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Background: Radiotherapy is an important treatment for patients with stage III/IV NSCLC, and due to its high incidence of radiation pneumonitis , it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model.Methods: This study retrospectively collected data from 91 stage III/IV NSCLC cases. Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. ROC, decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination. Results: Smoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (AUC: 0.67,95ci: 0.52–0.81), (AUC: 0.82,95ci: 0.70–0.94), (AUC: 0.90,95ci: 0.80–1.00), and (AUC:0.90,95ci: 0.80–1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(3.6%; score, 0–135), intermediate-(30.7%, 135–160) and high-risk group (80.0%, > 160). Conclusions: In our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonia at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient’s risk level after completion of radiation therapy.

Guohu Weng,1 Bo Zhou,2 Tao Liu,3 Zhengxin Huang,2 Shixiong Huang3 1Department of Encephalopathy, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou, 570203, Hainan, People’s Republic of China; 2Department of Cardiology, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou, 570203, Hainan, People’s Republic of China; 3Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, People’s Republic of ChinaCorrespondence: Shixiong HuangDepartment of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19 Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People’s Republic of ChinaTel/Fax +86-0898-68642129Email huangsx0813@163.comPurpose: Many researches have investigated the functions of tetramethylpyrazine (TMP) in Alzheimer’s disease (AD). This study aimed to discuss the underlying mechanism of TMP in AD mice.Methods: TMP (200 mg/kg) was administered to 6-month-old APP/PS1 transgenic mice, and behavioral changes and hippocampal nerve injury in AD mice were detected. Apoptosis and autophagy-related protein levels were detected. Changes in gene expression before and after TMP treatment were compared using transcriptome sequencing. The effects of Cullin 4B (CUL4B) overexpression and somatostatin receptor 4 (SSTR4) silencing on AD symptoms and SSTR4 ubiquitination in APP/PS1 mice were observed. SH-SY5Y and PC12 cells were treated with 25 μmol/L Aβ25– 35 and TMP to observe cell viability, apoptosis, and autophagy. Cell viability and apoptosis were measured again after treatment with proteasome inhibitor MG132 or lysosomal inhibitor 3-mA.Results: TMP treatment improved the behavioral cognition of APP/PS1 mice and improved the neuronal apoptosis and damage in brain tissue. CUL4B was significantly upregulated in APP/PS1 mouse brain tissue, and SSRT4 protein was downregulated, and the levels of CUL4B and SSRT4 were negatively correlated. TMP treatment downregulated CUL4B, inhibited SSRT4 ubiquitination and upregulated SSRT4 protein level in APP/PS1 mouse brain tissue, while CUL4B overexpression or SSRT4 silencing reversed the effect of TMP. TMP and MG132 improved the decreased activity, increased apoptosis and increased SSRT4 protein in SH-SY5Y and PC12 cells treated with Aβ25– 35, but not 3-mA. CUL4B overexpression promoted the ubiquitination of SSTR4 in cells, which partially reversed the effect of TMP.Conclusion: TMP could improve the cognitive ability of AD mice by inhibiting CUL4B expression and the ubiquitination degradation of SSTR, and alleviating neuronal apoptosis and injury. This study may offer a new therapeutic option for AD treatment.Keywords: Alzheimer disease, tetramethylpyrazine, somatostatin receptor 4, ubiquitination, Cullin 4B

Background: Cerebral ischemic/reperfusion injury (CIRI) is a key factor for the prognosis of ischemic stroke (IS), the leading disease in terms of global disability and fatality rates. Recent studies have shown that endoplasmic reticulum stress (ERS) may be a target against CIRI and that leptin, a peptide hormone, has neuroprotective activity to mitigate CIRI. Methods: An in vitro CIRI model was induced in primary cortical neurons by oxygen-glucose deprivation and reoxygenation (OGD/R) after pretreatment with LY294002 (10 µmol/L) and/or leptin (0.4 mg/L), and cell viability, neuronal morphology and endoplasmic reticulum (ER) dysfunction were evaluated. An in vivo CIRI model was established in rats by middle cerebral artery occlusion and reperfusion (MCAO/R) after the injection of LY294002 (10 μmol/L) and/or leptin (1 mg/kg), and neurological function, infarct volume, cerebral pathological changes, the expression of ERS-related proteins and cell apoptosis were examined. Results: In vitro, leptin treatment improved the cell survival rate, ameliorated neuronal pathological morphology and alleviated OGD/R-induced ERS. In vivo, administration of leptin significantly reduced the infarct volume, neurological deficit scores and neuronal apoptosis as well as pathological alterations. In addition, leptin suppressed MCAO/R-induced ERS and may decrease apoptosis by inhibiting ERS-related death and caspase 3 activation. It also regulated expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax in the cortex. Furthermore, the inhibitory effect of leptin on ERS was significantly decreased by the effective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Conclusions: These results confirm that ERS plays an important role in CIRI and that leptin can inhibit the activation of ERS through the PI3K/Akt pathway, thereby alleviating CIRI. These findings provide novel therapeutic targets for IS.

SUMMARY OBJECTIVE: The aim of this study was to investigate the value of next-generation sequencing for the diagnosis of Streptococcus suis meningitis. METHODS: Patients with meningitis in the Department of Neurology of the Hainan General Hospital were recruited and divided into a next-generation sequencing group and a control group. In the next-generation sequencing group, we used the next-generation sequencing method to detect the specific pathogenic bacteria in the patients. In the control group, we used the cerebrospinal fluid bacterial culture method to detect the specific pathogenic bacteria in the patients. RESULTS: A total of 28 participants were recruited for this study, with 14 participants in each group. The results showed similarities in both the average age and average course of the disease between the two groups (p>0.05). The white blood cell count, percentage of neutrophils, and level of C-reactive protein in the next-generation sequencing group were significantly higher than those in the control group (p0.05). In the next-generation sequencing group, all patients (100%) were detected as having had the S. suis meningitis infection by next-generation sequencing, while only 6 (43%) patients in the control group had been detected as having the S. suis meningitis infection by cerebrospinal fluid bacterial culture. CONCLUSIONS: The positive detection rate of S. suis by the next-generation sequencing method was significantly higher compared with using a cerebrospinal fluid bacterial culture. Therefore, the next-generation sequencing method is valuable for the diagnosis of S. suis meningitis and is worthy of clinical application.

// Tao Liu 1, * , Jianjun Li 2, * , Shixiong Huang 1 , Changqinq Li 2 , Zhongyan Zhao 1 , Guoqiang Wen 1 and Feng Chen 2 1 Department of Neurology, Hainan General Hospital, Haikou 570311, China 2 Department of Radiology, Hainan General Hospital, Haikou 570311, China * These authors contributed equally to this work Correspondence to: Feng Chen, email: fenger0802@163.com Keywords: pathological laughing and crying, resting-state fMRI, amplitude of low-frequency fluctuation, regional homogeneity Received: April 04, 2017 Accepted: June 24, 2017 Published: July 17, 2017 ABSTRACT We used resting-state functional magnetic resonance imaging to investigate the global spontaneous neural activity involved in pathological laughing and crying after stroke. Twelve pathological laughing and crying patients with isolated pontine infarction were included, along with 12 age- and gender-matched acute isolated pontine infarction patients without pathological laughing and crying, and 12 age- and gender-matched healthy controls. We examined both the amplitude of low-frequency fluctuation and the regional homogeneity in order to comprehensively evaluate the intrinsic activity in patients with post-stroke pathological laughing and crying. In the post-stroke pathological laughing and crying group, changes in these measures were observed mainly in components of the default mode network (medial prefrontal cortex/anterior cingulate cortex, middle temporal gyrus, inferior temporal gyrus, superior frontal gyrus, middle frontal gyrus and inferior parietal lobule), sensorimotor network (supplementary motor area, precentral gyrus and paracentral lobule), affective network (medial prefrontal cortex/anterior cingulate cortex, parahippocampal gyrus, middle temporal gyrus and inferior temporal gyrus) and cerebellar lobes (cerebellum posterior lobe). We therefore speculate that when disinhibition of the volitional system is lost, increased activation of the emotional system causes pathological laughing and crying.

Vascular dementia, secondary to Alzheimer’s dementia, ranks as one of the most frequent dementia types. The process of vascular dementia is divergent with other neurodegenerative dementias and thus reversible at the early cognitive disorder or mild dementia stages. The encephalography and neuroimaging data mining at different stages would bring neuromodulation strategies in practice; 15 mild cognitive impairment patients and 16 mild vascular dementia patients as well as 17 cognitive healthy controls were screened in this study. Cognitive tests such as Mini-Mental State Examination, Montreal cognitive assessment, voxel-based morphometry, electroencephalography, and standardized low-resolution brain electromagnetic tomography connectivity network were conducted. Compared with healthy group, voxel-based morphometry analysis showed a decrease in gray/cerebrospinal fluid ratio ( p

Backgroud: LGI1(leucine-richanti-glioma1protein) is one of the latest identified voltage-gated potassium channels related antigens. Anti-LGI1 encephalitis affected the limbic systems presenting with subacute onset of progressive neurological, cognitive, psychiatric disturbance and life threatening obstinate hyponatremia. However, Anti-LGI1 encephalitis was mostly considered to be non-malignancy related. The hyponatremia mechanism remains to be elusive. Case presentation: Here we firstly report a 71-year-old female diagnosed of anti-LGI1 encephalitis after renal clear cell carcinoma resection. The old female discovered a renal mass which was identified as renal clear cell carcinoma. Two months after the renal carcinoma resection, the patient fell down frequently and showed discontinuous neuro-psychiatric disorders manifested as memory decline, disorientation, and unintentional upper limb movements as typical faciobrachial dystonic seizure episode. She also had hyponatremia. The combination of her clinical presentations and laboratory assessments supported a diagnosis ofanti-LGI1 encephalitis and renal salt wasting. The Immunohistochemistry studies of the kidney resection indicated circulating LGI1 antibodies in sera might be binding to extracellular LGI1 predominantly in the proximal tubule where the major defect in solute transport exists in renal salt wasting. Conclusion: Anti-LGI1 encephalities with renal carcinoma indicated its paralimbic pathology origin. The early diagnosis and immune-modulation therapy could lead to good outcome. The hyponatremia in anti-LGI1 encephalitis was renal salt wasting instead of syndrome of inappropriate secretion of antidiuretic hormone.

The concentricity of BCS has captured wide attention; the findings of the current study may provide useful information on the centrifugal pathogenesis of BCS.This study aims to evaluate the performance of MRI, DWI and MRS in elucidating the pathogenesis of Balo's lesions expanding.Six clinically diagnosed BCS cases were reviewed, and the findings obtained by MRI, DWI and MRS were analyzed. DWI data were available for six patients, with the DWI and ADC imaging locations being central and peripheral layers of the index lesion. At TE 144ms, we calculated metabolite ratios of MRS at different depths of the demyelinating lesions and compared with the lesion on the opposite normal side for two patients.The ADC values of 18 typical concentric lesions revealed that the central lesion had the highest ADC value, followed by the internal ring, and the outermost layer had the lowest ADC value. The reduction in NAA/Cr and the increase in Cho/Cr were more evident in the central lesion than in the internal and outermost ring.The findings of DWI and MRS indicate Balo's concentric rings develop gradually and centrifugally. Of course, this hypothesis remains to be proved by further experimental studies.

Rationale Autoimmune thyroid diseases (ATDs) seldom affect intracranial pressure. Here, we describe a case of spontaneous intracranial hypotension (SIH) related to Hashimoto's thyroiditis (HT), which has never been previously published. Patient concerns A 54-year-old woman was admitted to our hospital due to sudden-onset postural headache, neck pain stiffness, visual blurring, nausea and vomiting. The headache was aggravated when the patient sat or stood up yet rapidly resolved within 1 minute after recumbency. Diagnosis The patient had a grade 1a diffusely palpable thyroid gland and the laboratory report revealed elevated titers of anti-thyroid antibodies, a diagnosis of HT was established. Gadolinium-enhanced magnetic resonance imaging exhibited dilatation of the venous sinuses, obvious diffuse pachymeningeal enhancement, and narrowing of the ventricular system, combined with the lumbar puncture pressure was 60 mmH20 in the lateral recumbent position, and a diagnosis of SIH was eatablished. Interventions The patient was placed on strict bed rest and hydrated for 15 days. Outcomes The headache was gradually relieved, a follow-up at 1 month after discharge revealed that the patient could stand and function normally. Lessons SIH can be related to ATD.

Objective: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD) have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD) maps. Methods: We tested this hypothesis using functional magnetic resonance imaging (fMRI) data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy controls (HCs) (n = 32) in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. Results: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC) and increased in the left cerebellum posterior lobe (CPL) and bilateral inferior parietal lobule (IPL) in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC), and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS) ( r =-0.432, P =0.012), and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD( r =0.519, P =0.002) in BQD individuals. Conclusions: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

Objectives: This study aimed to investigate the magnetic resonance imaging (MRI) characteristics and clinical and MRI follow-up findings of patients with neurological complications of enterovirus 71-related hand, foot and mouth disease. Methods: Data were collected from 12 patients who developed neurological complications of enterovirus 71-related hand, foot, and mouth disease during an enterovirus-71 outbreak in Hainan Province, China, from May 2008 to October 2011. Patients were followed up for 2 years. Results: In the six patients with brainstem encephalitis, MRI showed posterior brainstem abnormalities with hyperintense areas on T2-weighted images and hypointense areas on T1-weighted images. In the four patients with acute flaccid paralysis but no brainstem encephalitis, sagittal MRI images showed linear hyperintense areas in the anterior spinal cord, transverse T2-weighted images showed hyperintense areas in the spinal cord, and contrast-enhanced axial T1-weighted images showed strong enhancement of the anterior horns or nerve roots. In the two patients with aseptic meningitis, MRI showed widening of the subarachnoid space and ventricles. The MRI and clinical signs of aseptic meningitis resolved within 4 weeks in both patients. Patients with isolated pontine abnormalities recovered faster than those with multiple brainstem abnormalities, patients with isolated brainstem encephalitis recovered faster than those with associated acute flaccid paralysis, patients with paralysis of one limb recovered faster than those with paralysis of multiple limbs, and patients with isolated thoracolumbar cord abnormalities recovered faster than those with cervical cord abnormalities. Conclusions: MRI is useful for assessment of the neurological complications of enterovirus 71-related hand, foot, and mouth disease. Patients who develop neurological complications characteristically have MRI abnormalities of the posterior brainstem or bilateral anterior horns of parts of the spinal cord. The MRI findings can help to predict prognosis.