[Characteristics of autonomic neuropathy in patients with vestibular migraine].

Objective: To investigate the characteristics of autonomic neuropathy in patients with vestibular migraine (VM) by sympathetic skin reflex (SSR) and R-R interval variation (RRIV). Methods: Seventy-three patients with interseizure VM and 36 healthy controls in the Department of Neurology affiliated to Shanghai Fourth People's Hospital of Tongji University from November 1, 2019 to December 31, 2021 were prospectively enrolled. SSR and RRIV were performed and relevant parameters were recorded, including SSR latency, SSR amplitude, RRIV during calm breathing (R%), RRIV during deep breathing (D%), RRIV difference between deep breathing and calm breathing (D%-R%), RRIV ratio between deep breathing and calm breathing (D%/R%), and the difference and correlation of various parameters between VM patients and healthy controls were analyzed. Results: Among the 73 patients with VM, there were 12 males and 61 females, and aged (46±13) years. While among 36 healthy controls, there were 6 males and 30 females, and aged (46±7) years. Among the 73 VM patients, abnormal SSR, abnormal RRIV, abnormal SSR and RRIV, and abnormal SSR or RRIV was detected in 38 cases (52%), 17 cases (23%), 11 cases (15%) and 44 cases (60%), respectively. Compared with healthy controls, the lower extremity SSR latency [(1 719±289) ms] in VM patients was longer than that in control group [(1 500±349) ms] (P=0.001), but the upper extremity SSR amplitude [1.6 (0.8, 3.0) mV] was lower than that in control group [2.6 (1.8, 4.2) mV] (P=0.006). SSR amplitude, R% and D% were negatively correlated with age in VM patients (rs=-0.311, P=0.007; rs=-0.237, P=0.043; rs=-0.263, P=0.024, respectively). SSR of lower extremity in VM patients was longer than that of upper extremity [(1 719±289) ms vs (1 244±185) ms, P<0.001], but the amplitude of lower extremity was lower than that of upper extremity [0.8 (0.3, 1.7) mV vs 1.6 (0.8, 3.0) mV, P<0.001]. SSR latency of upper limb was positively correlated with SSR latency of lower limb (r=0.436, P<0.001), the amplitude of upper limb was positively correlated with amplitude of lower limb (rs=0.456, P<0.001), and D% was positively correlated with R% (rs=0.357, P=0.002). Conclusion: The autonomic neuropathy during VM interphase features with imbalance between sympathetic and parasympathetic nervous system, and the sympathetic nerve function is mainly impaired.

[Clinical implications of thrombolytic therapy for patients with acute intermediate-high risk pulmonary embolism in Tibet plateau, China].

At present, clinical studies and case reports of systemic thrombolytic therapy for patients with acute pulmonary embolism in Tibet Plateau are very rare. There is little understanding of the risk factors, clinical characteristics, and thrombolytic therapy for patients with acute pulmonary embolism at intermediate-high risk in Tibet Plateau. In this paper, we reported the data of 4 patients with acute intermediate-high risk pulmonary embolism treated with thrombolytic therapy in Lhasa People's Hospital. The demographic characteristics, clinical manifestations, treatment, and outcomes were analyzed. We summarized the clinical features and raised scientific issues. We aimed to provide basic data to improve the standardized diagnosis and treatment of acute pulmonary embolism in plateau, and to point out the direction of future clinical research in this field.

[Analysis of verification results of protective effects of hearing protectors in different industries].

Objective: To get insight into the current practice of noise reduction effect of workers as they wore hearing protectors in different domestic enterprises and the possible affected factors. Methods: From October 2020 to April 2021, using a random sampling method, 1197 workers exposed to noise in petrochemical factories, textile factories, and parts manufacturing factories were selected as the study subjects. The noise reduction effect of hearing protectors worn by workers in daily use was tested using a hearing protector suitability testing system. The personal sound attenuation level (PAR) was compared among workers in three enterprises, Targeted intervention and repetitive testing were conducted for workers who did not meet the noise reduction effect required by the enterprise, and the changes in PAR of workers before and after the intervention were compared. The comparison of baseline PARs between two or more groups was performed using the Mann Whitney test, the comparison of baseline PARs with post intervention PARs was performed using the Wilcoxon signed rank sum test, and the comparison of qualitative data between two or more groups was performed using the Chi square test. Results: The median baseline PAR for all workers was 15 dB. Men, age<30 years old, education level at or above college level, working experience of 5 to 15 years, and those who used hearing protectors for 5 to 15 years had higher PARs, with statistically significant differences (P<0.05). The median difference in baseline PAR among workers from three enterprises was statistically significant (H=175.06, P<0.01). The median PAR of subjects who did not pass the baseline increased from 3 dB to 21 dB after intervention (Z=-27.92, P<0.01) . Conclusion: Some workers wearing hearing protectors do not meet the required PAR, and low PARs may be related to incorrect wearing methods and incorrect selection of hearing protectors. As a tool for testing, training, and assisting in selection, the hearing protector suitability testing system is of great significance for worker hearing protection.

[Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension].

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

[Inter-laboratory comparison analysis of noise measurement in 91 occupational hygiene technical service organizations].

Objective: To understand the comparability of noise measurement results of various occupational hygiene technical service organizations in Guangdong Province by conducting inter-laboratory comparison of measuring instruments and personnel operation. Methods: In October 2020, the instrument comparison and personnel comparison among 91 occupational hygiene technical service organizations engaged in noise measurement in Guangdong Province were carried out in the form of fixed-point measurement and simulated workplace measurement, and the results were analyzed and evaluated by using the robust z-ratio score. Results: In the instrument comparison, 6 organizations had 1 or 2 outliers in their z-ratio scores, 2 organizations had 2 problematic values in their z-ratio scores, and a total of 8 organizations (accounting for 8.8%) were judged as unqualified; A total of 83 organizations (accounting for 91.2%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. In the personnel comparison, there were 11 organizations with 1 or 2 outliers in the z-ratio score, and 1 organization with 2 problematic values in the z-ratio score. A total of 12 organizations (13.2%) were judged as unqualified and 79 organizations (accounting for 86.8%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. Through comprehensive judgment, 20 organizations (22.0%) were judged as unqualified, and 71 organizations (78.0%) were judged as qualified. There was no statistically significant difference in the qualified rates of instrument comparison results, personnel comparison results and comprehensive evaluation results of non-private organizations and private organizations (P>0.05). There was no significant difference in the qualified rates of instrument comparison results and comprehensive evaluation results of qualified organizations and unqualified organizations (P>0.05), there was significant difference in the qualified rate of personnel comparison results (P<0.05) . Conclusion: The noise measurement results of some occupational health technical service organizations in Guangdong Province are generally comparable. To carry out inter-laboratory comparison of noise instrument performance and personnel operation ability of occupational hygiene technical service organizations, can comprehensively evaluate the testing process of each organization and find out the problems existing in each organization.

[Risk assessment on noise-induced hearing loss of 488 workers in a petrochemical plant].

Objective: To assess the risk of noise-induced hearing loss in workers from a petrochemical plant. Methods: In October 2020, 488 male workers exposed to noise in a petrochemical plant in Guangdong Province were selected by cluster sampling. Acoustics-Estimation of Noise-Induced Hearing Loss (ISO 1999: 2013) was used to assess the risk of noise-induced hearing loss of workers, and individual fit testing was used to evaluate the sound attenuation obtained by the workers. The risk assessment results and fitness test results of workers with different hearing levels were compared. Results: The average noise exposure equivalent sound level of the workers in the petrochemical plant was 86.7 dB (A) . The median of PARs (personal attenuation ratings) was 16 (4, 23) dB. There were statistically significant differences in age and service years among workers with different hearing results (P<0.05) , but no statistically significant differences in noise intensity and PARs (P>0.05) . According to risk assessment results of ISO 1999: 2013, the current risk of high-frequency hearing loss in 488 workers were negligible risk and acceptable risk. The risk of noise-induced deafness weredivided into three levels: negligible risk in 452 workers (92.7%) , medium risk in 27 workers (5.5%) and high risk in 9 workers (1.8%) . The risk of high-frequency hearing loss in next 5 to 15 years for workers with noise exposure level of >94 to 97 dB and >97 dB or above would be medium risk or above. The risk of noise-induced deafness in next 5 to 15 years for workers exposed to noise withlevel of 91 to 94 dB would be medium risk or above. Conclusion: The risk of noise-induced hearing loss in workers from the petrochemical plant is high in next 5 to 15 years, and noise prevention and control measures need to be strengthened. ISO1999: 2013 assessment method may underestimate the risk of hearing loss among workers.

Room temperature mid-infrared fiber lasing beyond 5 µm in chalcogenide glass small-core step index fiber.

This Letter, to the best of our knowledge, reports mid-infrared fiber lasing beyond 5 µm at room temperature for the first time, Ce3+-doped, chalcogenide glass, step index fiber employed in-band pumping with a 4.15 µm quantum cascade laser. The lasing fiber is was 64 mm long, with a calculated numerical aperture of 0.48 at the lasing wavelengths. The core glass was Ge15As21Ga1Se63 atomic % (at. %), doped with 500 parts-per-million-by-weight Ce, with a 9 µm core diameter. The cladding glass was Ge21Sb10Se69 at. % with a 190 µm outer diameter. As pump power increases continuous wave lasing corresponding to the 2F7/2→2F5/2, transition in the Ce3+ ion occurs at 5.14 µm, 5.17 µm, and 5.28 µm.

[Study on the expression of microRNA-1825 in serum of pre-operative and post-operative patients with breast cancer].

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients(n=92), post-operative breast cancer patients(n=64) and healthy subjects(n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA (r=0.274, P=0.008) and CA15-3 (r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95%CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

[Analysis on job burnout status and its influencing factors among female workers of labor-intensive enterprises].

Objective: To analyze the status and its influencing factors of job burnout among female workers of labor-intensive enterprises. Methods: A total of 750 female workers from 5 labor-intensive enterprises in Guangdong Province were selected as the study subjects by random cluster sampling method in August, 2019. 665 valid questionnaires were collected, and the effective recovery rate was 88.67%. The Maslach Burnout Inventory-General Survey was used to assess job burnout and its influencing factors were analyzed. Results: Among 665 female workers, 429 (64.51%) found to have different levels of burnout, among which 380 (57.14%) were mild to moderate burnout and 49 (7.37%) were severe burnout. The comprehensive scores of job burnout in different age, marital status, current post working age, working time per week, personal monthly income, working system and occupational stress groups were statistically significant (P<0.01) . There were significant differences in the score of emotional exhaustion in different age, marital status, current working age, working time per week, personal monthly income and occupational stress groups (P<0.05) . There were significant differences in the dimensions of depersonalization in different age, weekly work time, personal monthly income, working system and occupational stress groups (P<0.05) . There were significant differences in the dimensions of low individual achievement in different education levels, weekly work time, working system and occupational stress groups (P<0.05) . Conclusion: The female workers of labor-intensive enterprises are generally have mild to moderate job burnout. The main influencing factors of job burnout are weekly work time and occupational stress.

High-Brightness Continuous-Wave Electron Beams from Superconducting Radio-Frequency Photoemission Gun.

Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK_{2}Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC/bunch) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.

Mitochondrial Damage due to Hypoxia and Its Forensic Significance.

ABSTRACT: Mitochondria are the special organelle in eukaryotic cells. Their main functions are to synthesize energy required for cell activity by oxidative phosphorylation. Most of the oxygen absorbed by the body is consumed in the mitochondria. The precise diagnosis of mechanical asphyxia is one of the difficulties in forensic pathology practice. Forensic pathologists have been trying to find a reliable and sensitive marker for the diagnosis of mechanical asphyxia. Mitochondria are very sensitive to hypoxic environments, and the markers of mitochondrion damage can be used as a basis for the diagnosis of mechanical asphyxia. The purpose of this paper is to review the research progress on mitochondrial damage in hypoxic environments and to explore the possibility of using markers of mitochondrion damage in forensic pathological practice.

MicroRNA-466a-3p attenuates allergic nasal inflammation in mice by targeting GATA3.

Allergic rhinitis is thought to be an allergic disease associated with immunoglobulin (Ig)E-mediated immune response, characterized by increased T helper type 2 (Th2) cytokine production, elevated eosinophil levels in the nasal mucosa and induced nasal secretions. MicroRNA (miRNA) microarray data revealed that the expression level of miR-466a-3p was significantly decreased. Notably, GATA binding protein (GATA-3) was identified as one of its target genes through miRNA target prediction web tools. The expression levels of miR-466a-3p were altered by mimics and lentivirus both in vivo and in vitro, similar to those of GATA-3. Furthermore, the symptoms and histology of allergic rhinitis as well as the levels of serum IgE and interleukin (IL)-4 were examined in different groups of mice. Interestingly, the results for lentiviral miR-466a-3p-treated allergic rhinitis mice were relatively similar to normal mice, compared to allergic rhinitis mice without treatment. Also, miR-466a-3p negatively regulated GATA-3 expression in allergic rhinitis mice, indicating the participant of Th2-cell responses in allergic rhinitis. Taken together, our findings highlight a new perspective on the role of miR-466a-3p in allergic rhinitis. In addition, this study provides a theoretical framework and experimental reference for future research targeting microRNAs as therapeutic targets and diagnostic biomarkers of allergic rhinitis.

[Differences in circRNA expression profiles between HER-2-positive breast cancer cells and normal mammary epithelial cells].

Objective: To investigate the differential expression profiles of circular RNA (circRNA) in human epidermal growth factor receptor 2 (HER-2) positive breast cancer cells and normal mammary epithelial cells, and to develop novel diagnostic and therapeutic markers for HER-2 positive breast cancer. Methods: Total RNA were extracted from HER-2 positive breast cancer cell SK-BR-3 and normal mammary epithelial cell MCF10A. RNA quality was detected using NanoDrop ND-1000. Rnase R was applied to remove linear RNA and enrich circRNAs. After amplification and reverse transcription into fluorescent complementary RNA (cRNA) using random primer, the labeled cRNAs were hybridized onto the Arraystar Human circRNA Arrays. The raw data were extracted and the acquired array images were subjected to quantile normalization followed by heat map and volcano plot analysis. The expression of circRNAs with large fold change was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in the differentially expressed circRNAs and circRNA-microRNA (miRNA) network was constructed. Results: The total RNA extracted from SK-BR-3 and MCF10A had high integrity and quality. The expression profiles of circRNA in SK-BR-3 and MCF10A cells were significantly different shown by fluorescent expression signals. Compared with MCF10A cells, there were 6 584 up-regulated circRNAs and 6254 down-regulated circRNAs in SK-BR-3 cells. There were 348 circRNAs with |log(2)FC|≥2, of which 153 were up-regulated and 195 were down-regulated. Moreover, 8 circRNAs with |log(2)FC|>5. Among them, 5 were up-regulated in SK-BR-3 cells, including hsa_circRNA_074595 (|log(2)FC|=7.84), hsa_circRNA_074598 (|log(2)FC|=6.50), hsa_circRNA_085362 (|log(2)FC|=5.86), hsa_circRNA_101379 (|log(2)FC|=5.71) and hsa_circRNA_406683 (|log(2)FC|=5.34); as well as 3 were down-regulated, including hsa_circRNA_021714 (|log(2)FC|=5.46), hsa_circRNA_100777 (|log(2)FC|=5.40), and hsa_circRNA_100796 (|log(2)FC|=5.03). The expression levels of hsa_circRNA_074595, hsa_circRNA_074598 and hsa_circRNA_100777 were further validated by RT-qPCR in consistent with the results of microarray. GO analysis showed that differentially expressed circRNAs were significantly enriched in the biological process of heart development (P<0.001), cellular component in the cell adhesion-related components (P<0.001), molecular function in protein serine/threonine kinase activity (P<0.001). KEGG analysis revealed that differentially expressed circRNAs were significantly enriched in the PI3K-Akt signaling pathway. Conclusions: The expression profile of circRNA in HER-2 positive breast cancer cells is significantly different from that in normal mammary epithelial cells. The differentially expressed circRNAs may be served as potential diagnostic or therapeutic targets for HER-2 positive breast cancer.

Research Progress on Age Estimation Based on DNA Methylation.

ABSTRACT: Age estimation is of great significance in the fields of criminal investigation and forensic identification. It can provide the age information of individuals to judicial departments to facilitate the development of judicial work. In recent years, age estimation methods expanded from the morphological level to the molecular biology level. With the rapid development of epigenetics represented by DNA methylation, and the advancement of DNA methylation detection technology together with the detection platform, many age estimation methods based on DNA methylation biomarkers, or using several biological fluids, such as blood, blood stains, saliva, semen stains, etc. are developed. Currently, researches related to age estimation based on DNA methylation are relatively widely carried out. This paper summarizes the researches on age estimation based on DNA methylation, in order to provide references for related studies and forensic applications.

[Primary study on the relationship between high-risk HPV infection and vaginal cervical microbiota].

Objective: To understand characteristics of vaginal cervical microbiota in high-risk HPV (hrHPV) infected women and to uncover the relationship between hrHPV infection and vaginal cervical microbiota. Methods: All participants were randomly selected from Peking University First Hospital from September to October of 2017, including 5 subjects of control group, 5 cases of HPV16/18 group, 5 cases of other hrHPV infected group and 3 cases of cervical squamous carcinoma group. All subjects were required to fill in a questionnaire, and cervical and vaginal discharges were separately collected for microscopic examination and new generation sequencing targeting the variable region (V3-V4) of bacterial 16S rRNA gene. Results: Vaginal microbiota analysis: (1) 6 major phylum were found in vaginal microbiota:Firmicutes, Bacteroidetes, Fusobacteria, Actinobacteria, Tenericutes and Proteobacteria. Firmicutes contributed to the majority of normal vaginal flora, Bacteroidetes and Fusobacteria increased in hrHPV infected ones, while Fusobacteria showed significant difference in cervical carcinoma group. (2) Lactobacillus occupied most of normal vaginal flora while genus like Gardnella, Prevotella, Atopobium, Megasphaera and Sneathia increased in hrHPV infected subjects, Sneathia showed significant difference in cervical carcinoma group. (3) No significant difference had been calculated in Alpha diversity of four groups (P=0.073) . Cervical microbiota analysis: (1) Microbial diversity of cervical microbiota was higher than that of vaginal microbiota. (2) Significant difference had been found in Alpha diversity of four groups (P=0.046) . (3) Proteobacteria in normal cervical flora was much more than that in vagina, and Proteobacteria increased significantly in hrHPV infected cervical discharge. (3) Chlamydia increased significantly in cervical carcinoma group. Conclusions: The diversity of cervical microbiota is higher than that of vaginal microbiota. Change in cervical microbiota is more obvious than that of vagina in hrHPV infected subjects. Fusobacteria-Sneathia and Chlamydia significantly increase in cervical carcinoma group. Proteobacteria might relate to hrHPV infection.

Adeno-associated virus-mediated expression of myostatin propeptide improves the growth of skeletal muscle and attenuates hyperglycemia in db/db mice.

Inhibition of myostatin, a negative growth modulator for muscle, can functionally enhance muscle mass and improve glucose and fat metabolism in myostatin propeptide (MPRO) transgenic mice. This study was to investigate whether myostatin inhibition by adeno-associated virus (AAV)-mediated gene delivery of MPRO could improve muscle mass and achieve therapeutic effects on glucose regulation and lipid metabolism in the db/db mice and the mechanisms involved in that process. Eight-week-old male db/db mice were administered saline, AAV-GFP and AAV-MPRO/Fc vectors and monitored random blood glucose levels and body weight for 36 weeks. Body weight gain was not different during follow-up among the groups, but AAV-MPRO/Fc vectors resulted high level of MPRO in the blood companied by an increase in skeletal muscle mass and muscle hypertrophy. In addition, AAV-MPRO/Fc-treated db/db mice showed significantly lower blood glucose and insulin levels and significantly increased glucose tolerance and insulin sensitivity compared with the control groups (P<0.05). Moreover, these mice exhibited lower triglyceride (TG) and free fatty acid (FFA) content in the skeletal muscle, although no difference was observed in fat pad weights and serum TG and FFA levels. Finally, AAV-MPRO/Fc-treated mice had enhanced insulin signaling in the skeletal muscle. These data suggest that AAV-mediated MPRO therapy may provide an important clue for potential clinical applications to prevent type II diabetes, and these studies confirm that MPRO is a therapeutic target for type II diabetes.

The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis.

Juvenile amyotrophic lateral sclerosis (JALS) occurs at an age of onset below 25 years with a heterogeneous disease onset location, variable progression and survival time. To investigate whether an ALS gene profile could resolve any aspects of clinical symptom heterogeneity, we have used targeted sequencing technology in a cohort of 12 JALS patients of Chinese descent. We detected 5 likely pathogenic mutations, 2 in familial probands and 3 in sporadic patients. One was a known TARDBP mutation (p.G348V) and 4 were FUS frameshift mutations including a known p.Gln519Ilefs*9 mutation and 3 novel mutations, p.Gly515Valfs*14, p.Gly486Profs*30, and p.Arg498Alafs*32. Of the 4 FUS mutations, 2 were able to be confirmed as de novo mutations. The TARDBP mutation carrier showed a classic ALS phenotype. All patients with FUS mutations experienced limb weakness at an early age and developed bulbar symptoms during the disease course. FUS mutations have previously been associated with increased JALS disease progression, however, we found a large range 12 to 84 months in disease survival (mean 58.2 months). Our results justify future screening for variants in FUS as it remains the most frequent genetic determinant of early onset, JALS (found in 30% of our patients).

Lack of Association between SLC6A11 Genetic Polymorphisms and Drug Resistant Epilepsy in Chinese Han Population.

BACKGROUND: Epilepsy is one of the most common chronic neurological diseases. A recent study has implicated that the genetic variants of the SLC6A11 gene encoding GAT-3, an astrocytic GABA transporter, may influence the efficacy of antiepileptic drugs (AEDs) in the Korean population. METHODS: This study aims to investigate the possible associations between SLC6A11 gene and drug resistance in Chinese epilepsy patients. Genomic DNA from 240 drug resistant epilepsy (DRE) patients and 336 drug responsive epilepsy patients was tested for the polymorphisms using Illumina GoldenGate assay. RESULTS: None of the 14 tagSNP alleles and genotypes were found to be related to DRE. The frequencies of haplotype 5 was obviously lower in DRE patients than that in drug responsive epilepsy patients (1% vs. 4%, OR = 2.56 [0.107 - 0.763], p = 0.01). However, after the correction of multiple comparisons with Bonferroni's method, we found that haplotype 5 was not associated with DRE. CONCLUSIONS: Our study suggested no existing association between the 14 SNPs of SLC6A11 and AEDs efficacy in the Chinese Han population.

In Touch With the Mechanosensitive Piezo Channels: Structure, Ion Permeation, and Mechanotransduction.

Mechanotransduction, the conversion of mechanical forces into biological signals, plays critical roles in various physiological and pathophysiological processes in mammals, such as conscious sensing of touch, pain, and sound, as well as unconscious sensing of blood flow-associated shear stress, urine flow, and bladder distention. Among the various molecules involved in mechanotransduction, mechanosensitive (MS) cation channels have long been postulated to represent one critical class of mechanotransducers that directly and rapidly converts mechanical force into electrochemical signals. Despite the awareness of their functional significance, the molecular identities of MS cation channels in mammals had remained elusive for decades till the groundbreaking finding that the Piezo family of genes, including Piezo1 and Piezo2, constitutes their essential components. Since their identification about 6years ago, tremendous progress has been made in understanding their physiological and pathophysiological importance in mechanotransduction and their structure-function relationships of being the prototypic class of mammalian MS cation channels. On the one hand, Piezo proteins have been demonstrated to serve as physiologically and pathophysiologically important mechanotransducers for most, if not all, mechanotransduction processes. On the other hand, they have been shown to form a remarkable three-bladed, propeller-shaped homotrimeric channel complex comprising a separable ion-conducting pore module and mechanotransduction modules. In this chapter, we review the major advancements, with a particular focus on the structural and biophysical features that enable Piezo proteins to serve as sophisticated MS cation channels for force sensing, transduction, and ion conduction.

[Adult Stature Estimation by Multiple Parameters of Body Torso Segment].

OBJECTIVES: To promote the further research on body stature estimation and the innovative applications based on the distances between the anatomical landmarks on body torso surface. METHODS: A specification for the collection of distances between the anatomical landmarks on body torso surface was established. The data of 933 cases of adult population in Yangtze River Delta region were collected. Multiple linear regression method was used to statistical analyse and establish the regression equation of stature estimation. RESULTS: A regression equation about 5 variables including gender （x1）, cervical vertebrae-coccyx line （x2）, sterna-pubis line （x3）, distance between acromion and iliospinale anterius （x4） and shoulder breadth （x5）, and stature （y） was established, y=105.406+5.414 x1+0.436 x2+0.286 x3+0.225 x4+ 0.193 x5. CONCLUSIONS: The method is suitable for the rapid, simple and accurate estimation of stature for the forensic experts.