Effects of 6-month customized home-based exercise on motor development, bone strength, and parental stress in children with simple congenital heart disease: a single-blinded randomized clinical trial.

BACKGROUND: New "noncardiac" problems in children with congenital heart disease (CHD), such as developmental delay or long-term neurodevelopmental impairments, have attracted considerable attention in recent years. It is hypothesized that exercise might attenuate CHD-associated neurodevelopmental impairments; however, this has not been thoroughly investigated. The objective of this prospective, single-blinded, randomized controlled experiment was to evaluate the impact of customized home-based exercise for children with CHD. METHODS: Children aged 0-5 years with echocardiography-confirmed simple CHD subtypes who were scheduled to undergo cardiac catheterization were screened for enrolment. Among 420 screened CHD children, 192 were enrolled and randomly assigned at a 1:1 ratio to receive a 6-month intervention (30 min daily customized home-based exercise program with supervision for no less than 5 days per week, combined with home-based exercise education) or control treatment (home-based education). The primary outcome was motor development (gross motor quotient (GMQ), fine motor quotient (FMQ), and total motor quotient (TMQ)). The secondary outcomes were cardiac function and structure, bone quality, physical development, parental anxiety, caregiver burden, and quality of life. Children and their families were assessed before and 1, 3, and 6 months after catheterization; 183 (95.3%) children were included in the primary analysis. RESULTS: After 6-month treatment, the intervention group significantly increased their motor quotient, which was consistently higher than that of the control group (GMQ p < 0.0001, FMQ p = 0.02, TMQ p < 0.001). The physical developments in height, weight, and circumferences of the upper-arm, chest, and head were also significantly improved by exercise (all p < 0.017). No significant improvements in the bone strength or the cardiac structure and function were found among patients in the intervention group (all p > 0.017). For parents, higher quality of life level (total score p = 0.016) was observed in the intervention group; while effects of exercise on the anxiety (rude score p = 0.159, standard score p = 0.159) or the Zarit caregiver burden scale score (p = 0.404) were non-significant. No adverse events occurred during the study period. CONCLUSIONS: Customized home-based exercise improved motor development in children with CHD. While the long-term effects of parent training in home-based exercise are unknown, the study results suggest positive outcomes. TRIAL REGISTRATION: A home-based exercise program in congenital heart disease children with cardiac catheterization: a randomized controlled trial. ( http://www.chictr.org.cn/ , ChiCTR-IOR-16007762, January 14, 2016).

Compound heterozygous mutations in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. METHODS: In this study, whole-exome sequencing and cosegregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro gene expressions were used to analyze the pathogenicity of a novel CFTR mutation. RESULTS: We identified compound heterozygous mutations of CFTR comprising the known disease-causing variant c.1210-11T>G (also known as IVS9-5 T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. CONCLUSION: Our study revealed that compound heterozygous mutations of CFTR are involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.

Application of the six-minute Walk Test in Assessment of the Cardiopulmonary Function of Children with Idiopathic Scoliosis.

STUDY DESIGN: A retrospective observational study. OBSJECTIVE: To assess whether the 6-minute walk test (6MWT) can predict cardiopulmonary function in children with idiopathic scoliosis (IS) as an alternative to the cardiopulmonary exercise test (CPET). SUMMARY OF BACKGROUND DATA: Cardiopulmonary functional impairment in the setting of IS is a common health problem. A simple and convenient assessment method is needed. METHODS: We recruited 65 children (eight male, 57 female) aged 10.70-14.84 years old with IS. Radiographic characteristics of the cohort were measured, including Risser's sign and Cobb angle. We measured cardiopulmonary exercise tolerance using both the 6MWT and CPET and their corresponding indicators, including six-minute walking distance (6MWD) and peak oxygen uptake (peak VO2), respectively. Pearson correlation analysis was used to determine the relationship between 6MWT indicators and IS parameters. Linear regression models were used to explore the relationship between 6MWT and CPET response indicators. RESULTS: Over a third of the cohort (35.4%) had a Risser's sign grade of 0, with 21.5% in grade 2 and 3, respectively. The cohort's mean Cobb angle was 26.02 degrees. 6MWD was significantly positively correlated with Risser's sign (R=0.258; P=0.038) and change in respiratory rate (△RR) positively correlated with vertebral rotation (R=0.264; P=0.034). 6MWD positively correlated with peak VO2, peak VO2/heart rate (HR) and metabolic equivalents (METs), and negatively correlated with ventilation equivalent of carbon dioxide slope (VE/VCO2 slope) (P<0.05). These four CPET indicators were found to be predicted from 6MWD in the linear regression model (P<0.05). CONCLUSION: CPET response indicators, especially peak VO2, can be predicted using 6MWD among other factors. The 6MWT can therefore be used to rapidly and efficiently predict the cardiorespiratory tolerance of children with IS. LEVEL OF EVIDENCE: 3.

Effect of virtual reality combined with repetitive transcranial magnetic stimulation on musculoskeletal pain and motor development in children with spastic cerebral palsy: a protocol for a randomized controlled clinical trial.

PURPOSE: This trial aims to investigate the efficacy and safety of virtual reality (VR) combined with repetitive transcranial magnetic stimulation (rTMS) for improving musculoskeletal pain and motor development in children with unilateral spastic cerebral palsy (CP). METHODS: This study protocol is for a randomized controlled trial consisting of 2 treatment sessions (3 days/week for 4 weeks in each session, with a 1-week interval between sessions). We will recruit children aged 3-10 years with unilateral spastic CP (Gross Motor Function Classification System level I or II). Participants will be randomly divided into 3 groups: the VR + rTMS group (immersive VR intervention, rTMS and routine rehabilitation therapy), rTMS group (rTMS and routine rehabilitation therapy), and control group (sham rTMS and routine rehabilitation therapy). VR therapy will involve a daily 40-minute movement training session in a fully immersive environment. rTMS will be applied at 1 Hz over the primary motor cortex for 20 min on the contralateral side. The stimulation intensity will be set at 90% of the resting motor threshold, with 1200 pulses applied. A daily 60-minute routine rehabilitation therapy session including motor training and training in activities of daily living will be administered to all participants. The primary outcome will be pain intensity, assessed by the Revised Face, Legs, Activity, Cry, and Consolability Scale (R-FLACC). The secondary outcomes will include motor development, evaluated by the 66-item version of the Gross Motor Function Measure (GMFM-66) and Fine Motor Function Measure (FMFM); balance capacity, measured by the interactive balance system; activities of daily living; and quality of life, measured by the Barthel index and the Chinese version of the Cerebral Palsy Quality of Life scale for Children (C-CP QOL-Child). Safety will be monitored, and adverse events will be recorded during and after treatment. DISCUSSION: Combined application of VR therapy and rTMS may reveal additive effects on pain management and motor development in children with spastic CP, but further high-quality research is needed. The results of this trial may indicate whether VR therapy combined with rTMS achieves a better analgesic effect and improves the motor development of children with spastic CP. TRIAL REGISTRATION: Registration number: ChiCTR230069853. Trial registration date: 28 March 2023. Prospectively registered.

A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia.

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.

Event-Based Optimal Stealthy False Data-Injection Attacks Against Remote State Estimation Systems.

Security is a crucial issue for cyber-physical systems, and has become a hot topic up to date. From the perspective of malicious attackers, this article aims to devise an efficient scheme on false data-injection (FDI) attacks such that the performance on remote state estimation is degraded as much as possible. First, an event-based stealthy FDI attack mechanism is introduced to selectively inject false data while evading a residual-based anomaly detector. Compared with some existing methods, the main advantage of this mechanism is that it decides when to launch the FDI attacks dynamically according to real-time residuals. Second, the state estimation error covariance of the compromised system is used to evaluate the performance degradation under FDI attacks, and the larger the state estimation error covariance, the more the performance degradation. Moreover, under attack stealthiness constraints, an optimal strategy is presented to maximize the trace of the state estimation error covariance. Finally, simulation experiments are carried out to illustrate the superiority of the proposed method compared with some existing ones.

Dynamic Changes and Influencing Factors of Vegetation in the "Green Heart" Zone of the Chang-Zhu-Tan Urban Agglomeration during the Past 21 Years.

As a policy, protected green space in the rapidly developing the Chang-Zhu-Tan Urban Agglomeration is of great practical significance to study the vegetation changes and influencing factors in the Green Heart area. In this paper, data processing, grading and area statistics were carried out for the maximum value of normalized differential vegetation index (NDVI) from 2000 to 2020. Combined with Theil-Sen median trend analysis and Mann-Kendall, the change trend of long-time series NDVI was studied, and investigation of NDVI influencing factors, processes and mechanisms using geographical detectors. The results showed that: (1) The spatial distribution characteristics of NDVI in the study area were high in the middle and inlaid transition between adjacent grades. Except for the low grades, the distribution of NDVI in other grades was relatively scattered, and the overall trend of NDVI change was rising. (2) Population density was the main factor affecting NDVI changes, with an explanatory power of up to 40%, followed by elevation, precipitation and minimum temperature. (3) The influence of influencing factors on the change of NDVI was not the result of independent action of a single factor, but the result of the interaction between human factors and natural factors, and the factor combinations with greater interaction had significant differences in the spatial distribution of NDVI.

Correlation between CFTR variants and outcomes of ART in patients with CAVD in Central China.

Biallelic variants in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) are the main pathogenic factor of congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of the vas deferens (CUAVD). However, there are few reports about the correlation between CFTR variant and outcomes of assisted reproductive technology (ART) in CAVD patients of China. In this study, 104 patients with CAVD were recruited in Central China, and provided gene detection by the whole-exome sequencing, among them 69% (72/104) carried at least one variant in CFTR and one carried adhesion G protein-coupled receptor G2 (ADGRG2) variant. A total of 81 CAVD patients were treated with ART, of which 21 and 60 carried none or at least one variant in CFTR, respectively. The fertilization rate, cleavage rate, effective embryo rate, implantation rate, clinical pregnancy rate and live birth rate per fresh embryo transfer were compared between patients with and without CFTR variants. It was found that the ART outcomes had no significant difference whether the patients carried the CFTR variant or not. In addition, all of the offspring were healthy after follow-up. In conclusion, rare CFTR variants may play a major role in patients with CAVD in Central China, which were greatly different from other descent. There was no significant difference in ART outcomes in CAVD patients with or without CFTR variants. The limitations of this study were that there was no statistical analysis of the sperm quality through TESA and conclusions were relatively limited due to the small sample size of the study.

Regional disparity in epidemiological characteristics of adolescent scoliosis in China: Data from a screening program.

Objective: We investigated regional disparities in rates of scoliosis among adolescents in western and eastern China and the dominant factors underlying these disparities. Methods: This cross-sectional study used data from a school scoliosis screening program conducted in two typical areas: Yangpu District of Shanghai (eastern China) and Tianzhu Tibetan Autonomous County of Gansu Province (western China), during October 2020 to February 2021. Participants included adolescents aged 12-16 years (4,240 in Shanghai and 2,510 in Gansu Province). School scoliosis screening data were obtained on age, sex, height, weight and BMI, and region as well. We screened angles of trunk rotation in level of proximal thoracic (T1-T4), main thoracic (T5-T12), and lumbar (T12-L4) by the forward bend test with scoliometer. An angle of trunk rotation ≥5° was used as the criterion to identify suspected scoliosis. Results: The proportion of suspected scoliosis was lower in Shanghai (6.9%) than in Gansu (8.6%). Angle of trunk rotation tended to increase with age in Shanghai, peaking at 15 years, but decreased with age in Gansu, and bottomed at 15 years. The angle of trunk rotation in the proximal thoracic, main thoracic, and lumbar part of the spine appeared to be larger in Gansu adolescents and in Shanghai female adolescents. Age was a relevant factor in angle trunk rotation in regression models and interacted with region as well. Conclusion: We found regional and age- and sex-related disparities in rates of suspected scoliosis.

Effect of Wearable Sensor-Based Exercise on Musculoskeletal Disorders in Individuals With Neurodegenerative Diseases: A Systematic Review and Meta-Analysis.

Background: The application of wearable sensor technology in an exercise intervention provides a new method for the standardization and accuracy of intervention. Considering that the deterioration of musculoskeletal conditions is of serious concern in patients with neurodegenerative diseases, it is worthwhile to clarify the effect of wearable sensor-based exercise on musculoskeletal disorders in such patients compared with traditional exercise. Methods: Five health science-related databases, including PubMed, Cochrane Library, Embase, Web of Science, and Ebsco Cumulative Index to Nursing and Allied Health, were systematically searched. The protocol number of the study is PROSPERO CRD42022319763. Randomized controlled trials (RCTs) that were published up to March 2022 and written in English were included. Balance was the primary outcome measure, comprising questionnaires on postural stability and computerized dynamic posturography. The secondary outcome measures are motor symptoms, mobility ability, functional gait abilities, fall-associated self-efficacy, and adverse events. Stata version 16.0 was used for statistical analysis, and the weighted mean difference (WMD) was selected as the effect size with a 95% confidence interval (CI). Results: Fifteen RCTs involving 488 participants with mean ages ranging from 58.6 to 81.6 years were included in this review, with 14 of them being pooled in a quantitative meta-analysis. Only five included studies showed a low risk of bias. The Berg balance scale (BBS) was used in nine studies, and the pooled data showed a significant improvement in the wearable sensor-based exercise group compared with the traditional exercise group after 3-12-week intervention (WMD = 1.43; 95% CI, 0.50 to 2.36, P = 0.003). A significant change in visual score was found both post-assessment and at 1-month follow-up assessment (WMD = 4.38; 95% CI, 1.69 to 7.07, P = 0.001; I2 = 0.0%). However, no significant differences were found between the two groups in the secondary outcome measures (all p > 0.05). No major adverse events were reported. Conclusion: The wearable sensor-based exercise had advantages in improving balance in patients with neurodegenerative diseases, while there was a lack of evidence in motor symptoms, mobility, and functional gait ability enhancement. Future studies are recommended to construct a comprehensive rehabilitation treatment system for the improvement in both postural control and quality of life. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/, identifier CRD42022319763.

Unique CoWO4@WO3 heterostructured nanosheets with superior electrochemical performances for all-solid-state supercapacitors.

Transition metal oxide-based battery-type electrode materials with well-defined nanostructure have shown great potential in supercapacitors, due to their high electrical conductivity and superior redox activity. Herein, promising CoWO4@WO3-1 heterostructured nanosheets with rich oxygen vacancies are designed via a two-step in situ construction process and following thermal treatment. The CoWO4@WO3-1 heterostructured nanosheet arrays grown on a flexible carbon cloth substrate can provide an effective nanoporous framework, facilitate electrons/ions transport, and generate effective synergistic effect of high conductivity from WO3 and superior redox activity from CoWO4. As a result, the as-prepared CoWO4@WO3-1 electrodes exhibit a high area specific capacity of 578.6 mF cm-2 at a current density of 0.5 mA cm-2 and keep 98.38% capacity retention at 20 mA cm-2 over 30 000 cycles. Additionally, all-solid-state supercapacitors assembled with CoWO4@WO3-1 as cathodes and Ov-NiMoO4 as anodes show a maximum area energy density of 13.93 mW h cm-2 and power density of 6502.11 mW cm-2, keeping outstanding cycling stability of 98.1% capacity retention over 20 000 cycles.

Ethnic Disparity in the Incidence of Scoliosis Among Adolescents in Tianzhu Tibetan Autonomous County, China.

Objectives: To determine the influence of ethnic disparities, socioeconomic status (SES) and hukou on the incidence of scoliosis. Methods: We enrolled 2,445 junior high school students (Han: 1,153; ethnic minorities: 1,292) aged 12-16 years from two schools in Tianzhu Tibetan Autonomous County, Gansu Province from November 2020 to February 2021. We measured the angle of trunk rotation (ATR) using a scoliometer. Two-factor analysis of variance was used to comparatively analyze differences in the ATR according to ethnicity, age, sex, body mass index (BMI), and SES between the groups. Associations between risk factors and scoliosis were estimated using odds ratios and 95% confidence intervals with an unconditional multivariate logistic regression model for the two groups. Results: Adolescents with Han ethnicity were more likely to have scoliosis than their ethnic minority counterparts (10.8% vs. 7.1%, P < 0.05). The ATR value in the Han group decreased with age whereas the minority group showed an upward trend (P < 0.05). The difference between ethnic groups was not significant, only at level 3. In particular, the ATR values among Han girls were significantly higher than those of ethnic minority girls (P < 0.05). Compared with Han adolescents, the BMI of ethnic minorities had a greater impact on the ATR. A statistically significant difference in SES was found between the two ethnic groups (P < 0.05). Hukou and parents' occupation had an important influence on the onset of scoliosis. Conclusions: Han adolescents had higher ATR values and were more likely to have scoliosis than ethnic minority adolescents in our study. Growth and development indicators (height and BMI) and differences in SES between the two groups played an important role.

The effect of intestinal flora intervention on bone development in children: A systematic review and meta-analysis.

BACKGROUND: The intestinal flora is involved in the bone development of children through a variety of mechanisms, but it remains unclear whether intervention of the intestinal flora can enhance children's bone development. METHODS: Six databases (PubMed, Web of Science, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health, and China National Knowledge Infrastructure) were searched for all English and Chinese studies published up to August 2021. Stata version 16.0 (StataCorp, College Station, TX, USA) was used. Bone mass density and biochemical markers related to bone metabolism were reported as the primary outcome, and the secondary outcomes were anthropometric parameters such as height, height Z score for age, and height velocity. Intergroup differences were determined by standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: A total of 3245 participants from 20 RCTs and 370 participants from 8 crossover trials were included in the study. Significant differences were found in bone mineral density (SMD 0.47; 95% CI, 0.28 to 0.66; p < 0.001; I2 = 0.00%) and total serum calcium (SMD 1.07; 95% CI, 0.39 to 1.74; p < 0.001; I2 = 61.9%), as well as in height Z score for age (SMD = 0.11; 95% CI, 0.00 to 0.22; P = 0.044; I2 = 0%). The overall quality of evidence ranged from moderate to very low. CONCLUSIONS: This systematic review and meta-analysis suggested that intestinal flora intervention was an effective method of improving bone mineral density, serum calcium, and height in infants, children, and adolescents. Future studies with a larger sample size and longer intervention period are needed. The protocol of this systematic review was registered in PROSPERO and the registered number was CRD42021282606.

Stealthy false data injection attacks with resource constraints against multi-sensor estimation systems.

This paper mainly investigates how to maximally degrade estimation performance of a cyber-physical system under limited resource. A stealthy false data injection (FDI) attack scheme is proposed to only attack partial sensor channels of a multi-sensor estimation system. The attack stealthiness condition and the compromised estimation error covariance are respectively derived, and then the stealthy attack problem is formed as a constrained optimization problem. An explicit solution of the optimal attack strategy is given and proven. Furthermore, the relationship between the compromised estimation error covariance and the attacked sensor is analyzed, and then the sensor selection principle is derived to decide which sensor channel should be attacked. Finally, two numerical simulation examples are provided to confirm the theoretical analysis results.

Identification and expression profiles of the YABBY transcription factors in wheat.

BACKGROUND: YABBY is a plant-specific transcription factor (TF) that belongs to the zinc finger protein superfamily and is composed of a C2-C2 domain at the N-terminus and a YABBY domain at the C-terminus. It plays a role in plant development and growth. METHODS: In this study, 20 YABBY TFs were identified in the wheat genome. Phylogenetic relationships, collinearity relationships, gene structures, conserved motifs, and expression patterns were analyzed. RESULTS: Twenty TaYABBY TFs were distributed unevenly on 15 chromosomes. Collinearity analysis showed that these genes have a close relationship with monocot plants. The phylogenetic tree of wheat YABBYs classified these TaYABBYs into FIL, YAB2, INO, and CRC clades. Gene structure and conserved motif analyses showed that they share similar components in the same clades. Expression profile analysis showed that many TaYABBY genes have high expression levels in leaf tissues and are regulated by abiotic stresses, especially salt stress. Our results provide a basis for further functional characterization of the YABBY gene family.

Three-dimensional corrective exercise therapy for idiopathic scoliosis: study protocol for a prospective non-randomized trial.

BACKGROUND: Although physiotherapeutic scoliosis-specific exercises (PSSEs) with or without other conservative treatments may improve scoliotic deformities, the evidence is insufficient. Three-dimensional corrective exercises (TDCEs) for scoliosis are based on the theory of PSSEs and are characterized by a combination of outpatient treatment and home-based exercise. This study aims to evaluate the effectiveness of TDCEs for idiopathic scoliosis (IS). METHODS: The participants will be divided into two age- and sex-matched groups: an experimental group (EG) treated with three-dimensional corrective exercise therapy (TDCET) and a control group (CG) receiving generalized exercise therapy. In each arm, mild and moderate IS cases will be reclassified based on the Cobb angle and biopsy results. The primary endpoint is the change in the largest Cobb angle; the secondary endpoints are the sagittal index, forced vital capacity, peak oxygen uptake, and peak oxygen uptake. Sixty-six patients with mild IS and 78 patients with moderate IS will be included. DISCUSSION: This study is the first controlled trial to systematically assess the effectiveness of TDCEs for IS. In addition to TDCET including three-dimensional corrective exercises, family rehabilitation and basic body awareness therapy may help patients adopt supportive attitudes and appropriate behaviours, thus enhancing their compliance with exercises and achieving better outcomes. TRIAL REGISTRATION: The study protocol was registered at www.clinicaltrials.gov (number identifier: NCT04539522 ). Registered on August 27, 2020.

Identifying the dose response relationship between seminal metal at low levels and semen quality using restricted cubic spline function.

Environmental exposure to metals, including essential and nonessential elements, may be related to semen quality. Our goal was to explore the continuous relationship between seminal metals and sperm parameters. A restricted cubic spline (RCS) was applied to automatic selection criteria to ascertain the optimal smoothing degree. We recruited 841 male volunteers from Henan Province, China. Eighteen seminal metals, namely Al, Cr, Mn, Cu, Zn, Se, As, Ni, Cd, Pb, Co, V, Rb, Ag, Ba, TI, Fe, and Li, and 21 semen parameters were detected. Seminal malondialdehyde (MDA) was also detected to express oxidative stress. We revealed a non-linear relationship of the vanadium and chromium exposure to semen parameters. There were inverse 'U' shapes found between seminal Cr and sperm concentrations, total sperm count, and semen quality. The best semen quality was observed when the seminal Cr concentration was 5.05 ppb, and an increase or decrease in chromium concentration led to decreased semen quality. The V concentration was associated with reduced sperm concentration, total sperm count, normal morphology, and progressive motility at high doses (V > 0.58 ppb). Seminal MDA had a strong adverse association with sperm motility parameters, such as curve line velocity (VCL) (P < 0.001), straight line velocity (VSL) (P = 0.004), velocity of average path (VAP) (P < 0.001), and lateral head movement (ALH) (P = 0.001), whereas it was adversely associated with seminal Zn (ß [95% confidence interval (CI)], -0.28(-0.41-0.16), P < 0.001) after adjusting for confounding factors. Our findings represent the curves of the dose-response relationship between seminal Cr, seminal V, and semen quality, in which seminal MDA was a good indicator of sperm movement. These models provide new insight into the dose-relationship between metal exposure and semen quality, and further investigation is needed to validate this.

Investigation on Quality of Life and Economic Burden of Children with Cerebral Palsy in Changzhou.

Based on the data of children with cerebral palsy (CP) in Changzhou obtained by the Disabled Persons' Federation, this study sampled some children with CP and investigated their survival status, treatment cost, and family burden so as to provide scientific decision-making basis and policy suggestions for coping with disease hazards and improving children's quality of life. In this study, a simple random sampling method was used to conduct household surveys of the selected children with CP. The economic burden of CP is measured by direct and indirect methods, and the quality of life of patients of children with CP and their families is analyzed qualitatively and quantitatively by the EuroQol Five Dimensions (EQ-5D) Questionnaire. The average family economic burden of each case of CP in Changzhou was about 4,188,500 yuan, of which the direct medical burden was 205,800 yuan and the indirect economic burden was 3,982,700 yuan. The socioeconomic burden of CP in Changzhou is as high as about 2.244 billion yuan. From the EQ-5D measurement results of 55 children with CP, the average index score was 0.423, which was lower than the national general population level. The proportions of patients with CP who have problems in the five aspects of action, self-care, daily activities, pain/discomfort, and anxiety/depression are 72.73%, 81.82%, 81.82%, 83.64%, and 92.73%, respectively, which are significantly higher than those of the national general population. The average score of the Visual Analogue Scale (VAS) is 58.09, which is significantly lower than the national general population level. The only major factor affecting the quality of life of patients with CP and their families is the health status represented by the EQ-5D score. To liberate and develop the labor ability of patients and their direct caregivers through clinical treatment, rehabilitation, and special education is the most effective way to reduce the socioeconomic burden of CP. Relevant government departments should perform their duties, integrate social assistance resources, implement early intervention, and launch targeted support and assistance policy.

Novel exon mutation in SYCE1 gene is associated with non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is a common cause of male infertility, and genetic problems, such as chromosomal abnormalities and gene mutations, are important causes of NOA. Our centre received a case of NOA, in which no mature sperm was found during microdissection testicular sperm extraction. A postoperative pathological examination revealed that testicular spermatogenesis was blocked. Target region capture combined with high-throughput sequencing was used to screen for male infertility-related gene mutations. Sanger sequencing further confirmed that the SYCE1 gene, a central component of the synaptonemal complex (SC) during meiosis, had a homozygous deletion mutation in the tenth exon (c.689_690del; p.F230fs). Through molecular biological studies, we discovered altered expression and nuclear localization of the endogenous mutant SYCE1. To verify the effects in vitro, wild- and mutated-type SYCE1 vectors were constructed and transfected into a human cell line. The results showed that the expression and molecular weight were decreased for SYCE1 containing c.689_690del. In addition, mutated SYCE1 was abnormally located in the cytoplasm rather than in the nucleus. In summary, our research suggests that the novel homozygous mutation (c.689_690del; p.F230fs) altered the SYCE1 expression pattern and may have disturbed SC assembly, leading to male infertility and to a barrier to gamete formation. We reported for the first time that a frameshift mutation occurred in the exon region of SYCE1 in an NOA patient. This study is beneficial for accurate NOA diagnosis and the development of corresponding gene therapy strategies.

A Novel Noncanonical Splicing Mutation of ANOS1 Gene in Siblings with Kallmann Syndrome Identified by Whole-Exome Sequencing.

Kallmann syndrome (KS) is a rare genetic disorder that is characterized by idiopathic hypogonadotropic hypogonadism associated with anosmia. Genetic variants in ANOS1 gene are the most common mutations associated with X-linked recessive form of KS. Canonical ± 1 or 2 splice site variants in ANOS1 have been described to be responsible for KS. Here, we identified a novel noncanonical splice site variant (c.1062+4T>C) in ANOS1 gene in two siblings with KS by whole-exome sequencing (WES). Sanger sequencing showed this mutation was inherited from their mother, whose brother was a KS patient as well. Through the functional assay in vitro, we found that this mutation resulted in a 50-bp deletion of exon 7, which caused frameshift mutation leading to a premature termination of translation and a truncated anosmin-1 protein. Our results revealed that this noncanonical splice site variant is involved in KS. Thus, it is suggested that we should pay attention to the noncanonical splice site variants when using molecular genetic diagnostics of KS.