DNA Methylation and mRNA Expression of B7-H3 Gene in Ankylosing Spondylitis: A Case-Control Study.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory arthritis, with a high prevalence in patients in their mid-20s. Its pathogenesis is not well understood; however, genetic factors likely play a critical role. Epigenetic DNA changes may be involved in the pathogenesis of AS. In this study, we explored the methylation and transcription levels of the B7-H3 gene and its association with AS in an eastern Chinese Han population. METHODS: Peripheral blood of AS patients and healthy controls was used to extract genomic DNA and B7-H3 methylation levels were analyzed using sodium bisulfite followed by multiplex polymerase chain reaction. SPSS software was used to determine the statistical significance of the results. RESULTS: Hypomethylation of the promoter of the B7-H3 gene was observed in AS patients, whereas the B7-H3 gene expression was significantly enhanced in AS patients. CONCLUSION: Epigenetic modifications of B7-H3 were associated with susceptibility to AS. Hypomethylation of the B7-H3 promoter, which leads to B7-H3 overexpression, may be involved in the pathogenesis of AS.

Telomere length in patients with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Telomere length (TL) as a biomarker of aging was associated with many age-related diseases. The relationship between TL and osteoarthritis (OA), the most common form of joint diseases, had been investigated in a number of studies, but with the result inconsistent. AIMS: The purpose of this study was to systematically evaluate the relationship between TL and OA. METHODS: Until January 1, 2021, PubMed, Web of Science and Cochrane Library were comprehensively retrieved for relevant literatures. Quality of included literature was assessed using the Newcastle-Ottawa Scale (NOS) assessment scale. The pooled standard mean difference (SMD) with 95% confidence interval (CI) of Leukocytes TL was calculated using random-effect model. Subgroup analysis and meta-regression were used to investigate the potential source of heterogeneity. RESULTS: Six original studies containing 678 OA patients and 1457 healthy controls were included in this meta-analysis. All six included studies were case-control designed. Pooled results showed that patients with OA had a shorter TL in peripheral blood leukocytes (PBLs) compared with healthy controls, (SMD = - 0.32, 95% CI - 0.57 to - 0.06, Z = - 2.45, P = 0.014). Subgroup and meta-regression analysis showed that sex ratio and body mass index (BMI) were possible sources of heterogeneity. Publication bias was not observed. CONCLUSION: The TL of PBLs in patients with OA was shorter than that of healthy controls, suggesting that PBLs TL may be closely associated with the pathogenesis and progression of OA.

Non-Contact Heart Rate Detection When Face Information Is Missing during Online Learning.

Research shows that physiological signals can provide objective data support for the analysis of human emotions. At present, non-contact heart rate data have been employed in the research of medicine, intelligent transportation, smart education, etc. However, it is hard to detect heart rate data using non-contact traditional methods during head rotation, especially when face information is missing in scenarios such as online teaching/learning. Traditional remote photoplethysmography (rPPG) methods require a static, full frontal face within a fixed distance for heart rate detection. These strict requirements make it impractical to measure heart rate data in real-world scenarios, as a lot of videos only partially record the subjects' face information, such as profile, too small distance, and wearing a mask. The current algorithm aims to solve the problem of head deflections between 30 degrees and 45 degrees by employing a symmetry substitution method, which can replace the undetected region of interest (ROI) with the detectable one. When face information is partially missing, our algorithm uses face-eye location to determine ROI. The results show that the method in this paper can solve certain practical problems related to heart rate detection, with a root mean square error (RMSE) under 7.64 bpm.

Formant and voice source properties in two male Kunqu Opera roles: a pilot study.

OBJECTIVE: This investigation analyzes flow glottogram and electroglottogram (EGG) parameters as well as the relationship between formant frequencies and partials in two male Kunqu Opera roles, Colorful face (CF) and Old man (OM). PARTICIPANTS AND METHODS: Four male professional Kunqu Opera singers volunteered as participants, 2 singers for each role. Using inverse filtering of the audio signal flow glottogram parameters and formant frequencies were measured in each note of scales. Two EGG parameters, contact quotient (CoQ) and speed quotient, were measured. RESULTS: Formant tuning was observed only in 1 of the OM singers and appeared in a pitch range lower than the passaggio range of Western male opera singers. Both the CF and the OM role singers showed high CoQ values and low values of the normalized amplitude quotient in singing. For 3 of the 4 singers CoQ and the level difference between the first and second partials showed a positive and a negative correlation with fundamental frequency (F0), respectively. CONCLUSIONS: Formant tuning may be applied by a singer of the OM role, and both CF and OM role singers may use a rather pressed type of phonation, CF singers more than OM singers in the lower part of the pitch range. Most singers increased glottal adduction with rising F0.

Differences of RUNX2 gene promoter methylation and transcription level in ankylosing spondylitis.

BACKGROUND AND OBJECTIVE: Ankylosing spondylitis is a refractory immune disease that seriously affects the life and work of patients. Epigenetic modifications, especially DNA methylation, have become a research hotspot in complex diseases. We aim to explore the changes in runt-related transcription factor 2 (RUNX2) gene promoter methylation and transcription level in AS. METHOD: We detected the RUNX2 gene promoter methylation in 83 AS patients and 83 healthy controls (HCs), then inspected the mRNA difference of RUNX2 between 30 AS patients and 30 HCs by the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The RUNX2 gene promoter was hypomethylated in AS patients compared to HCs (p < .001). The research involved 4 CpG regions and 74 CpG sites of RUNX2, of which CpG-2, CpG-4 regions, and 18 CpG sites have been differentially methylated. The CpG-4 island methylation was negatively correlated with C-reactive protein (p < .05) in AS patients. In the qRT-PCR validation phase, the mRNA level of RUNX2 in AS patients was significantly higher than HCs (p < .05), and in AS patients who were treated with biologics, the methylation level of CpG-2 island showed a negative correlation to mRNA (p < .05). ROC results indicated that RUNX2 methylation and its transcription level have good potential to distinguish AS patients from HCs. CONCLUSION: The RUNX2 gene promoter was hypomethylated in AS patients. Meanwhile, the qRT-PCR verified the up-regulated expression on the transcription level, suggesting the abnormal methylation of RUNX2 contributes to the pathogenesis of AS.

PRICKLE1 gene methylation and abnormal transcription in Chinese patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory arthritis without a reliable biomarker. The role of methylation and mRNA expression of PRICKLE1 promoter in the pathogenesis of ankylosing spondylitis remains unclear. METHODS: A two-stage case-control design was used to detect the characteristics of methyl group and transcriptome of PRICKLE1 gene in Ankylosing spondylitis. The methylation degree of PRICKLE1 gene promoter region was tested by phosphate-sequencing, and further analyzed whether there was significant difference in methylation level of PRICKLE1 gene. The expression levels of PRICKLE1 mRNA in 50 AS patients and 50 healthy controls were detected by real-time quantitative PCR (RT-qPCR). RESULTS: Compared with healthy control group, the intensity of methylation in 4 ponds of PRICKLE1 in patients with Ankylosing spondylitis was low, and the mRNA levels were overexpressed (P = 0.017). ROC results showed that the sensitivity of PRICKLE1 was 68.67% and specificity was 71.43%. CONCLUSION: There is a significant change in the concentration of serum PRICKLE1 mRNA​in patients with Ankylosing spondylitis, and the degree of gene methylation is significantly reduced, suggesting that PRICKLE1 gene maybe involved in the pathogenesis of Ankylosing spondylitis, which may be useful for predicting the occurrence of AS and finding new early screening indicators.

Prevalence and risk of COVID-19 in patients with rheumatic diseases: a systematic review and meta-analysis.

OBJECTIVES: COVID-19 pandemic has already had a tremendous impact on the process of human society; the survival of mankind and the healthy living environment deterioration with the influence will last for many years. This meta-analysis aims to assess the risk of COVID-19 in patients with rheumatic diseases. METHODS: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) were systematically searched with no language restriction up to July 5, 2021. The pooled rates were synthesized by fixed effect model or random effect model depending on heterogeneity. RESULTS: A total of 83 articles were included in this meta-analysis. The incidence of COVID-19 in patient with rheumatic diseases was 0.0190 (95% CI: 0.0136-0.0252), and the hospitalization rate, intensive care unit admission rate, mechanical ventilation rate, and case fatality rate of patients with rheumatic diseases infected with COVID-19 were 0.4396 (95% CI: 0.3899-0.4898), 0.0635 (95% CI: 0.0453-0.0836), 0.0461 (95% CI: 0.0330-0.0609), and 0.0346 (95% CI: 0.0218-0.0493), respectively. CONCLUSIONS: Our research shows that patients with rheumatic diseases have great risk of COVID-19. Differences in COVID-19 incidence, hospitalization rates, and mortality rates in regions were statistically significant. We still need to pay attention to the risk of COVID-19 in patients with rheumatic diseases. KEY POINTS: • Although the risk of COVID-19 in patients with rheumatic diseases has been discussed in previous meta-analysis, their research directions were inconsistent, and few studies focus on prevalence or serious outcomes of COVID-19 in patient with rheumatic diseases, while the quality of these articles was variable. • The incidence of COVID-19 and serious clinical outcomes in patients with rheumatic diseases were still high along with differential risks in most regions. • The use of glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs did not affect the hospitalization rate and mortality in rheumatism patients with COVID-19.

Association of CTLA-4 (+49 A/G) polymorphism with susceptibility to autoimmune diseases: A meta-analysis with trial sequential analysis.

OBJECTIVES: In recent years, more and more studies have been focusing on the association between Cytotoxic T lymphocyte antigen-4 (CTLA-4) (+49 A/G) gene polymorphism and autoimmune diseases. However, the results of previous studies are still controversial. The meta-analysis is aiming at determining the association in CTLA-4 (+49 A/G) gene rs231775 polymorphism and ankylosing spondylitis (AS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE). METHODS: We searched PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM) up to November 2020, use random or fixed-effect models to perform meta-analysis to compare alleles and other genetic models, including homozygous, heterozygous, recessive and dominant models. The odds ratio (OR) with a 95% confidence interval (95% CI) was used to assess the correlation between CTLA-4 (+49 A/G) gene polymorphism and the genetic affectability of AS, RA, and SLE. Meanwhile, we used sequential trial analysis (TSA) to analyze the reliability of the results. Finally, we searched the relevant data of genome-wide association studies (GWAS) to further verify the accuracy of the experimental results. RESULTS: 47 studies with 11,893 cases and 12,032 healthy controls were included. The rs231775 G allele was relevant to high risk of autoimmune disease over all people (P < 0.05). The G allele of rs231775 was significantly related to RA susceptibility (P < 0.05), but not with AS or SLE. Subgroup analysis by ethnicity indicated that rs231775 G allele was closely related to RA in Caucasian populations and Mongolian populations (P < 0.05). A strong connection within rs231775 G allele and AS affectability was uncovered in Caucasian populations (P < 0.05). The analysis of the TSA shows that the meta-analysis can draw the conclusion. CONCLUSION: CTLA-4 (+49 A/G) gene rs231775 G allele increases the risk of autoimmune diseases in Caucasian populations. And it also increases the risk of RA in Caucasian and Mongolian populations. More sample size and more elaborately designed studies are needed to elucidate the relationship in CTLA-4 (+49 A/G) gene rs231775 G allele and autoimmune diseases, especially AS, SLE.

Single nucleotide polymorphisms of TRAF2 and TRAF5 gene in ankylosing spondylitis: a case-control study.

Objective To investigate the role of eight locus polymorphisms of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF5 gene and their interaction in the susceptibility to ankylosing spondylitis (AS) in Chinese Han population. Methods Eight single nucleotide polymorphisms (SNPs) of TRAF2 (rs3750511, rs10781522, rs17250673, rs59471504) and TRAF5 (rs6540679, rs12569232, rs4951523, rs7514863) gene were genotyped in 673 AS patients and 687 controls. Results The SNPs of TRAF2 and TRAF5 do not indicate a correlation with the susceptibility of AS in Chinese Han population. Genotype frequencies of rs3750511 were statistically significant in females between patients and controls. The allele frequencies of rs10781522 and genotype frequencies of rs3750511 were statistically significant between groups of different diseases activity. One three-locus model, TRAF2 (rs10781522, rs17250673) and TRAF5 (rs12569232), had a maximum testing accuracy of 52.67% and a maximum cross-validation consistency (10/10) that was significant at the level of P = 0.0001, after determined empirically by permutation testing. As to environmental variables, only marginal association was found between sleep quality and AS susceptibility. Conclusion TRAF2 rs3750511 polymorphism may be associated with the susceptibility and severity of AS. Besides, the interaction of TRAF2 and TRAF5 genes may be associated with AS susceptibility, but many open questions remain.

The development of phonological awareness and Pinyin knowledge in Mandarin-speaking school-aged children.

PURPOSE: The writing of Chinese is non-alphabetic, but children in China learn Pinyin, a Romanised alphabetic system, to facilitate literacy development. This research investigates how Mandarin phonological awareness (PA) develops, and how it interacts with Pinyin in school-aged Mandarin-speaking children in China. METHOD: In Beijing, 182 students in grades two through four (ages ranged between 91 and 135 months) were tested for PA (syllable manipulation and onset-rime oddity tasks) and Pinyin knowledge (Pinyin symbol naming and syllable reading tasks). ANOVAs were used to examine their developmental trajectories. Partial correlations and linear regressions were used to examine the relationships between PA and Pinyin knowledge. RESULT: Syllable awareness has already reached the ceiling level by grade two, while onset-rime awareness is still developing across grades. The ability to name Pinyin symbols decreases over time, while the ability to read syllables written in Pinyin stays invariant across grades. PA and Pinyin knowledge are significantly correlated, and the results of linear regression indicated that the relationship between PA and Pinyin syllable reading is bi-directional. CONCLUSION: This study suggests that Mandarin PA development shows features characteristic of a non-alphabetic language with Pinyin knowledge playing a crucial role. Implications for theory and practice of Mandarin-speaking children's literacy development are discussed.

Voice Characteristics of Young Girl Role in Kunqu Opera.

Three electroglottographic parameters, fundamental frequency, contact quotient, and speed quotient were analyzed for two singers of Young girl role in Kunqu Opera. Each singer performed three conditions, singing, stage speech, and reading lyrics. The phonation types adopted in different conditions were explored based on electroglottographic parameters. Fundamental frequency, contact quotient, and speed quotient showed different distributions among conditions. Five phonation types were used in singing and stage speech, which include (1) breathy voice, (2) modal voice with low degree of posterior glottal adduction, (3) modal voice, (4) falsetto, and (5) falsetto with high degree of posterior glottal adduction. The phonation strategies partly showed differences between singers. Different phonation type collocations were employed in singing and stage speech. The relationship between phonation types and pitch was complex. The phonation types actually used were different from and more complex than those in traditional Kunqu Opera singing theory.

Comparison Study of Vocal Attack Time in Patients With Cleft Palate With and Without Glottal Stop in Mandarin.

Glottal stop (GS) is a typical compensatory articulation, which has a great impact on speech intelligibility in patients with cleft palate. It is usually detected by perceptual analysis. The aim of this study is to investigate the utility of vocal attack time (VAT) values in patients with cleft palate with and without GS, when unaspirated monosyllables are articulated in Mandarin, by using electroglottography. Unaspirated monosyllables /pa/ /pi/ /pu/ /ta/ /ti/ /tu/ /ka/ /ki/ /ku/ with tone one were analyzed. A total of 575 tokens were obtained from 42 patients with cleft palate, divided into a GS category (n = 312 tokens) and a nonglottal stop (NGS) category (n = 263 tokens), as assessed perceptually by three judges. Sound pressure and electroglottography recordings were also obtained from these tokens. The time lag of the cross-correlation function was used to gain VAT values. The results showed that the mean VAT values of tokens from the GS category (-0.25 ms) was significantly shorter than that of tokens in the NGS category (3.19 ms) (t = 7.326, P < 0.001). The results also showed that there was no significant difference in VAT values between the different combined monosyllables both in GS and in NGS group. The conclusion that can be drawn from this study is that the VAT value was sensitively decreased in cleft palate Mandarin speakers with GS comparing to those without GS.

Mass spectrometry-based metabolomics and chemometric analysis of Pu-erh teas of various origins.

Pu-erh tea is one of the most popular tea beverages in China. Storage time, fermentation process and origin of production affect quality and price of Pu-erh teas. High resolution mass spectrometry-based metabolomics approach, NIR combined with chemometric analysis were used to profile water soluble metabolites from raw Bingdao Pu-erh teas stored for 1-10 years and teas from various production sites. Year prediction models with good rate of recognition were established using partial least squares analysis and factor analysis. 38 characteristic compounds were identified that can be used to distinguish length of storage of Pu-erh teas. 19 characteristic compounds were found that can be used to differentiate raw and ripened teas. Cluster analysis of Pu-erh teas from different sites showed correlation between geographical distribution of the sites and composition of the water extracts. The research provides guidance for discrimination of Pu-erh teas and helps establish a healthy tea market.

Vocal Attack Time of Different Pitch Levels and Vowels in Mandarin.

The purpose of this study was to investigate how vocal attack time (VAT) varies when young adults articulate the three vertex vowels in Mandarin Chinese at five linguistically unconstrained pitch levels. Sound pressure and electroglottographic signals were recorded simultaneously from 53 male and 53 female subjects saying sustained /A/, /i/, and /u/ at five equally spaced pitch heights, each being higher than the preceding one. Then analyses of means, variance, and correlation were performed to explore the relationships of VAT/pitch levels and VAT/vowels. Findings were As mean STs (semitone) increase linearly from levels 1 to 5, mean VATs decrease nonlinearly in a big group of subjects but increase nonlinearly in a small group of them. Based on the body-cover model of F0 control, data here lead to the guess that different people incline to use different strategies in increasing pitch height. When males, females, and males plus females are considered as a whole, average STs and VATs tend to be positively correlated among the three vertex vowels.

Loudness and pitch of Kunqu opera.

Equivalent sound level (Leq), sound pressure level (SPL), and fundamental frequency (F0) are analyzed in each of five Kunqu Opera roles, Young girl and Young woman, Young man, Old man, and Colorful face. Their pitch ranges are similar to those of some western opera singers (alto, alto, tenor, baritone, and baritone, respectively). Differences among tasks, conditions (stage speech, singing, and reading lyrics), singers, and roles are examined. For all singers, Leq of stage speech and singing were considerably higher than that of conversational speech. Interrole differences of Leq among tasks and singers were larger than the intrarole differences. For most roles, time domain variation of SPL differed between roles both in singing and stage speech. In singing, as compared with stage speech, SPL distribution was more concentrated and variation of SPL with time was smaller. With regard to gender and age, male roles had higher mean Leq and lower average F0, MF0, as compared with female roles. Female singers showed a wider F0 distribution for singing than for stage speech, whereas the opposite was true for male singers. The Leq of stage speech was higher than in singing for young personages. Younger female personages showed higher Leq, whereas older male personages had higher Leq. The roles performed with higher Leq tended to be sung at a lower MF0.

Long-term-average spectrum characteristics of Kunqu Opera singers' speaking, singing and stage speech.

Long-term-average spectrum (LTAS) characteristics were analyzed for ten Kunqu Opera singers, two in each of five roles. Each singer performed singing, stage speech, and conversational speech. Differences between the roles and between their performances of these three conditions are examined. After compensating for Leq difference LTAS characteristics still differ between the roles but are similar for the three conditions, especially for Colorful face (CF) and Old man roles, and especially between reading and singing. The curves show no evidence of a singer's formant cluster peak, but the CF role demonstrates a speaker's formant peak near 3 kHz. The LTAS characteristics deviate markedly from non-singers' standard conversational speech as well as from those of Western opera singing.

Quantitative high-speed laryngoscopic analysis of vocal fold vibration in fatigued voice of young karaoke singers.

PURPOSE: The present study aimed to determine whether there were physiological differences in the vocal fold vibration between nonfatigued and fatigued voices using high-speed laryngoscopic imaging and quantitative analysis. METHODS: Twenty participants aged from 18 to 23 years (mean, 21.2 years; standard deviation, 1.3 years) with normal voice were recruited to participate in an extended singing task. Vocal fatigue was induced using a singing task. High-speed laryngoscopic image recordings of /i/ phonation were taken before and after the singing task. The laryngoscopic images were semiautomatically analyzed with the quantitative high-speed video processing program to extract indices related to the anteroposterior dimension (length), transverse dimension (width), and the speed of opening and closing. RESULTS: Significant reduction in the glottal length-to-width ratio index was found after vocal fatigue. Physiologically, this indicated either a significantly shorter (anteroposteriorly) or a wider (transversely) glottis after vocal fatigue. CONCLUSION: The high-speed imaging technique using quantitative analysis has the potential for early identification of vocally fatigued voice.

A preliminary study of a quantitative analysis method for high speed laryngoscopic images.

High speed laryngoscopic study provides new information on the vocal fold vibratory patterns which has not been made possible before. Qualitative analysis of high speed laryngoscopic images is commonly reported in the literature. However, quantitative studies are necessary to provide objective measures for research and clinical purposes. This study reports the development of the High Speed Video Processing Program in analysing high-speed laryngoscopic video images obtained from 15 non-dysphonic speakers. Nine glottal ratio indices that represented the full opened glottal area, glottal width and glottal length were computed using the processing program. Data from two dysphonic participants were included to illustrate the manifestation of these glottal measures in dysphonic voices. Some of these glottal ratio index measures showed high variability across participants. However, significant differences were found in a number of index measures among the creaky, modal and falsetto registers in the non-dysphonic participants. In addition, the glottal area ratio index was found to be specifically sensitive in detecting dysphonia in high speed glottal images. The proposed semi-automatic High Speed Video Processing Program showed value in the analysis of high speed laryngoscopic images.