The clinical and genetic spectrum of mitochondrial diseases in China: A multicenter retrospective cross-sectional study.

Mitochondrial diseases (MtDs) present diverse clinical phenotypes, yet large-scale studies are hindered by their rarity. This retrospective, multicenter study, conducted across five Chinese hospitals' neurology departments from 2009 to 2019, aimed to address this gap. Nationwide, 1351 patients were enrolled, with a median onset age of 14.

Demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases: a retrospective cross-sectional study.

Background: This study aimed to explore the demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases.

Methods: This retrospective cross-sectional study enrolled patients diagnosed with mitochondrial diseases from the Department of Neurology at Peking University First Hospital between January 2010 and December 2021. A questionnaire covering demographic characteristics, diagnostic dilemma, treatment, economic aspects, and caregiver stress was administered, and disability was assessed using the modified Rankin Scale (mRS).

Meta-analysis application to hERG safety evaluation in clinical trials.

One objective of meta-analysis, which synthesizes evidence across multiple studies, is to assess the consistency and investigate the heterogeneity across studies. In this project, we performed a meta-analysis on moxifloxacin (positive control in QT assessment studies) data to characterize the exposure-response relationship and determine the safety margin associated with 10-msec QTc effects for moxifloxacin based on 26 thorough QT studies submitted to the FDA. Multiple meta-analysis methods were used (including two novel methods) to evaluate the exposure-response relationship and estimate the critical concentration and the corresponding confidence interval of moxifloxacin associated with a 10-msec QTc effect based on the concentration-QTc models.

Multiomics analysis reveals serine catabolism as a potential therapeutic target for MELAS.

Mitochondrial disease is a devastating genetic disorder, with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and m.3243A>G being the most common phenotype and genotype, respectively. The treatment for MELAS patients is still less effective.

Use of Artificial Intelligence to Improve the Calculation of Percent Adhesion for Transdermal and Topical Delivery Systems.

Adhesion is a critical quality attribute and performance characteristic for transdermal and topical delivery systems (TDS). Regulatory agencies recommend in vivo skin adhesion studies to support the approval of TDS in both new drug applications and abbreviated new drug applications. The current assessment approach in such studies is based on the visual observation of the percent adhesion, defined as the ratio of the area of TDS attached to the skin to the total area of the TDS.

The clinical, myopathological, and genetic analysis of 155 Chinese mitochondrial ophthalmoplegia patients with mitochondrial DNA single large deletions.

Background: Progressive external ophthalmoplegia (PEO) is a common subtype of mitochondrial encephalomyopathy.

Objective: The study aimed to investigate the relationship between mitochondrial DNA (mtDNA) abnormalities, muscle pathology, and clinical manifestations in Chinese patients with single large-scale mtDNA deletion presenting with PEO.

Methods: This is a retrospective single-center study.

Diazo-carboxyl Click Derivatization Enables Sensitive Analysis of Carboxylic Acid Metabolites in Biosamples.

Carboxylic acids are central metabolites in bioenergetics, signal transduction, and post-translation protein regulation. However, the quantitative analysis of carboxylic acids as an indispensable part of metabolomics is prohibitively challenging, particularly in trace amounts of biosamples. Here we report a diazo-carboxyl/hydroxylamine-ketone double click derivatization method for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids.

Patterns of myelinated nerve fibers loss in transthyretin amyloid polyneuropathy and mimics.

Objective: The present study was intended to analyze the characteristics of myelinated nerve fibers density (MFD) of transthyretin amyloid polyneuropathy (ATTR-PN) and other similar neuropathies.

Methods: A total of 41 patients with ATTR-PN, 58 patients of other common peripheral neuropathies, and 17 age-and gender-matched controls who visited the First Hospital of Peking University and performed sural nerve biopsy between June 2007 and August 2021 were included for analysis of MFD.

Results: Except the vasculitic neuropathy group, the total and small MFD of patients in the ATTR-PN group were significantly lower than those of other disease groups.

Skeletal Muscle Involvement Pattern of Hereditary Transthyretin Amyloidosis: A Study Based on Muscle MRI.

Objects: This study was intended to explore the characteristics of muscle magnetic resonance imaging (MRI) of patients with hereditary transthyretin amyloidosis (ATTRv amyloidosis) prospectively.

Methods: The clinical data of 20 patients with ATTRv amyloidosis at our hospital between July 2020 and August 2021 were analyzed. MRI of lower limbs including calf muscles was performed in all these 20 patients and MRI of thigh muscles was performed in 16 of them.

Circulating cell-free mtDNA release is associated with the activation of cGAS-STING pathway and inflammation in mitochondrial diseases.

Background: There is increasing evidence for the role of inflammation in the pathogenesis of mitochondrial diseases (MDs). However, the mechanisms underlying mutation-induced inflammation in MD remain elusive. Our previous study suggested that mitophagy is impaired in the skeletal muscle of those with MD, likely causing mitochondrial DNA (mtDNA) release and thereby triggering inflammation.

Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions.

Objectives: This study aimed to investigate the clinical and genetic spectrum in Chinese patients with multiple mtDNA deletions presenting with autosomal-inherited mitochondrial progressive external ophthalmoplegia (PEO).

Methods: Long-range polymerase chain reaction and massively parallel sequencing of the mitochondrial genome were performed to detect deletions in muscle mtDNA of 274 unrelated families. Then, targeted next generation sequencing was used to detect nuclear gene variations in patients with multiple mtDNA deletions.

Widespread Mislocalization of FUS Is Associated With Mitochondrial Abnormalities in Skeletal Muscle in Amyotrophic Lateral Sclerosis With FUS Mutations.

Mutations in the fused in sarcoma (FUS) gene have been reported to be the most common genetic cause of early-onset amyotrophic lateral sclerosis (ALS); cytoplasmic inclusions containing FUS protein are the predominant pathological feature. Recent studies indicated that mutant FUS impaired neuromuscular junctions and induced muscle intrinsic toxicity in cell and animal models. However, the role of FUS in muscle degeneration remains unclear.

Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans.

Modeling the NaCl diffusion in beef during brining process.

An in-depth understanding of mass transfer during brining process is important for improving the quality and characteristics of meat products. In this study, a fitted equation of time and NaCl concentrations in the aqueous phase of beef was established to calculate the NaCl diffusion coefficient for simulation. A three-dimensional simulating model of mass transfer was developed to evaluate the NaCl diffusion in beef during brining process.

Electrical impedance estimation for pork tissues during chilled storage.

The impedance and physicochemistry of pork loins at five chilled storage periods (0, 1, 3, 7, 15 days) were characterized in order to explore the effects of chilling on the cell physiological status of pork tissues. The impedance spectra were analyzed by an equivalent circuit model with needle and bar electrodes. Meat traits including cooking loss, color, pH, texture properties and electrical conductivity were measured.

Appendicular skeletal muscle mass: A more sensitive biomarker of disease severity than BMI in adults with mitochondrial diseases.

The study aimed to evaluate the body composition of patients with mitochondrial diseases (MD) and correlate it with disease severity. Overall, 89 patients (age ≥ 18 years) with MD were recruited, including 49 with chronic progressive external ophthalmoplegia (CPEO) and 40 with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). Body composition, including fat mass index (FMI), fat-free mass index (FFMI), skeletal muscle mass index (SMI), and appendicular skeletal muscle mass index (ASMI), were examined using multifrequency bioelectric impedance analysis.

Levetiracetam administration is correlated with lower mortality in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes: a retrospective study.

Background: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS.