[Analysis of the characteristics of patients with amyotrophic lateral sclerosis with neuromuscular junction dysfunction prior to motor neuron degeneration].

Objective: To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation (RNS) test results on the accessory nerve and negative needle electromyography (EMG) test results on the sternocleidomastoid with the goal to enrich the knowledge of disease progression in patients with ALS. Methods: The clinical data of 612 patients diagnosed with ALS at the Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to August 2022 were collected. In total, 267 cases had undergone EMG tests on the sternocleidomastoid following a positive 3 Hz RNS test result on the accessory nerve, who were selected as the study subjects. The differences in clinical indicators were compared between RNS (+)/EMG (-) group and RNS (+)/EMG (+) group. A binomial distribution model with multiple variables was built to quantitatively analyze the major factors and their effects. Results: At the initial visit, 15.8% of patients with ALS were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid, accounting for 36.3% of RNS (+) patients. The decremental range of the 3 Hz RNS test delivered to the accessory nerve in these patients [-14% (-19%, -12%)] was lower than that in patients with RNS (+)/EMG (+) [-17% (-23%, -13%)] (P<0.05), while the ratio of upper limb onset (64.9%) and non-definite diagnosis (28.9%) were higher [54.7% and 13.5% for patients with RNS (+)/EMG (+), P<0.05]. Furthermore, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score [40 (37, 42)], body mass index (BMI) [23.8 (22.0, 25.4) kg/m2] and forced vital capacity (FVC) [92.8% (76.6%, 103.8%)] were higher in patients with RNS(+)/EMG(+) (P<0.05). The multivariate model suggested that, in patients with RNS (+)/EMG (-), the ratio of upper limb onset to lower limb onset was 1.04, while that of upper limb onset to bulbar onset was 2.02, and that of lower limb onset to bulbar onset was 1.94. The ratio of non-definite ALS to definite ALS was 1.13. The ALSFRS-R score, BMI, and FVC had a protective contribution to the electrophysiological function of the motor neurons. The ratio of the effect size of the ALSFRS-R or BMI to that of FVC was 3.37 and 1.14, respectively. Conclusions: Patients with ALS that were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid had a smaller decremental range of the compound muscle action potential amplitude, and a higher proportion of upper limb onset and non-definite ALS. A higher ALSFRS-R score, BMI, and FVC have a protective effect to the electrophysiological function of motor neurons. The effect size of the ALSFRS-R score is the largest, followed by BMI and FVC.

[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

[Novel MFN2, BSCL2 and LRSAM1 variants in a cohort of Chinese patients with Charcot-Marie-Tooth disease].

Objective: Charcot-Marie-Tooth disease (CMT) comprises a group of clinically and genetically heterogeneous inherited neuropathies with an estimated prevalence of 1 in 2500. This study aimed to analyze the clinical and mutational characteristics of Chinese CMT patients with MFN2, BSCL2 and LRSAM1 variants. Methods: In this study, genetic analysis was performed in 206 Chinese patients at Chinese PLA General Hospital from December 2012 to March 2020 with clinical diagnosis of CMT, and reported variants of MFN2, BSCL2 and LRSAM1 related to CMT2. Results: We reported ten MFN2 mutations in ten unrelated patients (7 male, 3 female), two of whom had positive family history. Three novel mutations were detected including c.475-2A>G (splicing); c.687dupA (p.E230Rfs*16) and c.558dupT (p.S186fs). We reported three BSCL2 mutations of four unrelated patients, including c.461C>G (p.S154W), c.461C>T(p.S154L), and novel variants of c.1309G>C (p.A437P) and c.845C>T (p.A282V). Furthermore, two novel variants of LRSAM1, including c.1930G>T (p.G644C) and c.1178T>A (p.L393Q) were detected in two unrelated patients. Conclusion: Mutational spectrum of MFN2-, BSCL2-and LRSAM1-related CMT disease is expanded with the identification of novel variants in Chinese patients.

[Analysis of disease progression rate and related factors in amyotrophic lateral sclerosis patients at initial visit].

Objective: To find out the relationship of the progression rate of amyotrophic lateral sclerosis (ALS) patients with relevant clinical indicators at initial visit so as to enrich the knowledge of ALS at its early stage. Methods: The clinical data of 282 patients diagnosed with ALS at Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to March 2021 were collected in order to make a retrospective analysis of the dynamic change of the progression rate (ΔFS) and influencing factors, and thus a classification of the progression rate will be summarized. Results: Among 282 patients, 164 were males and 118 were females. The age of onset was (53±11) years old. The ΔFS had a negative exponential relationship with delay time of diagnosis no matter what kinds of onset the patients experienced (upper limb onset, lower limb onset or bulbar onset). The ΔFS for the limb function sub-group had a similar functional relationship with diagnostic delay in patients with either upper limb onset or lower limb onset. The statistical model indicated that the disease progression rate of ALS at initial visit can be classified into three types (high speed type: ΔFS≥1.0 score/month; moderate speed type: 0.5≤ΔFS<1.0 score/month; low speed type: ΔFS<0.5 score/month). The critical values of the three types in patients with upper limb onset were 8 and 20 months, while 9 and 24 months for lower limb onset patients, and 9 and 36 months for bulbar onset patients. At initial visit, there were significant statistical differences among these three types in age at onset (P=0.008), diagnostic delay (P<0.001), ALS functional rating scale-revised (ALSFRS-R) score (P<0.001) and onset site (P=0.006). The age at onset in moderate speed type was significantly greater than that of the slow speed type [(54.9±10.4) years vs (50.2±9.6) years, P=0.002]. The diagnostic delay in high speed type [6 (4, 10) months] was significantly shorter than that in moderate speed type [12 (8, 19) months, P<0.001] and low speed type [22 (14, 36) months, P<0.001], and the moderate speed type was shorter in comparison with low speed type (P<0.001). As for the ALSFRS-R score, the high speed type [36(32, 39)] was significantly lower than the moderate speed type [39 (36, 42), P<0.001] and low speed type [42 (39, 44), P<0.001], and the moderate speed type was lower in comparison with low speed type (P=0.002). The proportion of cases with upper limb onset in high speed type (20.3%) was significantly lower than that in low speed type (42.2%, P<0.001) and moderate speed type (37.5%, P=0.014). By contrast, the proportion of cases with lower limb onset in high speed type (39.2%) was significantly higher than that in low speed type (28.9%, P=0.023), however no difference was shown between the fast speed type and moderate speed type (32.0%, P=0.061). There was no difference among these three progression types in patients with bulbar onset. Conclusions: The disease progression rate of ALS at initial visit can be classified into three types including high speed, moderate speed and low speed. At early stage of ALS, ΔFS is affected by onset age, onset site, diagnostic delay and ALSFRS-R score.

[Electrophysiological features of patients with subacute combined degeneration].

Objective: To investigate the electrophysiological features of patients with subacute combined degeneration (SCD). Methods: The electrophysiological data of 85 hospitalized patients in Department of Neurology, First Medical Centre, Chinese PLA General Hospital from January 2014 to September 2018 were retrospectively analyzed. Results: Abnormality rate of motor nerve conduction (27.4%(93/339)) was lower than that of sensory nerve conduction (45.9%(107/233)) (P<0.001). Abnormality of sensory nerve action potential amplitude was more frequent than conduction velocity abnormality (22.7%(53/233) vs 4.7%(11/233), P=0.001). Abnormality rate of needle electromyogram (EMG) was higher in lower limbs than upper limbs (31.9%(59/185) vs 5.7%(5/87), P<0.001). Spontaneous potentials were unrelated to disease duration or severity. Abnormal somatosensory evoked potential (SEP) results appeared more frequent in lower limbs (80.8%(118/146)) than upper limbs (61.1%(77/126)) (P<0.001). SEP abnormalities (71.7%(195/272)) were more common than nerve conduction abnormalities (35.0%(200/572)). Abnormal findings presented in 15/16 of visual evoked potential (VEP) studies. Neurological severity score were correlated with electrophysiological findings. Conclusions: Posterior funiculus is more likely to be affected than peripheral nerves in SCD patients. The sensory nerves rather than motor nerves, lower limbs rather than upper limbs, axons of sensory nerves rather than myelin, are more severely affected. Electrophysiological tests can provide evidence in early diagnosis, lesions location, and disease severity evaluation for SCD.

MiR-365a-3p suppresses proliferation and invasion of Hep-2 cells through targeting ten-eleven translocation 1 (TET1).

miRNAs are among the most important factors that regulate gene expression. According to bioinformatic analysis, miR-365a-3p was predicted to interact with the TET1 mRNA. We predicted that it might affect tumor biological processes through TET1. TET1 interference and miR-365a-3p inhibitor constructs were generated. qRT-PCR was used to verify the expression level of miR-365a-3p and TET1 in Hep-2 and BESB-2B cells. qRT-PCR and Western blot were used to confirm the TET1 expression level in Hep-2 and miR-365a-3p inhibitor cells. Cell proliferation, cell cycle progression and cell invasion were further studied to identify the relationship between TET1 and miR-365a-3p. Luciferase reporter gene assays were used to find the binding site of miR-365a-3p in the 3'-UTR (3'-untranslated region) of the TET1 mRNA. TET1 was weakly expressed in Hep-2 cells and highly expressed in BESB-2B cells, while miR-143-3p and miR-365a-3p were highly expressed in Hep-2 cells and lowly expressed in BESB-2B cells. Inhibiting miR-365a-3p could up-regulate the expression of TET1. The negative effects of miR-365a-3p on cell proliferation, cell cycle progression and cell invasion could be abolished by TET1 interference. The binding site of miR-365a-3p was in the 3'-UTR of the TET1 mRNA. TET1 is one of the targets of miR-365a-3p. miR-365a-3p regulates the biological behavior of laryngeal cancer by down-regulating TET1.

[Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of Chinese origin].

Objective: To investigate all coding regions of amyotrophic lateral sclerosis (ALS)-related gene Senataxin (SETX) in sporadic amyotrophic lateral sclerosis patients of Chinese origin. Methods: From January 2010 to December 2014, the peripheral venous blood samples and clinical data were collected from 311 patients with sporadic amyotrophic lateral sclerosis (SALS) and 311 healthy controls who were of Chinese ancestry from the Department of Neurology, Chinese PLA General Hospital.Genomic DNA was extracted from peripheral venous blood of all participants using standard methods. The coding regions of SETX were amplified by polymerase chain reaction (PCR) and screened for mutations using next-generation sequencing technology. The online software SIFT and PolyPhen-2 were used to analyze the conservation of an altered amino acid and predict the potential pathogenicity of identified mutations. The SPSS 22.0 software was used to analyze the clinical feature of all participants. Results: Tenkinds of rare and one novel nonsynonymous mutations were identified and were absent in 311 controls. Twelve (3.86%) patients carried one SETX gene mutation. Five (1.61%) out of above-mentioned 12 patients carried highly pathogenic mutations including p. Pro1868Leu (c.5603G>A), p. Pro1331Leu (c.3992G>A), p. Glu756Val (c.2267T>A), p. Leu564Val (c.1690A>C), and p. Asn144Ser (c.431T>C). Patients carried SETX mutations were not different from other patients in onset age. Conclusion: Mutations in SETX are likely to be a pathogenesis for Chinese sporadic amyotrophic lateral sclerosis.

[Analysis of the clinical and electrophysiological characteristics of multifocal motor neuropathy].

Ten patients diagnosed with multifocal motor neuropathy (MMN) were recruited in the Department of Neurology at Chinese PLA General Hospital from January 1, 2009 to August 31, 2015. The clinical and electrophysiological features were analyzed retrospectively. All patients complained of progressive asymmetric limb weakness, which was more severe in distal than in proximal. Five presented muscle atrophy. None had sensory disturbances. All suffered diminished or disappeared tendon reflex, whereas Babinski signs were negative. Multi-focal conduction block (CB) was confirmed by nerve conduction studies (NCS) in all patients and 7 showed spontaneous potentials in needle electrode electromyography. Abnormal sensory nerve conduction was seen in 3 patients. Laboratory test revealed anti-ganglioside GM1 antibody in cerebrospinal fluid (CSF) in 6 cases and elevated CSF protein in 7 cases. Limb weakness alleviated greatly in 9 cases after intravenous immunoglobulin (IVIg) treatment. But the other one reported poor response, who had long course of disease, serious limb weakness and obvious muscle atrophy. Motor nerve damage is the most important manifestation of MMN and sensory nerve damage may also appear. NCS is essential to the diagnosis of this disease, with CB as the characteristic electrophysiological feature. IVIg is an effective treatment.

[Analysis of a Chinese Charcot-Marie-Tooth disease type 2D pedigree].

Objective: To achieve definite diagnosis in a clinically diagnosed Charcot-Marie-Tooth disease (CMT) pedigree and broaden the mutational diversity of CMT-related mutations in Chinese Han population. Methods: Patients clinically diagnosed with CMT were recruited from Department of Neurology, Chinese PLA General Hospital between December, 2012 to June, 2016. Clinical examination, laboratory tests, nerve conduction studies, and molecular and bioinformatics analyses were performed on a clinically diagnosed CMT pedigree. Results: In the pedigree, a GARS mutation (c.794C>T, p. S265F) was identified and CMT2D was diagnosed. Conclusion: The newly identified GARS mutation has broaden the mutational diversity of CMT2D in Chinese Han population.

[Characteristics of repetitive nerve stimulation in 53 cases of amyotrophic lateral sclerosis].

Objective: To investigate the feature of repetitive nerve stimulation (RNS) in patients with amyotrophic lateral sclerosis (ALS) and correlation between RNS and clinical features and electromyography (EMG) findings of the corresponding muscle. Methods: Needle EMG and RNS were performed in 53 patients with ALS, who were recruited into Department of Neurology of Chinese PLA general hospital during April to December in 2016. Decrement of the compond muscle action potential (CMAP) in response to RNS of different nerves and stimulus frequencies was compared. The effects of gender, age of onset, disease duration, region of onset, ALS functional rating scale-revised (ALSFRS-R) and rate of disease progression (ΔFS) on the decrement were analyzed. Results: 49.1% of patients with ALS had decremental responses to low frequency RNS (LF-RNS) in accessory nerve, which was lower in ulnar nerve (4.3%) and common peroneal nerve (2.6%). Decremental responses of accessory nerve at 3 Hz were observed in 49.1% of patients with ALS, more frequent than 30.2% at 1 Hz. None of the patients had increased responses to high frequency RNS. Patients with upper-limb-onset, longer disease duration and lower ALSFRS-R tended to have more frequent decrement of CMAP in response to RNS. The decrement with LF-RNS of accessory nerve was in concert with neurogenic damage of sternocleidomastoid muscle with needle EMG (r=0.365, P=0.007). There were 3 patients who had decremental responses to LF-RNS in accessory nerve without clinical involvement and neurogenic damage of sternocleidomastoid muscle. Conclusions: There is significant decrement of CMAP in response to LF-RNS of accessory nerve in patients with ALS, which may reveal neuromuscular junction (NMJ) impairment. It may indicated a dying-back pattern of disease progression which derived from motor neuron terminal or NMJ to neuronal soma that some patients with ALS have decremental responses in RNS without clinical involvement and neurogenic damage of sternocleidomastoid muscle.

[An analysis of characteristics of nerve conduction in 154 cases of amyotrophic lateral sclerosis].

Objective: To analyze the features of nerve conduction in patients with amyotrophic lateral sclerosis (ALS), and explore the correlation between compound muscle action potential (CMAP) amplitude and disease duration and revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Methods: Standard motor and sensory nerve conduction studies were performed in 154 patients with ALS. The following parameters were collected including CMAP amplitude, distal motor latency (DML), motor conduction velocity, sensory conduction velocity and sensory nerve action potential amplitude. Regression study was done to explore the correlation between CMAP amplitude and disease duration and ALSFRS-R. Results: Motor nerve conduction abnormalities were presented in a majority of the patients with prolonged DML in the tibial nerve, median nerve and ulnar nerve as the most common form (61.06%-81.42%), followed by decreased CMAP amplitude (30.12%-53.98%), decreased MCV (12.05%-16.81%) and absence of CMAP (2.65%-9.73%). Sensory nerve conduction abnormalities were detected in a small proportion of patients and the decreased SCV, decreased SNAP amplitude and absence of SNAP in the sural nerve, median nerve and ulnar nerve were found in 1.22%-2.73%, 0-1.82% and 0-1.22% patients respectively. No correlation was found between CMAP of the common peroneal nerve, tibial nerve, median nerve and ulnar nerve and the disease duration (P>0.05), while significant positive correlation was established between CMAP amplitude of the median nerve and ulnar nerve and ALSFRS-R (r=0.273, P=0.016; r=0.357, P=0.001). Conclusions: Motor nerve conduction is abnormal in a majority of ALS patients with prolonged DML as the most common form, while abnormal sensory nerve conduction is only found in a few of ALS patients. CMAP amplitude of the median nerve and ulnar nerve might be of certain clinical value in evaluating the severity of ALS.

[Needle electromyography features and values of paraspinal muscle parameters in assessment of respiratory function of patients with amyotrophic lateral sclerosis].

Objective: To analyze the features of needle electromyography (EMG) in patients with amyotrophic lateral sclerosis (ALS), and explore the correlation between EMG parameters of the tenth thoracic paraspinal muscle and disease duration, rate of disease progression, forced vital capacity (FVC) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Methods: Standard EMG was recorded from unilateral sternocleidomastoid muscle and/or tongue muscles, upper and lower limbs muscles and the tenth thoracic paraspinal muscle in 112 patients with definite ALS between March 2012 and June 2013 in the Department of Neurology at Chinese PLA General Hospital. Parameters studies included spontaneous potentials, duration and amplitude of motor unit potentials (MUP), pattern of recruitment. Results: EMG revealed diffuse neurogenic changes in each case. Fibrillation potential or positive sharp waves were found in some muscles in all of patients, and both of them were found in most of the cases. Fasciculation potentials (FPs) were found in 8 patients and accompanied with fibrillation potential and positive sharp waves in 5 of them. Complex repetitive discharges (CRDs) were found in only 1 patient. Duration and amplitude of MUP was prolonged and increased in ALS patients, and the rate of high amplitude and decreased recruitment pattern were 35.71% and 72.32%, respectively. Logistic regression analysis revealed an association of the FVC loss with the drop of ALSFRS-R and peak amplitude of the tenth thoracic paraspinal muscle. Conclusions: The abnormal spontaneous activity with high frequency are fibrillation potentials and/or positive sharp waves. However, FPs is observed in a small number of patients and CRDs is rarely seen in ALS. The ALSFRS-R and peak amplitude of thetenth thoracic paraspinal muscle may be of certain clinical value in estimating the severity of disease especially the respiratory dysfunction in ALS patients.

[Clinical and electrophysiological studies of oxaliplatin-induced peripheral neuropathy].

OBJECTIVE: To identify the sensitive scales and the early change of nerve conduction for chronic oxaliplatin-induced peripheral neuropathy (OXLIPN), and to investigate correlation between the symptoms of acute OXLIPN and chronic OXLIPN. METHODS: Between December 2014 and August 2015, 16 colorectal cancer patients confirmed by pathology, from department of Oncology, Chinese PLA General Hospital, scheduled to receive XELOX, completed the acute neurotoxic symptoms questionnaire at the end of 1 cycles and the scales of TNSc and NCI-CTC at the baseline and the end of 4 cycles. Nerve conduction studies (bilateral peroneal nerves and sural nerves) were performed in 11 patients at the baseline and the end of 4 cycles. RESULTS: After chemotherapy, TNSc increased 1-9 points for all cases, while NCI-CTC increased 1 point for only 9 cases, the remaining 7 cases had the same NCI-CTC score before and after chemotherapy, where TNSc increased 1-6 points. Left sural nerve a-SNAP (amplitude of sensory nerve action potential) was (15.3±5.8)µV before chemotherapy and(12.3±5.0)µV after chemotherapy. Right sural nerve a-SNAP was (17.4±8.6)µV before chemotherapy and (13.3±6.7)µV after chemotherapy. After chemotherapy, these datum were significantly reduced for left peroneal nerve distal and proximal a-CMAP (amplitude of compound muscle action potential), bilateral sural nerve a-SNAP and left sural nerve SCV (sensory conduction velocity) (P<0.05). After chemotherapy, TNSc was correlated significantly with the acute neurotoxic symptoms questionnaire (Spearman r=0.698, P=0.003). CONCLUSIONS: TNSc is more sensitive to the severity and changes in chronic OXLIPN than NCI-CTC. Sural nerve a-SNAP has a higher sensitivity for the early changes of nerve conduction studies in chronic OXLIPN. Patients who have more symptoms of acute OXLIPN are those who eventually develop more severe chronic OXLIPN.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome in China.

BACKGROUND/AIM: The clinical characteristics of POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome in China are largely unknown. This work thus studied the clinical manifestations of POEMS syndrome in China. METHODS: We retrospectively reviewed the medical records of 82 patients with POEMS syndrome in our hospital and made a comparison with those reported outside China. RESULTS: There were 82 patients. Forty (49%) were 45 years old or younger. Sensorimotor deficits were the common initial symptoms. The clinical manifestations are as follows: (i) peripheral neuropathy and abnormal electromyogram were seen in all patients (100%); (ii) organomegaly was present in 72 patients (88%); 61 of them (74%) had splenomegaly; (iii) endocrinopathy was present in 74 cases (90%); hypothyroidism was seen in 51 of 70 patients (73%); (iv) 60 patients (73%) had monoclonal plasmaproliferative disorder; only 22 of 40 (55%) had M-protein; (v) skin changes were seen in 71 patients (87%); (vi) 68 patients (83%) had oedema and effusions; of these, hydropericardium was seen in 23 patients (28%); (vii) 35 of 55 patients (64%) had abnormal electrocardiogram and only 21 of 46 (46%) had bone lesions in X-ray. CONCLUSIONS: POEMS syndrome in China has its own distinctive features, parts of which are commoner in the young people, the higher frequency of splenomegaly, hypothyroidism, hydropericardium and abnormal electrocardiogram, as well as the lower M-protein and bone lesions in X-ray.

[Effect of dynamic balance during the onset of benign paroxysmal positional vertigo on residual dizziness after successful repositioning: a multicenter prospective cohort study].

Objective: To explore the characteristics of dynamic balance during the onset of benign paroxysmal positional vertigo (BPPV) and its prediction of residual symptoms after successful repositioning. Methods: From January 2018 to August 2019, patients diagnosed with unilateral posterior semicircular canal or horizontal semicircular canal BPPV were consecutively enrolled from five otolaryngology clinics in Shanghai. The dynamic balance function was measured by sensory organization test (SOT) before repositioning maneuver, and the residual symptoms and its duration were followed up from one week to up to three months. Results: A total of 260 patients were recruited. After excluding 17 cases, 243 cases were successfully followed up including 89 males and 154 females, with an average age of (52.9±13.0) years. There were 175 cases of posterior semicircular BPPV, 61 cases of horizontal semicircular BPPV and 7 cases of canal conversion (from horizontal to posterior semicircular). Among 243 patients, 118 cases reported residual symptoms, with an incidence of 48.6%. The results of SOT showed that 58.0%(141/243) of the patients had abnormal vestibular input and 41.6%(101/243) were categorized as "near falls". With respect to the detailed residual symptoms, 47 cases (39.8%) reported unsteadiness or floating, 35 cases (29.7%) had fogginess/heaviness feeling, 22 cases (18.6%) had transient dizzy while head moving, and 15 cases (12.7%) reported that the symptom was too subtle to describe. Compared with the group without residual symptoms, the group with residual symptoms had more abnormal vestibular input(χ²=67.25, P<0.001) and near falls(χ²=74.78, P<0.001) as identified by SOT test. Cox proportional hazards regression failed to reveal any SOT results having significantly impact on the duration of residual symptoms [abnormal vestibular input (HR= 0.93, 95%CI: 0.48, 1.80), and near falls (HR= 0.90, 95%CI: 0.56, 1.46)]. Kaplan-Meier survival analysis showed that there was no significant difference in the duration of residual symptoms among patients with different SOT manifestations [Log rank (Mantel-Cox) test, P>0.05]. Conclusions: The impaired dynamic balance during the onset of BPPV is characterized by "abnormal vestibular input". The residual symptoms are mainly characterized by unsteadiness or floating feeling. The defect of dynamic balance function is a predictor of the residual symptoms after successful repositioning, but not for the duration of such symptoms.

Long noncoding RNA LINC00511 promoted cell proliferation and invasion via regulating miR-124-3p/EZH2 pathway in gastric cancer.

OBJECTIVE: Growing evidence has shown that long non-coding RNAs (lncRNAs) can serve as prospective markers for survival in patients with gastric cancer (GC). In this study, we mainly focused on the potential roles of LINC00511 in the development process of GC. PATIENTS AND METHODS: RT-PCR was used to detect the expressions of LINC00511 and miR-124-3p in GC tumor tissues, adjacent tissues and GC cell lines. Furthermore, correlations between LINC00511 with miR-124-3p, and miR-124-3p with EZH2, were analyzed by Correlation analysis. Moreover, the overall survival (OS) of patients was analyzed using Kaplan-Meier method. Additionally, proliferation ability was measured by CCK-8 assay and invasion ability of GC cell line was detected by transwell assay. Besides, Western blot was performed to measure protein levels of GC tissues and GC cell lines. Finally, Dual-Luciferase reporter assay was performed to prove the potential binding sites between LINC00511 and miR-124-3p, miR-124-3p and EZH2. RESULTS: We found that LINC00511 was significantly increased in GC tissues and GC cell lines, which was associated with tumor growth, metastasis and predicted poor diagnosis of GC patients. MiR-124-3p was decreased in GC tissues and GC cell lines, which was negatively correlated with LINC00511 and EZH2. Furthermore, EZH2 was increased in GC tissues and GC cell lines, which was positively correlated with LINC00511. Moreover, LINC00511 inhibition repressed cell proliferation and invasion in MKN28 cells, the protein levels of Cyclin D1, ICAM-1, VCAM-1 and N-cadherin were repressed, while E-cadherin was increased. Besides, Luciferase gene reporter assay indicated that LINC00511 could sponge with miR-124-3p, which could directly target at EZH2, an oncogenic gene. We found that miR-124-3p/EZH2 axis regulated cell proliferation and invasion in MKN28 cells. Finally, the inhibited cell proliferation and invasion abilities were eliminated following with miR-124-3p inhibition in MKN28 cells with LINC00511 knockdown. CONCLUSIONS: According to the results, we found that LINC00511 was increased in GC tissues, which was associated with the poor OS in patients with GC. We uncovered a previously unappreciated LINC00511/miR-124-3p/EZH2 signaling axis in promoting cell proliferation and invasion in GC patients and GC cell lines, which suggested that it might be a potential target for treating human GC.

[Human ear finite element model study of the effects of ear canal and middle ear cavity on air conduction and bone conduction].

Objective:To study the influence of the ear canal and middle ear cavity on air conduction and bone conduction. Method:A finite element model of the human middle ear was established. By establishing the external ear canal and the middle ear cavity, we evaluated the effects of the external canal and the middle ear cavity on air conduction and bone conduction. Result:In air conduction, the external canal improved the stapes response at the frequency range of 0.5 kHz to 6 kHz, and the maximum increase was 11 dB at 3 kHz. The middle ear cavity mainly reduced the response of stapes at mid-low frequency, with the drops of 2-4 dB under 2 kHz; in bone conduction, ear canal slightly reduced the low-frequency response, but increased the response of the stapes at the mid-high frequency, with a maximum increase of 1.9 dB at 1.5 kHz. The middle ear cavity mainly increased the stapes response at mid-frequency near 1.5 kHz, with a maximum increase of 2.5 dB. Conclusion:Our results show that, in air conduction, the ear canal significantly increases the middle-frequency response, while the middle ear cavity decreases the low-mid frequency response. Whereas, the ear canal and the middle ear cavity have slightly effect on bone conduction.

AUNX1, a novel locus responsible for X linked recessive auditory and peripheral neuropathy, maps to Xq23-27.3.

BACKGROUND: We report here the genetic characterisation of a large five generation Chinese family with the phenotypic features of auditory neuropathy and progressive peripheral sensory neuropathy, and the genetic feature of X linked recessive inheritance. Disease onset was at adolescence (at an average age of 13 years for six affected subjects). The degree of hearing impairment varied from mild to severe, with decreased otoacoustic emissions; auditory brainstem responses were lacking from onset. METHODS: Two-point and multipoint model based linkage analysis using the MILNK and LINKMAP programs of the FASTLINK software package produced maximum two-point and multipoint LOD scores of 2.41 and 2.41, respectively. RESULTS: These findings define a novel X linked auditory neuropathy locus/region (AUNX1, Xq23-q27.3). This region is 42.09 cM long and contains a 28.07 Mb region with flanking markers DXS1220 and DXS8084, according to the Rutgers Combined Linkage-Physical Map, build 35. However, mutation screen of the candidate gene SLC6A14 within the region did not identify the causative genetic determinant for this large Chinese family.

[The significance of lymphocyte to monocyte ratio in peripheral blood of patients with benign and malignant laryngeal lesions].

Objective:The aim of this study is to investigate the value of preoperative peripheral blood lymphocyte to monocyte ratio (LMR) in differentiating laryngeal squamous cell carcinoma (LSCC), laryngeal precancerous lesions (LPL) and laryngeal benign lesions (LBL). Method:Four hundred and five cases of laryngeal lesions diagnosed by pathology (154 cases of LSCC, 83 cases of LPL and 168 cases of LBL) were collected. LSCC group was further divided into T1 group, T2 group and T3-4 group based on T stage. The levels of neutrophils, lymphocytes, monocytes, hemoglobin, platelet and other blood indexes were measured, as well as compared the LMR, neutrophil to lymphocyte ratio (NLR) and other parameters in each group. Result:The LMR and NLR in LBL, LPL and LSCC groups was 4.88±1.65 and 4.61±1.59, 3.92±1.77 and 2.11±0.79, 2.08±0.77 and 2.63±1.69, respectively. The LMR in the LSCC group was significantly lower than those in the LBL and LPL group (P<0.01), whereas the NLR was significantly higher than those in LBL and LPL group (P<0.05). Either LMR or NLR between the LBL and LPL group was not statistically different (P>0.05). The LMR of patients with local advanced (T3-4) stage in the LSCC group was lower than that in the early or medium stage (T1-2), while the NLR was higher and the difference was statistically significant (P<0.05). There was no significant difference in platelet, white blood cell and neutrophil count between LBL, LPL and LSCC (P>0.05). Conclusion:We, for the first time, compared LMR in different laryngeal lesions and found that LMR and NLR as a systemic inflammatory index have a certain reference value for to differentiate LSCC from LPL and LBL.

A novel HLA-G allele, HLA-G*01:01:01:07, was identified in a Chinese patient with Posner-Schlossman syndrome.

A novel HLA-G allele, HLA-G*01:01:01:07, was identified in a Chinese patient with Posner-Schlossman syndrome.