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PBX1 is a transcription factor that can promote the occurrence of various tumors and play a reg-ulatory role in tumor growth, metastasis, invasion, and drug resistance. Furthermore, a variant generated by fusion of E2A and PBX1, E2A-PBX1, has been found in 25% of patients with childhood acute lymphoblastic leukemia. Thus, PBX1 is a potential therapeutic target for many cancers. Here, we describe the structure of PBX1 and E2A-PBX1 as well as the molecular mecha-nisms whereby these proteins promote tumorigenesis to provide future research directions for developing new treatments. We show that PBX1 and E2A-PBX1 induce the development of highly malignant and difficult-to-treat solid and blood tumors. The development of specific drugs against their targets may be a good therapeutic strategy for PBX1-related cancers. Furthermore, we strongly recommend E2A-PBX1 as one of the genes for prenatal screening to reduce the incidence of childhood hematological malignancies.

ObjectivesThe study aimed to estimate the role of liver fibrosis in the association between occupational physical activity (OPA) and blood pressure (BP), which is modified by lifestyle factors.MethodsThe questionnaire survey and physical examination were completed among 992 construction workers in Wuhan, China. Associations between OPA or lifestyle factors and liver fibrosis indices and blood pressure were assessed using generalized additive models. The mediation analysis was used to evaluate the role of liver fibrosis in the association between OPA and lifestyle factors and BP.ResultsModerate/high OPA group workers had an increased risk of liver fibrosis [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.16–2.47, P < 0.05] compared with low OPA group workers. Smoking or drinking alcohol was related to liver fibrosis (aspartate aminotransferase to platelet ratio index: OR = 2.22, 95% CI: 1.07–4.62 or OR = 2.04, 95% CI: 1.00–4.15; P < 0.05). Compared with non-drinkers, drinkers were related to a 2.35-mmHg increase in systolic blood pressure (95% CI: 0.09–4.61), and a 1.60-mmHg increase in diastolic blood pressure (95% CI: 0.08–3.13; P < 0.05). We found a significant pathway, “OPA → liver fibrosis → blood pressure elevation,” and lifestyle factors played a regulatory role in the pathway.ConclusionOPA or lifestyle factors were associated with liver fibrosis indices or BP in construction workers. Furthermore, the association between OPA and BP may be partially mediated by liver fibrosis; lifestyle factors strengthen the relationship between OPA and BP and the mediation role of liver fibrosis in the relationship.

Objective We aim to describe the long-term outcome of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) after immune treatment in a Chinese cohort.Methods Between March 2015 and March 2023, 89 patients fulfilling the criteria for CIDP were followed up for a median of 22 months after treatment. Nine had positive antibodies against nodal-paranodal cell-adhesion molecules. Patients were treated according to clinical requirements with prednisone, intravenous immunoglobulin (IVIg) and/or immunosuppressant.Results A total of 78/89 patients had decreased inflammatory neuropathy cause and treatment (INCAT) scores at the last follow-up. For CIDP patients treated with steroids, 35 were stable without relapse after cessation or with a small maintenance dose; 2 relapsed at a high dose (20 mg/day); 15 relapsed at a low dosage (

BackgroundAs a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated.MethodsUsing a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed.ResultsAt 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process.ConclusionsThis study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

The efficient exploitation of coalbed methane (CBM) bears the safety responsibility of ensuring the efficient production of coal mines and reducing the gas accidents. At the same time, it undertakes the important mission of supplying the clean energy and contributing to the realization of the dual carbon goal. A novel idea of using supercritical carbon dioxide (SC-CO2) shock fracturing to stimulate CBM was proposed. This technique utilizes the high-pressure SC-CO2 to dynamically fracture the coal body, and cooperates with the energy shock and tube-casing injection to realize the multiple and continuous injection, so that the coal reservoir creates complex fracture networks with a certain scale that are not controlled by in-situ stress. This technique has some advantages such as water-free, environmental protection, safety and high efficiency. A self-developed true triaxial SC-CO2 shock fracturing experimental system was used to conduct the laboratory fracturing experiment of high-rank and low-rank coal rocks, and the borehole pressure characteristics and fracture patterns were compared with the conventional water fracturing and the SC-CO2 fracturing. The results show that the tortuosity and complexity of coal fractures in the SC-CO2 shock fracturing are higher than that of the conventional water fracturing and the SC-CO2 fracturing. Consequently, the fracture networks in which main fractures, micro-fractures and bedding fractures connected with each other are created. With the increase of shock pressure, the fracture becomes branched. There is a reasonable range of shock pressure for specific coal to ensure the generation of fracture networks and reduce the pulverized coal. The SC-CO2 shock fracturing is suitable for primary structured coal. In the field applications, it requires less professional equipment and has strong controllability. The conventional CO2 fracturing equipment and shock tools can meet the fracturing requirements. The SC-CO2 shock fracturing has the advantages of sufficient fracturing energy, little damage to the wellbore, and low economic cost. It can be used as a new reserve technique for revitalizing old CBM areas and reforming new CBM areas. It is suggested that the combination of the SC-CO2 shock fracturing and the water fracturing should be adopted in the field application to ensure the generation of fracture networks, the expansion of the scope of stimulation and the long-term conductivity. This research verifies the feasibility of the SC-CO2 shock fracturing to exploit CBM, which is expected to provide a new idea for the integration of efficient CBM exploitation and CO2 geological storage.

Objective To investigate the effects of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage. Methods Prospectively, 80 patients with refractory postpartum hemorrhage in Chengdu Fifth People′s Hospital from June 2019 to June 2022 were selected and grouped according to the random number table method. The control group (n=40) was treated with Bakri balloon compression, and the observation group (n=40) was treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression. The bleeding-related indexes and adverse effects were observed in both groups, and the prenatal and 24 h postpartum oxidative stress, coagulation function and inflammatory factors were compared between the two groups. Results The blood loss in the observation group and the control group was (683.96±146.52) vs(796.63±152.41)mL during operation, (812.46±161.53) vs(965.39±166.22)mL in 2 h after delivery, (899.53±178.74) vs(1 084.31±203.67)mL in 24 h after delivery, and the transfusion volume was (512.31±104.76) vs(683.25±113.52)mL, and the onset time of hemostasis was (14.63±3.18) vs (21.72±5.29) min (P0.05). At 24 h postpartum, NE, Cor, SOD and MDA were higher than those before delivery in both groups, but the observation group was lower than the control group (P

Abstract Background Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre‐existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression. Methods In this study, we investigated the effects of DM on CRC progression in a streptozotocin‐induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA‐seq. Results Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM‐CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4+ T cells, CD8+ T cells and mucosal‐associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM. Conclusion For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre‐existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.

BackgroundExtranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract.Case presentationWe encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes.ConclusionWe reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients.

Abstract Background Dog Bone™ button fixation is frequently used to treat acromioclavicular joint (ACJ) dislocation. However, various studies have reported complications after fixation. Objective To investigate the effect of the coracoid bone tunnel location on the treatment of ACJ dislocation through single-tunnel coracoclavicular (CC) ligament fixation with the Dog Bone™ button. Methods Six cadaveric shoulders were used. Each specimen was subjected to five testing conditions in the following order: (1) normal ACJ (Gn); (2) acromioclavicular and CC ligaments were removed (G0); (3) CC ligament reconstruction was performed using the Dog Bone™ technique, and the coracoid bone tunnel was at the center of the coracoid base (G1); (4) reconstruction was performed at 5 mm distal from the G1 site, along the axis of the coracoid (G2); (5) reconstruction was performed at 10 mm distal from the G1 site, along the axis of the coracoid (G3). The angles of pronation and supination of the clavicle under the same load (30 N) were measured. Next, a finite element (FE) model was created using computed tomography (CT) images of the normal shoulder. Model 1 (M1), model 2 (M2), and model 3 (M3) correspond to G1, G2, and G3, respectively. A force of 70 N was applied as a vertical upward load to the distal clavicle. Subsequently, the von Mises stress, the strain LE along the FiberWire, and the displacement nephogram of the three models were obtained. Results After single-tunnel CC ligament fixation using the Dog Bone™ technique, the clavicle in the G2 group (20.50 (19.50, 21.25) °, 20.00 (18.75, 21.25) °) had the best rotational stability. The peak von Mises stress, the strain LE along the FiberWire, and the maximum displacement were smaller in M2 than in M1 and M3. Conclusions When the coracoid bone tunnel was located 5 mm anterior to the center of the coracoid base (along the axis of the coracoid), the clavicle showed greater rotational stability.

Abstract Background Studies have reported that a noncoding hexanucleotide repeat in C9ORF72, is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasian population, nevertheless it is rare in Chinese population. Therefore, we aimed to investigate the mutation spectrum of Chinese ALS patients with FTD (ALS-FTD). Methods ALS patients with and without cognitive impairments were enrolled. Clinical features were collected including age, sex, disease duration, ALSFRS-r, family history and cognitive evaluation. Thirty-six ALS genes were screened by whole exome sequencing (WES) and repeat-primed polymerase chain reaction (PCR) were used for detection of and abnormal repeat expansions of C9ORF72. Results A total of 1208 patients, including 66 familial ALS (FALS) and 1142 sporadic ALS (SALS) patients were included. Twenty-three patients with sporadic ALS and one familial ALS index had concomitant FTD, which accounts for 1.99% (24/1208) of patients with ALS. In sporadic ALS-FTD, one case harboring C9ORF72 expansion variant, two cases harboring ANXA11 variants and one individual carrying CCNF variant were identified. A recurrent UBQLN2 variant was detected in a familial ALS-FTD patient. All of the ALS-FTD patients carrying variants in known causative genes manifested motor symptom onset (two bulbar onset and three limb onset) and developed cognitive impairment thereafter. It is not easy to draw a conclusion of the genotype-phenotype association in ALS-FTD with certain variants, limited by the small number of patients. Conclusion Our findings provide an overview of spectrum of genetic variants in Chinese ALS-FTD patients. Variants of uncertain significance in UBQLN2, ANXA11 and CCNF were identified and further studies are required for causal relations of these variants with ALS-FTD.

Supercritical CO2 fracturing is an important development trend to reach the goal of ''dual carbon'' and avoid the problem that hydraulic fracturing is influenced by water resource. In order to clarify the transport characteristics of proppant in the fractures induced by supercritical CO2 fracturing, this paper reconstructs the fracture surface of rock samples after supercritical CO2 fracturing using the laser morphological scanning technology, and establishes a model of proppant carrying and transport of supercritical CO2 in tortuous fractures on the basis of CFD-DEM method. In addition, the transport and placement characteristics of proppant in tortuous fractures are analyzed by comparing with flat fractures, and the effects of proppant density, injection rate of proppant carrying liquid, proppant concentration and other key parameters on proppant transport and distribution in fractures are investigated. And the following research results are obtained. First, compared with those in flat fractures, the flow paths of the proppant carrying supercritical CO2 liquid in tortuous fractures are tortuous and diverse, and the proppant presents stronger fluctuations and jumps laterally and vertically during its transport. Second, the proppant placement in tortuous fractures morphologically presents a wavy or even clustered non-uniform distribution. Third, low-density proppant has a better pass-ability in tortuous fractures, and the high injection rate can reduce the influence of tortuous fracture structure on proppant blocking. Fourth, if the concentration of injected proppant in the tortuous fracture is too low, good fracturing support effect cannot be achieved, and the optimal value under the simulation conditions in this paper is around 3%. In conclusion, the simulation results are of important theoretical and engineering significance to understanding the mechanism of proppant blocking in the pumping process of proppant carrying liquid for supercritical CO2 fracturing and optimizing the field fracturing design.

Cognitive green computing (CGC) is widely used in the Internet of Things (IoT) for the smart city. As the power system of the smart city, the smart grid has benefited from CGC, which can achieve the dynamic regulation of the electric energy and resource integration optimization. However, it is still challenging for improving the identification accuracy and the performance of the load model in the smart grid. In this paper, we present a novel algorithm framework based on reinforcement learning (RL) to improve the performance of non-invasive load monitoring and identification (NILMI). In this model, a knowledge base of load power facilities (LPF-KB) architecture is designed to facilitate the load data-shared collection and storage; utilizing deep convolutional neural networks (DNNs) structure based on the attentional mechanism to enhance the representations learning of load features; using RL-based Monte-Carlo tree search (MCTS) method to construct an optimal strategy network, and to realize the online combined load prediction without relying on the prior knowledge. We use the massive experiment on the real-world datasets of household appliances to evaluate the performance of our method. The experimental results show that our approach has remarkable performance in reducing the load online identification error rate. Our model is a generic model, and it can be widely used in practical load monitoring identification and the power prediction system.

Abstract. Background:. Epigenetics, and especially DNA methylation, contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). This study aimed to investigate the role of DNA methylation in SALS using whole blood of SALS patients. Methods:. In total, 32 SALS patients and 32 healthy controls were enrolled in this study. DNA was isolated from whole blood collected from the participants. DNA methylation profiles were generated using Infinium MethylationEPIC BeadChip. Results:. We identified 34 significant differentially methylated positions (DMPs) in whole blood from SALS patients, compared with the healthy controls. Of these DMPs, five were hypermethylated and 29 were hypomethylated; they corresponded to 13 genes. For the DMPs, ATAD3B and BLK were hypermethylated, whereas DDO, IQCE, ABCB1, DNAH9, FIGN, NRP1, TMEM87B, CCSAP, ST6GALNAC5, MYOM2, and RUSC1-AS1 were hypomethylated. We also identified 12 differentially methylated regions (DMRs), related to 12 genes (NWD1, LDHD, CIS, IQCE, TNF, PDE1C, LGALS1, CSNK1E, LRRC23, ENO2, ELOVL2, and ELOVL2-AS1). According to data from the Kyoto Encyclopedia of Genes and Genomes database, DNAH9 and TNF are involved in the amyotrophic lateral sclerosis (ALS) pathway. Correlation analysis between clinical features and DNA methylation profiling indicated that the methylation level of ELOVL2 and ARID1B was positively associated with the age of onset (r = 0.86, adjust P = 0.001) and disease duration (r = 0.83, adjust P = 0.01), respectively. Conclusions:. We found aberrant methylation in DMP- and DMR-related genes, implying that many epigenetic alterations, such as the hypomethylation of DNAH9 and TNF, play important roles in ALS etiology. These findings can be helpful for developing new therapeutic interventions.

Pre-B-cell leukemia homeobox transcription factor 1 (PBX1) is a member of the TALE (three-amino acid loop extension) family and functions as a homeodomain transcription factor (TF). When dimerized with other TALE proteins, it can act as a pioneer factor and provide regulatory sequences via interaction with partners. In vertebrates, PBX1 is expressed during the blastula stage, and its germline variations in humans are interrelated with syndromic anomalies of the kidney, which plays an important role in hematopoiesis and immunity among vertebrates. Herein, we summarize the existing data on PBX1 functions and the impact of PBX1 on renal tumors, PBX1-deficient animal models, and blood vessels in mammalian kidneys. The data indicated that the interaction of PBX1 with different partners such as the HOX genes is responsible for abnormal proliferation and variation of the embryonic mesenchyme, while truncating variants were shown to cause milder phenotypes (mostly cryptorchidism and deafness). Although such interactions have been identified to be the cause of many defects in mammals, some phenotypic variations are yet to be understood. Thus, further research on the TALE family is required.

Abstract Background Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. Methods Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. Results The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0–3) in ALS and 0 (0–0) in non-ALS patients (P

AbstractUnusual rainfall is the primary cause of the failure of the tailing dams, and overtopping is the most representative model of the tailing dam failure. The upstream tailing dam was selected as the research object to study the whole process of breach extension and the overtopping dam-failure mechanism under the full-scale rainfall condition. The results showed that the significant size grading phenomenon in the front, middle, and end of the tailing pond was obvious due to the flow separation effect, and its average particle diameter was D50. At different moments of rainfall, the height of the infiltration line at different positions of the dam body was different; at the rainfall of 3600 s, the height of the infiltration line lagged behind the height of the tailing pond, and this phenomenon from the tail of pond to the outside of the dam slope became more obvious. After the rainfall of 3600 s, the height of the infiltration line lagging behind the water level in the pond basically disappeared, and the rate of infiltration line rise kept pace with the rate of water level. The process of overtopping dam-failure experienced dam overtopping (gully erosion), formation of a multistepped small “scarp,” breach rapid expansion, formation of large “scarp,” and burst (fan-shaped formation). The width and depth of the breach showed a positive correlation, and the widening rate of the breach was 3 to 8 times of the deepening rate, especially in the middle of the dam break, widening behavior occupied the dominant factor. The shape of the dam body after failure was parabolic, and the dam body had obvious elevation changes. These results provide the theoretical guidance and engineering application value for improving the theory and early warning model of the upstream tailing dam.

Abstract Objectives The aim of this study was to assess and compare the diagnostic utility of a new diagnostic criteria for amyotrophic lateral sclerosis (ALS), abbreviated as the ‘Gold Coast Criteria’, with the revised El Escorial (rEEC) and Awaji criteria. Methods Clinical and electrophysiological data of 1185 patients from January 2014 to December 2019 in the Peking Union Medical College Hospital ALS database were reviewed. The sensitivity of the Gold Coast criteria was compared to that of the possible rEEC and Awaji criteria (defined by the proportion of patients categorized as definite, probable, or possible ALS). Results A final diagnosis of ALS was recorded in 1162 patients. The sensitivity of the Gold Coast criteria (96.6%, 95% confidence interval [CI] = 95.3%–97.5%) was greater than that of the rEEC (85.1%, 95%CI = 82.9%–87.1%) and Awaji (85.3%, 95%CI = 83.2%–87.3%). In addition, the sensitivity of the novel criteria maintained robust across subgroups, and the advantage was more prominent in limb-onset ALS patients and those who completed electromyographic tests. In those who did not achieve any of the rEEC diagnostic categories, the sensitivity of Gold Coast criteria was 84.4%. Conclusions The current study demonstrated that the Gold Coast criteria exhibited greater diagnostic sensitivity than the rEEC and Awaji criteria in a Chinese ALS population. The application of the Gold Coast criteria should be considered in clinical practice and future therapeutic trials.

Abstract Background The regeneration of muscle cells from stem cells is an intricate process, and various genes are included in the process such as myoD, mf5, mf6, etc. The key genes and pathways in the differentiating stages are various. Therefore, the differential expression of key genes after 4 weeks of differentiation were investigated in our study. Method Three published gene expression profiles, GSE131125, GSE148994, and GSE149055, about the comparisons of pluripotent stem cells to differentiated cells after 4 weeks were obtained from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were obtained for further analysis such as protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analysis. After hub genes and key pathways were obtained, we manipulated in vitro cell research for substantiation such as immunohistochemical staining and semi-quantitative analysis and quantitative real-time PCR. Results A total of 824 DEGs including 350 upregulated genes and 474 downregulated genes were identified in the three GSEs. Nineteen hub genes were identified from the PPI network. The GO and KEGG pathway analyses confirmed that myogenic differentiation at 4 weeks was strongly associated with pathway in cancer, PI3K pathway, actin cytoskeleton regulation and metabolic pathway, biosynthesis of antibodies, and cell cycle. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis. Meanwhile, the core genes in each pathway were identified from the GSEA analysis. The in vitro cell research revealed that actin cytoskeleton and myoD were upregulated after 4-week differentiation. Conclusions The research revealed the potential hub genes and key pathways after 4-week differentiation of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration, paving a way for more accurate treatment for muscle dysfunction.

Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.

Abstract Background Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the objective of the present study was to identify the signaling pathways and paracrine factors by which MSC-derived exosomes promote de novo skin tissue regeneration in response to wound healing. Methods In vitro and in vivo skin wound healing models were created by treating immortalized human keratinocytes (HaCaT) with hydrogen peroxide (H2O2) and excising full-thickness mouse skin, respectively. Exosomes were extracted from human umbilical cord Wharton’s jelly MSCs (hucMSC-Ex) by ultracentrifugation of cell culture supernatant. Results The hucMSC-Ex treatment significantly increased HaCaT cell proliferation and migration in a time- and dose-dependent manner, suppressed HaCaT apoptosis induced with H2O2 by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). The animal experiments showed that relative to hucMSCs, hucMSC-Ex attenuated full-thickness skin wounding by enhancing epidermal re-epithelialization and dermal angiogenesis. Conclusions These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings.

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system. The incidence rate is 0.1%–12% and 80% of nervous system adverse reactions occur within the first four months of application. ICIs can cause diseases of various parts of the nervous system including central nervous system diseases such as aseptic meningitis, meningeal encephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis, etc., and peripheral neuropathy such as cranial nerve peripheral neuropathy, multifocal nerve root neuropathy, Guillain‐Barré syndrome, spinal nerve root neuropathy, myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be difficult. Physicians require a specific collection of nervous system symptoms and signs, combined with supplementary examinations including imaging, cerebrospinal fluid cytology, EEG or electromyography in order to exclude infection or malignant tumor before reaching a final diagnosis. With regard to treatment, ICIs should be discontinued in severe cases, and large doses of glucocorticoid or gamma globulin administered, and supportive treatment may be necessary. If severe adverse reactions of the nervous system occur, the prognosis could be poor.

Traditional methods of multi-label text classification, particularly deep learning, have achieved remarkable results. However, most of these methods use word2vec technology to represent sequential text information, while ignoring the logic and internal hierarchy of the text itself. Although these approaches can learn the hypothetical hierarchy and logic of the text, it is unexplained. In addition, the traditional approach treats labels as independent individuals and ignores the relationships between them, which not only does not reflect reality but also causes significant loss of semantic information. In this paper, we propose a novel Hierarchical Graph Transformer based deep learning model for large-scale multi-label text classification. We first model the text into a graph structure that can embody the different semantics of the text and the connections between them. We then use a multi-layer transformer structure with a multi-head attention mechanism at the word, sentence, and graph levels to fully capture the features of the text and observe the importance of the separate parts. Finally, we use the hierarchical relationship of the labels to generate the representation of the labels, and design a weighted loss function based on the semantic distances of the labels. Extensive experiments conducted on three benchmark datasets demonstrated that the proposed model can realistically capture the hierarchy and logic of text and improve performance compared with the state-of-the-art methods.

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system, with the incidence rate ranging from 0.1% to 12%, and 80% occurring within the first 4 months of ICI application. It can cause lesions in various parts of the nervous system, including aseptic meningitis, meningoencephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis and other central nervous system diseases. It can also cause cranial peripheral neuropathy, multifocal radicular neuropathy, Guillain-Barre syndrome, spinal radicular neuropathy and myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be made by sufficient collection of disease manifestations combined with imaging, cerebrospinal fluid examinations, electro-encephalogram or electro myography to exclude infection or tumor progression. In the treatment of severe cases, ICIs should be discontinued and treated with high doses of glucocorticoid or gamma globulin with systemic support. After neurological adverse reactions, the prognosis of severe cases is poor.

Tissues and organs undergo structural deterioration and functional decline during aging. DNA damage is considered a major cause of stem cell senescence. Although stem cells develop sophisticated DNA repair systems, when the intrinsic and extrinsic insults exceed the DNA repair capacity, cellular senescence, and age-related diseases inevitably occur. Therefore, the prevention and alleviation of DNA damage is an alternative to DNA repair in attenuating stem cell senescence and preventing age-related diseases. Pre-B-cell leukaemia homeobox 1 (PBX1) participates in maintaining the pluripotency of human embryonic and haematopoietic stem cells. Our recent studies showed that PBX1 promotes hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation, decreases cellular senescence and apoptosis, and enhances induced pluripotent stem cell generation. Whether PBX1 attenuates HF-MSC senescence and apoptosis by alleviating DNA damage or by enhancing DNA repair remains unknown. In this study, we aimed to determine the effects of PBX1 on the intrinsic ROS or extrinsic H2O2-induced cellular senescence of HF-MSCs. To this end, we generated HF-MSCs overexpressing either PBX1, or poly (ADP-ribose) polymerase 1, or both. Our results showed that PBX1 overexpression attenuates HF-MSC senescence and apoptosis by alleviating reactive oxygen species (ROS)-mediated DNA damage instead of enhancing DNA repair. This is the first study to report that PBX1 attenuates stem cell senescence and apoptosis by alleviating DNA damage. It provides new insight into the mechanism of stem cell senescence and lays the foundation for the development of strategies for age-related disease prevention and treatment, and in particular, hair follicle repair and regeneration.

The prognosis for endocrine-independent prostate carcinoma is still poor due to its highly metastatic feature. In the present work, TPX2 (the targeting protein for Xklp2), which is known as a micro-tubulin interacted protein, was identified as a novel coactivator of ETS-1, a transcription factor that plays a central role in mediating the metastasis of human malignancies. TPX2 enhanced the transcription factor activation of ETS-1 and increased the expression of ETS-1’s downstream metastasis-related genes, such as mmp3 or mmp9, induced by HGF (hepatocyte growth factor), a typical agonist of the HGF/c-MET/ETS-1 pathway. The protein-interaction between TPX2 and ETS-1 was examined using immunoprecipitation (IP). TPX2 enhanced the accumulation of ETS-1 in the nuclear and the recruitment of its binding element (EST binding site, EBS) located in the promoter region of its downstream gene, mmp9. Moreover, TPX2 enhanced the in vitro or in vivo invasion of a typical endocrine-independent prostate carcinoma cell line, PC-3. Therefore, TPX2 enhanced the activation of the HGF/ETS-1 pathway to enhance the invasion of endocrine-independent prostate carcinoma cells and thus it would be a promising target for prostate carcinoma treatment.

Prostate cancer remains a significant cause of cancer-related deaths in male population. More recently, accumulating evidence continues to implicate long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in various types of cancers, including prostate cancer. The current study aimed to elucidate the role of lncRNA AGAP2-AS1/miR-195-5p/PDZ and LIM domain 5 (PDLIM5) in prostate cancer progression. Initially, microarray expression profiles were applied to screen differentially expressed lncRNAs/miRNAs/genes associated with prostate cancer. Dual-luciferase reporter and RNA pull-down/RIP assays were subsequently performed to explore the interactions among lncRNA AGAP2-AS1, miR-195-5p, and PDLIM5, after which their expression was detected in cancer tissues and cells. Next, gain- and loss-of-function approaches were employed to elucidate the mechanism of lncRNA AGAP2-AS1/miR-195-5p/PDLIM5 in the processes of cell proliferation, migration and invasion as well as tumor growth. LncRNA AGAP2-AS1 was found to be highly expressed in prostate cancer. Silencing of lncRNA AGAP2-AS1 contributed to the suppression of proliferation, migration and invasion of cancer cells in vitro. Besides, lncRNA AGAP2-AS1 could bind to miR-195-5p which targeted PDLIM5 and subsequently downregulated its expression, ultimately impeding the progression of prostate cancer. Additionally, lncRNA AGAP2-AS1 inhibition led to an up-regulated expression of miR-195-5p and down-regulated PDLIM5 expression, resulting in delayed tumor growth in vivo. Taken together, the key findings of our study demonstrated that lncRNA AGAP2-AS1 silencing exerted suppressive effects on the development of prostate cancer via the miR-195-5p-dependent downregulation of PDLIM5. Our findings highlighted the potential of lncRNA AGAP2-AS1 as a promising novel molecular target for prostate cancer therapy.

Introduction: Motor nerve conduction block (CB) is the main electrophysiological feature of multifocal motor neuropathy (MMN). Increased cross-sectional area (CSA) can be detected by nerve ultrasound in MMN. In this study, we aim to analyze the correlation between CB and CSA in MMN.Methods: Twelve patients with MMN were recruited. Ultrasonography tests and motor nerve conduction studies (NCSs) were performed on median and ulnar nerves simultaneously. CSA was measured at 10 consecutive sites on those nerves, meanwhile nerves were traced continuously and recorded thoroughly under ultrasound.Results: In motor NCSs, 12 definite CB and 12 probable CB areas were detected across standard segments of median and ulnar nerves. With ultrasound studies, increased CSA was detected at 36 sites. There were 9 standard segments with CB and increased CSA, 15 segments with CB but normal CSA, and 27 segments with increased CSA but no CB.Discussion: In MMN, motor nerve CB was not always consistent with increased CSA.

Objective: To explore the correlation between afterdischarges in motor nerve conduction studies and clinical motor hyperexcitability in patients with voltage-gated potassium channels (VGKC) antibodies. Methods: Six patients with positive serum antibodies to contactin-associated protein-like 2 (CASPR2) or/and leucine-rich glioma-inactivated protein 1 (LGI1) were recruited, including 5 with autoimmune encephalitis, and 1 with cramp-fasciculation syndrome. Electromyography (EMG), nerve conduction studies (NCS) and F waves were performed, and afterdischarges were assessed. One patient was followed up. Results: Five patients had clinical evidence of peripheral motor nerve hyperexcitability (myokymia or cramp), and four of them had abnormal spontaneous firing in concentric needle electromyography (EMG). Prolonged afterdischarges following normal M waves were present in all six patients, including the two patients who had no EMG evidence of peripheral nerve hyperexcitability (PNH). Afterdischarges disappeared after treatment with intravenous immunoglobulin (IVIG). Conclusion: The afterdischarges in motor nerve conduction study might be a sensitive indicator of peripheral motor nerve hyperexcitability in patients with VGKC antibodies. Significance: Afterdischarges in motor nerve conduction study might be more sensitive than needle electromyography for detecting peripheral motor nerve hyperexcitability, and could disappear gradually in accordance with clinical improvement and reduction of antibodies. Keywords: Afterdischarges, VGKC, Autoimmune encephalitis, Peripheral nerve hyperexcitability, F wave, M wave

The F-wave test allows for the non-invasive assessment of spinal motoneuron excitability. We investigated the difference in spinal motoneuron dysfunction between the first dorsal interosseous (FDI) and abductor digit minimi (ADM) muscles by investigating F-waves and to assess the contribution of spinal mechanisms to split-hand syndrome in patients with amyotrophic lateral sclerosis (ALS). Sixty-five consecutive ALS patients and twenty age- and gender-matched healthy controls (HCs) were enrolled. Motor nerve conduction studies and F-waves were performed bilaterally on median and ulnar nerves in all subjects. HCs revealed prominently longer F-wave latencies, lower chronodispersion, mean F-wave amplitude, and mean and maximal F/M amplitude ratio (P < 0.001) in the FDI compared to the ADM. However, no significant differences in almost all F-wave parameters between the FDI and ADM were observed in ALS patients with affected hands except the minimal and mean F-wave latency. These data suggest that excitability is greatly changed in the spinal motoneurons innervating the FDI. Furthermore, the mean F-wave amplitude (r = 0.454, P = 0.002) of the FDI was significantly correlated with the FDI/ADM CMAP amplitude ratio in ALS patients with affected hands but not of the ADM. Our findings suggested that the dysfunction of spinal motoneurons between the FDI and ADM was different in ALS, and spinal motoneuron dysfunction was associated with development of the split-hand phenomenon.

Background: The muscle patterns involved in the “split-leg” syndrome of amyotrophic lateral sclerosis (ALS) remains controversial. We sought to evaluate and reassess the pattern of the extensor digitorum brevis (EDB) and the abductor hallucis (AH) muscles' involvement in split-leg syndrome in ALS.Methods: We recruited 60 consecutive patients with ALS and 25 healthy controls (HCs). Compound muscle action potentials (CMAPs) and F-waves were recorded over the EDB and AH muscles in all subjects. For comparison, we classified patients into two categories based on the presence or absence of lower limbs symptoms.Results: The EDB/AH CMAP amplitude ratio was significantly reduced in patients with affected legs (0.33 ± 0.21, P = 0.007), whereas patients with unaffected legs had a ratio similar to that of the HCs. The EDB/AH ratios for the F-wave latencies, mean F-wave amplitude, mean F/M amplitude ratio, and the persistence of the total repeater F-wave shapes (index Freps) of the EDB-AH, were significantly increased in the affected leg group, whereas the EDB/AH ratio for F-wave persistence was significantly reduced. These findings indicated a greater loss of lower motor neurons (LMNs) innervating the EDB and dysfunction of spinal motoneurons innervating the EDB. In the unaffected leg group, the EDB, but not the AH, F-wave latencies, mean and maximal F/M amplitude ratios, and index Freps were significantly altered. Receiver operating characteristic curve analysis suggested that the EDB F-wave latencies, mean F/M amplitude ratios, and index Freqs (area under the curve [AUC] > 0.8) more strongly differentiated patients with ALS from the HCs compared to the EDB/AH CMAP amplitude ratio (AUC = 0.61). Notably, the EDB maximal F-wave latency and index Freqs reliably differentiated patients with unaffected legs (HCs), with AUCs of 0.83 (95% CI 0.76–0.91) and 0.81 (95% CI 0.72–0.89), sensitivities of 76 and 78%, and specificities of 76 and 78%, respectively.Conclusions: These results suggest preferential EDB compared to AH involvement in the split-leg syndrome of ALS. The EDB maximal F-wave latency and index Freqs robustly differentiated patients with ALS from HCs, which might facilitate an earlier identification of ALS.

Objective: To evaluate the frequency and clinical features of restless legs syndrome (RLS) in a group of Chinese patients with amyotrophic lateral sclerosis (ALS).Methods: 109 Patients included in this study fulfilled the revised El Escorial diagnostic criteria for clinically definite, probable and lab-supported probable ALS, and a group of 109 control subjects was matched for age and sex to the ALS group. Disease severity was assessed by the revised ALS functional rating scale (ALSFRS-R). The diagnosis of RLS was made according to the criteria of the International RLS Study Group. Other characteristics including sleep quality, excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), depression and anxiety were also evaluated in ALS patients.Results: RLS was significantly more frequent in ALS patients than in control subjects (14.6 vs. 0.9%; P < 0.05). Compared to those without RLS, ALS patients with RLS reported a higher frequency of anxiety and EDS. ALS patients with RLS showed more severe legs dysfunction. EDS and legs function scores of the ALSFRS-R were independent factors significantly associated with RLS in ALS patients.Conclusions: Our findings suggest that Chinese ALS patients exhibit a high frequency of RLS symptoms and that these patients may benefit from recognition of the condition and optimized management of its symptoms. Moreover, ALS patients might cause circadian rhythms disturbance and our study further supports that ALS is a heterogeneous disorder involving multiple systems; further studies are needed to confirm these preliminary findings.

Several studies have attempted to reduce diagnostic delay and identify biomarkers for drug development in amyotrophic lateral sclerosis (ALS). In this study, we aimed to evaluate the diagnostic accuracy for ALS of cerebrospinal fluid (CSF) neurofilament (Nf), Tau protein, and inflammatory factors such as interleukin (IL)-2, IL-6, IL-10, IL-15, and granulocyte-macrophage colony-stimulating factor (GMCSF) in Chinese patients. Our prospective study measured the concentration of phosphorylated Nf heavy chain (pNfH), Nf light chain (NfL), Tau, pTau, and inflammatory factors in the CSF of 85 patients. Detailed clinical data and laboratory, neuroimaging, and neurophysiological findings were recorded. The concentrations of pNfH and NfL were higher in the ALS group than in the control group. At the 1104 pg/mL pNfH cutoff, the specificity was 68.8%, the sensitivity 100%, and the area under the curve (AUC) 0.907. At the 1,139 pg/mL NfL cutoff, the specificity was 56.3%, the sensitivity 96.2%, and the AUC 0.775. There was no significant difference in the concentrations of Tau, pTau, IL-2, IL-6, IL-10, IL-15, and GMCSF between the ALS and control groups (p > 0.05). In the ALS group, the concentration of pNfH in the CSF was correlated with disease duration (r = −0.475, p < 0.001). This is the first prospective study to confirm the diagnostic value of Nf for ALS in Chinese patients.

Introduction: Motor nerve conduction blocks (CBs) could be detected in both acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). We aimed to identify the correlation between CBs and functional outcome in the two subtypes of GBS.Methods: Motor nerve conduction studies were performed in 17 patients with AIDP and 23 with AMAN. All patients were treated with intravenous immunoglobulin, and their disabilities were evaluated with Hughes functional grading scale before treatment, 1 month and 6 months after onset.Results: AMAN with CBs had higher reduction of Hughes grade (indicating more improved outcomes) at 1 month (1.71 ± 0.83 vs. 1 ± 0.67, p = 0.034) than AIDP with CBs. AMAN with CBs had higher reduction of Hughes grade at 1 month (1.71 ± 0.83 vs. 0.56 ± 0.73, p = 0.002) than AMAN without CBs. The reduction of Hughes grade at 1 month showed no significant difference between AIDP with and without CBs.Discussion: Motor nerve CBs in AMAN indicated better prognosis than in AIDP.

ObjectiveTo characterize the patterns of brain atrophy and perfusion as measured by arterial spin labeling (ASL)-MRI, in amyotrophic lateral sclerosis (ALS) patients with varying levels of cognitive deficit, including ALS with frontotemporal dementia (FTD).MethodsA total of 55 ALS patients and 20 healthy controls (HCs) were included, and all participants underwent neuropsychological assessments and MRI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n = 27), ALS with cognitive impairment (ALS-Ci, n = 17), and ALS-FTD (n = 11). Voxel-based comparisons of gray matter (GM) changes and cerebral blood flow (CBF) were conducted among the subgroups.ResultsThe whole-brain comparisons of GM changes and CBF among ALS-Ci, ALS-Cn, and HCs were not significantly different. However, the ALS-FTD patients demonstrated a similar pattern of GM loss and hypoperfusion with more significant alterations in the left frontal and temporal lobe compared with the HCs, ALS-Cn, and ALS-Ci patients. Decreased CBF was found in many of the same brain areas wherein structural alterations occurred, although isolated GM loss and hypoperfusion were also observed. In addition, for both GM and CBF abnormalities, a similar pattern of changes was found in the comparisons of ALS-FTD vs. ALS-Ci, ALS-FTD vs. ALS-Cn, and ALS-FTD vs. HCs, with the differences being most significant between ALS-FTD and HCs.ConclusionThe cognitive status of ALS patients is associated with different patterns of GM changes and cerebral perfusion. ASL-MRI might be a useful tool with which to investigate the pathological burden of ALS and to disclose the early signature of possible cognitive impairment.

The current perception threshold (CPT) is a device which can evaluate different sensory fibers quantitatively through different frequencies of the electrical stimulus and has been applied in clinical practice. Previous studies have implied that CPT values may be affected by age, gender, and other factors, yet not conclusively. The objective of our study is to clarify the influencing factors of CPT values and establish a reference value range. Twenty healthy volunteers recruited publicly and 146 subjects who took CPT tests in the census of the national project cardiovascular and cerebrovascular diseases in rural areas of China from 2013 to 2015 were analyzed. Past medical history and demographic characteristics such as age, gender, and occupation were collected. Each subject was tested on the left index finger (or back of the left hand) and the right hallux. CPT values of 2000, 250, and 5 Hz on both sites were recorded for statistical analysis. Gender differences were shown at 2000 Hz CPT on the back of the hand and hallux (p < 0.01), and male subjects had a higher CPT. Age had a positive correlation with 250 Hz CPT on the index finger (p < 0.05, r = 1.5), 2000 Hz CPT on the back of the hand (p < 0.001, r = 1.2) and index finger (p < 0.05, r = 2.5). Manual workers had a higher 250 Hz CPT on the hallux than mental workers (p < 0.01). After investigating the impact of different factors on CPT testing, we established the reference value for subjects with different characteristics.

Layer 2/3 (L2/3) excitatory neurons in the neocortex make major contributions to corticocortical connections and therefore function to integrate information across cortical areas and hemispheres. Recent evidence suggests that excitatory neurons in L2/3 can have different properties. Sparse evidence from previous studies suggests that L2 neurons located at the border between L1 and L2 (referred to as L2 marginal neurons, L2MNs), have a morphology distinct from a typical pyramidal neuron. However, whether the membrane properties and input/output properties of L2MNs are different from those of typical pyramidal neurons in L2/3 is unknown. Here we addressed these questions in a slice preparation of mouse temporal cortex. We found that L2MNs were homogeneous in intrinsic membrane properties but appeared diverse in morphology. In agreement with previous studies, L2MNs either had oblique apical dendrites or had no obvious apical dendrites. The tufts of both apical and basal dendrites of these neurons invaded L1 extensively. All L2MNs showed a regular firing pattern with moderate adaptation. Compared with typical L2/3 pyramidal neurons that showed regular spiking (RS) activity (neurons), L2MNs showed a higher firing rate, larger sag ratio, and higher input resistance. No difference in the amplitude of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively), evoked by stimulation of L1, was found between the two types of neurons, but the IPSPs in L2MNs had a slower time course than those in L2/3 RS cells. In paired recordings, unitary EPSPs showed no significant differences between synapses formed by L2MNs and those formed by L2/3 RS neurons. However, short-term synaptic depression (STSD) examined with a L2MN as the presynaptic neuron was greater when another L2MN was the postsynaptic neuron than when a L2/3 RS neuron was the postsynaptic neuron. The distinct morphological features of L2MNs found here have developmental implications, and the differences in electrophysiological properties between L2MNs and other L2/3 pyramidal neurons suggest that they play different functional roles in cortical networks.

A-wave was observed in patients with motor neuron disease (1). However, data on the characteristics and clinical significance of A-waves in patients with amyotrophic lateral sclerosis (ALS) have been scarce. The F-wave studies of 83 patients with ALS and 63 normal participants which were conducted previously at the Department of Neurology in Peking Union Medical College Hospital were retrospectively reviewed to determine the occurrence of A-waves in ALS. A-waves occurred more frequently in ALS patients than in normal controls. For the median and peroneal nerves, the frequencies of nerves with A-waves and frequencies of patients with A-waves were comparable between the ALS patients and normal controls. For the ulnar and tibial nerves, the frequencies of nerves with A-waves and frequencies of patients with A-waves were significantly increased in the ALS patients compared with those of the normal participants. Disease progression rate was slower in the ALS patients with A-waves (0.73 ± 0.99) than that in the ALS patients without A-waves (0.87 ± 0.55, P = 0.007). No correlations were found between the amplitudes of F-waves with A-waves and those of A-waves in the ulnar nerves (r = 0.423, P = 0.149). No correlations were found between the persistence of F-waves with A-waves and the persistence of A-waves in the ulnar nerves as well (r = 0.219, P = 0.473). The occurrence of A-waves may indicate dysfunction of lower motor neurons and possibly imply a relatively slower degenerative process.

ObjectiveTo evaluate serum creatine kinase (CK) levels of amyotrophic lateral sclerosis (ALS) patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients.MethodsWe analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI), serum creatinine (Cr), and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan–Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS.ResultsBaseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20–2,574 U/L), and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169) versus 117 (111) U/L, p

ObjectiveTo describe the characteristics of patients with amyotrophic lateral sclerosis (ALS) and myasthenia gravis (MG) overlap syndrome and explore the relationship between the two diseases.MethodsWe conducted a search of medical records at Peking Union Medical University Hospital from 1983 to 2015 for coexistence of ALS and MG and searched the PubMed database for all literature describing ALS and MG overlap syndrome published through December 2016. We analyzed the clinical and neurophysiological characteristics of patients by groups according to strict diagnostic criteria.ResultsWe presented 2 patients in our database with combined ALS and MG, and together with 25 cases reported in the literature, the patients were divided into 4 groups: 12 patients with MG followed by ALS, 8 patients with ALS followed by MG, 5 ALS patients with false-positive anti-acetylcholine receptor, and the other 2 ALS patients with only myasthenia symptoms. Most patients had limb onset ALS, and myasthenia symptoms mainly affected ocular and bulbar muscles. Clinical and neurophysiological characteristics were summarized.ConclusionThese findings support the conclusion that immunological mechanisms and alterations in the neuromuscular junction are related to ALS pathogenesis.

IntroductionMultiple sites measurement of cross-sectional areas (CSA) by ultrasound was performed to differentiate Charcot–Marie–Tooth type 1A (CMT1A) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsNine patients with CMT1A, 28 patients with CIDP, and 14 healthy controls (HC) were recruited prospectively. Consecutive ultrasonography scanning was performed from wrist to axilla on median and ulnar nerves. CSAs were measured at 10 predetermined sites of each nerve.ResultsCMT1A had significantly larger CSAs at all sites of median and ulnar nerves (p

OBJECTIVES:The accurate and early diagnosis of amyotrophic lateral sclerosis (ALS) is important for extending the life expectancy of patients. However, previous studies that have assessed the diagnostic sensitivities of the Awaji criteria (AC) and the revised El Escorial criteria (rEEC) in patients with ALS have been inconsistent, most of them were consensual regarding the advantage of Awaji over conventional criteria. Our study sought to compare the roles of AC and rEEC in the diagnosis of ALS. METHODS:Data from a total of 294 consecutive patients with ALS were collected between January 2014 and August 2015 in the Peking Union Medical College Hospital. The clinical and electrophysiological records of 247 patients were eventually analyzed. The primary outcome measures were the sensitivities of the AC and rEEC for the diagnosis of ALS. RESULTS:The sensitivity of probable or definite ALS as diagnosed with the AC (78%) was greater than that of the rEEC (36%, P

Daphniphyllum calycinum (DC), a main component of Chinese patent drug Fengliao-Changweikang, is effectively used to cure bowel disease in the clinic. It was recorded that DC possessed slight toxicity, which was caused by the alkaloids existing in its extract. Unfortunately, to date the toxicity level and toxic constituents are still unclear. The present study is designed to illustrate the acute toxicity and induced organ damages of the total alkaloids as well as to determine the toxic constituents. Based on the above studies, not only was the acute toxicity determined but also hepatic toxicity was characterized by increased plasma biomarkers of ALT and AST and liver cell inflammatory infiltrate as well necrosis that was firstly observed. Significantly, deoxycalyciphylline B exhibited exactly the same hepatic toxicity so it was identified as the main toxic constituent in DC. An obvious dose-effect relationship between the toxic compound and induced hepatic injuries was also observed. Moreover, the Chinese patent drug Fengliao-Changweikang contained low levels of the toxic compound, compared with the total alkaloids. Therefore, this Chinese patent drug could be regarded to be safe in this point of view.