[摘 要] 目的：探究甘氨胆酸（GCA）对肺腺癌A549细胞移植瘤小鼠放射治疗敏感性的影响及其机制。方法：建立A549人肺腺癌细胞裸鼠移植瘤模型，随机分为移植瘤对照组（对照组）、GCA组、放疗组（RT组）和GCA + 放疗组（GCA + RT组）。RT组和GCA + RT组接受单次10  Gy照射，GCA组及GCA + RT组连续7 d每日灌胃GCA 280  mg/kg。间隔2 d测量1次移植瘤体积，末次给药后处死小鼠并取移植瘤组织，检测移植瘤组织中超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GSH-Px）活性，qPCR法和WB法分别检测放疗关键基因（MCM6、ITGA6、CASP3等）mRNA和蛋白表达水平，H-E染色观察移植瘤组织的形态变化。通过GEO（GSE276500、GSE294906、GSE218171）及TCGA数据库数据验证放疗关键基因。结果：GCA单用对瘤体生长有一定抑制作用，但联合放疗的GCA + RT组相比单纯放疗组表现出放疗抵抗的效应（P < 0.05）。GCA处理显著提高移植瘤组织SOD活性（P < 0.01）、降低GSH-Px活性（P < 0.01），提示GCA可改变移植瘤抗氧化酶平衡，减弱放疗诱导的氧化应激。GCA干预上调移植瘤组织中MCM6与ITGA6 mRNA表达、下调CASP3 mRNA表达（均P < 0.05）。GCA + RT组移植瘤组织中的MCM6蛋白表达显著高于对照组（P < 0.05）。H-E染色显示，GCA组部分瘤组织坏死，而GCA + RT组坏死组织面积较RT组有所缩小。GEO和TCGA数据库验证支持MCM6、ITGA6高表达与放疗抵抗和预后不良相关。结论：GCA通过增强SOD活性、降低GSH-Px活性并上调ITGA6、MCM6的表达改变氧化应激与关键信号网络，从而削弱A549移植瘤对放疗的敏感性。

Supraclinoid internal carotid artery(ICA)fenestration is a rare vascular developmental variant,and this anomaly may be associated with aneurysm formation.Whether the fenestration is originated from the embryonic development of the ICA or the posterior communicating artery(PCoA)remains controversial.This article retrospectively analyzed the imaging data,diagnosis and treatment process of one patient with supraclinoid ICA fenestration combined with an aneurysm,and further literature review was conducted combining with the case study.The aim of this study was to analyze the etiology of supraclinoid ICA fenestration and its correlation with aneurysm formation,in order to improve clinicians' understanding of this rare anomaly and facilitate the formulation of appropriate treatment plans.

Supraclinoid internal carotid artery(ICA)fenestration is a rare vascular developmental variant,and this anomaly may be associated with aneurysm formation.Whether the fenestration is originated from the embryonic development of the ICA or the posterior communicating artery(PCoA)remains controversial.This article retrospectively analyzed the imaging data,diagnosis and treatment process of one patient with supraclinoid ICA fenestration combined with an aneurysm,and further literature review was conducted combining with the case study.The aim of this study was to analyze the etiology of supraclinoid ICA fenestration and its correlation with aneurysm formation,in order to improve clinicians' understanding of this rare anomaly and facilitate the formulation of appropriate treatment plans.

Objective To observe value of echocardiographic evaluation on infants with pulmonary atresia and intact ventricular septum(PA/IVS)for surgical decision and post operation right ventricle(RV)development.Methods Forty-six PA/IVS infants who underwent pulmonary valve(PV)annuloplasty(group A,n=25),PV annuloplasty and RV outflow tract reconstruction with/without additional systemic-to-pulmonary artery shunt(group B,n=15),and systemic-to-pulmonary artery shunt and atrial septal enlargement(group C,n=6)were retrospectively enrolled.Status of RV developments were compared among groups before operation as well as 1 and 6 months after operation.Results The presentation age in group B was younger than,while in group C was older than that in group A(both P＜0.05).Before operation,tricuspid valve(TV)annulus diameter,TV annulus Z-score and TV/mitral valve(MV)annulus ratio in groups B and C were both smaller than those in group A(all P＜0.05),whereas RV/left ventricle(LV)longitudinal diameter ratio in group B was larger and PV annulus Z-score in group C was smaller than those in group A(both P＜0.05).Meanwhile,preoperative PV annulus Z-score and RV/LV longitudinal diameter ratio in group B were both larger than those in group C(both P＜0.05).One month after operations,TV annulus diameter,TV annulus Z-score and TV/MV annulus ratio in group B and C,as well as PV annulus diameter,PV annulus Z-score and RV/LV longitudinal diameter ratio in group C were all smaller than those in group A(all P＜0.05),while PV annulus diameter,PV annulus Z-score and RV/LV longitudinal diameter ratio in group C were all smaller than those in group B(all P＜0.05).Six months after operations,no significant difference of TV annulus diameter,PV annulus diameter,PV annulus Z-score,TV/MV annulus ratio nor RV/LV longitudinal diameter ratio was found between group A and B(all P＞0.05),but the above indexes in group C were all lower than those in group A and B(all P＜0.05).Besides,no significant difference of TV annulus Z-score was found between group A and B(P＞0.05),which were lower in group C than in group A(P＜0.05).Conclusion Echocardiographic evaluation on PA/IVS infants was helpful to establishment of forward blood flow from RV to pulmonary arteries in time,hence promoting RV development.

Polycystic ovary syndrome (PCOS) is one of the most common gynaecological endocrine diseases in women and the main cause of anovulatory infertility. Compared with women with normal ovulation, PCOS patients are more likely to face ovarian hyperstimulation syndrome, poor-quality of oocyte and fertilization failure in assisted reproduction treatment, so ovulation induction in PCOS patients has attracted much attention in the reproductive field. Progestin-primed ovarian stimulation (PPOS) protocol uses exogenous progesterone effectively to block luteinizing hormone surge to achieve ideal number of retrieved oocytes, embryo quality and pregnancy outcomes. This article reviews the mechanism, clinical application and development of PPOS protocol in PCOS patients.

Polycystic ovary syndrome (PCOS) is one of the most common gynaecological endocrine diseases in women and the main cause of anovulatory infertility. Compared with women with normal ovulation, PCOS patients are more likely to face ovarian hyperstimulation syndrome, poor-quality of oocyte and fertilization failure in assisted reproduction treatment, so ovulation induction in PCOS patients has attracted much attention in the reproductive field. Progestin-primed ovarian stimulation (PPOS) protocol uses exogenous progesterone effectively to block luteinizing hormone surge to achieve ideal number of retrieved oocytes, embryo quality and pregnancy outcomes. This article reviews the mechanism, clinical application and development of PPOS protocol in PCOS patients.

ObjectiveTo investigate the deafness genetic mutation spectrum in nonsyndromic hearing impairment (NSHI) associated with enlarged vestibular aqueducts (EVA). MethodsFrom October, 2015 to August, 2016, 85 patients with NSHI from Hubei Yichang Special Education School were examined with temporal bone CT, and 20 deafness-related gene mutations in GJB2, GJB3, SLC26A4 and mtDNA 12S rRNA were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ResultsA total of 31 patients were found EVA with temporal bone CT. Compared with non-EVA patients, the proportion of deafness-related gene mutations was more in patients with EVA (χ² = 11.160, P = 0.001), especially for c.919-2A>G mutation of SLC26A4 (χ² = 23.870, P < 0.001). ConclusionThe deafness gene mutation spectrum is different in NSHI patients with or without EVA. It is needed to optimize genetic testing scheme for deafness for early diagnosis and intervention of NSHI associated with EVA.

ObjectiveTo explore the application value of CT pulmonary angiography (CTPA) in assessing the severity of acute pulmonary embolism (APE) and right heart function in rehabilitation patients. MethodsFrom January, 2013 to January, 2020, 133 inpatients (94 positive and 39 negative) who underwent CTPA examination in Beijing Bo'ai Hospital were involved. Positive patients were further divided into mild, moderate and severe groups based on the pulmonary artery obstruction index (PAOI). The clinical parameters and right heart function indicators were compared. Spearman correlation analysis was used to analyze the correlation between PAOI, and clinical parameters and right heart function indicators, and Logistic regression analysis was used to predict the risk factors of APE. ResultsThere was significant difference in lower extremity venous thrombosis, D-dimer, oxygen partial pressure, PAOI and left process of interventricular septum among four groups (H ≥ 12.350, P < 0.01). PAOI was moderately positively correlated with D-dimer (r = 0.443, P < 0.001) and left process of interventricular septum (r = 0.520, P < 0.001), and was weakly positively correlated with lower extremity venous thrombosis (r = 0.399, P < 0.001), left pulmonary artery diameter (r = 0.213, P = 0.014) and inferior vena cava regurgitation (r = 0.229, P = 0.008). Lower extremity venous thrombosis (OR = 7.708, P < 0.001) and left process of interventricular septum (OR = 3.641, P = 0.008) were independent risk factors for the onset of APE. The combination of the two indicators was effective for diagnosis of APE, and AUC was 0.795 (95% CI 0.715 to 0.874). ConclusionCTPA may be applied to evaluate the severity of APE and right heart function in rehabilitation patients.

Objective: To elucidate clinical characteristics and build a prognostic nomogram for patients with vulvar cancer. Methods: The study population was drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned to training and validation sets. Cox proportional hazards model and competing risk model were used to identify the prognostic parameters of overall survival (OS) and cancer-specific survival (CSS) to construct a nomogram. The nomogram was assessed by concordance index (C-index), area under the curve (AUC), calibration plot, and decision curve analysis (DCA). Results: A total of 20,716 patients were included in epidemiological analysis, of whom 7,025 patients were selected in survival analysis, including 4,215 and 2,810 in training and validation sets, respectively. The multivariate Cox model showed that the predictors for OS were age, marital status, histopathology, differentiation and tumor node metastasis (TNM) stages, whether to undergo surgery and chemotherapy. However, the predictors for CSS were age, race, differentiation and TNM stages, whether to undergo surgery and radiation. The C-index for OS and CSS in the training set were 0.76 and 0.80. The AUC in the training set for 1-, 3- and 5-year OS and CSS were 0.84, 0.81, 0.80 and 0.88, 0.85, 0.83, respectively, which was similar in the validation set. The calibration curves showed good agreement between prediction and actual observations. DCA revealed that the nomogram had a better discrimination than TNM stages. Conclusions The nomogram showed accurate prognostic prediction in OS and CSS for vulvar cancer, which could provide guidance to clinical practice.

Objective:To develop a neural network model for the evaluation of glomerular filtration rate (GFR) based on multilayer perceptual neural network, and to compare with the improved Chinese based creatinine GFR evaluation formula (C-GFR cr) and the evaluation formula (EPI-GFR cr) of the American Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for the clinical applicability of multilayer perceptual neural network model in evaluating GFR. Methods:A total of 684 chronic kidney disease (CKD) patients used for developing a modified version of China′s based creatinine GFR evaluation formula were taken as the research object. The data of 454 patients were randomly selected as the development group and the data of the other 230 patients were as the verification group. The multilayer perceptual neural network GFR evaluation model (M-GFR cr) was established. With the double plasma GFR as the reference value (rGFR), the correlation, mean difference, mean absolute difference, precision and accuracy of C-GFR cr, EPI-GFR cr and M-GFR cr were compared. Results:Among the 684 CKD patients, there were 352 males and 332 females, with age of (49.9±15.8) years. The correlation between M-GFR cr and rGFR was the highest (Pearson correlation =0.93, P<0.001). The mean difference of M-GFR cr was lower than that of C-GFR cr ( Z=9.929, P<0.001) and EPI-GFR cr ( Z=10.573, P<0.001). The mean absolute difference of M-GFR cr was also lower than that of C-GFR cr ( Z=3.953, P<0.001) and EPI-GFR cr ( Z=4.210, P<0.001). The accuracy of ±15% of M-GFR cr was higher than that of C-GFR cr ( χ2=26.068, P<0.001) and EPI-GFR cr ( χ2=23.154, P<0.001). The accuracy of ±30% of M-GFR cr was also higher than that of C-GFR cr ( χ2=8.264, P=0.001) and EPI-GFR cr ( χ2=11.963, P=0.001). The results of different stages of CKD showed that in the early stage of CKD (CKD 1-2), the mean difference of M-GFR cr was lower than that of C-GFR cr ( Z=7.401, P<0.001) and EPI-GFR cr ( Z=8.096, P<0.001); the mean absolute difference of M-GFR cr was also lower than that of C-GFR cr ( Z=4.723, P<0.001) and EPI-GFR cr ( Z=4.946, P<0.001); the accuracy of ±15% of M-GFR cr was higher than that of C-GFR cr ( χ2=23.547, P<0.001) and EPI-GFR cr ( χ2=26.421, P<0.001); the accuracy of ±30% of M-GFR cr was also higher than that of C-GFR cr ( χ2=12.089, P=0.001) and EPI-GFR cr ( χ2=16.168, P<0.001). But there was no significant difference in the applicability among C-GFR cr, EPI-GFR cr and M-GFR cr in the advanced stages of CKD (CKD 3-5). Conclusion:Compared with the improved Chinese based creatinine GFR evaluation formula C-GFR cr and CKD-EPI evaluation formula EPI-GFR cr, the accuracy of multilayer perceptual neural network model to evaluate GFR in CKD patients has been significantly improved, especially in CKD 1-2 stage.