[Diagnostic value of F wave changes in patients with Charcot-Marie-Tooth1A and chronic inflammatory demyelinating polyneuropathy].

OBJECTIVE: To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared. RESULTS: The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ2=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody. CONCLUSION: The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.

[Genetic distribution in Chinese patients with hereditary peripheral neuropathy].

OBJECTIVE: To analyze the distribution characteristics of hereditary peripheral neuropathy (HPN) pathogenic genes in Chinese Han population, and to explore the potential pathogenesis and treatment prospects of HPN and related diseases. METHODS: Six hundred and fifty-six index patients with HPN were enrolled in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to May 2022. The PMP22 duplication and deletion mutations were screened and validated by multiplex ligation probe amplification technique. The next-generation sequencing gene panel or whole exome sequencing was used, and the suspected genes were validated by Sanger sequencing. RESULTS: Charcot-Marie-Tooth (CMT) accounted for 74.3% (495/666) of the patients with HPN, of whom 69.1% (342/495) were genetically confirmed. The most common genes of CMT were PMP22 duplication, MFN2 and GJB1 mutations, which accounted for 71.3% (244/342) of the patients with genetically confirmed CMT. Hereditary motor neuropathy (HMN) accounted for 16.1% (107/666) of HPN, and 43% (46/107) of HPN was genetically confirmed. The most common genes of HMN were HSPB1, aminoacyl tRNA synthetases and SORD mutations, which accounted for 56.5% (26/46) of the patients with genetically confirmed HMN. Most genes associated with HMN could cause different phenotypes. HMN and CMT shared many genes (e.g. HSPB1, GARS, IGHMBP2). Some genes associated with dHMN-plus shared genes associated with amyotrophic lateral sclerosis (KIF5A, FIG4, DCTN1, SETX, VRK1), hereditary spastic paraplegia (KIF5A, ZFYVE26, BSCL2) and spinal muscular atrophy (MORC2, IGHMBP, DNAJB2), suggesting that HMN was a continuum rather than a distinct entity. Hereditary sensor and autosomal neuropathy (HSAN) accounted for a small proportion of 2.6% (17/666) in HPN. The most common pathogenic gene was SPTLC1 mutation. TTR was the main gene causing hereditary amyloid peripheral neuropathy. The most common types of gene mutations were p.A117S and p.V50M. The symptoms were characterized by late-onset and prominent autonomic nerve involvement. CONCLUSION: CMT and HMN are the most common diseases of HPN. There is a large overlap between HMN and motor-CMT2 pathogenic genes, and some HMN pathogenic genes overlap with amyotrophic lateral sclerosis, hereditary spastic hemiplegia and spinal muscular atrophy, suggesting that there may be a potential common pathogenic pathway between different diseases.

[The diagnostic value of tremor analysis for defining the Parkinson's disease subtype].

Objective: To find more objective evidence and support for clinical classification of Parkinson's disease by means of tremor analysis in patients with early confirmed Parkinson's disease. Methods: A cross-sectional study was conducted to collect 65 patients with early Parkinson's disease treated in the Third Hospital of Peking University from January 2015 to December 2016. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn-Yahr scale (H-Y scale), Mini-mental state examination (MMSE), Hamilton depression scale (HAMD) were recorded in all patients. According to the ratio of UPDRS rigidity score to tremor score, the patients were divided into tremor dominant (TD), postural instability/gait difficulty (PIGD) and mixed types. All patients were examined by tremor analysis and the results were analyzed and compared. Results: Among the 65 patients, the mean age of onset was (63±10) years, the course of disease was (14±8) months. Twenty-one patients were classified to TD group, 28 patients were classified to PIGD type, and 16 patients with mixed type. There was no significant difference in frequency and amplitude of tremor between the three groups (P>0.05), but the proportion of alternating contraction and harmonic resonance of active and antagonistic muscles in TD group was significantly higher (P<0.05). Twenty patients (71.4%) in TD group showed typical Parkinson's disease manifestations in tremor analysis. Only four patients (14.3%) in PIGD group showed the typical manifestations. More patients in PIGD group showed no clear main peak of tremor at rest. Some patients showed 6-8 Hz/sec peak frequency in posture position and simultaneous contraction of the active and antagonist muscles. These two manifestations occured simultaneously in mixed type patients, including 10 cases (62.5%) with typical Parkinson's disease manifestations. Conclusion: As an objective electrophysiological method to evaluate tremor type, tremor analysis can be used as an important assistant method for clinical classification of Parkinson's disease. It can provide information of the pathway of pathological loss in different types and give important hints in prognosis and treatment.

[Diagnostic value of tremor analysis in identifying the early Parkinson's syndrome].

OBJECTIVE: To investigate the diagnostic value of tremor analysis in early stages of Parkinson's syndrome, when the clinical symptoms of tremor onset are not unilaterally often able for a definite diagnosis to be made. METHODS: We included 70 patients with unilateral tremor, under 45 years old and disease duration within 3 years enrolled in Peking University Third Hospital from January, 2014 to December 2015. We recorded clinical features, unified Parkinson's disease rating scale (UPDRS)-III, non-motor symptom (NMS) scores. Tremor analysis and transcranial sonography were performed for all the patients. Based on the results of tremor analysis, we arbitrarily divided the patients into 3 groups: (1) The patients with classical Parkinson's syndrome manifestations on one side (25 cases); (2) The patients with classical Parkinson's syndrome manifestations on both sides (15 cases); (3) The patients with no classical Parkinson's syndrome manifestations (30 cases). The patients were monitored every 6 months to 3 years, until the final diagnosis was made. RESULTS: There was no significant difference in age, gender distribution, Hamilton depression scale (HAMD) scores and H-Y scores among the three groups (P>0.05). The average UPDRS-III motor scores of the three groups were significantly different (P=0.001), with 18.23, 18.79 and 14.67, respectively. The average scores of NMS were significantly different, with 15.81, 17.07 and 9.90, respectively (P<0.001). The positive rates of transcranial sonography (TCS) in the three groups were 48.0%, 60.0% and 26.67%, with no significant difference (P=0.702). After three years of follow-up, 35 patients (50%) met the diagnostic criteria of Parkinson's disease of International Parkinson and Movement Disorder Society (MDS) in 2015, 19 patients (27.1%) met the criteria of idiopathic tremor, and 7 patients (10%) met the criteria of Parkinson's plus syndrome. The sensitivity and specificity of tremor analysis for early diagnosis of Parkinson's disease were 82.8% and 68.6%, respectively. Compared with TCS, the sensitivity and specificity of TCS were 65.7% and 62.9%. There were consistency (Kappa=0.568) and significant difference (P=0.031) between the two methods. CONCLUSION: Tremor analysis is sensitive and a superior way in identifying early Parkinson's syndrome patients with tremor dominant manifestation. The combination of non-motor symptoms and transcranial sonography are also needed at diagnosis.

[Clinical and neuroimaging features in 6 patients with corticobasal syndrome].

The clinical and imaging data in 6 patients with corticobasal syndrome were retrospectively analyzed. Six patients presented asymmetric clinical symptoms, including 5 with cognitive impairment, 6 with emotional disorders, 2 with cortical sensory deficit, 5 with lalopathy, and 4 with apraxia. All patients developed limb dystonia and limb or trunk stiffness, 4 with tumble, 4 with bradykinesia, and 2 with tremor. Brain magnetic resonance imaging (MRI) showed that 4 patients had unilateral cerebral atrophy and 2 had mild atrophy of bilateral hippocampus. Localized low glucose metabolism in the unilateral cerebral lobe was seen in four patients by positron emission computed tomography (PET) examination, suggesting that PET is helpful for the diagnosis of corticobasal syndrome.

[The clinical analysis of diabetic patients with chronic inflammatory demyelinating polyradiculoneuropathy].

To explore clinical characteristics, electrophysiological findings and treatment response in diabetic patients with chronic inflammatory demyelinating polyradiculoneuropathy (DM-CIDP). Thirty-six CIDP patients were identified, 10 were DM-CIDP and 26 were non-DM-CIDP. Clinical medical records, electrophysiological data and treatment were retrospectively reviewed. DM-CIDP patients were significantly older than non-DM-CIDP patients [(56.7±10.0) years old vs. (40.4±16.9) years old, P=0.001]. However, clinical characteristics and abnormalities of electrophysiological tests in both groups were comparable. DM-CIDP subjects responded to corticosteroids or intravenous immunoglobulin, thus with better prognosis.

[Inhibitory effect of DAPT on Notch signaling pathway in curcumin mediated photodynamic therapy for cervical cancer xenografts in nude mice].

Objective: Curcumin was used as photosensitizers in photodynamic therapy on cervical cancer xenografts in nude mice.Analysis the expression changes of Notch and downstream gene as NF-κB and VEGF before and after DAPT inhibition of Notch signaling pathway in vivo experiments.Our aim was to investigate the possible mechanism of Notch signaling pathway in the treatment of cervical cancer with PDT. Methods: A cervical cancer model of nude mice was established by subcutaneous inoculation of human cervical cancer Me180 cells 200 µl.After the success of the model, the experimental animals were divided into 4 groups (model group, curcumin PDT group, simple DAPT group, curcumin-PDT+ DAPT group), each group was 12.Tumor volume changes were analyzed and HE staining was observed in each group.MRNA and protein expression of Notch1 and its downstream NF-κB, VEGF were detected by RT-PCR, immunohistochemistry and Western blot before and after inhibition of Notch signaling pathway by DAPT. Results: Except the control group, the tumor volume of the other three groups remained unchanged or slightly reduced after 1-7 days of treatment.The difference was significant (P<0.05). HE staining showed the most obvious necrosis of curcumin-PDT group with DAPT.Both DAPT and curcumin-PDT could reduce the expression level of Notch1 in mRNA.The inhibition rates were 42.17% and 40.54%, respectively.And the inhibitory effect of curcumin-PDT with DAPT on Notch-1 was the strongest (79.22%) (P<0.01), and two of them had synergistic effect after combination with curcumin-PDT.But the expression of Notch-2 has no obvious inhibitory effect (P>0.05). Both DAPT and curcumin-PDT can inhibit the protein expression of Notch1, NF-κB and VEGF, and two of them have synergistic effect after combined use. Conclusions: DAPT can effectively block the Notch signaling pathway and inhibit the proliferation of cervical cancer cell line Me180.The application of DAPT to inhibit Notch signaling pathway after photodynamic therapy can achieve synergistic effect, which is mainly related to the down-regulation of the expression of Notch1 and NF-κB.Notch signaling pathway may be one of the targets of curcumin-PDT photodynamic therapy.

[Assessment of upper motor neuron dysfunction by triple stimulation technique in patients with Charcot-Marie-Tooth disease].

OBJECTIVE: To investigate the presence of upper motor neuron dysfunction in patients with Charcot-Marie-Tooth disease (CMT) by triple stimulation technique (TST) to provide evidence for gene diagnosis. METHODS: A total of 65 CMT patients confirmed by genetic testing from Peking University Third Hospital between August 2013 and August 2015, underwent physical examination and routine electrophysiological tests and triple stimulation technique. The TST combined transcranial magnetic stimulation (TMS) of the motor cortex with peripheral collision studies. The results were expressed by the TST amplitude ratio (TST test/ TST control). Based on the result of physical examination and the ratio of TST, the function of upper motor neuron was assessed. RESULTS: All of the CMT patients had typical presentations and were confirmed genetically. Hyperreflexia, Babinski sign and muscular hypertonia were discovered in lower limbs in 7 CMT patients, while 2 patients complicated with hyperreflexia and Hoffmann sign in upper limbs. TST amplitude ratio was significantly altered in 10 patients, including 5 patients with pyramid sign: hyperreflexia, Babinski sign and muscular hypertonia was discovered in lower limbs while 2 patients complicated with hyperreflexia and Hoffmann sign in upper limbs. The disease-causing mutations were: MFN2 mutations in 5 patients, 1 patient with BSCL2 mutation, 3 patients with GJB1 mutations and 1 patient with GDAP mutation. In summary, 18.5% (12 patients) of the 65 CMT patients had upper motor neuron dysfunction based on the result of physical examination and the ratio of TST. CONCLUSION: Upper motor neuron dysfunction may be found in CMT patients, which may provide clues for the testing of disease-causing mutations.

[The clinical, radiological and prognostic factor analysis of medullary infarction].

OBJECTIVE: To investigate the clinical and radiological features of medullary infarction (MI), and to compare the clinical characteristics of lateral medullary infarction (LMI) and medial medullary infarction (MMI). METHODS: Patients diagnosed as acute MI who were treated from January 2009 to December 2014 in Department of Neurology, Peking University Third Hospital, were retrospectively enrolled in the study and data were analyzed including risk factors, clinical features, laboratory findings, radiological characteristics, etiology and outcomes. RESULTS: A total of 62 cases of MI were enrolled with 48 cases of LMI and 14 cases of MMI , including 2 cases of bilateral MMI. The mean onset age of LMI and MMI was 60.2±12.3 and 56.9±14.2, respectively. The frequently affected location of LMI was the middle and upper part of medulla [40 cases (83.3%)]. The common symptoms and signs of LMI were dizzy (38 cases , 79.2%), sensory disturbance (33 cases , 68.8%), dysarthria ( 32 cases , 66.7%), dysphagia (30 cases , 62.5%), diminished pharyngeal reflex (30 cases, 62.5%), Horner's sign (29 cases, 60.4%), ataxia (26 cases, 54.2%) and nausea or vomiting (25 cases, 52.1%). The frequently affected location of MMI was the upper part of medulla (13 cases, 92.9%). The common symptoms and signs of MMI were motor dysfunction (12 cases, 85.7%), sensory disturbances (11 cases, 78.6%), dizzy (10 cases, 71.4%) and dysarthria (10 cases, 71.4%). Infarctions caused by atherosclerosis were found in 35 cases of LMI (72.9%) and 12 cases of MMI (85.7%). Five cases (10.4%) of LMI died in hospital, while 1 case (7.1%) of MMI died in hospital. No lesion was found in 16 cases (25.8%) by MRI-DWI within the first 24 hours of onset. CONCLUSIONS: Our study showes that the mean onset age of LMI is older than that of MMI. The lesion of LMI is frequently located in the upper and middle medulla, whereas the lesion of MMI is mostly in the upper medulla. The prognosis of LMI is worse than that of MMI. Atherosclerosis of the vertebral arteries is the predominant vascular pathology in MI.

High spatial and temporal resolution charge exchange recombination spectroscopy on the HL-2A tokamak.

A 32/64-channel charge exchange recombination spectroscopy (CXRS) diagnostic system is developed on the HL-2A tokamak (R = 1.65 m, a = 0.4 m), monitoring plasma ion temperature and toroidal rotation velocity simultaneously. A high throughput spectrometer (F/2.8) and a pitch-controlled fiber bundle enable the temporal resolution of the system up to 400 Hz. The observation geometry and an optimized optic system enable the highest radial resolution up to ∼1 cm at the plasma edge. The CXRS system monitors the carbon line emission (C VI, n = 8-7, 529.06 nm) whose Doppler broadening and Doppler shift provide ion temperature and plasma rotation velocity during the neutral beam injection. The composite CX spectral data are analyzed by the atomic data and analysis structure charge exchange spectroscopy fitting (ADAS CXSFIT) code. First experimental results are shown for the case of HL-2A plasmas with sawtooth oscillations, electron cyclotron resonance heating, and edge transport barrier during the high-confinement mode (H-mode).

Observation of turbulence suppression after electron-cyclotron-resonance-heating switch-off on the HL-2A tokamak.

The formation of a transient internal transport barrier (ITB) is observed after the electron-cyclotron-resonance-heating (ECRH) switch-off in the HL-2A plasmas, characterized by transient increase of central electron temperature. The newly developed correlation reflectometer provided direct measurements showing reduction of turbulence in the region of steepened gradients for the period of ITB formation triggered by the ECRH switch-off. Furthermore, the reduction of core turbulence is correlated in time with the appearance of a low-frequency mode with a spectrally broad poloidal structure that peaks near zero frequency in the core region. These structures have low poloidal mode number, high poloidal correlation, and short radial correlation and are strongly coupled with high-frequency ambient turbulence. Observation indicates that these structures play important roles in the reduction of the core turbulence and in improvements of the core transport after the off-axis ECRH is turned off.

KL-6, a human MUC1 mucin, is expressed early in premature lung.

KL-6, one of the MUC1 antigens, is a mucin-like high-molecular-weight glycoprotein, which is strongly expressed on type II pneumocytes. Serum levels of KL-6 have been shown to correlate with activity of interstitial pneumonia (IP). During embryonic development, MUC1 expression coincides with the onset of epithelial sheet and glandular formation. To investigate the potential role of KL-6 in lung morphogenesis, we examined KL-6 expression by immunohistochemistry on autopsied lung tissue specimens of 35 neonates and infants with gestational age from 23 to 40 weeks. Hyaline membranes (HMs) were detected in 13 of 35 cases. Simultaneously, antibody against surfactant protein A (SP-A) was employed in the study which is a distinct marker for type II pneumocytes. In all cases studied with gestational age above 23 weeks, staining for KL-6 was strongly positive in alveolar epithelial cells and in HMs found in 13 cases, whereas immunoreaction for PE10 varied depending on gestational age and duration of postnatal survival. Our findings suggest that KL-6 is expressed earlier in premature lung and may act as an important factor contributing to morphogenesis and function of developing lung in early gestation.

Caregiver AOD use, case substantiation, and AOD treatment: studies based on two southwestern counties.

This article includes two separate studies: the first explores the impact of caregiver AOD use on CPS case substantiation; the second compares CPS-involved and CPS-noninvolved females in AOD treatment systems. Results suggest that cases with indications of AOD use are more likely to be substantiated than cases without; and increasing numbers of children and younger maternal ages are risk factors for CPS involvement among AOD-using women. Related findings are also presented, followed by implications for practice and research.

Osteoclast-like giant cell tumor of the pancreas with metastases to gallbladder and lymph nodes. A case report.

Osteoclast-like giant cell tumor of the pancreas (OGTP) is a rare neoplasm, of which the histogenesis is still controversial. Here we report a case of OGTP involving the head of the pancreas in a 71-year-old woman with metastases to the gallbladder and lymph nodes. The primary and metastatic tumors had identical histopathological, immunohistochemical, ultrastructural and molecular biological features. Microscopically, the tumors were characterized by atypical, often pleomorphic mononuclear cells associated with the proliferation of benign-appearing osteoclast-like giant cells (OGCs). Electron microscopic observation provided ultrastructural evidence of epithelial differentiation of the mononuclear cells, including microvilli and desmosomes, which was not obtained for OGCs. On immunohistochemical study, OGCs stained for CD68 (KP-1), LCA and HAM56, whereas mononuclear cells only reacted with PCNA. These findings clearly suggest that mononuclear cells are capable of differentiation and proliferation and may have been the only true tumor cells in this neoplasm, and that OGCs may have been a paraneoplastic product of this rare tumor. On examination of DNA from dewaxed sections of the tumor, we found no p53 mutation in the tumor tissue, but found two K-ras mutations in codon 12; this pattern of mutation commonly occurs in pancreatic carcinoma, indicating a somewhat genetic relationship of OGTP to pancreatic carcinoma. Although OGTP often has a favorable prognosis, the outcome in the present case was poor due to early tumor spread, with less than two years postoperative survival.