2018年 · 第131卷第18期

Background: Nowadays, it is widely known that decremental responses in low-frequency repetitive nerve stimulation (LF-RNS) are frequently observed in patients with amyotrophic lateral sclerosis (ALS). The pathological mechanism of this phenomenon remains unknown. This study aimed to illuminate the features of RNS in Chinese patients with ALS. Methods: Clinical and electrophysiological data of 146 probable and definite ALS patients who underwent RNS were retrospectively enrolled and analyzed. LF-RNS (3 Hz) was performed in trapezius, deltoid, abductor digiti minimi (ADM), quadriceps femoris, and tibialis anterior. High-frequency RNS (HF-RNS, 10 Hz) was performed only in ADM. The two-sample t-test and Chi-squared test were used for statistical analysis. Results: Decremental responses to LF-RNS (≥10%) in at least one muscle were detected in 83 (56.8%) of the cases and were most commonly seen in trapezius and deltoid. The incidence of decremental response was higher in patients with upper limb onset. Incremental responses to HF-RNS (≥60%) in ADM were observed in 6 (5.6%) of the cases. In 106 muscles with decremental response, 62 (57.4%) muscles had a continuous decremental pattern, more than a U-shape pattern (37 cases, 34.3%). Nineteen cases showed definite decrements in LF-RNS tests in trapezius, while no abnormalities were found in the electromyography and neurological examination of the sternocleidomastoid muscle, supplied by the accessory nerve as well. Conclusions: Decremental responses in the RNS are commonly observed in ALS patients. The findings regarding the trapezius indicated that some ALS onsets could be initiated by a "dying back" process, with destruction of neuromuscular junctions (NMJs) before motor neurons. Incremental responses in the ADM implied damage of the NMJs involved both the post and presynaptic membranes.

Background: Whether the Glasgow Coma Scale (GCS) can assess intubated patients is still a topic of controversy. We compared the test performance of the GCS motor component (GCS-M)/Simplified Motor Score (SMS) to the total of the GCS in predicting the outcomes of intubated acute severe cerebral vascular disease patients. Methods: A retrospective analysis of prospectively collected observational data was performed. Between January 2012 and October 2015, 106 consecutive acute severe cerebral vascular disease patients with intubation were included in the study. GCS, GCS-M, GCS eye-opening component, and SMS were documented on admission and at 24, 48, and 72 h after admission to Neurointensive Care Unit (NCU). Outcomes were death and unfavorable prognosis (modified Rankin Scale: 5–6) at NCU discharge. The receiver operating characteristic (ROC) curve was obtained to determine the prognostic performance and best cutoff value for each scoring system. Comparison of the area under the ROC curves (AUCs) was performed using the Z-test. Results: Of 106 patients included in the study, 41 (38.7%) patients died, and 69 (65.1%) patients had poor prognosis when discharged from NCU. The four time points within 72 h of admission to the NCU were equivalent for each scale’s predictive power, except that 0 h was the best for each scale in predicting outcomes of patients with right-hemisphere lesions. Nonsignificant difference was found between GCS-M AUCs and GCS AUCs in predicting death at 0 h (0.721 vs. 0.717, Z = 0.135, P= 0.893) and 72 h (0.730 vs. 0.765, Z = 1.887, P= 0.060), in predicting poor prognosis at 0 h (0.827 vs. 0.819, Z = 0.395, P= 0.693), 24 h (0.771 vs. 0.760, Z = 0.944, P= 0.345), 48 h (0.732 vs. 0.741, Z = 0.593, P= 0.590), and 72 h (0.775 vs. 0.780, Z = 0.302, P= 0.763). AUCs in predicting death for patients with left-hemisphere lesions ranged from 0.700 to 0.804 for GCS-M and from 0.700 to 0.824 for GCS, in predicting poor prognosis ranged from 0.841 to 0.969 for GCS-M and from 0.875 to 0.969 for GCS, with no significant difference between GCS-M AUCs and GCS AUCs within 72 h (P> 0.05). No significant difference between GCS-M AUCs and GCS AUCs was found in predicting death (0.964 vs. 0.964, P= 1.000) and poor prognosis (1.000 vs. 1.000, P= 1.000) for patients with right-hemisphere lesions at 0 h. AUCs in predicting death for patients with brainstem or cerebella were poor for GCS-M (<0.700), in predicting poor prognosis ranged from 0.727 to 0.801 for GCS-M and from 0.704 to 0.820 for GCS, with no significant difference between GCS-M AUCs and GCS AUCs within 72 h (P> 0.05). The SMS AUCs (<0.700) in predicting outcomes were poor. Conclusions: The GCS-M approaches the same test performance as the GCS in assessing the prognosis of intubated acute severe cerebral vascular disease patients. The GCS-M could be accurately and reliably applied in patients with hemisphere lesions, but caution must be taken for patients with brainstem or cerebella lesions.

Background: Histopathology identified the anatomical and molecular abnormalities of brainstem nuclei in migraine patients. However, the exact whole brainstem structural changes in vivo have not yet been identified in medication-overuse headache (MOH) transformed from migraine. The aim of this study was to investigate the regional volume changes over the whole brainstem in the MOH patients using voxel-based morphometry (VBM) in vivo. Methods: High-resolution three-dimensional structural images were obtained using a 3.0-Tesla magnetic resonance system from 36 MOH patients and 32 normal controls (NCs) who were consecutively recruited from the International Headache Center, Chinese People’s Liberation Army General Hospital, from March 2013 to June 2016. VBM was used to assess the brainstem structural alteration in the MOH patients, and voxel-wise correlation was performed to evaluate the relationship with the clinical characteristics. Results: The brainstem region with increased volume located in the left ventrolateral periaqueductal gray (MNI coordinate: -1, -33, -8), ventral tegmental area (MNI coordinate: 0, -22, -12), bilateral substantia nigra (MNI coordinate: -8, -16, -12, 9, -16, -12), and trigeminal root entry zone (MNI coordinate: -19, -29, -31; 19, -32, -29) in MOH patients compared with NCs. The headache visual analog scale score was positively related with the left rostral ventromedial medulla (RVM) (MNI coordinate: -1, -37, -56; cluster size: 20; r = 0.602) in the MOH patients. Conclusions: The regional volume gain of brainstem could underlie the neuromechanism of impaired ascending and descending pathway in the MOH patients, and the left RVM volume alteration could imply the impaired tolerance of nociceptive pain input and could be used to assess the headache disability in the MOH patients.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. Methods: Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing. Results: The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient’s mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES. Conclusions: The present study described a "tripe trouble" with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.

Background: The effectiveness of the combination of electroacupuncture (EA) and behavioral training (BT) for mid/advanced cerebral infarction (M/ACI) and related mechanisms remains unclear. This study aimed to investigate the combined effects on the learning-memory ability and event-related potential P300 in rats with M/ACI. Methods: Eighty rats with M/ACI were divided into Group Model (M), Group EA, Group BT, and Group EA-BT (n = 20) according to the random number with five healthy rats in Group Control (CON). On the 6th week after modeling, EA, BT, and EA-BT were given to Group EA, Group BT, and Group EA-BT, respectively, whereas Group M and Group CON were not given any intervention. Y-maze test and P300 were recorded before and after the intervention. Results: After intervention, the P300 latency was lower and the amplitude was higher in the Group EA-BT, Group EA, and Group BT than before (for latency, t = −7.638, −4.334, and −5.916; for amplitude, t = 8.125, 3.846, and 5.238; P< 0.01), with Group EA-BT superior to Group EA (for latency, t = −3.708; for amplitude, t = 3.653; P< 0.01) and Group BT (for latency, t = −2.067; for amplitude, t = 2.816; P< 0.05), with no significant difference between Group BT and EA (for latency, t= −1.439; for amplitude, t = 1.075; P> 0.05). While the performances of Y-maze tests in the Group EA-BT, Group EA, and Group BT were all better than before (t = 10.359, 4.520, and 7.791, P< 0.01), with Group EA-BT better than Group EA (t = 5.627, P< 0.01) and Group BT (t = 2.913, P< 0.01) respectively, and Group BT better than Group EA (t = 2.912, P< 0.01). Conclusion: EA or BT can affect P300 in rats with M/ACI, and the combination of these two methods can significantly improve the learning-memory ability.

Background: Arterial grafts had better mid-term and long-term patency than saphenous vein grafts in coronary artery bypass grafting (CABG). We summarized our experience with total arterial off-pump coronary artery bypass grafting (OPCAB) and assessed the early clinical results, surgical complications, and follow-up. Methods: From January 2007 to May 2017, 508 coronary artery disease patients undergoing total arterial OPCAB were enrolled. Clinical features, approaches, outcomes of surgical treatments, and follow-up data of these patients were studied retrospectively. A total of 122 patients underwent single left internal mammary artery (IMA)-left anterior descending artery grafts, whereas the other 386 patients underwent multiple vessel grafts. Results: The average distal anastomosis was 2.34 ± 0.97 (range: 1–4). All the patients were discharged from hospital except one died. A total of 457 (90.32%) patients were followed up. In the 4-, 7-, and 10-year follow-up groups, the rate of death from any cause was 1.19%, 6.47%, and 10.67%; rate of cardiac death was 0.60%, 2.88%, and 3.33%; rate of repeat revascularization was 0.00%, 3.60%, and 8.67%; rate of ischemic symptoms was 1.79%, 7.91%, and 11.33%; and incidence of stroke was 2.38%, 4.32%, and 6.67%, respectively. Poor medication adherence was observed in 9.38% of the follow-up population. Conclusions: Total arterial OPCAB with bilateral IMA, radial artery, and right gastroepiploic artery grafting yielded satisfactory early and midterm outcomes in this patient group, without a significant increase in early mortality or morbidity. Moreover, the long-term outcomes are also positive.

Background: The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA). Methods: A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann–Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results: A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II–IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124–4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P = 0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed. Conclusions: These results provide evidence and explain that higher doses of CD34+ and CD14+ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.

Background: Estrogen receptor (ER) and progesterone receptor (PR) are involved in endometriosis, but the involvement of microRNAs (miRNAs) is unknown. The aim of the study was to explore the correlation between miRNA and ER/PR in uterine tissues of rats with endometriosis during the implantation window. Methods: Twenty female Sprague-Dawley rats were randomized in three groups: endometriosis (n = 7), fat tissue control (n = 6), and normal (n = 7) groups. The female rats were mated and sacrificed on day 5 (implantation). Uterine tissues were obtained for hematoxylin-eosin staining, immunohistochemistry, and miRNA expression. Reverse transcription polymerase chain reaction (RT-PCR) was used to validate the expression of rno-miR-29c-3p, rno-miR-34c-5p, rno-miR-141-5p, rno-miR-24-1-5p, and rno-miR-490-5p. Results: The 475 miRNAs were found to differentially express between the endometriosis and normal control groups, with 127 being upregulated and 348 being downregulated. Expression of five miRNAs (rno-miR-29c-3p, rno-miR-34c-5p, rno-miR-141-5p, rno-miR-24-1-5p, and rno-miR-490-5p) were validated by RT-PCR and found to be differentially expressed among the three groups. Expression of ER and PR proteins (immunohistochemistry) in the glandular epithelium and endometrial stroma was significantly different among the three groups (all P< 0.05). Five miRNAs were involved in pathways probably taking part in implantation and fertility. Conclusions: The results suggested that miRNAs, ER, and PR could play important roles in the embryo implantation period of rats with endometriosis. These miRNAs might play a role in endometrial receptivity in endometriosis.

Background: Idiopathic pulmonary fibrosis (IPF) is an age-related and progressive interstitial lung disease. Up to 20% of cases of IPF cluster in families, genetic factors contribute significantly to the pathogenesis of the disease. This study aimed to explore the association between rare genetic variants and IPF in Chinese Han families. Methods: A Han family, comprising three IPF patients and five unaffected their first-degree relatives, and 100 ethnically matched control individuals from North China were enrolled in this study. Peripheral blood was collected, and genomic DNA was extracted. To elucidate if rare genetic variants are associated with the familial IPF, we performed whole-exome sequencing of affected members from a Chinese Han IPF family. Candidate rare variants were then confirmed by Sanger sequencing. Results: We identified a potentially damaging rare variant-a heterozygous mutation c.2146G>A in exon 6 of the gene encoding for telomerase reverse transcriptase (TERT), which results in an amino acid substitution (p.Ala716Thr). We confirmed the missense mutation by Sanger sequencing in all the affected family members but did not detect this mutation in 100 ethnically matched healthy controls. Patients carried this mutation were characterized by the frequently acute exacerbation of IPF phenotype, with poor prognosis. The mean time to death was 2.8 years after diagnosis. Conclusion: Using next-generation sequencing technology in familial IPF patients, we identified the heterozygous rare variant in TERT gene, and strengthened the importance of genetic variants in telomere-related pathogenesis in Chinese IPF patients.

Background: Serum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features. Methods: One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg− group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student’s t-test was obtained to analyze continuous variable. Results: No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg− group (χ2 = 40.34, P< 0.001; OR = 39.87). Conclusions: Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.

Objective: A comprehensive review of the network regulation of exosomes and microRNAs (miRNAs) in neurodegenerative diseases was done, centering on the mechanism of the formation of exosomes and miRNAs and the sorting mechanism of exosomal miRNAs, with the aim to provide a theoretical basis in the search of biomarkers and the treatment of neurodegenerative diseases. Data Sources: The comprehensive search used online literature databases including NCBI PubMed, Web of Science, Google Scholar, and Baidu Scholar. Study Selection: The study selection was based on the following keywords: exosomes, miRNAs, central nervous system (CNS), and neurodegenerative diseases. The time limit for literature retrieval was from the year 2000 to 2018, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type. Results: Exosomes are the smallest nanoscale membranous microvesicles secreted by cells and contain important miRNAs, among other rich contents. In the CNS, exosomes can transport amyloid β-protein, α-synuclein, Huntington-associated protein 1, and superoxide dismutase I to other cells. These events relieve the abnormal accumulation of proteins and aggravating neurological diseases. In some neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, miRNAs are pathologically altered as an inexorable course, suggesting that miRNAs may contribute neurodegeneration. Exosomes and miRNAs form a network to regulate the homeostasis of the CNS, both synergistically and individually. Conclusion: The network of exosomes and miRNAs that regulates CNS homeostasis is a promising biomarker for the diagnosis and treatment of neurodegenerative diseases.