Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Integrated Mechanism of Immune Response Modulation by Arctium Lappa L. Fructans Based on Microbiome and Metabolomics Technologies.

Arctium lappa L. is widely consumed for its various biological effects, and polysaccharides are its main functional components. The present study aimed to evaluate the immunoregulatory effects of the main polysaccharides from burdock (ALP-1) and reveal the underlying mechanisms. ALP-1 consisted of fructose and glucose (14.57:1) and had a molecular weight of 2757 Da, with typical characteristics of (1 → 2)-linked linear fructans. Oral intake of ALP-1 significantly increased the number of colonic goblet cells, serum immunoglobulin A and immunoglobulin G levels, and fecal secretory immunoglobulin A content as well as up-regulated antioxidant enzymes and increased short chain fatty acid production. In addition, ALP-1 administration regulated pro/anti-inflammatory cytokines (i.e., interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, interferon-γ, and IL-10), intestinal microbiota structure, and the spatial information on key metabolites. Some gut-microbiota-mediated metabolic processes were also significantly altered. These results indicated that ALP-1 could exert beneficial effects on immune responses and intestinal health in healthy mice.

Revealing the effect of conductive carbon materials on the sodium storage performance of sodium iron sulfate.

Na2Fe2(SO4)3 (NFS), as a promising cathode for sodium-ion batteries, is still plagued by its poor intrinsic conductivity. In general, hybridization with carbon materials is an effective strategy to improve the sodium storage performance of NFS. However, the role of carbon materials in the electrochemical performance of NFS cathode materials has not been thoroughly investigated. Herein, the effect of carbon materials was revealed by employing various conductive carbon materials as carbon sources. Among these, the NFS coated with Ketjen Black (NFS@KB) shows the largest specific surface area, which is beneficial for electrolyte penetration and rapid ionic/electronic migration, leading to improved electrochemical performance. Therefore, NFS@KB shows a long cycle life (74.6 mA h g-1 after 1000 cycles), superior rate performance (61.5 mA h g-1 at a 5.0 A g-1), and good temperature tolerance (-10 °C to 60 °C). Besides, the practicality of the NFS@KB cathode was further demonstrated by assembling a NFS@KB//hard carbon full cell. Therefore, this research indicates that a suitable carbon material for the NFS cathode can greatly activate the sodium storage performance.

Fabrication of caffeoylquinic acid-loaded burdock polysaccharide nanoparticles and their antioxidant activity in hydrogen peroxide-damaged HepaRG cells.

Herein, burdock polysaccharide (BP) and modified burdock polysaccharide (MBP) were prepared, followed by the fabrication of chlorogenic acid (CA)-BP, CA-MBP, isochlorogenic acid A (ICA)-BP, and ICA-MBP nanoparticles. Afterward, the structural characteristics, physical stability, digestive characteristics, and antioxidant activity of hydrogen peroxide (H2O2)-damaged HepaRG cells were evaluated. The result indicated that the loading capacities of CA in BP-CA and MBP-CA were 0.14 and 0.53 µg/mg, respectively. Conversely, the loading capacities of ICA in BP-ICA and MBP-ICA were 0.36 and 0.60 µg/mg, respectively. Four complex nanoparticles exhibited excellent physical stability under different pH values, temperatures, and ionic concentrations, especially MBP-CA and MBP-ICA. Moreover, four complex nanoparticles could protect caffeoylquinic acid from being released in gastric fluid. All six samples exhibited high antioxidant activity in H2O2-induced HepaRG cells, especially BP and MBP-CA. These findings indicated that caffeoylquinic acid-polysaccharide complexes were successfully prepared and highlighted the potential of polysaccharides as natural carriers for hydrophobic bioactive molecules.

Outcomes of Filtering Surgery Versus Clear Lens Extraction in Young Patients With Angle-Closure Glaucoma.

PURPOSE: To compare the effect of filtering surgery versus clear lens extraction in young patients with medically uncontrolled angle-closure glaucoma (ACG). DESIGN: Retrospective, nonrandomized, comparative, interventional study. METHODS: We reviewed the medical charts of patients with the following scenarios: (1) age ≤40 years; (2) diagnosis of ACG without cataract, including primary angle-closure glaucoma (PACG), nanophthalmic ACG, and ACG combined with retinal dystrophies; and (3) ACG undergoing filtering surgery or clear lens extraction. The main outcomes including intraocular pressure (IOP), number of medications, best-corrected visual acuity, and severe complications were extracted at the postoperative early (within 1 week) and late stage (>3 months) follow-up. RESULTS: Data from 160 eyes of 130 young patients with ACG were available. Eyes with 76 PACG, 12 nanophthalmic ACG, and 26 ACG with retinal diseases underwent filtering surgery, whereas eyes with 22 PACG, 12 nanophthalmic ACG, and 12 ACG with retinal diseases received clear lens extraction. Overall, filtering surgery and clear lens extraction resulted in significant but comparable IOP and drug reductions at the postoperative late stage in each ACG subgroup, with similar complete success rates between 2 treatments (all P > .05). Regarding the safety, filtering surgery and patients with retinal diseases were independent factors associated with postoperative malignant glaucoma (P < .05 in both multivariable logistic regression models). CONCLUSIONS: This study highlights that the efficacy of clear lens extraction is comparable to that of filtering surgery in medically uncontrolled ACG in young patients, but clear lens extraction is safer, especially for young patients with ACG comorbid with retinal diseases.

Case Report: The application of metagenomic next generation sequencing in diagnosing fungal malignant external otitis: a report of two cases.

Background: Most of malignant external otitis (MEO) cases reported in the literature are attributed to Pseudomonas aeruginosa. Fungal infections in MEO are also likely but extremely rare. And conventional microbiology tests is difficult to diagnose. Case description: Two patients were diagnosed with Fungal malignant external otitis (FMEO) due to Aspergillus by metagenomic Next-Generation Sequencing (mNGS) and recovered after comprehensive treatment including operation and voriconazole. The antifungal treatment was delayed due to repeated cultures of secretions being negative and pathological examination showed granulation tissue proliferation with extensive neutrophil infiltration. Conclusion: mNGS might be helpful for patients suspected with FMEO, especially when conventional microbiology tests were negative.

The Influence of Pulmonary Veins' Anatomic Features and Catheter Coaxiality on Cryoballoon Ablation Results for Paroxysmal Atrial Fibrillation.

A total of 172 consecutive patients with sympathetic paroxysmal atrial fibrillation who received cryoballoon (CB) ablation from 2020 to 2021 were retrospectively analyzed in this study. Catheter coaxiality and anatomic features of pulmonary veins (PVs) on computed tomography images were explored by several parameters and their influence on the cryoablation results was then analyzed. The rate of incomplete CB occlusion was significantly higher for inferior than superior PVs. A multivariate analysis revealed that a short distance (<6.3 mm) from PV ostium to first branch (D-PVB) and a small angle (<32.5°) of first branch were independent predict factors for an incomplete CB occlusion in right inferior PVs (RIPVs). A combination of D-PVB and angle of first branch could elevate the predictor value for an incomplete balloon occlusion with a sensitivity of 0.85 and specificity of 1.0 for RIPVs. For PVs with a perfect balloon occlusion, the best catheter coaxiality was observed in right superior PV while the worst catheter coaxiality was observed in RIPV. A more aggressive catheter manipulation with a "7" or "reverse-U" shape of long sheath could obtain a better catheter coaxiality compared with conventional manipulation strategy for RIPVs. In Conclusion, a short D-PVB and a small angle of first branch were independent predict factors for an incomplete CB occlusion in RIPVs. A more aggressive catheter manipulation strategy was recommended to achieve a complete balloon occlusion and a better catheter coaxiality for RIPVs.

Water-gas ratio characteristics and development concepts for water-producing gas reservoirs.

Water production from gas wells is a key factor affecting the effectiveness of gas-reservoir development, and it poses serious challenges in terms of increasing the degree of recovery during the waterless production stage and reducing the impact of water production on gas-reservoir development in the middle and later periods. Thus, gas reservoirs must be efficiently exploited on the basis of identifying gas-water layers accurately, defining gas-water relationships, and understanding gas-water production performance. Accordingly, this study analyzes the production characteristics in gas reservoirs with different gas-water relationships, and it summarizes the rules that determine water-gas ratios. The results reveal that the water-gas ratio increases rapidly in the early stage of water production, but after a period of time, it enters a relatively stable state in which it is almost a fixed value. According to the material balance equation, the theoretically calculated water-gas ratio is fully consistent with the production rules for an entire confined gas reservoir. This shows that the reality of gas-well-water production must be faced, and that the development of water-bearing gas reservoirs must accommodate gas and water co-production. The gas-water relationship, water body scale, and reservoir heterogeneity determine the time of water breakthrough and the water-gas ratio. Therefore, we should change the traditional "water fear" concept in gas-field development, aim for an overall improvement in recovery, face up to the fact that gas wells produce water, and coordinate the development of multi-wells for entire gas reservoirs, all of which will achieve the ultimate goal of improved gas recovery.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Endothelial exosomes work as a functional mediator to activate macrophages.

Introduction: Intercellular communication is essential for almost all physiological and pathological processes. Endothelial cell (EC)-derived exosomes, working as mediators for intercellular information exchange, are involved in the pathophysiological mechanisms of atherosclerosis. However, the effect of inflamed endothelial exosomes on the function of macrophages (Mϕ) is poorly defined. This study aims to unravel how exosomes derived from tumor necrosis factor-α (TNF-α)-stimulated ECs (exo-T) affect Mϕ in vitro. Methods and results: Exosomes derived from untreated ECs (exo) and exo-T were identified by using TEM, NTA, and western blot, and we observed that PKH67-labeled exo/exo-T were taken up by Mϕ. Exposure to exo-T for 24 h not only skewed Mϕ to the M1 subtype and exacerbated lipid deposition, but also promoted Mϕ apoptosis, while it did not significantly affect Mϕ migration, as detected by RT-qPCR, Dil-ox-LDL uptake assay, flow cytometry, wound healing assay, and transwell assay, respectively. In addition, exo/exo-T-related microRNA-Seq revealed 104 significantly differentially expressed microRNAs (DE-miRNAs). The target genes of DE-miRNAs were mainly enriched functionally in metabolic pathways, MAPK signaling pathway, etc., as determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We further demonstrated by immunoblotting that exo-T intervention improves the phosphorylation of MAPK/NF-κB-related proteins. Discussion and conclusion: Collectively, this study reveals that inflamed endothelial exosomes (TNF-α-stimulated EC-derived exosomes) work as a functional mediator to affect Mϕ function and may activate Mϕ through MAPK/NF-κB signaling pathways.

Three-muscle surgery for large-angle esotropia in chronic sixth nerve palsy: comparison of two approaches.

AIMS: To report the effect of two three-muscle surgeries, inferior rectus belly transposition plus augmented superior rectus transposition plus medial rectus recession (ISM) and modified vertical rectus belly transposition plus medial rectus recession (VM), in the management of large-angle esotropia in Chinese patients with chronic sixth nerve palsy. METHODS: Twenty-eight consecutive patients with large-angle esotropia ≥50Δ were prospectively enrolled and underwent either ISM or VM. Main outcomes included preoperative and postoperative deviation in primary position, abduction limitation and complications. Follow-up was at least 6 months. RESULTS: Of the included patients, 13 underwent ISM and 15 underwent VM. Preoperatively, ISM group displayed larger esotropia and more severe abduction limitation. 27 patients completed the follow-up. The postoperative horizontal deviation and abduction limitation were similar in both groups. At the last follow-up, ISM group demonstrated greater improvement of abduction limitation than VM group in both grading (group difference -2.1, p<0.001) and quantitation (group difference 2.6 mm, p=0.001). However, eight (30%) patients revealed an induced adduction limitation ≤-1. Of the 22 patients with unilateral palsy, more esotropia of 14.8Δ was corrected in ISM group, compared with VM group (p=0.003). Three patients (14%) developed vertical diplopia and three (14%) developed torsional diplopia. Unexpectedly, keratitis was observed in 4 of 27 (15%) patients, all with concurrent fifth and/or seventh nerve palsy. Three patients aggravated to corneal ulceration. CONCLUSIONS: Two three-muscle surgeries, ISM and VM were both effective for large-angle esotropia in Chinese patients with chronic sixth nerve palsy. However, attention should be paid to potential complications.

Capillaries segmentation of NIR-II images and its application in ischemic stroke.

Fluorescence imaging in the second near-infrared window (NIR-II) offers µm resolution blood vessel information noninvasively, which is crucial for the diagnosis and surgery treatment of some blood vessel-related diseases. However, only a few blood vessel segmentation algorithms have been done for the NIR-II images so far. Here, we proposed a vessel segmentation algorithm that used multi-scale enhancement and fractional differential to enhance capillaries, and then segmented vessels based on the blood vessels' tubular characteristics. Experimental results showed that this method could effectively suppress the point and lump tissue noise influence during vascular segmentation. The accuracy of vessel identification by other algorithms dropped below 30%, while our algorithm still achieved an accuracy of around 50% in deep vessel segmentation experiments with the 6.5 mm Intralipid. So it had the advantage of accurately detecting deep and dim blood capillaries. Meanwhile, the vascular density quantization algorithm had been successfully applied to the mice's ischemic stroke evaluations for the first time. In addition, this algorithm can provide the quantified vessel features under physiological or pathological conditions, which could be used to accurately evaluate the stroke drugs' therapeutic effect in the future.

Photoacoustic Effect of Near-Infrared Absorbing Organic Molecules via Click Chemistry.

Near-infrared dyes were developed to be contrast agents due to their ability to improve the productivity of photoacoustic (PA) imaging and photothermal therapy (PTT) treatments. During the article, we described in detail the PA and PT effects of a category of organic molecules. F4-TCNQ could potentially cause a red-shift in the peak PA intensity. The results show that the PTT intensity of the near-infrared dyes with phenyl groups were higher than near-infrared dyes with thiophene groups. We also investigated the photodynamic treatment effect of C1b to demonstrate that these dyes are highly desirable in biochemistry. The high photoacoustic intensity of the organic molecules and the good yield of reactive oxygen species could indicate that these dyes have good potential for a wide range of imaging applications. Finally, we embedded the dye (C1b) in a liposomal hydrophobic phospholipid bilayer (C1b⊂L) to facilitate the application of hydrophobic dyes in biomedical applications, which can be absorbed by cells with good compatible and high stability for the imaging of cellular PA.

Oxygen-Vacancy-Induced Synaptic Plasticity in an Electrospun InGdO Nanofiber Transistor for a Gas Sensory System with a Learning Function.

The perceptual learning function of a simulating human body is very important for constructing a neural computing system and a brainlike computer in the future. The sense of smell is an important part of the human sensory nervous system. However, current gas sensors simply convert gas concentrations into electrical signals and do not have the same learning and memory function as synapses. To solve this problem, we propose a new sensing idea to induce and activate the synaptic properties of transistors by adjusting the oxygen vacancy in the active layer. This sensor combines gas detection with synaptic memory and learning and overcomes the disadvantage of the separation of synaptic transistors and sensors, thus greatly reducing the cost of production. This work combines the detection of N,N-dimethylformamide (DMF) gas with the synaptic mechanism of human olfactory nerves. We successfully fabricated an InGdO nanofiber field-effect transistor by electrostatic spinning and simulated the response of human olfactory synapses to target gas by regulating the oxygen vacancy of the InGdO nanofiber. The synaptic transistor response under different concentrations of unmodulated pulses is tested, and the pavlovian conditioned reflex experiment is simulated successfully. This work provides a new idea of a gas sensor device, which is very important for the development of high-performance gas sensors and bionic electronic devices in the future.

Mg-doped InSnO nanofiber field-effect transistor for methanol gas detection at room temperature.

Research on high-performance gas sensors for detecting toxic and harmful methanol gas is still a very important issue. For gas sensors, it is very important to be able to achieve low concentration detection at room temperature. In this work, we used the electrospinning method to prepare Mg-doped InSnO nanofiber field-effect transistors (FETs) methanol gas sensor. When the Mg element doping concentration is 2.3 mol.%, InSnO nanofiber FET exhibits excellent electrical properties, including higher mobility of 3.17 cm2V-1s-1, threshold voltage of 1.51 V, subthreshold swing of 0.42 V/decade, the excellent on/off current ratio is about 108and the positive bias stress stability of the InSnO nanofiber FET through Mg doping has been greatly improved. In addition, the InSnMgO nanofiber FET gas sensor exhibits acceptable gas selectivity and sensitivity to methanol gas at room temperature. In the methanol gas sensor test at room temperature, when the methanol gas concentration is 60 ppm at room temperature, the response value of the InSnMgO nanofiber FET gas sensor is 81.92; and when the methanol concentration is 5 ppm, the response value is still 1.21. This work provides an effective and novel way to build a gas sensor at room temperature and use it to detect methanol gas at room temperature.

Role of the Hippo-YAP/NF-κB signaling pathway crosstalk in regulating biological behaviors of macrophages under titanium ion exposure.

The presence of metal ions, such as titanium (Ti) ions, is toxic to adjacent tissues of implants. Indeed, Ti ions may induce an inflammatory response through the NF-κB pathway, thus causing damage to soft and hard tissues. The involvement of Yes-associated protein (YAP), a key factor of the Hippo pathway, in an immuno-inflammatory response has been confirmed, whereas its role in Ti ion-mediated inflammation has not been elucidated. Therefore, this study aimed to investigate the role of signal crosstalk between the Hippo/YAP and NF-κB signaling pathways in the pro-inflammatory effect of Ti ions on macrophages. In our work, RAW264.7 cells were cocultured with Ti ions. The migration capacity of macrophages under Ti ion exposure was measured by transwell assay. Western blot analysis was used to detect the expressions of related proteins. Polymerase chain reaction was used to evaluate the expression of pro-inflammatory cytokines. The nucleus translocation of YAP and P65 was visualized and analyzed via immunofluorescence staining. The results showed that the migration of macrophages was promoted under Ti ion exposure. Ten parts per million Ti ions induced nuclear expression of YAP and activated the NF-κB pathway, which finally upregulated the expression of pro-inflammatory cytokines in macrophages. Moreover, the inhibition of the NF-κB pathway rescued the reduction of YAP expression under Ti ion exposure. Most importantly, the overexpression of YAP exacerbated the inflammatory response mediated by Ti ions through the NF-κB pathway. In summary, this study explored the mechanism of Hippo-YAP/NF-κB pathway crosstalk involved in the regulation of macrophage behaviors under Ti ion exposure.

Enhanced corrosion resistance of zinc-containing nanowires-modified titanium surface under exposure to oxidizing microenvironment.

Titanium (Ti) and its alloys as bio-implants have excellent biocompatibilities and osteogenic properties after modification of chemical composition and topography via various methods. The corrosion resistance of these modified materials is of great importance for changing oral system, while few researches have reported this point. Recently, oxidative corrosion induced by cellular metabolites has been well concerned. In this study, we explored the corrosion behaviors of four common materials (commercially pure Ti, cp-Ti; Sandblasting and acid etching-modified Ti, Ti-SLA; nanowires-modified Ti, Ti-NW; and zinc-containing nanowires-modified Ti, Ti-NW-Zn) with excellent biocompatibilities and osteogenic capacities under the macrophages induced-oxidizing microenvironment. The results showed that the materials immersed into a high oxidizing environment were more vulnerable to corrode. Meanwhile, different surfaces also showed various corrosion susceptibilities under oxidizing condition. Samples embed with zinc element exhibited more excellent corrosion resistance compared with other three surfaces exposure to excessive H2O2. Besides, we found that zinc-decorated Ti surfaces inhibited the adhesion and proliferation of macrophages on its surface and induced the M2 states of macrophages to better healing and tissue reconstruction. Most importantly, zinc-decorated Ti surfaces markedly increased the expressions of antioxidant enzyme relative genes in macrophages. It improved the oxidation microenvironment around the materials and further protected their properties. In summary, our results demonstrated that Ti-NW-Zn surfaces not only provided excellent corrosion resistance properties, but also inhibited the adhesion of macrophages. These aspects were necessary for maintaining osseointegration capacity and enhancing the corrosion resistance of Ti in numerous medical applications, particularly in dentistry.

A family with Danon disease caused by a splice site mutation in LAMP2 that generates a truncated protein.

BACKGROUND: Danon disease is an X-linked dominant hereditary condition caused by mutations in the gene encoding lysosomal-associated membrane protein 2 (LAMP2), leading to failure of lysosome binding to autophagosomes, accumulation of glycogen in the heart, and abnormal cardiac function. METHODS: We describe identification of a mutation in LAMP2, c.741+1G>T, in a family with Danon disease by whole exome sequencing. RESULTS: Pathology examination of patient skeletal muscle biopsy showed myogenic damage and autophagic vacuoles with sarcolemmal features (AVSF). Numerous autophagic vacuoles accumulated in muscle cells were detected by electron microscopy, indicating abnormal autophagy function. CONCLUSION: The mutation did not result in loss of mRNA exons; rather, a 6-nucleotide (two-codon) insertion, where the latter was a stop codon, leading to early termination of LAMP2 protein translation. The resulting truncated protein lacks an important transmembrane domain, which will impair lysosome/autophagosome fusion, damage autophagy function, and result in the clinical manifestations of Danon disease.

Whole-exome sequencing reveals a novel mutation of MT-ND5 gene in a mitochondrial cardiomyopathy pedigree: Patients who show biventricular hypertrophy, hyperlactacidemia, pulmonary hypertension, and decreased exercise tolerance.

OBJECTIVE: The aim of the present study was to determine whether pathogenic mutations were present in families with mitochondrial cardiomyopathy that presented during adolescence. METHODS: The proband was a 21-year-old man who presented clinically with palpitations, chest tightness, pulmonary hypertension, and limited exercise tolerance. Cardiac magnetic resonance imaging studies showed biventricular cardiac hypertrophy. We determine whether pathogenic mutations were present by whole-exome sequencing (WES) in families. RESULTS: Screening of the family using tandem mass spectrometry showed elevated lactic acid levels, glutaric aciduria, a mildly increased glutarylcarnitine-to-octanoylcarnitine ratio, and normal blood α-glucosidase, which was consistent with a respiratory chain complex 1 metabolic disorder. We identified a novel mutation of MT-ND5, c.1315A>G (p.Thr439Ala). Skeletal muscle biopsy histology showed predominantly ragged red fibers and few ragged blue fibers, which was consistent with mitochondrial myopathy. CONCLUSION: In the present study, we identified a novel mutation of MT-ND5, c.1315A>G (p.Thr439Ala), in a family pedigree using WES.

Swallowing-induced atrial tachycardia: case report.

A 53-year-old man presented with heart palpitations while swallowing. Electrophysiologic study (EPS) and immunohistochemical results of his esophageal leiomyoma suggested that swallowing-induced atrial tachycardia is related with neural reflex. S100-immunopositive nerve fibers are demonstrated sympathetic nerves which possibly explain the mechanism. Metoprolol tartrate tablets are effective in our patient.