ObjectiveTo investigate the clinical phenotypes of familial hypercholesterolemia (FH) caused by exon 13 A606T mutation in low deusity lipoprotein receptor.MethodsClinical data of the suffered family were collected and analyzed,as well as measurement of perivascular intima-medial thickness and follow-mediated-dilation function by ultrasonography.ResultsThere were totally 11 sufferers including 4 males and 9 females,aged 8-90 years,with 2 homozygotes and 9 heterozygotes.Among them, one homozygote showed angina pectoris and hematuria,both homozygotes had skin xanthomata.TC,TG,LDL-C and HDL-C were(7.39 ± 1.30) mmol/L,(0.93 ± 0.36) mmol/L,( 11.76 ± 1.10) mmol/L and ( 1.22 ±0.17) mmol/L,respectively.The left/right sided intima-medial thickness of the common,internal,external and bulb carotid artery were ( 1.15 ±0.45) mm/( 1.30 ±0.60) mm,(0.82 ±0.30) mm/( 1.00 -0.66)mm,(0.77 ±0.28) mm/(0.78 ±0.30) mm and ( 1.40 ±0.59) mm/( 1.46 ±0.71 ) mm respectively.The brachial artery flow mediated dilation rate was (4.85 ±4.80)％.Echocardiography revealed 2 patients with cardiac valvular disease and 3 with atrium septum aneurysm. ConclusionFH patients show a variety of phenotypes incuding extraordinary hypercholesterolemia,subcutaneous xanthomata and premature coronary heart disease.

Objective:To explore the influence of the contours of different parts of the human body on the setup errors of Catalyst HD optical surface imaging (OSI) system-guided radiotherapy.Methods:Using the 3D printing technology, arc- and oval arc-shaped phantoms with base angles of 5°-45° (step length: 5°) were designed to simulate the contours of different body parts of patients. A Catalyst HD system was employed for monitoring, during which the gains and integration time of the system were adjusted. The treatment couches were manually moved (range: -5 mm to 5 mm, with a step length of 2 mm). The ratios of transverse to longitudinal dimensions of all phantoms were recorded. The recorded items also included couch value errors in the anterior-posterior (AP), inferior-superior (SI), and left-right (LR) directions for transversely and longitudinally placed phantoms, as well as the setup errors monitored using the Catalyst HD system. Then, this study presented an analysis of the correlation between phantoms for different body contours and the gains and integration time of the Catalyst HD system. The purpose was to compare the setup errors under the two different placement conditions of phantoms and to analyze the correlation between the monitored values of the Catalyst HD system and couch values.Results:There was a significant linear negative correlation between the gain and the logarithm of integration time required for monitoring using the Catalyst HD system, with a slope of -0.001. There was a certain functional relationship between the intercept and the ratio of the transverse to longitudinal dimensions of the phantoms. Under the same gain, the integration time decreased with an increase in the base angles of phantoms. The Catalyst HD system showed different monitoring accuracy under different placement conditions of the phantoms ( Z = -8.59 to -0.02, P < 0.05), with the monitoring accuracy in the LR and AP directions higher in the transverse position. The correlation between the monitored values of the Catalyst HD system and the actual couch values increased in the LR and SI directions with an increase in the base angle of the phantoms, showing a strong correlation in the case of base angles of ≥ 25°. Furthermore, the correlation was always significant in the AP direction ( R > 0.9). Conclusions:When the best surface images are obtained using the Catalyst HD system, the gains and integration time of the system are correlated with body surface contours. The Catalyst HD system shows high monitoring accuracy in the AP direction. This system shows high accuracy in all directions when the ratios of transverse to longitudinal dimensions are ≤ 2 or the base angles ≥ 25°.

Humans ; Heart Ventricles ; Behcet Syndrome/complications* ; Heart ; Heart Diseases ; Ventricular Dysfunction, Left

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which manifests with both motor and non-motor symptoms. Circadian rhythm dysregulation, as one of the most challenging non-motor features of PD, usually appears long before obvious motor symptoms. Moreover, the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis, and it has emerged as a hot topic in PD research. In this review, we briefly introduce the circadian rhythm and circadian rhythm-related genes, and then summarize recent research progress on the altered circadian rhythm in PD, ranging from clinical features to the possible causes of PD-related circadian disorders. We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD, but also shed light on the better management of PD.

Parkinson's disease (PD) is a multifaceted disease in which environmental variables combined with genetic predisposition cause dopaminergic (DAergic) neuron loss in the substantia nigra pars compacta. The mutation of leucine-rich repeat kinase 2 (Lrrk2) is the most common autosomal dominant mutation in PD, and it has also been reported in sporadic cases. A growing body of research suggests that circadian rhythm disruption, particularly sleep-wake abnormality, is common during the early phase of PD. Our present study aimed to evaluate the impact of sleep deprivation (SD) on motor ability, sleep performance, and PD pathologies in Lrrk2^G2019S transgenic mice. After two months of SD, Lrrk2^G2019S mice at 12 months of age showed an exacerbated PD-like phenotype with motor deficits, a reduced striatal DA level, degenerated DAergic neurons, and altered sleep structure and biological rhythm accompanied by the decreased protein expression level of circadian locomotor output cycles kaput Lrrk2 gene in the brain. All these changes persisted and were even more evident in 18-month-old mice after 6 months of follow-up. Moreover, a significant increase in α-synuclein aggregation was found in SD-treated transgenic mice at 18 months of age. Taken together, our findings indicate that sleep abnormalities, as a risk factor, may contribute to the pathogenesis and progression of PD. Early detection of sleep disorders and improvement of sleep quality may help to delay disease progression and provide long-term clinical benefits.
Animals ; Electroencephalography ; Leucine/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Mice ; Mice, Transgenic ; Mutation ; Parkinson Disease/metabolism* ; Sleep Deprivation/complications* ; alpha-Synuclein/genetics*

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.