Specific electromyography characteristics can distinguish longitudinally extensive transverse myelitis from congestive myelopathy due to spinal dural arteriovenous fistula: a retrospective study.

Aims/Background Although electromyography has been extensively used in the diagnosis of neurological diseases, there is no comprehensive understanding of the electromyography manifestations of spinal dural arteriovenous fistula. Given the widespread use of electromyography in the diagnosis of neurological conditions, it is worthwhile to holistically analyse the electromyography findings of spinal dural arteriovenous fistula to differentiate it from neurological diseases that share similar clinical manifestations. The aim of this study is to evaluate whether electromyography can distinguish spinal dural arteriovenous fistula from longitudinally extensive transverse myelitis. Methods We holistically reviewed files of all patients who were diagnosed with spinal dural arteriovenous fistula or longitudinally extensive transverse myelitis at The First Medical Centre of PLA General Hospital from 1 January 2010 to 31 December 2020. We compared the symptomology, epidemiology, and imaging results of patients with spinal dural arteriovenous fistula and longitudinally extensive transverse myelitis, placing emphasis on their electromyography manifestations. Student's t test was used to analyse normally distributed data, while Chi-square test was used to compare classification statistics. Results Lesions of spinal dural arteriovenous fistula shown on images tend to appear at lower lumbar and sacral segments, whereas lesions of the cervical and upper thoracic segments are more characteristic of longitudinally extensive transverse myelitis. Spinal dural arteriovenous fistula patients and longitudinally extensive transverse myelitis patients overlap in terms of clinical manifestations. After comparison, the two groups of patients had different demographics (age, sex), onset mode, predisposing factors before onset, and electromyographic features. The electromyographic features of patients with spinal dural arteriovenous fistula were associated with neurogenic damage (p < 0.001). Conclusions In patients with spinal dural arteriovenous fistula, electromyography can help clinicians to identify early disease, avoid patient treatment delay, and eliminate unnecessary treatment.

Strategies for Preventing Esophageal Stenosis After Endoscopic Submucosal Dissection and Progress in Stem Cell-Based Therapies.

Endoscopic submucosal dissection (ESD) has been widely used in the early neoplasia of the esophagus. However, postoperative esophageal stenosis is a big problem, particularly when a large circumferential proportion of esophageal mucosa is resected. Currently, there are several methods available to prevent esophageal stenosis after ESD, including steroid administration, esophageal stent implantation, and endoscopic balloon dilation (EBD). However, the therapeutic effects of these are not yet satisfactory. Stem cell-based therapies has shown promising potential in reconstructing tissue structure and restoring tissue function. In this study, we discussed the current strategies for preventing esophageal stenosis after ESD and perspectives of stem cell-based therapies for the prevention of esophageal stenosis.

The association of psychological stress with metabolic syndrome and its components: cross-sectional and bidirectional two-sample Mendelian randomization analyses.

Background: Metabolic syndrome (MetS) is a group of co-occurring conditions that increase the risk of cardiovascular disease, which include the conditions of hypertension, overweight or obesity, hyperglycemia, and dyslipidemia. Psychological stress is gradually being taken seriously, stemming from the imbalance between environmental demands and individual perceptions. However, the potential causal relationship between psychological stress and MetS remains unclear. Method: We conducted cross-sectional and bidirectional Mendelian randomization (MR) analyses to clarify the potential causal relationship of psychological stress with MetS and its components. Multivariable logistic regression models were used to adjust for potential confounders in the cross-sectional study of the Chinese population, including 4,933 individuals (70.1% men; mean age, 46.13 ± 8.25). Stratified analyses of sexual characteristics were also performed. Bidirectional MR analyses were further carried out to verify causality based on summary-level genome-wide association studies in the European population, using the main analysis of the inverse variance-weighted method. Results: We found that higher psychological stress levels were cross-sectionally associated with an increased risk of hypertension in men (odds ratio (OR), 1.341; 95% confidence interval (CI), 1.023-1.758; p = 0.034); moreover, higher levels of hypertension were cross-sectionally associated with an increased risk of psychological stress in men and the total population (men: OR, 1.545 (95% CI, 1.113-2.145); p = 0.009; total population: OR, 1.327 (95% CI, 1.025-1.718); p = 0.032). Genetically predicted hypertension was causally associated with a higher risk of psychological stress in the inverse-variance weighted MR model (OR, 2.386 (95% CI, 1.209-4.710); p = 0.012). However, there was no association between psychological stress and MetS or the other three risk factors (overweight or obesity, hyperglycemia, and dyslipidemia) in cross-sectional and MR analyses. Conclusion: Although we did not observe an association between psychological stress and MetS, we found associations between psychological stress and hypertension both in cross-sectional and MR studies, which may have implications for targeting hypertension-related factors in interventions to improve mental and metabolic health. Further study is needed to confirm our findings.

Piezo1 suppression reduces demyelination after intracerebral hemorrhage.

Piezo1 is a mechanically-gated calcium channel. Recent studies have shown that Piezo1, a mechanically-gated calcium channel, can attenuate both psychosine- and lipopolysaccharide-induced demyelination. Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage, in this study, we investigated the role of Piezo1 in intracerebral hemorrhage. We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon (within 48 hours) after intracerebral hemorrhage, primarily in oligodendrocytes. Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema, myelin sheath loss, and degeneration in injured tissue, a substantial reduction in oligodendrocyte apoptosis, and a significant improvement in neurological function. In addition, we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway. These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage, as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath, thereby improving neuronal function after intracerebral hemorrhage.

A case of diffuse large B-cell lymphoma with interstitial pneumonia.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving "full coverage" treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome.

Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

Vitamin E administration erases an enhanced oxidation in multiple sclerosis.

Systemic peroxidation status has been reported as a pathogenic factor for multiple sclerosis (MS). Systemically elevated oxidation levels are associated with serum lipid peroxidation and somatic telomere length (TL) shortening. We investigated whether vitamin E (VE) administration suppresses peroxidation and improves clinical symptoms in 34 MS patients. We analyzed serum lipid peroxidation and degree of TL in circulating leukocytes of MS patients before and after VE treatment. The oxidation level was enhanced and TL was shortened in MS. The MS population treated with VE 400 mg/day for 3 months showed significantly reduced serum lipid oxidation level with maintenance of TL. These findings showed that systemic peroxidation is associated with the development of MS. Antioxidants such as vitamin E can be candidates for supplementary therapeutic agents for MS.

Patients with multiple sclerosis show increased oxidative stress markers and somatic telomere length shortening.

Lipid peroxidation due to oxidative stress (OS) may play an important role in the pathogenesis of chronic systemic inflammatory diseases such as multiple sclerosis (MS). Telomeres, repeated sequences that cap chromosome ends, undergo shortening with each cycle of cell division, resulting in cellular senescence. Research regarding telomere shortening has provided novel insight into the pathogenesis of various diseases. We hypothesized that OS damage leads to inflammatory reactions, which subsequently shortens the telomere length in MS. We enrolled 59 patients with MS, and age- and gender-matched 60 healthy controls. We divided MS subjects into three groups matched for age and gender according to the severity of disability: relatively benign course (BMS), secondary progressive MS, and primary progressive MS (PPMS). We analyzed the telomere length in peripheral blood mononuclear cells and the 8-iso-PGF2α concentration in urine, a reliable and stable marker of lipid peroxidation in vivo. The data showed significant higher levels of urinary 8-iso-PGF2α in MS subjects than in the controls. The lag-time, which represents the direct measurement of the resistance of low-density lipoprotein to oxidation, was shorter in the PPMS subjects than in the groups. Compared to that observed in the controls, the mean telomere length was significantly shorter in the PPMS group, whereas no significant telomere shortening was found between the controls and other subjects. Our data suggest that a decreased telomere length and enhanced lipid peroxidation reflects the severest stage of MS.

[Correlation between lacunar cerebral infarction and serum uric acid level in elderly male hypertension patients].

OBJECTIVE: To study the correlation between lacunar cerebral infarction and level of serum uric acid in elderly male hypertension patients. METHODS: Ninety-eight elderly male hypertension patients were enrolled in this study. They all underwent cerebral magnetic resonance imaging (MRI) scan, and their clinical and laboratory data were collected. The patients were divided into the 1st group (n = 32), the 2nd group (n = 32) and the 3rd group (n = 34) according to the level of serum uric acid. RESULTS: The numbers of lacuner infarction, serum creatinine, urea and high density lipoprotein(HDL) were significantly diferrent from the other groups. The numbers of lacuner infarction were positively related with serum uric acid and urea. Multiple variant analysis showed that serum uric acid was the independent factor of the numbers of lacuner infarction. CONCLUSION: The elevated level of serum uric acid may contribute to the risk factors of lacuner infarction.

Different levels of hypoxia regulate telomere length and telomerase activity.

This study was designed to identify changes in telomere length and telomerase activity in human umbilical vein endothelial cells (HUVECs) exposed to various levels of hypoxia. Mild hypoxia (10%, 15% oxygen) increased telomere length, which did not appear to change under severe hypoxia (1% oxygen). Telomerase activity in HUVECs correlated inversely with oxygen concentration. Endothelial cell telomere elongation with telomerase activation in conditions of mild hypoxia was demonstrated in this study. High telomerase activity may contribute to hypoxia-related telomere elongation. The best cell growth and longest telomere length were observed at 10% O(2), and this percentage may therefore be the optimal level for maintaining vascular endothelial cells. In addition, elevated telomerase activity maintains telomere length within normal range in conditions of severe hypoxia (1% O(2)). The telomere length distribution in HUVECs under hypoxia seems to be regulated by a balance between telomere attrition by hypoxia and telomere elongation by enhanced telomerase activity acting on telomeres, perhaps in a telomere-length dependent manner.

The Subtelomere of Short Telomeres is Hypermethylated in Alzheimer's Disease.

Telomere shortening has been reported to be related to oxidative stress (OS) associated with the aging process and aging-associated diseases, including Alzheimer's disease (AD). We measured the methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells of 34 AD patients and 49 healthy controls by a Southern blotting analysis, using methylation-sensitive and - insensitive restriction enzyme isoschizomers, MspI and HpaII. AD patients bore normal mean telomere lengths and had an unchanged distribution of the telomere length in peripheral leukocytes. However, the subtelomeres in the shortest telomeres were relatively more methylated in AD patients of both genders, compared with age-matched controls. We observed that the pathogenesis of AD was associated with the epigenetic condition of the subtelomere, but not on the overall telomere length and distribution. The relative elevation of subtelomeric methylation of short telomeres in peripheral blood leukocytes may be a characteristic of AD. This implies that leukocytes containing short telomeres with less methylated subtelomeres tend to be removed faster from the peripheral blood in AD patients.

[Neuropsychological features of elderly patients with mild cognitive impairment susceptible to Alzheimer's disease].

OBJECTIVE: To explore the neuropsychological features of elderly patients with mild cognitive impairment (MCI) susceptible to Alzheimer's disease (AD). METHODS: A total of 47 patients with MCI diagnosed from June to October 2008 and 21 controls with normal cognition at the same convalescent camp were selected and followed up for two years. Montreal cognitive assessment (MoCA), mini mental state examination (MMSE) and clock drawing test (CDT) were performed for all subjects at the onset of study and repeated annually. RESULTS: At Month 12, the visuospatial skill scores of MCI patients decreased significantly versus those of the control (0.6 ± 0.7 vs 0.1 ± 0.6, P = 0.008). No one progressed to AD in neither groups. And at Month 24, both visuospatial skill scores (0.9 ± 0.9 vs 0.4 ± 0.9) and attention scores (1.0 ± 1.0 vs 0.2 ± 0.8) of MCI patients declined significantly versus the control (P = 0.021, 0.001). Among 47 MCI patients, 7 progressed to AD. No obvious difference existed in the score of all items between the AD converters and non-converters at baseline. However, the scores of MMSE (27.6 ± 0.8 vs 28.9 ± 1.0), MoCA (24.3 ± 3.1 vs 27.9 ± 1.6) and such MoCA subitems as visuospatial skill (3.9 ± 0.7 vs 4.5 ± 0.6), language (1.86 ± 0.38 vs 2.65 ± 0.53) and delayed recall (2.1 ± 1.5 vs 3.9 ± 1.0) of the converters were obviously lower than those of the non-converters at Month 12 (P < 0.05). Furthermore, all other scores of the AD converters, except for designation and abstract, were significantly lower than those of the non-converters at Month 24 (P < 0.05). CONCLUSION: The visuospatial skill, executive function, delayed recall and language function of MCI patients progressing to AD tend to have early impairment and significant changes. It may be useful to predict AD among the MCI patients.

Alteration of telomere length and subtelomeric methylation in human endothelial cell under different levels of hypoxia.

BACKGROUND AND AIMS: Hypoxia-associated changes of telomeric structure in cell cultures have been analyzed mainly in cancer cells, stem cells, or cells transduced with vectors containing the telomerase gene, but not in somatic cells. The stability of telomere structure has been reported to be associated with subtelomeric methylation status. However, there are no reports of epigenetic alterations of telomeric regions of human somatic cells under hypoxia. This study aims at detecting and analyzing the subtelomeric methylation status in human somatic cells cultured under hypoxia. METHODS: Mean telomere length and telomerase activity of human umbilical vein endothelial cells (HUVECs) cultured in hypoxic conditions were measured. Subtelomeric methylation status of these cells was assessed by genomic Southern blot with telomere DNA probe using methylation-sensitive and -insensitive isoschizomers, MspI and HpaII. RESULTS: The telomerase activity in HUVECs correlated inversely with the oxygen concentration. Mild hypoxia (10 or 15% oxygen) increased the telomere lengths, whereas the telomere lengths did not appear to change when <1% O(2). The subtelomere of the shortest telomere range was methylated the most at 1% O(2). CONCLUSIONS: Subtelomeric hypermethylation of short telomeres at 1% O(2) compared to milder hypoxia implied that the subtelomeric hypermethylation may yield telomere stability and favor the cell survival of short telomere-bearing cells.

Effect of vitamin E administration on the elevated oxygen stress and the telomeric and subtelomeric status in Alzheimer's disease.

BACKGROUND: Oxidative stress (OS) may be involved in the neurodegenerative process in Alzheimer's disease (AD). Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, are sensitive to OS, and serve as markers of a cell's replicative history. Telomere length shortening has been reported to relate to OS with aging process and aging-associated diseases, but the telomeric changes were not always identical, especially in change of telomere length distribution and subtelomeric methylation. The involvement of an OS-associated telomere change in the pathogenesis of AD has been discussed for decades, and the telomere length and telomerase activity were analyzed. However, other telomeric factors, such as the telomere distribution and subtelomeric methylation status, have not yet been analyzed. OBJECTIVE: The subtelomeric methylation status as well as the telomere length were studied in AD with an antioxidant vitamin in terms of OS. METHODS: We measured urinary 8-iso-PGF2α, a lipid-peroxidation product as an OS marker, and methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells by Southern blotting in AD patients before and after vitamin E treatment. RESULTS: The level of urinary 8-iso-PGF2α was found to have increased in AD. Middle-ranged telomeres (4.4-9.4 kb) increased and the shortest telomeres (<4.4 kb) decreased in AD patients. Telomeres were more methylated in both long telomeres and in short telomeres in AD compared with the control. The oral administration of the antioxidant vitamin E in 400 mg/day for 6 months in AD patients partly reversed AD-associated alterations in OS marker levels. CONCLUSIONS: AD patients showed an elevated OS marker level, and vitamin E lowered the OS level. In comparison with controls, AD patients showed shorter telomere lengths. Cells with short and long telomeres bore relatively hypermethylated subtelomeres in AD patients. Aging-associated accumulation of cells bearing short telomeres was not observed in AD. These results imply that long telomeres with hypomethylation tend to shorten faster, and cells bearing short telomeres with hypomethylation tend to more easily enter into a senescent state under elevated OS stress in AD. However, no significant effect on the altered telomeric profiles in AD patients could be detected after a 6-month administration of vitamin E.

S-Nitrosylation of mitogen activated protein kinase phosphatase-1 suppresses radiation-induced apoptosis.

Radiotherapy is a key modality for head and neck cancer (HNC) treatment. Mitogen activated protein kinase phosphatase-1 (MKP-1) protein levels are elevated in various tumors and are negatively correlated with efficacy of chemo- or radio-therapy. However, the mechanisms underlying the moderate radiosensitivity of HNC and the increased MKP-1 protein levels are still dismal. Here we show that S-nitrosylation of MKP-1 on Cysteine 258 enhances MKP-1 protein stability, phosphatase activity, and MKP-1-mediated anti-apoptotic effect on HNC radiotherapy. Co-culturing MKP-1 transfected HNC cell lines with activated macrophages for mimicking the microenvironment of the irradiated cancer cells further confirms that S-nitrosylation-mediated increase of MKP-1 activity correlates with decrease of HNC radiosensitivity. Therefore, S-nitrosylation of MKP-1 presents a novel mechanism underlying the enhanced MKP-1 expression levels and MKP-1-mediated radio-resistance in head and neck cancer.

Antibacterial potential of hGlyrichin encoded by a human gene.

Emerging multidrug-resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero-immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin-resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42-60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero-immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide.

Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction.

Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.