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The phanerocrystalline aggregate (single mineral particle size greater than 20 μm), which is mainly composed of α-quartz and has technological value, is called quartzite jade. Black quartzite jade from Linwu, Hunan Province, has gained significant market popularity due to its fine texture and aesthetic appeal. This study aims to provide a comprehensive analysis of this less-explored variety, focusing on its mineral composition, microstructure, spectral characteristics, and chemical properties. A combination of gemological assessments, polarizing microscopy, infrared spectroscopy, X-ray diffraction (XRD), total organic carbon (TOC) analysis, and X-ray fluorescence spectrometry (XRF) was utilized to investigate these features systematically. Additionally, the origin of color is discussed. Results indicate that the quartzite jade from Linwu primarily consists of α-quartz along with varying amounts of muscovite, andalusite, graphite, rutile, and other trace minerals. Infrared analysis reveals characteristic peaks at 479 cm -1 , 540 cm -1 , 778 cm -1 , 796 cm -1 , 1086 cm -1 and 1173 cm -1 . The presence of absorption double peaks between 700–800 cm -1 suggests enhanced particle arrangement within the internal structure of the sample; this indicates a well-organized Si–O bond configuration and a high degree of crystallization within the specimen. Based on metamorphic rock discriminant factor (DF) determinants showing negative values for all samples alongside an Al 2 O 3 to TiO 2 ratio ranging from 19 to 29 implies these samples are medium to low-temperature metasomatic parametamorphic rocks formed via regional metamorphism, combined with the average total organic carbon (TOC) content of 1.27%, further suggesting that Linwu’s quartzy autolith is silicon-rich clay shale. The predominant factor contributing to the sample’s black coloration is attributed to its substantial graphite content.

Cancer treatment-induced thrombocytopenia (CTIT) is a common adverse effect in malignant tumor patients, significantly increasing the risk of bleeding and negatively impacting treatment efficacy and quality of life. Current treatment options for CTIT primarily include platelet transfusion, recombinant human interleukin-11 (rhIL-11), recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists (TPO-RAs). However, these methods have their limitations; for instance, platelet transfusions may cause adverse reactions, and the efficacy and safety of rhTPO and TPO-RAs remain controversial. This review aims to summarize the current treatment landscape for CTIT and explore new therapeutic advancement, including the potential role of traditional Chinese medicine, in order to provide more effective treatment strategies for clinical practice.

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). Results A total of 183 patients (mean age: 16 (IQR: 12–25), 49.72% males) were enrolled, including 124 pediatric patients and 59 adult patients. MELAS (106. 57.92%) and Leigh syndrome (37, 20.22%) were predominant among the mitochondrial disease subtypes. Among them, 132 (72.13%) patients were initially misdiagnosed with other diseases, 58 (31.69%) patients visited 2 hospitals before confirmed as mitochondrial disease, and 39 (21.31%) patients visited 3 hospitals before confirmed as mitochondrial disease. Metabolic modifiers were the most common type of drugs used, including several dietary supplements such as L-carnitine (117, 63.93%), Coenzyme Q10 (102, 55.74%), idebenone (82, 44.81%), and vitamins (99, 54.10%) for proper mitochondrial function. Mothers are the primary caregivers for both children (36.29%) and adults (38.98%). The mRS score ranged from 0 to 5, 92.35% of the patients had different degrees of disability due to mitochondrial disease. The average monthly treatment cost was 3000 RMB for children and 3100 RMB for adults. Conclusions This study provided valuable insights into the characteristics and challenges of mitochondrial diseases, which underscores the need for improved awareness, diagnostic efficiency, and comprehensive support for patients and caregivers.

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. Clinical assessments, including muscle strength, usual gait speed, and disease severity determined by the Newcastle Mitochondrial Disease Adult Scale score (NMDAS), were performed. The comparisons between patients group and age- and gender-matched healthy controls, as well as the correlations between anthropometric measurements, body composition, and disease severity were analyzed. Height, weight, body mass index (BMI), FFMI, SMI, and ASMI were significantly lower in patients with MD than in healthy controls. Notably, low muscle mass was noted in 69.7% (62/89) of MD patients, with 22 patients also presenting with compromised physical performance as indicated by decreased gait speed, resulting in 24.7% satisfied the sarcopenia diagnostic criteria. Disease severity was more negatively correlated with ASMI than it was with height, weight, and BMI. Subgroup analysis showed that in the MELAS subgroup, disease severity was negatively correlated with height, weight, and ASMI; whereas in the CPEO subgroup, it was only negatively correlated with ASMI and SMI. Additionally, ASMI was positively associated with muscle strength. Altogether, compared with BMI, ASMI is a more sensitive biomarker predicting disease severity of MD, both in MELAS and CPEO patients.

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. Results A total of 40 Chinese PEO patients (10 males and 30 females) from 20 families were found to have multiple mtDNA deletions in this study, and the median age at onset was 35 (1–70) years. PEO and positive family history were the two prominent features of these patients, and ataxia, neuropathy, and hypogonadism were also present as onset symptoms in some patients. Fifteen of 20 probands with multiple mtDNA deletions were identified to carry nuclear gene variants; eight (40.0%) probands had variants within POLG, two (10.0%) within TWNK, two (10.0%) within RRM2B, two (10.0%) within TK2, and one (5.0%) within POLG2. A total of 24 variants were found in these five nuclear genes, of which 19 were novel. The causal nuclear genetic factors in five pedigrees remain undetermined. Conclusions The POLG gene is the most common disease‐causing gene in this group of PEO patients with multiple mtDNA deletions. While inherited PEO is the most prominent symptoms in these patients, genotypic and phenotypic heterogeneity still exist, for example in onset age, initial symptoms, and accompanying manifestations. Progressive external ophthalmoplegia (PEO) is a clinically diverse mitochondrial disorder that is characterized by ptosis or weakness of extraocular muscles and often co‐occurs with multisystem involvement. This study aimed to investigate the clinical and genetic spectrum in Chinese patients with multiple mtDNA deletions presenting with autosomal‐inherited mitochondrial PEO. The POLG gene is the most common disease‐causing gene in this group of PEO patients with multiple mtDNA deletions. While inherited PEO is the most prominent symptoms in these patients, genotypic and phenotypic heterogeneity still exist, for example in onset age, initial symptoms, and accompanying manifestations.

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. There was an obvious negative correlation between the total MFD and the disease course in the ATTR‐PN group. The disease course of early‐onset and late‐onset symptoms was similar, but the loss of large myelinated nerve fibers (MF) was more severe for the latter. In addition, all late‐onset and most early‐onset patients had severely reduced MFD after a 2 years' disease course. The MFD in ATTR‐PN patients was negatively correlated with Neuropathy Impairment Score (NIS) and Norfolk Quality of life‐diabetic neuropathy (Norfolk QOL‐DN) score. Conclusion MF is lost differently in ATTR‐PN and in other common peripheral neuropathies. The late‐onset and early‐onset ATTR‐PN patients have different patterns of loss of large and small MF.

BackgroundThere 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. We here aimed to decipher the role of the cGAS-STING pathway in inflammatory process in MDs.MethodsWe investigated the levels of circulating cell-free mtDNA (ccf-mtDNA) in the serum of 104 patients with MDs. Immunofluorescence was performed in skeletal muscles in MDs and control. Biochemical analysis of muscle biopsies was conducted with western blot to detect cGAS, STING, TBK1, IRF3 and phosphorylated IRF3 (p-IRF3). RT-qPCR was performed to detect the downstream genes of type I interferon in skeletal muscles. Furthermore, a protein microarray was used to examine the cytokine levels in the serum of patients with MDs.ResultsWe found that ccf-mtDNA levels were significantly increased in those with MDs compared to the controls. Consistently, the immunofluorescent results showed that cytosolic dsDNA levels were increased in the muscle samples of MD patients. Biochemical analysis of muscle biopsies showed that cGAS, IRF3, and TBK1 protein levels were significantly increased in those with MDs, indicating that there was activation of the cGAS-STING pathway. RT-qPCR showed that downstream genes of type I interferon were upregulated in muscle samples of MDs. Protein microarray results showed that a total of six cytokines associated with the cGAS-STING pathway were significantly increased in MD patients (fold change > 1.2, p value < 0.05).ConclusionsThese findings suggest that increases in ccf-mtDNA levels is associated with the activation of the cGAS-STING pathway, thereby triggering inflammation in MDs.

Abstract 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. In this study, we investigated FUS protein distribution in skeletal muscle fibers in ALS-FUS. Our data show that cytoplasmic mislocalized FUS in the unaggregated form represented a remarkable pathological feature in affected muscle fibers in ALS-FUS. Additional studies found that cytoplasmic FUS colocalized with some mitochondria and was associated with mitochondrial swelling and disorganized cristae. RNA sequencing and quantitative real-time polymerase chain reaction analyses indicated downregulation of the key subunits of mitochondrial oxidative phosphorylation complexes in the affected skeletal muscle in ALS-FUS patients. Further immunoblot analysis showed increased levels of FUS, but decreased levels of Cox I (subunit of complex IV) in ALS-FUS patients compared with age-matched controls. This is the first demonstration of the close association of cytoplasmic mislocalized FUS with mitochondrial dysfunction in skeletal muscle, implicating the presence of a cell-autonomous mechanism in muscle degeneration in ALS.

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. Visually estimated percent adhesion by trained clinicians or trial participants creates variability and bias. In addition, trial participants are typically confined to clinical centers during the entire product wear period, which may lead to challenges when translating adhesion performance to the real world setting. In this work we propose to use artificial intelligence and mobile technologies to aid and automate the collection of photographic evidence and estimation of percent adhesion. We trained state-of-art deep learning models with advanced techniques and in-house curated data. Results indicate good performance from the trained models and the potential use of such models in clinical practice is further explored.

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. Patients with PEO who had a single large deletion in mitochondrial DNA were included in this study. The associations were analyzed between mtDNA deletion patterns, myopathological changes, and clinical characteristics. Results In total, 155 patients with mitochondrial PEO carrying single large‐scale mtDNA mutations were enrolled, including 137 chronic progressive external ophthalmoplegia (CPEO) and 18 Kearns–Sayre syndrome (KSS) patients. The onset ages were 9.61 ± 4.12 in KSS and 20.15 ± 9.06 in CPEO. The mtDNA deletions ranged from 2225 bp to 9131 bp, with m.8470_13446del being the most common. The KSS group showed longer deletions than the CPEO group (p = 0.004). Additionally, a higher number of deleted genes encoding respiratory chain complex subunits (p = 0.001) and tRNA genes (p = 0.009) were also observed in the KSS group. A weak negative correlation between the mtDNA deletion size and ages of onset (p < 0.001, r = −0.369) was observed. The proportion of ragged red fibers, ragged blue fibers, and cytochrome c negative fibers did not correlate significantly with onset ages (p > 0.05). However, a higher percentage of abnormal muscle fibers corresponds to an increased prevalence of exercise intolerance, limb muscle weakness, dysphagia, and cerebellar ataxia. Conclusion We reported a large Chinese cohort consisting of mitochondrial PEO patients with single large‐scale mtDNA deletions. Our results demonstrated that the length and locations of mtDNA deletions may influence onset ages and clinical phenotypes. The severity of muscle pathology could not only indicate diagnosis but also may be associated with clinical manifestations beyond the extraocular muscles. Figure A illustrates the ROC curve depicting the relationship between the age of onset and the disease diagnosis. The AUC for distinguishing CPEO and KSS by ages of onset was 0.874, having a maximum Youden index of 0.594, resulting in an optimum cut‐off point of 15.5 years. Figure B displays a moderate negative correlation between the mtDNA deletion size and onset ages (correlation coefficient r = −0.369).