Limitations of exome sequencing in detecting rare and undiagnosed diseases

While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results. Overall, 36/54 (67%) of total diagnoses were based on clinical findings and coding variants found by ES and 3/54 (6%) were based on clinical findings only. The remaining 15/54 (28%) required testing beyond ES. Of these, 7/15 (47%) had NCV, 6/15 (40%) CNV, and 2/15 (13%) had a RE or a DNA methylation disorder. Thus 18/54 (33%) of diagnoses were not solved exclusively by ES. Several methods were needed to detect and/or confirm the functional effects of the variants missed by ES, and in some cases by GS. These results indicate that tests to detect elusive variants should be considered after nondiagnostic preliminary steps. Further studies are needed to determine the cost‐effectiveness of tests beyond ES that provide diagnoses and insights to possible treatment.     

Surgical management of Squamous Cell Carcinoma of the lower lip: An experience of 109 cases

Objectives: We are presenting our experience collected from a series of 109 cases with SCC of the lower lip focusing on clinical features of patients and surgical approach. Study Design: We retrospectively analyzed medical records of patients diagnosed with Squamous Cell Carcinoma (SCC) of the lower lip at the Oral and Maxillofacial surgery at Xi’an Jiaotong University during a period between 1999 and 2008. Results: A total of 109 patients with lip cancer were included in the study. When no frozen-section test was performed, the neoplasia was removed with a margin of at least 6 mm. Different surgical techniques were used for lip reconstruction after tumor excision. Neck dissection was performed in all patients with clinically palpable lymph nodes. Median follow-up was 38 months. During follow-up, recurrence occurred in 5 patients, 3 patients developed neck metastases, distant metastases developed in 1 patient. Five patients died during observation period. Conclusions: The patient-related and defect-related issues must be taken into consideration during reconstruction for surgical defect. For N0 patients, we recommend wait-and-see policy. Early detection, careful follow-up and prompt neck is essential for the successful treatment. Key words:Lip cancer, surgical management, reconstruction.     

Diagnosis of binge eating disorder: Discrepancies between a questionnaire and clinical interview

Binge eating is a common problem among obese individuals, and a simple, accurate way to identify obese binge eaters is needed. This study measured the concordance of the Binge Eating Scale (BES) and the Eating Disorder Examination (EDE). Women seeking obesity treatment (N = 126) were identified as binge eaters or nonbinge eaters using the BES, and then interviewed by clinicians blind to BES score using the EDE, a semistructured interview considered to be the “gold standard” for eating disorder diagnosis. The BES accurately identified nonbinge eaters; 39 of 42 (92.9%) BES-identified nonbinge eaters were confirmed by the EDE. However, the BES did not accurately identify binge eaters; only 43 of the 83 (51.8%) BES-identified binge eaters were confirmed by the EDE. Reasons for the discrepancy between the BES and the EDE in the identification of binge eaters were explored, and modifications to the BES that might improve its accuracy were considered. © 1995 by John Wiley & Sons, Inc.     

Binge eating disorder: A multisite field trial of the diagnostic criteria

Diagnostic criteria have been developed for a new eating disorder, binge eating disorder (BED), to describe the many individuals who have problems with recurrent binge eating but do not engage in the characteristic compensatory behaviors of bulimia nervosa, vomiting, or use of laxatives. The results of a multisite field trial involving 1,984 subjects indicate that the disorder is common (30.1%) among subjects attending hospital-affiliated weight control programs, but is relatively rare in the community (2.0%). The disorder is more common in females than in males and is associated with severity of obesity and a history of marked weight fluctuations. Based on these results, the DSM-IV Work Group on Eating Disorders has recommended that the disorder be considered for inclusion in DSM-IV, either as an official category or in an appendix of categories requiring further study.     

CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers

Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in 11 cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P < .001). Our study demonstrates the utility of immunohistochemical staining for CD44 in distinguishing prostatic small cell neuroendocrine carcinoma from its mimickers including prostatic adenocarcinoma of Gleason 5 pattern and small cell neuroendocrine carcinomas of other organs. CD44 is the first marker that shows a high degree of tissue/organ specificity for small cell neuroendocrine carcinomas. Because CD44 is a putative marker of prostate cancer stem cells, the strong and diffuse expression of CD44 and the lack of expression of prostate luminal differentiation markers androgen receptor and prostatic specific antigen in prostatic small cell neuroendocrine carcinomas suggest that the tumor cells may retain cancer stem cell features.     

景天通脉方对实验性兔动脉粥样硬化的影响

目的 评价不同剂量景天通脉方对动脉粥样硬化斑块的抑制作用。方法 健康新西兰兔54只随机分为：正常对照组, 高胆固醇组(模型组), 血脂康组, 景天通脉方小、中、大剂量组, 共6组;除正常对照组外,其余大鼠采用高胆固醇饲料并免疫损伤诱发的动脉粥样硬化斑块模型, 观察各组血脂和C-反应蛋白（CRP）以及主动脉斑块/内膜面积比、内/中膜厚度比等并比较。结果 对血脂的影响：模型组与正常对照组比较,血清总胆固醇（TC）、 甘油三酯（TG）及低密度脂蛋白胆固醇（LDL-C）均升高, 差异均有统计学意义（P<0.05）;血脂康组及景天通脉方小、中、大剂量组TC、LDL-C均明显低于模型组（P<0.05）, 景天通脉方中剂量组明显低于小、大剂量组及血脂康组（P<0.05）;TG景天通脉方小、中、大剂量组及血脂康组与模型组比较差异无统计学意义（P>0.05）;而高密度脂蛋白胆固醇（HDL-C）景天通脉方大剂量组、血脂康组高于景天通脉方小、中剂量组, 正常对照组和模型组（P<0.05）。对CRP的影响：模型组明显高于正常对照组（P<0.05）, 景天通脉方3组、正常对照组、血脂康组间比较差异均无统计学意义（P>0.05）。 正常对照组无斑块和内、中膜增厚, 景天通脉方组与模型组比较, 斑块面积、内膜厚度、中膜厚度、斑块/内膜面积比、内/中膜厚度比均明显下降（P<0.05）, 景天通脉方中剂量组明显低于小、大剂量组及血脂康组（P<0.05）。结论 景天通脉方具有抑制动脉粥样硬化的作用, 可能是通过调脂、抗炎作用来完成,效应以中剂量（人的等效剂量）为佳。     

盐生肉苁蓉栽培品中苯乙醇苷类的指纹图谱研究

  目的 为规范化种植盐生肉苁蓉药材的质量研究提供基础研究资料。 方法 选择 RP-HPLC 建立盐生肉苁蓉补肾助阳功能特征成分的指纹图谱,并进行栽培品与野生品、不同生长期、不同药用部位指纹图谱的比较研究,采用计算机辅助相似度评价软件分析了相似度。 结果 种植基地药材的指纹图谱具有较高的相似度,其化学组成相似,相对比例也基本稳定。不同生长期和不同部位药材的指纹图谱也具有较好的一致性,但特征峰的含量存在明显差异。 结论 利用 RP-HPLC 指纹图谱可以较为全面地反映盐生肉苁蓉补肾助阳功能整体特征成分的内在质量,方法重现性好。     

新疆石榴皮化学成分研究

目的:研究新疆石榴皮(Punica granatum)的化学成分.方法:采用薄层色谱、硅胶柱色谱、MCI-gel CHP20P、Sephadex LH-20凝胶柱色谱等方法进行分离纯化,使用波谱分析技术和理化常数对照等方法对得到的化合物进行结构鉴定.结果:分离得到了10个化合物,分别为:没食子酸(1)、没食子甲酯(2)、鞣花酸(3)、(+)-儿茶素(4)、异槲皮苷(5)、D-甘露醇(6)、熊果酸(7)、齐墩果酸(8)、β-谷甾醇(9)、胡萝卜苷(10).结论:化合物1～10均、为首次从该植物中分离得到.