OBJECTIVE: To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter. RESULTS: The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance. CONCLUSION Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.
Autism Spectrum Disorder/genetics* ; Genomics ; Heterozygote ; Humans ; Mosaicism ; Whole Exome Sequencing

Objective To establish the precise finite element model of the head and neck based on human anatomical structure, so as to study neck injuries caused by rear impact at different speeds. Methods The model was based on CT scan images of the head and neck of human body. The Mimics software was used to reconstruct the three-dimensional (3D) bone, and the 3D solid ligaments, small joints and other tissues of the neck were improved and meshed by HyperMesh. The generated models included the head, 8 vertebrae (C1-T1), 6 intervertebral discs (annulus, nucleus pulposus and upper and lower cartilage endplates), facet joints (cartilage and joint capsule ligaments), ligaments, muscles, etc. Finally, the model verification and post-collision calculation were completed in the finite element post-processing software. Results The simulation results of the models under axial impact, front and back flexion and lateral flexion were compared with the experimental data to verify the effectiveness of the model. Then post-collision simulation at the speed of 20, 40, 60 and 80 km/h was conducted. At the speed of 20 km/h, there was no damage to the neck. At the speed of 40, 60 and 80 km/h, the ligament was the first to be damaged. As the speed increased, the stress on tissues of the neck increased continuously. At the speed of 80 km/h, the maximum stresses of the dense bone, cancellous bone and annulus of the cervical vertebrae were 226.4, 11.5, and 162.8 MPa, respectively. When the ligament strain reached the limit, tearing began to occur. Conclusions The finite element model of the head and neck established in this study has high bionics and effectiveness, and can be used for studying neck injury analysis in traffic accidents, which is helpful for the diagnosis, treatment and prevention of cervical spine injury to a certain extent.

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

Objective:To understand the incidence trend and temporal distribution of breast cancer and reproductive system cancers in women in different age groups and areas in China from 2006 to 2017.Methods:Based on the incidences of breast cancer, vulvar cancer, vaginal cancer, cervical cancer, uterine corpus cancer, and ovarian cancer in women, average age at diagnosis and cases in different age groups and areas in China were calculated, standardized through world population. Software Joinpoint 4.5.0.1 was used to calculate average annual percent of change (AAPC).Results:Between 2006 and 2017, the overall age-standardized incidence rate (ASIR) of the six cancers showed an increasing trend from 39.48/100 000 to 51.11/100 000 (AAPC=2.24%, 95% CI: 1.59%-2.89%). The increasing trend was more obvious in rural area (AAPC=4.65%,95% CI:3.67%-5.64%), whereas no significant increase was observed in urban area (AAPC=0.15%,95% CI:-0.26%-0.56%). Except uterine corpus cancer, the incidences of 5 cancers showed increasing trends. The incidences of cervical cancer showed similar upward trends in urban and rural areas. In urban area, the ASIRs of breast cancer, vaginal cancer and vulvar cancer showed no significant increase, while in rural area it showed significant increase. The ASIR of ovarian cancer showed a decreasing trend in urban area and an increasing trend in rural area. The average age at diagnosis increased for all the cancers, except uterine corpus cancer. However, after standardizing through world population, the increases in the standardized average age at diagnosis were observed only in cervical cancer and vaginal cancer from 49.11 and 55.15 years to 52.13 and 58.81 years, respectively. Conclusions:The overall ASIR of breast cancer and reproductive system cancers in women showed increase trend in China in 2006-2017, and the increase trend was more obvious in rural area than in urban area. Meanwhile, the accessibility to medical facilities in rural area needs to be improved to ensure medical care, early diagnosis and early treatment for the purpose of bridging the gap in female cancer incidence between rural area and urban area.