ITFG2, an immune-modulatory protein, targets ATP 5b to maintain mitochondrial function in myocardial infarction.

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.

No genetic causal association between dental caries and Alzheimer's disease: a bidirectional two-sample Mendelian randomization analysis.

Background: An increasing number of observational studies have suggested an association between dental caries and Alzheimer's disease (AD). The association between dental caries and Alzheimer's disease may be mediated by confounders or reverse causality. In this study, we conducted bidirectional two-sample Mendelian randomization (MR) to estimate the bidirectional causality between dental caries and AD. Materials and Methods: Genome-wide association study (GWAS) summary statistics of dental caries were extracted from a published meta-analysis which included a total of 487,823 participants. GWAS datasets of AD and AD onset age were obtained from the FinnGen bank. A bidirectional two-sample analysis was performed to explore the causality between dental caries and AD. Results: For the dental caries-AD causality estimation, there was no significant association between dental caries and AD, neither with the AD GWASs from the FinnGen database (OR: 1.041, p = 0.874) nor with those from the International Genomics of Alzheimer's Project (OR: 1.162, p = 0.409). In addition, the genetic susceptibility to dental caries was not related to the onset age of AD. No causality existed between dental caries and early-onset AD (OR: 0.515, p = 0.302) or late-onset AD (OR: 1.329, p = 0.347). For the AD-dental caries relationship, no causality was detected by the IVW method (OR: 1.000, p = 0.717). Findings from other MR methods were consistent. The pleiotropy test and sensitivity analysis confirmed the validity of these MR results. Conclusions: In this bidirectional MR study, robust evidence to support a bidirectional causal effect between dental caries and AD from the GWAS results within large-scale European-descent populations was absent. Having dental caries would not alter the onset age of AD.

Posterior pedicle screw fixation combined with local steroid injections for treating axial eosinophilic granulomas and atlantoaxial dislocation: A case report.

BACKGROUND: Eosinophilic granuloma (EG) is a proliferative condition that affects the cells of bone tissue. There are no specific clinical signs or imaging manifestations in the early stages of the disease, making it simple to overlook and misdiagnose. Because of the disease's rarity, there is presently no standardized treatment principle. There are few accounts of such occurrences affecting the axis among children. We discovered a case of a child whose EG resulted in atlantoaxial joint dislocation and destruction of the axial bone. CASE SUMMARY: After having pharyngeal discomfort for more than six months without a clear explanation, a 6-year-old boy was brought to our hospital. Following a careful evaluation, the pathology indicated a strong likelihood of an axial EG. Ultimately, we decided to treat the boy with posterior pedicle screw fixation and local steroid injections. CONCLUSION: EGs of the upper cervical spine are quite uncommon in children, and they are exceedingly easy to overlook or misdiagnose. Posterior pedicle screw fixation and local steroid injections are effective treatments for patients with axial EGs affecting the atlantoaxial junction.

Serial electrocardiogram recordings revealed a high prevalence of QT interval prolongation in patients with tuberculosis receiving fluoroquinolones.

BACKGROUND: Fluoroquinolones, crucial components of treatment regimens for drug-resistant tuberculosis (TB), are associated with QT interval prolongation and risks of fatal cardiac arrhythmias. However, few studies have explored dynamic changes in the QT interval in patients receiving QT-prolonging agents. METHODS: This prospective cohort study recruited hospitalized patients with TB who received fluoroquinolones. The study investigated the variability of the QT interval by using serial electrocardiograms (ECGs) recorded four times daily. This study analyzed the accuracy of intermittent and single-lead ECG monitoring in detecting QT interval prolongation. RESULTS: This study included 32 patients. The mean age was 68.6 ± 13.2 years. The results revealed mild-to-moderate and severe QT interval prolongation in 13 (41%) and 5 (16%) patients, respectively. The incremental yields in sensitivity of one to four daily ECG recordings were 61.0%, 26.1%, 5.6%, and 7.3% in detecting mild-to-moderate QT interval prolongation, and 66.7%, 20.0%, 6.7%, and 6.7% in detecting severe QT interval prolongation. The sensitivity levels of lead II and V5 ECGs in detecting mild-to-moderate and severe QT interval prolongation exceeded 80%, and their specificity levels exceeded 95%. CONCLUSION: This study revealed a high prevalence of QT interval prolongation in older patients with TB who receive fluoroquinolones, particularly those with multiple cardiovascular risk factors. Sparsely intermittent ECG monitoring, the prevailing strategy in active drug safety monitoring programs, is inadequate owing to multifactorial and circadian QT interval variability. Additional studies performing serial ECG monitoring are warranted to enhance the understanding of dynamic QT interval changes in patients receiving QT-prolonging anti-TB agents.

The value of serum albumin concentration in predicting functional outcome of status epilepticus: An observational study.

OBJECTIVE: Status epilepticus (SE) is a common neurological emergency with unsatisfying prognoses, and accurate prediction of functional outcome is beneficial in clinical decision-making. The relationship between serum albumin concentration and outcome of SE patients has yet to be unveiled. METHODS: Clinical profiles of SE patients admitted to Xiangya Hospital, Central South University, from April 2017 to November 2020, were analyzed retrospectively. Outcomes of SE patients at discharge were divided into two groups based on the modified Rankin Scale (mRS): favorable outcome (mRS: 0-3) and unfavorable outcome (mRS: 4-6). RESULTS: Fifty-one patients were enrolled. Unfavorable functional outcome at discharge was reported in 60.8% (31/51). Serum albumin concentration at admission and the Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT) score remained independent predictors for functional outcome of SE patients. A lower albumin concentration at admission and higher END-IT score indicated a higher chance of unfavorable outcome for SE patients. The cut-off value of serum albumin to predict unfavorable outcome was 35.2 g/L, with a sensitivity of 67.7% and specificity of 85.0%, and an area under the receiver operating characteristic curve (ROC) of .738 (95% CI: .600-.876, p = .004). The preferable END-IT score with optimal sensitivity (74.2%) and specificity (60%) was 2 and the area under the ROC was .742, with 95% CI of .608-.876 (p = .004). SIGNIFICANCE: Serum albumin concentration at admission and the END-IT score are two independent predictive factors for short-term outcome of SE patients, moreover, the serum albumin concentration is not inferior to the END-IT score in indicating functional outcome at discharge.

Evaluation of career planning group counseling and its effectiveness for intern male nursing students.

OBJECTIVE: To investigate the influence of group counselling on the career planning and career maturity of male nursing students. METHOD: Sixty male nursing students were randomly selected from a specific-level first-class hospital in Hunan Province from July to August 2020 by using the convenience sampling method and were subsequently divided into the control group and the experimental group using the random number table method. The control group received routine pre-job training, including aspects concerning the hospital profile, nurse etiquette, nursing core systems, professional ethics, nursing emergency treatment and career prospects and planning. In the experimental group, career planning group counselling was added after the regular pre-service training (once a week) with each session lasting 2 h for a total of six training sessions. At six weeks and three months after the intervention, the career status evaluation scale and the college students' career maturity scale were used to compare the career planning and career maturity status of the two groups of male nursing students. RESULTS: After six weeks and three months of intervention, all the dimensions and total scores of both the career status evaluation scale and the career maturity scale in the experimental group were superior to those in the control group with statistically significant differences (all P < 0.05). The repeated measures of variance analysis indicated that the differences in the total score for career planning and the four dimensions in terms of intergroup effect, time effect and interaction effect between the two groups were statistically significant (P < 0.05). The intergroup effect, time effect and interaction effect of the total score for vocational maturity, career goal, career confidence, career value, career freedom and career reference of the two groups were statistically significant (P < 0.05), while the time effect of the relative dependency dimension was also statistically significant (P < 0.05). CONCLUSION: Group counselling can significantly improve the career planning and career maturity status of male nursing students and has a certain long-term effect.

Pharmacological Treatments for Congenital Myasthenic Syndromes Caused by COLQ Mutations.

BACKGROUND: Congenital myasthenic syndromes (CMS) refer to a series of inherited disorders caused by defects in various proteins. Mutation in the collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) is the second-most common cause of CMS. However, data on pharmacological treatments are limited. OBJECTIVE: In this study, we reviewed related reports to determine the most appropriate pharmacological strategy for CMS caused by COLQ mutations. A literature review and meta-analysis were also performed. PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched to identify studies published in English before July 22, 2022. RESULTS: A total of 42 studies including 164 patients with CMS due to 72 different COLQ mutations were selected for evaluation. Most studies were case reports, and none were randomized clinical trials. Our meta-analysis revealed evidence that ß-adrenergic agonists, including salbutamol and ephedrine, can be used as first-line pharmacological treatments for CMS patients with COLQ mutations, as 98.7% of patients (74/75) treated with ß-adrenergic agonists showed positive effects. In addition, AChEIs should be avoided in CMS patients with COLQ mutations, as 90.5% (105/116) of patients treated with AChEIs showed either no or negative effects. CONCLUSION: (1) ß-adrenergic agonist therapy is the first pharmacological strategy for treating CMS with COLQ mutations. (2) AChEIs should be avoided in patients with CMS with COLQ mutations.

Impacts of springtime biomass burning in Southeast Asia on atmospheric carbonaceous components over the Beibu Gulf in China: Insights from aircraft observations.

Limited by the scarcity of in situ vertical observation data, the influences of biomass burning in Southeast Asia on major atmospheric carbonaceous compositions in downwind regions have not been thoroughly studied. In this study, aircraft observations were performed to obtain high time-resolved in situ vertical distributions of black carbon (BC) as well as carbon monoxide (CO) and carbon dioxide (CO2). Four types of profiles were revealed: Mode I (from 2000 to 3000 m, the BC, CO and CO2 concentrations were enhanced), Mode II (with increasing altitude, the BC, CO and CO2 concentrations almost decreased), Mode III (inhomogeneous vertical BC, CO and CO2 profiles with BC peaks were observed from 2500 to 3000 m) and Mode IV (the BC, CO and CO2 concentrations increased above 1500 m). Furthermore, simulations were conducted to calculate radiative forcing (RF) caused by BC and study the heating rate (HR) of BC in combination with the vertical BC profiles. A larger BC distribution in the atmosphere resulted in a sharp RF change from negative to positive values, imposing a nonnegligible influence on the atmospheric temperature profile, with maximum HR values ranging from 0.4 to 5.8 K/day. The values of the absorption Ångström exponent (AAE) were 1.46 ± 0.11 and 1.48 ± 0.17 at altitudes from 1000 to 2000 and 2000-3000 m, respectively. The average BC light absorption coefficient at the 370 nm wavelength (α BC (370)) accounted for 50.3 %-76.8 % of the α (370), while the brown carbon (BrC) light absorption coefficient at the 370 nm wavelength (α BrC (370)) contributed 23.2 %-49.7 % to the α (370) at altitudes of 1000-2000 m. At altitudes of 2000-3000 m, α BC (370) and α BrC (370) contributed 43.8 %-88.2 % and 11.8 %-56.2 % to the α (370), respectively. These findings show that calculations that consider the surface BC concentration but ignore the vertical BC distribution could result in massive uncertainties in estimating the RF and HR caused by BC. This study helped achieve a deeper understanding of the influences of biomass burning over the region of Southeast Asia on the profiles of atmospheric carbonaceous compositions and atmospheric BC absorption and its warming effect.

Calcitriol increases MBNL1 expression and alleviates myotonic dystrophy phenotypes in HSALR mouse models.

BACKGROUND: Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3' untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1. METHODS: All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice. RESULTS: In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells. CONCLUSION: Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.

Study on the sleep quality of women pregnant with a second child and the influencing factors.

OBJECTIVES: To investigate the sleep quality of women pregnant with a second child and the influencing factors and provide a scientific basis for health care guidance to clinically improve the sleep quality of pregnant women. METHODS: A total of 162 women pregnant with a second child at a first-class tertiary hospital in Changsha from January to August 2018 were selected as the research subjects. General demographic characteristics were collected, and the Pittsburgh Sleep Quality Index (PSQI) scale was used to assess their sleep quality. Multivariate logistic regression analysis was used to explore the influencing factors of the sleep quality of women pregnant with a second child. RESULTS: The PSQI score (except hypnotic drugs) and total score of pregnant women with second birth were higher than those of normal female population, and the difference was statistically significant (P < 0.05). Univariate analysis showed statistically significant differences in sleep quality among women pregnant with a second child of different ages, marital relationships, gender expectations, education levels, monthly family incomes, planned or unplanned pregnancy, and gestational weeks (P < 0.05). The results of the multi-factor analysis showed that the low education level (OR = 0.224, P = 0.001), low family monthly income (OR = 3.035, P = 0.014), expectation of gender (OR = 0.065, P = 0.038), and dissatisfaction with marital relationship (OR = 0.275, P = 0.001) were the primary risk factors of poor sleep quality of in women with second pregnant. CONCLUSIONS: The overall sleep quality of women pregnant with a second child is poor, and 37.65% have sleep quality problems. Low education levels, low family monthly incomes, fetal gender expectations, and poor relationship between husband and wife are the main factors affecting the sleep quality of women pregnant with a second child. Pregnant women with the above factors should pay attention to their sleep quality and take necessary measures for intervention and guidance to improve the level of health care during pregnancy.

A causal relationship between leukocyte telomere length and multiple sclerosis: A Mendelian randomization study.

Objectives: Multiple sclerosis (MS) is a chronic inflammatory autoimmune and degenerative disorder of the central nervous system. Telomeres are protective structures located at the ends of linear chromosomes, and leukocyte telomere length (LTL) is closely connected with cell aging and senescence. However, the relationship between LTL and the risk of MS remains unknown. Methods: We performed a two-sample Mendelian randomization (MR) to evaluate whether LTL was causally associated with MS risk. Results: In our MR analysis, 12 LTL-related variants were selected as valid instrumental variables, and a causal relationship between LTL and MS was suggested. The risk of MS nearly doubled as the genetically predicted LTL shortened by one standard deviation (SD) under the inverse variance weighted (IVW) fixed effect model (odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.52-2.62, p = 6.01e-07). Similar estimated causal effects were also observed under different MR models. The MR-Egger regression test did not reveal any evidence of directional pleiotropy (intercept = -0.005, stand error (SE) = 0.03, p = 0.87). The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis also indicated no directional pleiotropy or outliers for any LTL-related IVs (p-global test = 0.13). In addition, a leave-one-out sensitivity analysis showed similar findings, which further emphasized the validity and stability of the causal relationship. Conclusions: Our results suggest a potential causal effect of LTL on the risk of MS. Genetically predicted shorter LTL could increase the risk of MS in the European population. LTL should be noted and emphasized in the pathogenesis and treatment of MS.

Trends in global amyotrophic lateral sclerosis research from 2000 to 2022: A bibliometric analysis.

Background: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease affecting the motor neurons. Although much research has been conducted in this field, few bibliometric studies have been conducted. This study aimed to provide an overview of publishing characteristics and trends in ALS research since 2000 using a bibliometric analysis. Methods: We conducted a comprehensive literature search in the Web of Science (WOS) Core Collection database for scientific output related to ALS from 2000 to 2022. The retrieved dataset was refined using Google OpenRefine and analyzed using bibliometrix. Results: A total of 29,391 articles published since 2000 were retrieved, with an average annual growth rate of 6.35%. Ninety-six countries and regions contributed to ALS research, among which the United States had the dominant position with the highest number of publications (n = 8,202) and citations (n = 558,561). An association analysis was performed to form networks of country collaboration and keyword co-occurrence. The evolution of topic trends was demonstrated in terms of both frequency and proportion. Conclusion: The output of ALS research has increased steadily over the years, and the United States and Western Europe are leaders in this field. There is an upgradation in the pathomechanism and clinical research on ALS.

Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center.

Background: Glycogen storage disease (GSDs) is characterized by abnormally inherited glycogen metabolism. GSD IXd, which is caused by mutations in the PHKA1 gene, is an X-linked rare disease with mild myopathic symptoms. To date, only 13 patients with GSD IXd have been reported. In this study, we aimed to expand the clinicopathological-genetic spectrum of GSD IXd at a neuromuscular center in China. Methods: Data on patients diagnosed with GSD IXd at our neuromuscular center were collected retrospectively. Clinical features, electrophysiology, muscle pathology, and genetic information were analyzed. Results: Between 2015 and 2021, three patients were diagnosed with GSD IXd based on clinical manifestations, pathological findings, and genetic testing. One patient presented with mitochondrial myopathy. All patients exhibited muscle weakness and elevated levels of creatine kinase. Electromyography-detected myopathic changes were found in two patients, whereas one patient refused to undergo this examination. Pathological examinations in all patients revealed subsarcolemmal accumulation of glycogen under PAS staining. All patients had mutations in the PHKA1 gene and the patient with mitochondrial myopathy also had a mutation in the MT-TL1 gene. Conclusion: Our study expands the clinicogenotype and phenotype of GSD IXd in a Chinese population. Our study also expands the known mutation spectrum for GSD IXd, contributing to a better characterization and understanding of this ultrarare neuromuscular disorder.

Clinicopathological-genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre.

Congenital myasthenic syndrome (CMS) encompasses a heterogeneous group of inherited disorders affecting nerve transmission across the neuromuscular junction. The aim of this study was to characterize the clinical, physiological, pathohistological and genetic features of nine unrelated Chinese patients with CMS from a single neuromuscular centre. A total of nine patients aged from neonates to 34 years were enrolled who exhibited initial symptoms. Physical examinations revealed that all patients exhibited muscle weakness. Muscle biopsies demonstrated multiple myopathological changes, including increased fibre size variation, myofibrillar network disarray, necrosis, myofiber grouping, regeneration, fibre atrophy and angular fibres. Genetic testing revealed six different mutated genes, including AGRN (2/9), CHRNE (1/9), GFPT1 (1/9), GMPPB (1/9), PLEC (3/9) and SCN4A (1/9). In addition, patients exhibited differential responses to pharmacological treatment. Prompt utilization of genetic testing will identify novel variants and expand our understanding of the phenotype of this rare syndrome. Our findings contribute to the clinical, pathohistological and genetic spectrum of congenital myasthenic syndrome in China.

Corrigendum: A Systematic Review and Meta-Analysis of the Prevalence of Congenital Myopathy.

[This corrects the article DOI: 10.3389/fneur.2021.761636.].

Montelukast, cysteinyl leukotriene receptor 1 antagonist, inhibits cardiac fibrosis by activating APJ.

Montelukast, cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is used clinically for patients with asthma, chronic obstructive pulmonary diseases (COPD), and allergic rhinitis. It has been reported that CysLT1R antagonists could reduce the risks of cardiovascular diseases in animal studies. Cardiac fibrosis is one of the major causes of heart failure. But little is known about the role of Montelukast in cardiac fibrosis and its underlying mechanism. In transverse aortic constriction (TAC) mice, Montelukast improved cardiac pumping function and inhibited cardiac fibrosis by down-regulation of the proteins related to the fibrosis, such as connective tissue growth factor (CTGF), Transforming Growth Factor ß (TGF-ß), and Alpha-smooth muscle actin (α-SMA). Montelukast reduced cell proliferation and collagen production in neonatal cardiac fibroblasts (CFs) with the pretreatment of 20% serum, while down-regulating the expression of TGF-ß, CTGF and α-SMA. Molecules docking methods estimated a high affinity of Montelukast to Apelin receptor (APJ) and an effective chemical structure for Montelukast binding APJ. In Chinese hamster ovary (CHO) cells with stable overexpressing APJ, Montelukast inhibited forskolin (1 µM)-mediated cyclic adenosine monophosphate (cAMP) production and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation, while these effects were reversed by pertussis toxin (PTX) pretreatment. APJ silence disrupted the effects of Montelukast in CFs pretreatment by serum 20%. So we concluded that Montelukast inhibited cardiac fibrosis due presumably to the coupling to the APJ-mediated Gi signaling pathway, which may be a promising therapeutic target for cardiac fibrosis.

Spatiotemporal patterns and ozone sensitivity of gaseous carbonyls at eleven urban sites in southeastern China.

Gaseous carbonyls are essential trace gases for tropospheric chemistry and contribute significantly to the formation of ambient air ozone (O3) in densely populated regions, especially in China. Pollution characterization and the analysis of O3, nitrogen oxides, and volatile organic compounds (O3-NOX-VOCs) sensitivities of carbonyls were investigated from October 22 to 28, 2018 at eleven urban sites in nine cities in Fujian Province, southeastern China. The total mixing ratios of 15 kinds of gaseous carbonyls (Σ15OVOCs) was 12.15 ± 2.53 ppbv in Fujian Province. The concentrations in the eastern coastal regions were higher than those in the western mountainous regions. Formaldehyde, acetone, and acetaldehyde were the top three species of Σ15OVOCs concentration. Photochemical formation during the daytime and vehicle emission during the rush hours significantly contributed to formaldehyde and acetaldehyde. The shoe-making industry is well developed in Putian, where the acetone mixing ratio was significantly higher than in other cities. The O3-NOX-VOCs sensitivities at all urban sites were in VOC-limited or transitional regimes based on the ratios of formaldehyde to NO2; from morning to afternoon, the VOC-limited sensitivity decreased, and the NOX-limited sensitivity increased gradually. Formaldehyde contributed the most significant O3 formation potential (OFP) proportion of the Σ15OVOCs. The OFP of carbonyl species accounted for half of the total VOCs in Fuzhou and Putian, suggesting that more attention needs to be given to gaseous carbonyls control. Overall, the links inferred by this study provide evidence and clues to mitigate the increasing ambient O3 concentration on the west coast of the Taiwan Strait.

Findings of limb-girdle muscular dystrophy R7 telethonin-related patients from a Chinese neuromuscular center.

Limb-girdle muscular dystrophy (LGMD) is a group of clinically and genetically heterogeneous neuromuscular disorders. LGMD-R7, which is caused by telethonin gene (TCAP) mutations, is one of the rarest forms of LGMD, and only a small number of LGMD-R7 cases have been described and mostly include patients from Brazil. A total of two LGMD-R7 patients were enrolled at a Chinese neuromuscular center. Demographic and clinical data were collected. Laboratory investigations and electromyography were performed. Routine and immunohistochemistry staining of muscle specimens was performed, and a next-generation sequencing panel array for genes associated with hereditary neuromuscular disorders was used for analysis. The patients exhibited predominant muscle weakness. Electromyography revealed myopathic changes. The muscle biopsy showed myopathic features, such as increased fiber size variation, muscle fiber atrophy and regeneration, slight hyperplasia of the connective tissue, and disarray of the myofibrillar network. Two patients were confirmed to have mutations in the open reading frame of TCAP by next-generation sequencing. One patient had compound heterozygous mutations, and the other patient harbored a novel homozygous mutation. Western blotting analysis of the skeletal muscle lysate confirmed the absence of telethonin in the patients. We described two LGMD-R7 patients presenting a classical LGMD phenotype and a novel homozygous TCAP mutation. Our research expands the spectrum of LGMD-R7 due to TCAP mutations based on patients from a Chinese neuromuscular center.

Urinary p75ECD levels in patients with amyotrophic lateral sclerosis: a meta-analysis.

Objective: p75 neurotrophin receptor (p75NTR) is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). However, its role is not fully understood. The aim of this study was to evaluate the association between ALS and the extracellular domain of p75NTR(p75ECD) in urine. Methods: We conducted a comprehensive literature search using keywords in the PubMed, Embase, Science, and the Cochrane Library, and identified five case control studies, with the latest date of search being 18 April 2021. Results: The results showed that urinary p75ECD levels were significantly higher in patients with ALS compared to non-neurological control (weighted mean difference (WMD) = 4.18, 95% CI [2.525, 6.990], p < 0.001), and other neurological diseases (WMD = 6.005, 95% CI [1.596, 10.414], p = 0.008). Increased urinary p75ECD levels were inversely associated with ALSFRS-R in ALS patients (r = -0.32, 95% CI [-0.43, -0.21], p < 0.001). Conclusions: Given the associations between p75ECD and ALS found in this meta-analysis, urinary p75ECD levels have potential to be used as a diagnostic biomarker and a progression indicator in the future.

Hypoxia inducible factor-3α promotes osteosarcoma progression by activating KDM3A-mediated demethylation of SOX9.

Hypoxia/oxygen-sensing signally is closely associated with many tumor progressions, including osteosarcoma (OS). Previous research principally focused on the function of hypoxia-inducible factor (HIF)-1α and HIF-2α as the major hypoxia-associated transcription factors in OS, however, the role of HIF-3α has not been investigated. Our study found that HIF-3α was upregulated in OS tissues and cell lines. HIF-3α overexpression facilitated cell proliferation and invasion, and inhibited apoptosis, whereas HIF-3α knockdown showed the opposite results. Chromatin immunoprecipitation analysis revealed that lysine demethylase 3A (KDM3A) expression was transcriptionally activated by HIF-3α under hypoxia, and KDM3A occupied the SRY-box transcription factor 9 (SOX9) gene promoter region through H3 lysine 9 dimethylation (H3K9me2). Additionally, rescue results revealed that KDM3A or SOX9 overexpression reversed the effects of HIF-3α silence on cell functions. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway inhibitor cucurbitacin I suppressed the promotive effects of HIF-3α overexpression on cell proliferation, invasion and TAK2/STAT3 pathway. Finally, OS cell line MG-63 transfected with HIF-3α short hairpin RNA (HIF-3α shRNA) were subcutaneously injected into nude mice, and the results found that HIF-3α knockdown significantly inhibited the xenograft tumor growth of OS in vivo. In conclusion, this study reveals that HIF-3α promotes OS progression in vitro and in vivo by activating KDM3A-mediated SOX9 promoter demethylation, which may provide a potential therapeutic mechanism for OS.