Objective: To retrospectively analysely the electrophysiological and imaging features of isolated congenital anosmia (ICA) and to assess the clinical phenotypic characteristics and classification of ICA. Methods: Clinical data of 30 ICA patients in Beijing Anzhen Hospital from 2012 to 2019 was retrospectively reviewed, including 13 males and 17 females, aged (35±19) years. The control group consisted of 30 healthy people from medical examination center, including 13 males and 17 females, aged (39±14) years. The clinical characteristics of ICA were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERP) and olfactory pathway MRI. SPSS 17.0 software was used to compare the difference of olfactory function between the two groups. The correlation between olfactory bulb, olfactory sulcus structure and age was observed, and the clinical phenotype characteristics of ICA patients were analyzed. Results: The subjective olfactory function was completely lost in ICA patients. oERP was absent in all of the ICA patients, but showed normal N1 and P2 waves in controls. tERP could be evoked in 63.3% (19/30) of ICA patients, and signals in these patients showed higher amplitude in the N1 ((-10.33±6.93) μV vs (-5.11±2.71) μV, t=-10.113, P 0.05). Conclusions: ICA patients show neurophysiologic deficits and some anatomic differences compared with healthy controls. The absence of oERP combining with a depth of olfactory sulcus less than 8 mm is the important indicator for clinical diagnosis of ICA. The structure of olfactory bulb may be a critical factor for clinical classification of ICA.
Objective: To investigate the white matter integrity in patients with olfactory dysfunction using diffusion tensor imaging (DTI). Methods: Twenty-one patients with olfactory dysfunction and sixteen age, sex and level of education matched normal subjects were recruited in this study. Sniffin' Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired diffusion tensor images with a echo planar imaging (EPI) sequence from all subjects on a 3T scanner. The fractional anisotropy (FA) images were performed using DTI-studio, and bilateral piriform cortex, orbitofrontal cortex, hippocampus and insula cortex adjacent white matter as well as capsula interna were delineated from the FA images as the region of interest associated with olfactory (ROI(awo)) manually. Independent sample t test analysis was used to compare the FA value of all ROI(awo) between the controls and patients. Results: In olfactory dysfunction group, the FA value of adjacent white matter of right piriform cortex and orbitofrontal cortex were significantly lower than those of control group (0.42±0.05 (x±s) vs 0.45±0.05, 0.43±0.06 vs 0.49±0.07, t value was 2.32, 2.79, respectively, all P<0.05). The FA value of adjacent white matter of left piriform cortex and orbitofrontal cortex had no significant difference compared with those of control group (0.43±0.05 vs 0.45±0.04, 0.44±0.04 vs 0.47±0.06, t value was 1.65, 1.37, respectively, all P>0.05). The FA value of the adjacent white matter of bilateral hippocampus, insula cortex and capsula interna had no significant difference compared with those of control group, neither (0.45±0.08 vs 0.44±0.08, 0.45±0.09 vs 0.44±0.10, 0.41±0.08 vs 0.39±0.07, 0.41±0.07 vs 0.38±0.05, 0.64±0.08 vs 0.63±0.08, 0.64±0.07 vs 0.63±0.07, t value was 0.30, 0.15, 0.88, 1.34, 0.14, 0.35, respectively, all P>0.05). Conclusions: The patients with olfactory dysfunction showed abnormal white matter connection in the major primary and secondary olfactory cortex. The reduced white matter integrity in ROI(awo) might contribute to the pathogenesis of olfactory dysfunction.目的： 分析嗅觉障碍患者脑白质的完整性。 方法： 收集2014—2016年就诊于首都医科大学附属北京安贞医院耳鼻咽喉头颈外科的21例嗅觉障碍患者(患者组)与16例年龄、性别、受教育程度相匹配的健康志愿者(对照组)，对其进行Sniffin′ Sticks嗅觉功能测试及脑磁共振弥散张量成像(diffusion tensor imaging，DTI)检查。以DTI－studio软件处理脑DTI图像，得到各向异性分数(fractional anisotropy，FA)参数图，选择双侧梨状皮层、眶额皮层、海马、岛叶邻近脑白质和内囊为嗅觉相关感兴趣区(region of interest associated with olfactory，ROI(awo))，计算每个ROI(awo)的FA值。采用独立样本t检验比较患者组和对照组间ROI(awo)的FA值差异。 结果： 患者组右侧梨状皮层和右侧眶额皮层下脑白质的FA值均显著低于对照组[0.42±0.05(x±s，下同)比0.45±0.05，0.43±0.06比0.49±0.07，t值分别为2.32、2.79，P值均<0.05]。左侧梨状皮层、左侧眶额皮层下的脑白质FA值与对照组之间的差异无统计学意义(0.43±0.05比0.45±0.04，0.44±0.04比0.47±0.06，t值分别为1.65、1.37，P值均>0.05)。左右两侧海马、岛叶下方脑白质FA值与对照组之间的差异均无统计学意义(0.45±0.08比0.44±0.08，0.45±0.09比0.44±0.10，0.41±0.08比0.39±0.07，0.41±0.07比0.38±0.05，t值分别为0.30、0.15、0.88、1.34，P值均>0.05)。左右两侧内囊FA值与对照组之间的差异亦无统计学意义(0.64±0.08比0.63±0.08，0.64±0.07比0.63±0.07，t值分别为0.14、0.35，P值均>0.05)。 结论： 嗅觉障碍患者的初级、次级嗅觉皮层邻近脑白质可能存在结构连接障碍，ROI(awo)脑白质完整性的降低，可能是导致嗅觉障碍的发病机制之一。.
Objective: Using (18)F-fluorodeoxyglucose ((18)F-FDG) and microPET-CT to test the feasibility of (18)F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of (18)F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of (18)F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat's brain after PEA stimulation included bed nucleus and insula. Activation regions of rat's brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions: Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat's brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.目的： 利用氟代脱氧葡萄糖((18)F－ fluorodeoxyglucose，(18)F－FDG)小动物正电子发射型计算机断层显像(microPET－CT)，研究大鼠嗅觉相关脑区葡萄糖代谢在苯乙醇和异戊酸两种气味刺激下的应激反应，并对大鼠嗅觉中枢及其通路进行功能定位，验证正电子发射型计算机断层显像(PET－CT)作为新型嗅觉客观检查工具的可能性。 方法： 选取健康雄性SD大鼠6只，体重250～300 g，利用食物埋球试验验证大鼠嗅觉功能正常。对6只大鼠进行尾静脉注射(18)F－FDG，然后将清醒的大鼠放置于通风的玻璃笼中分别行洁净空气(第1天)、苯乙醇(第2天)和异戊酸(第3天)刺激30 min后，将大鼠麻醉行microPET－CT扫描，收集图像信息。依托MATLAB、SPM等软件采用逐像素方法分析大鼠脑部影像数据，利用配对t检验统计学方法进行数据分析。 结果： 苯乙醇气味刺激后激活的大鼠脑区为：终纹床核、脑岛；异戊酸气味刺激后激活的大鼠脑区主要为：嗅球、前嗅核、杏仁核、内嗅皮层、嗅觉皮质、梨状皮质、脑岛、前额叶皮质、扣带回和终纹床核(P<0.005，像素个数>20)。 结论： 利用microPET－CT技术，可以观察到不同气味的嗅觉刺激引起大鼠不同嗅觉相关脑区的代谢激活，且大鼠嗅觉相关脑区对异戊酸气味刺激反应更加强烈。.
Objective: To explore the clinical effects and the influence factors of olfactory training in the treatment of olfactory dysfunction. Methods: A total of 86 patients with olfactory dysfunction (49 post-infectious and 37 post-traumatic) in Beijing Anzhen Hospital during Dec 2016 to May 2017 were recruited in this prospective study. The clinical data of patients were analyzed, including gender, age, body mass index (BMI), course of disease, smoking history, drinking history, diabetes history, hypertension history, hyperlipidemia history, and anxiety visual analogue score (VAS). All patients were treated with olfactory training for 16 weeks, and all of them underwent Sniffin' Sticks olfactory test before and after treatment, which was evaluated by composite threshold-discrimination-identification score (TDI). SPSS 23.0 software, paired t test and univariate and multivariate Logistic regression analysis were used to analyze the data. Results: Eighty patients received treatment, including 46 post-infectious olfactory dysfunction and 34 post-traumatic olfactory dysfunction. After olfactory training, the total scores of TDI increased with statistically significant (18.3±8.6 vs 13.6±7.4, t=-6.158, P<0.05). The overall efficacy was 40% (32/80). The effective rate were 45.7% (21/46) in post-infectious olfactory dysfunction and 32.4% (11/34) in post-traumatic olfactory dysfunction respectively, with no statistically significant difference (χ(2)=1.441, P=0.230). Logistic regression analysis showed that the course of disease was an influence factor in the clinical curative effect (OR=0.881, 95%CI: 0.799-0.973, P=0.012). In patients with less than a year of olfactory dysfunction, the olfactory function improved obviously with the efficiency of 50.9% (29/57). Conclusion: Sixteen weeks of olfactory training provides a significant therapeutic effect on the post-infectious and post-traumatic olfactory dysfunction, and the olfactory training can achieve better therapeutic effects at the early stage.目的： 探讨嗅觉训练治疗嗅觉障碍的临床疗效及其影响因素。 方法： 2016年11月至2017年5月就诊于首都医科大学附属北京安贞医院的86例嗅觉障碍患者纳入本前瞻性研究，其中上呼吸道感染后嗅觉障碍患者49例，外伤性嗅觉障碍患者37例。入选时收集患者临床资料，包括性别、年龄、体质量指数(BMI)、病程、烟酒史、2型糖尿病等慢性病史、焦虑视觉模拟量表(VAS)评分。采用嗅觉训练治疗16周，并于治疗前后行Sniffin′ Sticks嗅觉测试，气味察觉阈、气味辨别能力和气味识别能力3项测试的得分总和组成TDI综合评分(composite threshold-discrimination-identification score，TDI)。采用SPSS 23.0软件对结果进行配对t检验、单因素及多因素Logistic回归分析。 结果： 共80例患者完成治疗方案，其中上呼吸道感染后嗅觉障碍患者46例，外伤性嗅觉障碍患者34例。治疗后TDI得分较治疗前升高，差异有统计学意义[(18.3±8.6)分比(13.6±7.4)分，t＝－6.158，P<0.05]。治疗总体有效率40.0%(32/80)。上呼吸道感染后嗅觉障碍治疗有效率45.7%(21/46)，外伤性嗅觉障碍治疗有效率32.4%(11/34)，二者差异无统计学意义(χ(2)＝1.441，P＝0.230)。Logistic回归分析显示，病程是影响嗅觉训练疗效的因素(OR＝0.881，95%CI：0.799～0.973，P＝0.012)，初发症状到开始嗅觉训练时间间隔≤1年的患者治疗有效率为50.9%(29/57)。 结论： 16周的嗅觉训练可有效治疗上呼吸道感染后和外伤性嗅觉障碍；早期进行嗅觉训练可取得更好的治疗效果。.
Objective:The purpose of this study was to evaluate the test-retest reliability of gustatory function using whole-mouth taste tests in healthy adults. Methods:Fifty healthy subjects were tested by whole-mouth taste test. The taste test involved 5 tastants（sour, sweet, salty, umami and bitter） and 7 concentrations. The tastant solutions were administered in a pseudo-random order starting with the lowest concentration. Record the perception and recognition scores of each tastant separately. The same operator performed test again by the same method two weeks later. The relative reliability and absolute reliability of the whole-mouth taste test were evaluated with intraclass correlation coefficient（ICC） and standard errors of measurement（SEM）, SEM% respectively. Results:The intraclass correlation coefficient of the perception scores of the sour, sweet, salty, umami and bitter in healthy subjects were from 0.753 to 0.819, ICC values of recognition score range from 0.751 to 0.828. In terms of absolute reliability, the SEM and SEM% values of perception scores were 0.329-0.463 and 6.60%-9.07% respectively; SEM of recognition scores were 0.425-0.581 and SEM%=9.09%-14.66%. Conclusion:The whole-mouth taste test could be a reliable tool for gustatory function test with good test-retest reliability in healthy adults.目的：对全口味觉功能检查法的信度进行评价，分析其在健康成人味觉功能中的一致性及可重复性。 方法：采用全口法对50例健康受试者进行味觉功能检查。味觉功能检查包括酸、甜、咸、鲜、苦五种味剂，每种味剂包含7个浓度梯度，采用伪随机顺序，从最低浓度开始，分别记录每种味剂的感知和识别得分。2周后由同一操作人员以相同方法进行第2次味觉功能检查。全口味觉检查法的相对信度及绝对信度分别使用组内相关系数（ICC）和标准误差（SEM）及SEM%评估。 结果：健康受试者酸、甜、咸、鲜和苦五种味剂感知得分的组内相关系数ICC=0.753~0.819，识别得分的ICC=0.751~0.828。五种味觉感知得分的SEM=0.329~0.463，SEM%=6.60%~9.07%；味觉识别得分的SEM=0.425~0.581，SEM%=9.09%~14.66%。 结论：全口法是一种可靠的主观味觉功能检查方法，在健康成人主观味觉功能评估中有良好的重测信度。.
To explore changes of olfactory and gustatory functions in patients with olfactory dysfunction.The 284 study subjects included 92 healthy volunteers, 92 with hyposmia and 100 with functional anosmia. Their olfactory and gustatory functions were examined using T&T olfactometer, olfactory event-related potentials (OERPs) and triple drop method, respectively.The T&T results showed that the difference between patients with hyposmia and functional anosmia and healthy subjects had statistical significance. The OERPs results showed that patients with olfactory dysfunction had N1 and P2 waves of prolonged latency and reduced amplitude when compared to healthy subjects with the difference of statistical significance. When compared to healthy subjects, patients with olfactory dysfunction had clear hypogeusia and the difference had statistical significance. There was no significant difference between female and male groups.It is suggested that the apparently concomitant hypogeusia is in patients with olfactory dysfunction. Decreased of olfactory and gustatory function exhibited little or no relationship with gender. Combined examinations of OERPs, T&T and triple drop method, could make it possible to reflect the overall chemical sensory functions in subjects systematically and provide scientific evidence for clinical diagnosis and treatment early.
ABSTRACT Fenvalerate (Fen), a widely used pesticide, is known to impair male reproductive functions by mechanisms that remain to be elucidated. Recent studies indicated that circadian clock genes may play an important role in successful male reproduction. The aim of this study was to determine the effects of Fen on circadian clock genes involved in the biosynthesis of testosterone using TM3 cells derived from mouse Leydig cells. Data demonstrated that the circadian rhythm of testosterone synthesis in TM3 cells was disturbed following Fen treatment as evidenced by changes in the circadian rhythmicity of core clock genes (Bmal1, Rev-erbα, Rorα). Further, the observed altered rhythms were accompanied by increased intracellular Ca2+ levels and modified steroidogenic acute regulatory (StAR) mRNA expression. Thus, data suggested that Fen inhibits testosterone synthesis via pathways involving intracellular Ca2+ and clock genes (Bmal1, Rev-Erbα, Rorα) as well as StAR mRNA expression in TM3 cells.
Objective:The purpose of this study was to compare the olfactory function examination results of patients with post-viral olfactory dysfunction（PVOD） in different prognostic groups and analyze prognostic factors, especially the influence of olfactory bulb volume（OBV） on prognosis, so as to provide objective basis for clinical diagnosis and treatment. Methods:After approval by the hospital ethics committee, the patients with PVOD admitted to Beijing Anzhen Hospital's outpatient department from January 2019 to December 2019 were followed up for at least 1 year. These patients completed the Sniffin' Sticks test and MRI examination of the olfactory pathway before treatment. According to the results of the Sniffin' Sticks test after 1 year follow-up（threshold-discrimination-identification（TDI） score of the patients was increased at least 6 points）, the patients were divided into two groups as the improvement group and the non-improvement group. The prognostic factors of PVOD patients were preliminarily determined by comparing the differences of various factors and the results of olfactory function examination between the two groups. Results:In this study, 47 patients with PVOD were included, with the smell improvement rate was 53.2%. Compared with the improvement group, the patients in the non-improvement group had longer duration, poorer initial olfactory function, higher olfactory threshold, and poorer olfactory discrimination and recognition ability（All P<0.01）. There was no statistical difference in terms of gender, age, allergic rhinitis and smoking between the two groups（All P>0.05）.The OBV of the non-improvement group was （59.48±23.92） mm³, which was significantly lower than that in the improvement group（[92.77±14.35]mm³, P<0.001）. Multiple logistic regression analysis showed that prognostic factors included course of disease（OR 0.677, 95%CI 0.461-0.993, P=0.046）, initial T value（OR 263.806, 95%CI 1.028-67 675.884, P=0.049） and OBV（OR 1.160, 95%CI 1.002-1.343, P=0.047）. The area under the receiver operating characteristic curve（ROC curve） of OBV was 0.888（0.797-0.979, P<0.001）. The correct diagnostic index of OBV≥78.50 mm³was used to determine the prognosis of olfactory function, with a specificity of 0.818 and a sensitivity of 0.840. The ROC curve analysis showed that the area under the ROC curve of duration was 0.822（0.703-0.940, P<0.001）. The correct diagnostic index of the duration ≤6 months was used to determine the prognosis of olfactory function, with a specificity of 0.727 and a sensitivity of 0.800. The area of T score was 0.793（0.662-0.924, P=0.001）. T score ≥1.25 was used as the correct diagnostic index to determine the prognosis of olfactory function. The specificity and sensitivity were 0.818 and 0.680, respectively. Conclusion:The prognosis of olfactory function in PVOD patients is related to the course of disease, the degree of olfactory loss and OBV. Those with no improvement in olfactory function have a longer disease course, aggravated olfactory damage and reduced OBV than those with improved olfactory function. The factors of Duration ≤6 months, T value ≥1.25 and OBV≥78.50 mm³suggested better prognosis, and the results of objective olfactory examination have greater value in evaluating the prognosis of olfactory function.目的：比较上呼吸道感染后嗅觉障碍（PVOD）患者不同预后组间的嗅觉功能检查结果，分析预后相关因素，尤其嗅球体积（OBV）对预后的影响，为临床诊疗提供客观依据。 方法：对2019年1月—2019年12月于北京安贞医院门诊就诊的PVOD患者进行≥1年的随访，这些患者在治疗前完成Sniffin'Sticks嗅觉测试、嗅通路MRI检查。根据1年随访期后Sniffin'Sticks嗅觉测试结果总分提高≥6分，将患者分为嗅觉功能改善组和嗅觉功能无改善组。比较两组间各因素和嗅觉功能检查结果的差异，初步确定影响PVOD患者的预后因素。 结果：共纳入47例PVOD患者，Sniffin'Sticks嗅觉测试复查结果显示嗅觉改善率为53.2%。与嗅觉功能改善组相比，嗅觉功能无改善组患者病程长，初始嗅觉功能差，嗅觉阈值高，嗅觉辨别和识别能力差（均P<0.01）。两组在性别、年龄、变应性鼻炎和吸烟方面差异均无统计学意义（均P>0.05）。嗅觉功能无改善组的OBV为（59.48±23.92） mm³，明显小于嗅觉功能改善组[（92.77±14.35） mm³]。经多元logistic回归分析预后相关因素包括病程（OR 0.677，95%CI 0.461~0.993，P=0.046），初始T值（OR 263.806，95%CI 1.028~67 675.884，P=0.049）和OBV（OR 1.160，95%CI 1.002~1.343，P=0.047）。ROC曲线分析结果显示，OBV在ROC曲线下面积为0.888（0.797~0.979，P<0.001），以OBV≥78.50 mm³ 正确诊断指数判断嗅觉功能预后良好，其特异性为0.818，敏感性为0.840；病程因素ROC曲线下面积为0.822（0.703~0.940，P<0.001），以病程≤6个月为正确诊断指数判断嗅觉功能预后良好，其特异性为0.727，敏感性为0.800；T值ROC曲线下面积为0.793（0.662~0.924，P=0.001），以T值≥1.25为正确诊断指数判断嗅觉功能预后较好，其特异性为0.818，敏感性为0.680。 结论：PVOD患者嗅觉功能预后与病程、嗅觉损伤程度和OBV有关。嗅觉功能无改善者较嗅觉功能改善者病程延长，嗅觉损伤程度加重和OBV减小。病程≤6个月，T值≥1.25和OBV≥78.50 mm³均提示预后良好，且客观嗅觉检查结果对嗅觉功能预后的评估价值更大。.
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