Clinical and genetic characteristics of myotonia congenita in Chinese population.

Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

Rituximab-induced gut microbiota changes in Chinese neuromyelitis optica spectrum disorders.

BACKGROUND: Recent evidence shows that immunosuppressive agents can affect the gut microbiota in autoimmune diseases. However, the relationship between the gut microbiome and B-cell depletion immunotherapy in neuromyelitis optica spectrum disorder (NMOSD) remains poorly understood. OBJECTIVES: To evaluate the distinct intestinal microbial patterns and serum cytokine levels after short-term rituximab treatment (three months) in patients with NMOSD. METHODS: Firstly, we conducted a cross-sectional study involving 46 treatment-naïve NMOSD patients and 48 matched healthy controls. We collected fecal specimens, which were then analyzed using next-generation sequencing, and quantified serum cytokines. Subsequently, fecal and serum samples were re-collected and re-evaluated in 31 of the 46 treatment-naïve NMOSD patients after RTX treatment. RESULTS: Comparing the gut microbiome of treatment-naïve NMOSD patients to that of healthy controls revealed low α-diversity and distinct microbial compositions in the former. The microbial composition in NMOSD patients underwent changes following three months of RTX treatment. Specifically, the levels of IL-17F and IL-6 decreased, while those of IL-10 and TNFα increased after RTX treatment. LEfSe analysis identified 27 KEGG categories with significantly differential abundances between NMOSD patients and RTX treatment group. CONCLUSIONS: Our study provides a comprehensive understanding of the gut microbiota landscape in the context of B-cell depletion immunotherapy. We observed dysbiosis in the gut microbiome of NMOSD patients, which was partially alleviated by three months of RTX treatment. This suggests that B-cell depletion may play a crucial role in driving changes in the gastrointestinal environment.

Clinical characteristics of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies.

BACKGROUND: An increasing number of cases of autoimmune encephalitis (AE) with co-existing multiple anti-neuronal antibodies have been reported in recent years. However, the clinical significance of the concurrent presence of multiple anti-neuronal antibodies in patients with AE remains unclear. METHODS: We retrospectively enrolled AE patients with multiple anti-neuronal antibodies treated at our center between August 2019 and February 2022. We also reviewed cases reported in multiple literature databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then the clinical and laboratory data of these cases were collected for review and summary. RESULTS: A total of 83 AE cases with multiple antibodies (9 cases from our center and 74 cases from the literatures reviewed) were identified. In our center, nine patients presented with encephalitis symptoms, clinically characterized as disturbed consciousness, seizures, cognitive impairment, and psychiatric disorders. Of the 83 cases, 73 cases had co-existence of 2 types of antibodies, 8 cases had 3 types, and 2 cases had 4 types. Thirty-nine cases (39/83, 46.9%) were confirmed or suspected of also having a tumor, of which the most common was lung cancer (28/83, 33.7%). Partial or complete recovery was achieved in 57 cases (57/83, 68.6%), while 26 cases (26/83, 31.3%) died during treatment or follow-up. CONCLUSIONS: AE with co-existing multiple anti-neuronal antibodies is a specific subgroup, that is increasingly recognized in clinical practice. The co-existence of multiple anti-neuronal antibodies has a major impact on clinical features, disease progression, and prognosis.

A comparison of random survival forest and Cox regression for prediction of mortality in patients with hemorrhagic stroke.

OBJECTIVE: To evaluate RSF and Cox models for mortality prediction of hemorrhagic stroke (HS) patients in intensive care unit (ICU). METHODS: In the training set, the optimal models were selected using five-fold cross-validation and grid search method. In the test set, the bootstrap method was used to validate. The area under the curve(AUC) was used for discrimination, Brier Score (BS) was used for calibration, positive predictive value(PPV), negative predictive value(NPV), and F1 score were combined to compare. RESULTS: A total of 2,990 HS patients were included. For predicting the 7-day mortality, the mean AUCs for RSF and Cox regression were 0.875 and 0.761, while the mean BS were 0.083 and 0.108. For predicting the 28-day mortality, the mean AUCs for RSF and Cox regression were 0.794 and 0.649, while the mean BS were 0.129 and 0.174. The mean AUCs of RSF and Cox versus conventional scores for predicting patients' 7-day mortality were 0.875 (RSF), 0.761 (COX), 0.736 (SAPS II), 0.723 (OASIS), 0.632 (SIRS), and 0.596 (SOFA), respectively. CONCLUSIONS: RSF provided a better clinical reference than Cox. Creatine, temperature, anion gap and sodium were important variables in both models.

Autophagic vacuolar myopathy involving the phenotype of spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is a form of autosomal dominant cerebellar ataxia with a wide range of clinical manifestations, including ataxia and pyramidal and extrapyramidal signs. A few SCA3 patients have been noticed to be predisposed to the development of inclusion body myositis. It is still unknown whether muscle can be primarily involved in the pathogenesis of SCA3. This study reported an SCA3 family in which the index patient initially presented with parkinsonism, sensory ataxia, and distal myopathy but the absence of cerebellar and pyramidal symptoms. The clinical and electrophysiological studies implied a possible combination of distal myopathy and sensory-motor neuropathy or neuronopathy. MRI muscle showed selective fat infiltration and absence of denervated edema-like changes, indicating the distal muscle weakness had a myopathic origin. Muscle pathology showed the myopathic involvement, besides neurogenic involvement, characterized by chronic myopathic changes with multiple autophagic vacuoles. Genetic screening revealed expanded CAG of 61 repeats in the ATXN3 gene, which showed co-segregation in the family. Besides the neurogenic origin, the myopathic origin may be partly attributed to the limb weakness of SCA3 patients, which expands the spectrum of the clinical manifestation of SCA3.

Subclinical peripheral neuropathy is common in neuronal intranuclear inclusion disease with dominant encephalopathy.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) is associated with CGG repeat expansion in the NOTCH2NLC gene. Although pure or dominant peripheral neuropathy has been described as a subtype of NIID in a few patients, most NIID patients predominantly show involvements of the central nervous system (CNS). It is necessary to further explore whether these patients have subclinical peripheral neuropathy. METHODS: Twenty-eight NIID patients, clinically characterized by CNS-dominant involvements, were recruited from two tertiary hospitals. Standard nerve conduction studies were performed in all patients. Skin and sural nerve biopsies were performed in 28 and 15 patients, respectively. Repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to screen the CGG repeat expansion in NOTCH2NLC. RESULTS: All 28 patients can be diagnosed with NIID based on skin pathological and genetic changes. All patients predominantly showed CNS symptoms mainly characterized by episodic encephalopathy and cognitive impairments, but no clinical symptoms of peripheral neuropathy could be observed initially. Electrophysiological abnormalities were found in 96.4% (27/28) of these patients, indicating that subclinical peripheral neuropathy is common in NIID patients with CNS-dominant type. Electrophysiological and neuropathological studies revealed that demyelinating degeneration was the main pathological pattern in these patients, although mild axonal degeneration was also observed in some patients. No significant association between CGG repeat size and the change of nerve conduction velocity was found in these patients. CONCLUSIONS: This study demonstrated that most patients with CNS-dominant NIID had subclinical peripheral neuropathy. Electrophysiological examination should be the routinely diagnostic workflow for every NIID patient.

Case report: Reversible encephalopathy associated with liposomal amphotericin B in a patient with cryptococcal meningitis.

Liposomal amphotericin B (L-AMB) is an anti-fungus medicine that has fewer side effects than traditional amphotericin B (AMB). Neurotoxicity of L-AMB has rarely been observed, and only one case of leukoencephalopathy during intravenous L-AMB has been reported. Herein, we described a patient with cryptococcal meningitis presenting with late-onset reversible encephalopathy associated with liposomal amphotericin B.

Juvenile-onset PSAT1-related neuropathy: A milder phenotype of serine deficiency disorder.

Background: Primary serine deficiency disorders have a broad range of the phenotypic spectrum. As an inborn error of metabolism, individuals with severe phenotype may be easily recognized with Neu-Laxova syndrome. However, late-onset mild phenotypes may be underdiagnosed and will lead to disastrous consequences due to treatment delays. Materials and Methods: Clinical features of patients with serine deficiency disorders were summarized in two unrelated patients. Skin and sural nerve biopsies were conducted on the patients. Whole exome sequencing (WES) was performed in the index patients. Sanger sequencing was used to analyze family cosegregation. Results: Patient 1 was a 19-year-old male presenting with infancy-onset ichthyosis and juvenile-onset neuropathy. Patient 2 was a 17-year-old male manifesting childhood-onset ichthyosis and juvenile-onset neuropathy. Except for nystagmus, no other developmental or neurodegenerative disorders were found in the patients. Electrophysiological studies indicated a severe sensorimotor axonal neuropathy with a possible demyelinating component. High-dose oral L-serine and glycine completely alleviated skin lesions and only slightly improved neuropathy symptoms. Skin biopsies showed typical features consistent with ichthyosis and severe loss of unmyelinated axons. Sural biopsies revealed a severe loss of axons and a few thinly myelinated fibers. WES found the same homozygous variant c.43G > C (p.A15P) in the PSAT1 gene, which was cosegregated in the two families. Conclusions: The skin and nervous system may be the main affected targets in serine deficiency disorders. Our patients show a more simple and mild phenotype of PSAT1-related serine deficiency disorder. The pathological changes and regenerative ability of skin and peripheral nerves determine their response to serine supplements.

FUS Mutation Causes Disordered Lipid Metabolism in Skeletal Muscle Associated with ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by dysfunction of the upper and lower motor neurons resulting in muscle weakness and wasting. Recently, several studies on ALS patients and ALS animal models indicated that intramuscular toxicity played a role in ALS disease progression; however, the mechanisms driving this are unknown. In this study, we explored the possible dysfunction of lipid metabolism in myocytes associated with ALS. Initially, skeletal muscle from 41 ALS patients, as well as 53 non-ALS control subjects, was investigated, and we identified that lipid droplet accumulation in the muscle fibers of ALS patients was significantly increased, especially in patients with FUS mutations. A myoblast (C2C12) cell line expressing mutant FUS (FUS-K510Q) was able to induce lipid droplet accumulation and mitochondrial dysfunction. Consistently, transgenic flies expressing FUS-K510Q under a muscle-specific driver showed elevated triglyceride levels in the flight muscles, as well as locomotor defects. Biochemical analysis of C2C12 cells and fly muscle tissues showed upregulation of PLIN2, and downregulation of ATGL and CPT1A, indicating inhibition of lipolysis and fatty acid ß-oxidation in muscle cells with FUS mutations. Our study provided a potential explanation for the pathogenesis associated with lipid droplets accumulating in skeletal muscle in ALS. Our data also suggested that disordered lipid metabolism and mitochondrial dysfunction play a crucial role in intramuscular toxicity in ALS.

Anti-dipeptidyl-peptidase-like protein 6 encephalitis with pure cerebellar ataxia: a case report.

BACKGROUND: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare autoimmune encephalitis. The clinical symptoms of anti-DPPX encephalitis are often severe, manifested as diarrhea/weight loss, central nervous system hyperexcitability and cognitive dysfunction. CASE PRESENTATION: An 18-year-old boy was admitted for 1-week-long cerebellar symptoms including dizziness, unsteady gait and frequent vomiting. Magnetic resonance imaging (MRI) displayed no abnormal findings. However, autoimmune encephalitis panel revealed anti-DPPX antibody was positive in the serum. This patient completely recovered after immunoglobulin and corticoids therapy. In addition, repeat serum antibody test for DPPX was negative within one month. CONCLUSION: In addition to the classic triad, anti-DPPX encephalitis may manifest as mild and rare symptoms due to lower antibody titers. Fast identification of rare symptoms can help to quickly diagnosis and effective treatment.

New Spiro-Sesquiterpenoids from the Marine Sponge Myrmekioderma sp.

Three new spiro-sesquiterpenoids, myrmekiones A-C (1-3), were isolated from the marine sponge Myrmekioderma sp. collected from the South China Sea. The structures of 1-3 were experimentally illuminated though comprehensive NMR spectra, X-ray diffraction analysis and calculated ECD. These three compounds possessed a special spiro skeleton. Compound 1 was characterized by a chamigrane-type structure, it is the first time to obtain the single-crystal of this type of oil compounds. 2 and 3 were a pair of diastereoisomers that possessed an acorane skeleton. This study expands the chemical diversity of marine origin spiro-metabolites.

Pathological changes of the sural nerve in patients with familial episodic pain syndrome.

BACKGROUND: Familial episodic pain syndrome type 3 (FEPS3) is an inherited disorder characterized by the early-childhood onset of severe episodic pain that primarily affects the distal extremities. As skin biopsy has revealed a reduction in intraepidermal nerve fiber density and degeneration of the unmyelinated axons, it remains unclear whether FEPS3 patients have pathological changes in the peripheral nerve. METHODS: The clinical features of patients with FEPS3 were summarized in a large autosomal dominant family. Sural nerve biopsies were conducted in two patients. Whole exome sequencing (WES) was performed in the index patient. Sanger sequencing was used to analyze family co-segregation. RESULTS: Fourteen members exhibited typical and uniform clinical phenotypes characterized by length-dependent and age-dependent severe episodic pain affecting the distal extremities, which can be relieved with anti-inflammatory medicine. The WES revealed a heterozygous mutation c.665G > A (p.R222H) in the SCN11A gene, which was co-segregated with the clinical phenotype in this family. A sural biopsy in patient V:1, who was experiencing episodic pain at 16 years old, showed normal structure, while the sural nerve in patient IV:1, whose pain attack had completely diminished at 42 years old, displayed a decrease of the density of unmyelinated axons with the axonal degeneration. CONCLUSIONS: The clinical phenotype of FEPS3 showed distinctive characteristics that likely arise from dysfunctional nociceptive neurons that lack detectable pathological alterations in the nerve fibers. Nevertheless, long-term dysfunction of the Nav1.9 channel may cause degeneration of the unmyelinated fibers in FEPS3 patient with pain remission.

Genetic spectrum in a cohort of patients with distal hereditary motor neuropathy.

BACKGROUND: Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of diseases characterized by exclusive degeneration of peripheral motor nerves, while only 20.0-47.8% of dHMN patients are genetically identified. Recently, GGC expansion in the 5'UTR of NOTCH2NLC has been associated with dHMN. Accordingly, short tandem repeat (STR) should be further explored in genetically unsolved patients with dHMN. METHODS: A total of 128 patients from 90 unrelated families were clinically diagnosed as dHMN, and underwent a comprehensively genetic screening. Skin biopsies were conducted with routine protocols. RESULTS: Most patients showed chronic distal weakness of lower limbs (121/128), while 20 patients initially had asymmetrical involvements, 14 had subclinical sensory abnormalities, 11 had pyramidal impairments, five had cerebellar disturbance, and four had hyperCKmia. The rate of genetic detection was achieved in 36.7% (33/90), and the rate increased to 46.7% (42/90) if patients with variants uncertain significance were included. The most common causative genes included chaperone-related genes (8/33, 24.2%), tRNA synthetase genes (4/33, 12.1%), and cytoskeleton-related genes (4/33, 12.1%). Additionally, two dominant inherited families were attributed to abnormal expansion of GGC repeats in the 5'UTR of NOTCH2NLC; and a patient with dHMN and cerebellar symptoms had CAG repeat expansion in the ATXN2 gene. Skin biopsy from patients with GGC expansion in NOTCH2NLC revealed typical intranuclear inclusions on histological and ultrastructural examinations. INTERPRETATIONS: This study further extends the genetic heterogeneity of dHMN. Given some dHMN patients may be associated with nucleotides repeat expansion, STR screening is necessary to perform in genetically unsolved patients.

Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation.

INTRODUCTION: Mutations in the GFPT1 gene are associated with a particular subtype of congenital myasthenia syndrome (CMS) called limb-girdle myasthenia with tubular aggregates. However, not all patients show tubular aggregates in muscle biopsy, suggesting the diversity of myopathology should be further investigated. METHODS: In this study, we reported two unrelated patients clinically characterized by easy fatigability, limb-girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole-exome screening. In addition, we summarized all GFPT1-related CMS patients with muscle biopsy in the literature. RESULTS: Pathogenic biallelic GFPT1 mutations were identified in the two patients. In patient one, muscle biopsy indicated vacuolar myopathic changes and atypical pathological changes of myofibrillar myopathy characterized by desmin deposits, Z-disc disorganization, and electronic dense granulofilamentous aggregation. In patient two, muscle biopsy showed typical myopathy with tubular aggregates. Among the 51 reported GFPT1-related CMS patients with muscle biopsy, most of them showed tubular aggregates myopathy, while rimmed vacuolar myopathy, autophagic vacuolar myopathy, mitochondria-like myopathy, neurogenic myopathy, and unspecific myopathic changes were also observed in some patients. These extra-synaptic pathological changes might be associated with GFPT1-deficiency hypoglycosylation and altered function of muscle-specific glycoproteins, as well as partly responsible for the permanent muscle weakness and resistance to acetylcholinesterase inhibitor therapy. CONCLUSIONS: Most patients with GFPT1-related CMS had tubular aggregates in the muscle biopsy, but some patients could show great diversities of the pathological change. The myopathological findings might be a biomarker to predict the prognosis of the disease.

Human viral encephalitis associated with suid herpesvirus 1.

BACKGROUND: Suid herpesvirus type 1 (SHV1) is a type of neurotropic virus able to infect various species. However, the clinical cases of human SHV1 encephalitis are still rarely reported, and the clinical characteristics, treatment, and prognosis of human SHV1 encephalitis are still unclear. METHODS: In this study, we reported 2 cases of human encephalitis associated with SHV1 infection and reviewed the other 18 cases from the literatures. A total of 20 cases with human SHV1 encephalitis were summarized and re-analyzed. RESULTS: Nineteen of 20 patients had a history of swine-related occupational exposure before illness onset. All patients initially presented with influenza-like symptoms and then developed seizures, disturbed consciousness, and endophthalmitis. All patients with clinical outcome of modified Rankin Scale of 5 or 6 suffered from rapid progressive respiratory failure. The results of cerebrospinal fluid (CSF) indicated aseptic or viral infection. MRI findings of SHV1 encephalitis were prone to distribute in temporal-frontal and insular cortex, which was similar to the pattern of herpes simplex virus encephalitis, while some cases with involvements of gray matter nuclei had a high rate of mortality. Metagenomic next-generation sequencing (mNGS) revealed that all patients had unique SHV1 sequences with variable reads in the CSF. CONCLUSIONS: The variant SHV1 can cause a new type of human viral encephalitis, characterized by acute, fulminating, and catastrophic central nervous system infection. Rapid progressive respiratory failure and extensive lesions of deep gray matter nuclei might be indicators to poor prognosis. No approved treatments for the encephalitis are available, but it is possible to diagnose encephalitis quickly by mNGS.

Benign monomelic amyotrophy of lower limb in a cohort of chinese patients.

BACKGROUND: Benign monomelic amyotrophy of lower limb (BMALL) is a neurogenic syndrome representing an unclear field. Further studies might be helpful to elucidate uncertainties regarding causation, outcome, and the risk of progression to amyotrophic lateral sclerosis (ALS). METHODS: According to the inclusion and exclusion criteria, 37 patients with BMALL were retrospectively collected in three neuromuscular centers from January 2012 to October 2018. The detailed medical data were summarized. Multiple laboratory tests were examined. Routine electrophysiological examinations, muscle MRI of lower limbs, and muscle biopsy were conducted. RESULTS: The cohort included 24 male and 13 female cases with median age of onset 47 years. Muscle MRI revealed that the distribution of involved muscles matched with the extent of fat infiltration, so the pattern muscle atrophy can be divided into the following four types: six patients with thigh atrophy (type I), 14 patients with leg atrophy (type II); 10 patients with disproportionate atrophy in both thigh and leg (type III); and seven patients with well-proportionate atrophy in both thigh and leg (type IV). Electrophysiological findings showed neurogenic pattern, spontaneous activity, and abnormal H reflex, which suggested a disorder of spinal anterior horn cell in the patients with types I-III. However, no electrophysiological abnormalities were found in the patients with type IV. Muscle pathology varied from almost normal pattern to advanced neurogenic pattern in nine biopsied patients. Follow-up showed that two patients with type II developed to ALS four years later, and all patients with type IV were in stable condition without any complaints. CONCLUSION: Muscle MRI was useful to exactly localize the distribution of involved muscles in BMALL patients. The distribution of atrophic muscles can be roughly divided into four types based on the MRI features. The classification of distributing types might be as an indicator for the prognosis of BMALL.

FUS P525L mutation causing amyotrophic lateral sclerosis and movement disorders.

BACKGROUND: Mutations in the fused in sarcoma (FUS) gene have been associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and essential tremor. Among the FUS mutations, p.P525L as a hot spot variant has been reported in more than 20 patients with ALS. Apart from the typical ALS phenotype, patients with p.P525L mutation exhibit some atypical symptoms. However, movement disorders related to p.P525L mutation have not been emphasized currently. METHODS: Two unrelated patients with ALS were evaluated through a set of clinical and laboratory tests. The genetic screening was performed through next-generation sequencing. Muscle biopsies were performed on the 2 patients. Muscle samples were stained according to standard histological and immunohistochemical procedures. RESULTS: The first patient presented with juvenile-onset neurogenic weakness and wasting and simultaneously had dropped head, ophthalmoplegia, tremor, involuntary movements, and cognitive impairments. The second patient showed a typical ALS phenotype and prominent adventitious movements. Genetic screening disclosed de novo p.P525L FUS mutation in the 2 patients by family cosegregation analysis. Muscle biopsy showed neurogenic patterns and numerous lipid droplets aggregating in the fibers. CONCLUSION: Apart from the typical ALS phenotype, patients with p.P525L mutation in the FUS gene can present with great clinical heterogeneity including multiple movement disorders. Numerous lipid droplets in muscle fibers indicate that skeletal muscle is likely an important therapeutic target for ALS.

Effect of Comprehensive Cerebral Protection Program on Cerebral Oxygen Metabolism and Vascular Endothelial Function in Elderly Patients with Acute Cerebral Infarction.

BACKGROUND: We aimed to explore the effect of comprehensive cerebral protection on cerebral oxygen metabolism and vascular endothelial function in elderly patients with acute cerebral infarction. METHODS: A total of 168 elderly patients with acute cerebral infarction treated in The First Affiliated Hospital of Nanchang University, China from January 2016 to January 2018 were selected. The patients were divided into a control group and an observation group using random number method, n=84. Patients in the observation group were given comprehensive cerebral protection treatment, and patients in the control group were treated with conventional standardized treatments. The changes of cerebral oxygen metabolism, hemorheology and vascular endothelial function before and after treatment were compared between the two groups. RESULTS: After treatment, oxygen content in arteries and internal jugular veins (Da-vO2), ofoxygen uptake fraction (OEF), Oxygen saturation (SpO2), nitric oxide (NO) were increased in both groups in comparison to before treatment, jugular venous oxygen saturation (SjvO2), brain oxygen uptake rate (ERO2), endothelin (ET), intracranial pressure (ICP), whole blood viscosity, plasma viscosity, reduced viscosity of whole blood, and hematocrit were decreased. However, the changes in the observation group were larger than those in the control group, the difference was statistically significant (P<0.05). CONCLUSION: The treatment of cerebral infarction in elderly patients with acute cerebral infarction can effectively improve the cerebral oxygen metabolism and vascular endothelial function and improve the blood rheology, which has important clinical value.

The pH-dependent elastic properties of nanoscale DNA films and the resultant bending signals for microcantilever biosensors.

The diverse mechanical properties of nanoscale DNA films on solid substrates have a close correlation with complex detection signals of micro-/nano-devices. This paper is devoted to formulating several multiscale models to study the effect of pH-dependent ionic inhomogeneity on the graded elastic properties of nanoscale DNA films and the resultant bending deflections of microcantilever biosensors. First, a modified inverse Debye length is introduced to improve the classical Poisson-Boltzmann equation for the electrical potential of DNA films to consider the inhomogeneous effect of hydrogen ions. Second, the graded characteristics of the particle distribution are taken into consideration for an improvement in Parsegian's mesoscopic potential for both attraction-dominated and repulsion-dominated films. Third, by the improved interchain interaction potential and the thought experiment about the compression of a macroscopic continuum DNA bar, we investigate the diversity of the elastic properties of single-stranded DNA (ssDNA) films due to pH variations. The relevant theoretical predictions quantitatively or qualitatively agree well with the relevant DNA experiments on the electrical potential, film thickness, condensation force, elastic modulus, and microcantilever deflections. The competition between attraction and repulsion among the fixed charges and the free ions endows the DNA film with mechanical properties such as a remarkable size effect and a non-monotonic behavior, and a negative elastic modulus is first revealed in the attraction-dominated ssDNA film. There exists a transition between the pH-sensitive parameter interval and the pH-insensitive one for the bending signals of microcantilevers, which is predominated by the initial stress effect in the DNA film.

Remnant lymph node metastases after neoadjuvant therapy and surgery in patients with pathologic T0 esophageal carcinoma impact on prognosis: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to evaluate the outcomes of patients with pathologic T0 esophageal carcinoma after neoadjuvant therapy and surgery. METHODS: We searched PubMed, Embase, Cochrane Library, and Medline databases from inception up to November 12, 2016. The meta-analysis was performed to compare odds ratios (OR) for overall survival (OS), disease-free survival (DFS), local control (LC), and distant control (DC). RESULTS: Eight published studies of 837 patients were included in the meta-analysis. Data showed that the ypT0N1 group was associated with worse outcomes compared with the ypT0N0 group. The pooled OR and 95% confidence interval (CI) for 3-year and 5-year OS were 3.08 [2.07, 4.57] and 4.27 [2.76, 6.59], respectively. Whereas, the pooled OR and 95% CI for 3-year and 5-year DFS were 3.90 [2.08, 7.34] and 5.17 [1.93, 13.87], respectively. The pooled OR and 95% CI for LR and DR were 4.52 [1.72, 11.91] and 2.65 [1.38, 5.09], respectively. CONCLUSIONS: Remnant lymph node metastases after neoadjuvant therapy and surgery in patients with pathologic T0 esophageal carcinoma portend poor survival, and it is an important prognostic factor.