科技大学同济医学院附属协和医院行附件包块手术患者的术前超声图像及临床资料.根据O-RADS 4中不同图像特征对应恶性风险指数差异大,将其分为A、B组,当评分4A且CA125<35 U/ml为良性,以病理诊断为"金标准",比较单独O-RADS、CA125及O-RADS联合CA125诊断卵巢肿瘤的敏感度、特异度及受试者工作特征曲线下面积(AUC).结果623例附件包块中,良性461例,恶性162例.O-RADS、CA125及联合诊断的敏感度分别为0.963、0.784,0.932,特异度分别为0.896、0.679和0.967,AUC分别为0.929、0.731和0.950.O-RADS单独评价与联合CA125诊断的敏感度差异无统计学意义(χ2=1.552,P=0.213),但均优于CA125(χ2=23.484、14.594,P均<0.001);联合诊断的特异度均高于单独O-RADS和CA125(χ2=18.553、131.827,P均<0.001);三者AUC差异有统计学意义(联合诊断与O-RADS:Z=2.241,P=0.025;联合诊断与CA125:Z=11.212,P<0.001;O-RADS与CA125:Z=9.155,P<0.001).结论O-RADS联合CA125有助于提高卵巢肿瘤的诊断效能.

微流控芯片技术是一种利用微通道处理或操纵微小流体的技术,具有体积轻、反应速度快、能耗低、样品及试剂用量少的特点和优点[1].微流控芯片技术已成为备受关注的前沿分析技术之一,在医药、生化分析以及化学合成等领域具有广阔的应用前景[2].微流控芯片技术在中药研究领域具有巨大的发展空间,在中药萃取与富集、分离检测、机制作用研究以及质量评价等方面,能显著提高研究效率,并为中药研究提供新的思路和方法,是一种极具潜力和前景的研究技术.目前对于微流控技术在中药领域中的应用有关的综述很少,且多为单一中药研究领域的总括分析,如药敏实验等.本文归纳总结了目前微流控技术在中药研究领域各方面的应用现状,对各部分实验应用可行性及实用性的文献成果进行了全面分析和提炼,现综述如下.

Supplemental Digital Content is available in the text Abstract Background: Previous studies have indicated the association of microRNA-146a/b (miR-146a/miR-146b) with pro-inflammatory cytokines production, lipopolysaccharide-mediated injuries and organ dysfunction, however, the correlation of miR-146a/miR-146b with disease risk, disease severity, biochemical indices, inflammatory cytokines and mortality of sepsis has not been explored, which was investigated in the present study. Methods: In total, 180 sepsis patients and 180 healthy controls were enrolled. The peripheral blood samples were collected from sepsis patients within 24 hour after admission and from healthy controls at enrolment. Furthermore, MiR-146a/miR-146b expressions in plasma were detected by reverse transcription quantitative polymerase chain reaction. Results: MiR-146a and miR-146b expressions were higher in sepsis patients compared to healthy controls. MiR-146a (AUC: 0.774, 95%CI: 0.727–0.820) and miR-146b (AUC: 0.897, 95%CI: 0.865–0.929) were both of good value in predicting increased sepsis risk, among which miR-146b presented a superior predictive value. In sepsis patients, MiR-146a expression was positively associated with miR-146b expression. Besides, MiR-146a and miR-146b expressions were positively correlated with acute pathologic and chronic health evaluation II score, sequential organ failure assessment score, serum creatinine, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17, while negatively correlated with albumin. Based on the survival status in 28-day follow-up, MiR-146a and miR-146b expression were both increased in survivors compared to deaths. miR-146b presented relatively good predictive for increased 28-day mortality risk (AUC: 0.703, 95%CI: 0.617–0.788), but MiR-146a was of poor value in predicting increased 28-day mortality risk (AUC: 0.599, 95%CI: 0.511–0.688). Conclusion: MiR-146b presents superior potential as a prognostic biomarker in sepsis patients compared to MiR-146a, which implies the clinical application of miR-146b in disease management of sepsis.

目的 探讨经阴道二维超声检查在子宫腺肌病临床诊断中的应用价值.方法 回顾性分析2014年1月至2016年7月华中科技大学同济医学院附属协和医院338例临床怀疑子宫腺肌病且行子宫切除术患者,152例经病理证实为子宫腺肌病,通过患者的临床资料和术前经阴道超声检查图像特征,分析经阴道二维超声检查诊断子宫腺肌病的灵敏度、特异度、阳性预测值、阴性预测值.结果 152例腺肌病患者术前均经阴道二维超声检查,超声诊断灵敏度86.8％(132/152)、特异度90.9％(169/186)、阳性预测值88.6％(132/149)、阴性预测值89.4％(169/189).超声误诊病例中,4例诊断为局灶性腺肌病,13例诊断为弥漫性腺肌病,且其中15例合并肌瘤,1例合并子宫内膜异位囊肿.152例腺肌病患者中,最常见临床症状是痛经,合并痛经者超声诊断103例(67.8％).从超声的各项声像特征来看,大多特征都有助于正确诊断子宫腺肌病(P<0.05),而肌壁间的小无回声区是否存在对超声诊断没有明显影响(P>0.05).结论 子宫腺肌病经阴道二维超声诊断有较高的灵敏度及特异度,尤其是局灶性腺肌病患者、有痛经症状者或合并卵巢子宫内膜异位囊肿患者,而合并子宫肌瘤患者的诊断较困难.

目的:考察山萘酚对人卵巢癌SKOV-3细胞生长、凋亡的影响及作用机制.方法:采用CCK-8法检测山萘酚对SK-OV-3细胞增殖的影响;流式细胞术和AnnexinV-FITC/PI凋亡试剂盒检测SKOV-3细胞的凋亡情况;RT-PCR检测NICDmRNA的表达;Western Blot方法检测Notch1蛋白的表达.结果:山萘酚对卵巢癌SKOV-3细胞有显著的增殖抑制作用,且呈一定的剂量依赖性;凋亡检测结果表明,山萘酚能够促进卵巢癌SKOV-3细胞凋亡的发生;RT-PCR结果显示山萘酚干预组(80 μmol· L-)NICD mRNA的表达水平明显降低(P＜0.05),Western Blot结果显示山萘酚干预组(80 μmol· L-1)Notch1蛋白表达水平显著降低(P＜0.05).结论:山萘酚能明显抑制卵巢癌SKOV-3细胞的体外增殖,诱导细胞凋亡其机制可能是通过干预Notch1的表达.

[This corrects the article DOI: 10.18632/oncotarget.20885.].

Ethnopharmacological relevance: Aidi injection is one of the most commonly used Chinese patent medicines for advanced non-small cell lung cancer (NSCLC). It is made from an extraction of Mylabris Phalerata, Radix Astragalus, Radix Ginseng, and Acanthopanax Senticosus. Aim of the study: The objective of this study is to evaluate the efficacy and safety of Aidi injection in combination with platinum-based chemotherapy for stage IIIB/IV NSCLC. Materials and methods: A systematic review and meta-analysis were performed following the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Trials were combined using Review Manager 5.3 and Comprehensive Meta-Analysis(CMA) 2.0. Dichotomous data were expressed as risk ratio (RR) and continuous outcomes as weighted mean difference (WMD), with their 95% confidence intervals (CI) respectively. All randomized controlled trials (RCTs) comparing Aidi injection plus platinum-based chemotherapy versus platinum-based chemotherapy, with efficacy and safety outcomes were selected. Disease Control Rate (DCR) was the primary outcome, Objective Response Rate (ORR), survival rate, quality of life (QOL), and toxic effects were the secondary outcomes. Results: 42 RCTs recruiting 4081 patients with stage IIIB/IV NSCLC were included, with overall low-moderate methodological quality. Compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy can increase relative benefit of DCR (RR = 1.13, 95% CI 1.09-1.16, P < 0.00001), ORR (RR = 1.26, 95% CI 1.18-1.36, P < 0.00001), improve 1-, 2-, 3-year survival rates (RR = 1.14, 95% CI 1.02-1.28, P = 0.03; RR = 1.31, 95% CI 1.05-1.64, P = 0.02; and RR = 1.88, 95% CI 1.32-2.67, P = 0.0005, respectively), QOL (RR = 1.80, 95% CI 1.61-2.01, P < 0.00001), and reduce severe (grade 3 and 4) toxicities by 36% (RR = 0.64, 95% CI 0.58-0.70, P < 0.00001). Conclusions: From the available evidence, compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy improves the clinical efficacy and alleviates the toxicity of chemotherapy in patients with stage IIIB/IV NSCLC. However, considering the intrinsic limitations of the included RCTs, well designed, rigorously performed, high-quality trials are still required to further assess and confirm the results.

Objective To evaluate the sonographic appearance and clinical practical value of using three -dimensional (3D) transvaginal ultrasound Inversion Rendering Technique in dingnosos of hydrosalpinx .Methods A cohort of 51 hospitalized pa-tients with hydrosalpinx confirmed by laparoscopic surgery from January 2011 to December 2011 were analyzed .The patients were scanned with two-dimensional (2D) and 3D transvaginal ultrasound (TVUS) with a mechanical 5 to 9 MHz 3D endovaginal probe.A routine pelvic examination was performed by 2D endovaginal ultrasound .A hydrosalpinx was suspected when a sausage-like or echo-free mass was seen around the ovary .3D volumes of the mass were acquired and were displayed in multiplanar and in-version imaging rendered modes .Results Identification of hydrosalpinx was from physical vaginal exam by gynecologists in 29/51 and by transvaginal color Doppler 2D ultrasound in 39/51.Eight cases were misdiagnosed as ovarian cysts , 2 cases were misdi-agnosed as parovarian cysts and 2 cases were missed entirely on transvaginal ultrasound .The diagnostic accuracy of 2D transvaginal ultrasound was 76%.Transvaginal 3D ultrasound suggested that 48 cases were hydrosalpinx , 2 were misdiagnosed as ovarian cysts and 1 case was misdiagnosed as parovarian cyst .3D inversion rendering displays offered a more complete stereoscopic display , showed tortuous patterns and trends , and internal structure of the hydrosalpinx and the relationship to the surrounding organs .The diagnostic accuracy for hydrosalpinx was 94%for 3D ultrasound.On ultrasound, concurrent fibroids (5 cases), adenomyosis (7 cases), and ovarian cyst (11 cases) were demonstrated.Pelvic fluid was seen in all 51 cases.Hydrosalpinx at laporascopy was bilateral in 13 and unilateral in 35.Conclusion 3D multiplanar and inversion rendering displays offer a more complete assess-ment of the hydrosalpinx compated to 2D imaging, including stereoscopic display , tortuous shape, and internal structure as well as the relationship of surrounding organs .The diagnostic accuracy of transvaginal 3D is better than the 2D ultrasonography for identi-fication of hydroslpinx .

BACKGROUND:Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. METHODS:We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. RESULTS:Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68-0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50-0.92) and flavonols (RR = 0.68, 95% CI = 0.58-0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71-1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger's test (p = 0.26). CONCLUSIONS:This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted.

Ethnopharmacological relevance: Shexiang Baoxin Pill (SXBXP) is a well-known Chinese patent medicine, widely used for Non-ST-elevation acute coronary syndromes (NSTE-ACS). It is composed of seven materia medicas or extracts (Moschus, Radix Ginseng, Calculus Bovis, Cortex Cinnamomi, Styrax, Venenum Bufonis and Borneolum Syntheticum).Aim of the study: This study is aimed to systematically review the relevant randomised controlled trials (RCTs) to determine the efficacy and safety of SXBXP for long-term management of NSTE-ACS.Materials and methods: A systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. All randomised controlled trials (RCTs) comparing long-term Shexiang Baoxin Pill with conventional treatment, with outcome measures relating to efficacy and safety were selected. Primary clinical outcome was the risk of cardiovascular events, secondary outcomes were hospitalizations, angina symptoms, electrocardiogram (ECG) measurements, and adverse events.Results: Eleven RCTs recruiting 1389 patients were included, the overall risk of bias of the included trials is high and the quality poor. Compared with conventional treatment alone, long-term Shexiang Baoxin Pill plus conventional treatment might be more effective in lowering the risk of cardiovascular events (RR=0.36, 95% CI 0.26-0.49, <0.00001), hospitalizations (RR=0.38, 95% CI 0.21-0.67, P=0.0009), and improving angina symptoms (RR=1.19, 95% CI 1.13-1.26, P < 0.00001), ECG measurements (RR=1.25, 95% CI 1.13-1.39, P < 0.00001). Overall rate of adverse events was not elevated (P=0.43).Conclusions: From the available evidence, SXBXP added to conventional treatment may have beneficial effects on the long-term outcomes of NSTE-ACS, without serious adverse events. However, given the high risk of bias and low quality of the included trials, currently, there is no adequate evidence to draw any conclusions about its routine use. Large, methodologically-sound trials are needed to further assess its effects.

Objective To discuss the value of placenta implantation related sonographic characteristics in prenatal diagnosis.Methods We retrospectively reviewed the medical records and ultrasound reports of 70 patients referred for suspected placenta accrete by prenatal ultrasound and delivered in our hospital.Placenta accreta was defined by clinical criteria at the time of delivery and by pathologic findings.Results The sonographic characteristics including:loss of the normal retroplacental clear space,more lacuna,fewer lacuna,Doppler abnormality,irregularity of uterine-bladder interface,their sensitivities (specificities) in the diagnosis of placenta implantation were 71.2％ (18.2％),35.6％ (100％),33.9％(36.4％),42.4％(81.8％),18.6％(90.9％) respectively,and their sensitivities(specificities) in predicting hysterectomy were 63.2％(23.5％),63.2％(82.4％),21.1％(54.9％),68.4％ (72.5％),36.8％(90.2％) respectively.Conclusions In all sonographic characteristics of placenta implantation,loss of the normal retroplacental clear space had high sensitivity and low specificity,easy to misdiagnosis,and its correct recognition is closely related to the experience of operator.More lacuna could recognize placental implantation in high specificity,and predict serious adverse pregnancy outcomes in high sensitivity,so had important value in the prenatal diagnosis of placental implantation.

Background The ductus arteriosus (DA) is one of the most important vessels of the fetal circulation. A variety of fetal congenital heart disease (CHD) may greatly influence the structure and flow patterns of the DA. This study was to investigate the structural characteristics of the DA and its value in the diagnosis of fetal CHD using fetal echocardiography combined with cardiovascular casting technology. Methods Twenty-six cases of a normal fetus and 20 cases of a fetus with CHD (10 cases of right-sided obstructive CHD and 10 cases of left-sided obstructive CHD) were enrolled in this study. The three-vessel view and the long axis view of the DA arch were chosen to observe the fetal DA. The diameters of the ascending aorta (AO) and the pulmonary artery trunk (PA) were measured on the left ventricular outflow tract view and the three-vessel view separately, and AO/DA and PA/DA values were calculated separately. The flow direction of the DA was recorded, and the blood flow peak velocity was measured using color and spectral Doppler technology. Cardiovascular cast specimens were made for fetuses secured from induced labor to facilitate further observations of the true form and connections of the DA. At the same time, heart and great vessel deformities were also recorded through careful observation of the cardiovascular cast. Results The following DA anomalies were observed: ① abnormal diameter (6 cases of stenosis and 9 cases of dilatation); ② abnormal blood flow direction (reverse flow in 5 cases); ③ abnormal blood flow speed (12 cases); ④ abnormal connection site (right-sided DA in 2 cases and a DA connection between the left pulmonary artery and the left subclavian artery in one case); and ⑤ absence of the DA in 2 cases. Compared with the control group, the DA diameter in the right-sided obstructive group was obviously narrowed; by contrast, the diameter of the DA in the left-sided obstructive group was obviously dilated. These differences were statistically significant (p < 0.05). Compared with the control group, the AO/DA values in the right- and left-sided obstructive groups were significantly increased and decreased, respectively. Finally, relative to the control group, the PA/DA values of the right- and left-sided obstructive groups were significantly reduced. Conclusions DA enlargement was often associated with left-sided obstructive CHD, whereas a small DA and reverse blood flow often indicated the presence of right-sided obstructive CHD. DA connections can manifest with multiple anatomical variations. During fetal echocardiography, evaluation of the DA is very important; such analyses may help search for associated cardiac defects whenever a diagnosis of CHD is made.

This study assessed the clinical application of transvaginal three-dimensional ultrasound (3D TVUS) in the diagnosis of congenital uterine malformation. A retrospective study was performed on 62 patients with congenital uterine malformation confirmed hysteroscopically and/or laparoscopically. The patients were subjected to transvaginal two-dimensional ultrasound (2D TVUS) and 3D TVUS. The accuracy rate was compared between the two methods. The accuracy rate of 3D TVUS was (98.38%, 61/62), higher than that of 2D TVUS (80.65%, 50/62). 3D TVUS coronal plane imaging could demonstrate the internal shape of the endometrial cavity and the external contour of the uterine fundus. It allowed accurate measurement on the coronary plane, and could three-dimensionally show the image of cervical tube, thereby providing information for the diagnosis of some complex uterine malformation. 3D TVUS imaging can obtain comprehensive information of the uterus malformation, and it is superior to 2D TVUS for the diagnosis of congenital uterine malformations, especially complex uterine anomaly.

This study examined the effect of cholic acid (CA) on cultured cardiac myocytes (CMs) from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intrahepatic cholestasis of pregnancy (ICP). Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 μmol/L Ca2+-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.

目的 探讨经阴道三维超声新技术Omniview对先天性子宫畸形的诊断价值.方法 对30例经腹腔镜和(或)宫腔镜检查确诊为先天性子宫畸形患者的二维超声和三维超声Omniview检查资料进行回顾性分析,对二维和三维超声检查结果进行比较.结果 经阴道三维超声成像诊断准确率为100％ (30/30),二维超声诊断准确率为80％ (24/30).经阴道三维超声新技术Omniview可以沿着子宫的弧度对其形态结构进行描记,可以采取直线、弧线和曲线方式获取新的平面,对复杂解剖结构的切面分析具有很大的灵活性.可以从多个平面成像直观显示子宫腔内部结构及子宫底部的外观形态,立体感强,可以很好地在切面上进行准确测量,同时可对宫颈管进行三维成像,为一些复杂的子宫畸形提供了诊断依据.结论 经阴道三维超声新技术Omniview成像能够获得子宫畸形全面的信息,弥补了传统三维超声只能从3个正交平面来诊断子宫畸形的不足.对复杂的子宫畸形诊断明显优于二维超声,使诊断和分类更为准确和详细.

Two-dimensional ultrasound is used in diagnosis of typical uterine malformations.Besides displaying uterine shape and status of intrauterine,three-dimension ultrasound can also quantify the level of malformation with character in harmlessness,low cost,high repeatability and accuracy comparing two-dimension and hysterosalpingography uterosalpingography.It has being applied in diagnosis of complex uterine malformations more and more.

Objective:To explore the effect and value of the short-hairpin RNA (shRNA) targeting Livin (shLivin) in enhancing chemo-sensitivity of cervical cancer cell SiHa.Methods:The divided experimental groups was as follows: control group, SiHa-shLivin group (SiHa cells were transfected with shLivin)and SiHa-shVector group(SiHa cells were transfected with shVector).Cisplatin, Taxol and doxorubicin were used as chemotherapy drugs.MTT was performed to assess cell proliferation and half inhibitory concentrations of chemotherapy drugs were calculated.Cell apoptosis was analyzed by flow cytometry.Results:After silencing of Livin gene by shLivin, significant decreases in IC50 of cisplatin, Taxol and doxorubicin were observed in SiHa cells (P<0.001).There was no difference in IC50 of all the chemotherapy drugs between control group and SiHa-shVector group(P>0.05).Apoptosis rates after treatment with IC50 of drugs were significantly increased (P<0.001).There was no difference in Apoptosis rates between control group and SiHa-shVector group(P>0.05).Conclusions: Livin is hopeful to be a molecular target for increasing the chemotherapeutic response of cervical cancer cells.Gene silencing of Livin mediated by RNA interference which can increasing the chemotherapeutic response may be a new means of gene therapy for cervical cancer.