Clinical and neurophysiological characteristics of epilepsy with blink inducing / 中华神经科杂志

Objective:To summarize the clinical and neurophysiological characteristics of epilepsy with blink inducing.Methods:The patients with epilepsy with blink test positive who received 24 h-video-electroencephalography (24 h-VEEG) monitoring from May 2017 to May 2022 in the Xijing Hospital, the Air Force Military Medical University were enrolled. Their clinical and electrophysiological characteristics were studied and they were followed up to observe their prognosis.Results:A total of 42 patients with epilepsy with blink test positive were collected, 1 of whom was lost to follow-up. The remaining 41 patients included 18 males (44%) and 23 females (56%), whose age was 3 to 12 (8.1±2.6) years. Self-limited epilepsy with centrotemporal spikes (SeLECTS) was diagnosed in 35 patients, self-limited epilepsy with autonomic seizures in 3, and developmental epileptic encephalopathy with spike-and-wave activation in sleep in 3, respectively. The electrical status epilepticus during sleep (ESES) was found in 31 patients (76%), whereas 10 (24%) without ESES. Thirty-two patients experienced 24 h-VEEG monitoring more than twice, and 23 of them were seizure free, of whom blink inducing disappeared in 14 patients and existed in 9 in the last 24 h-VEEG monitoring. Among the 9 patients who were not seizure free, blink inducing disappeared in 3 patients and remained in 6. There was no statistically significant difference between the two groups ( P>0.05). The age of the patients whose blink inducing disappeared in the last 24 h-VEEG monitoring after treatment was (11.3±3.1) years. Meanwhile the age of the patients whose blink inducing remained was (9.1±2.3) years, and the difference between the two groups was statistically significant ( t=2.254, P=0.030). Conclusions:Blink inducing is highly age-dependent and common in self-limited focal epilepsy and developmental epileptic encephalopathy, especially in SeLECTS. Moreover, patients with ESES are more likely to be blink test positive. There was no correlation between blink inducing and seizure outcome.

An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.

Interpretation of concepts related to electrical status epilepticus / 中风与神经疾病杂志

@#Electrical status epilepticus is a special electroencephalogram phenomenon，which means that the spike and slow waves are almost continuously emitted during the wake-sleep phases. Related concepts are epileptic encephalopathy with electrical status epilepticus during slow wave sleep，electrical status epilepticus in sleep，and subclinical electrographic seizures. The above related concepts are widely used in clinical practice，but there is a lack of unified criteria. There are abuses and misuses of these concepts. Clarifying related concepts is of great significance for scientific research and clinical practice.

Anti-GAD65 antibody-associated stiff-person syndrome:A clinical analysis of four cases / 中风与神经疾病杂志

@#Objective To investigate the clinical features,electrophysiological results,treatment regimen,and prognosis of anti-GAD65 antibody-associated stiff-person syndrome. Methods A retrospective analysis was performed for four patients with anti-GAD65 antibody-associated stiff-person syndrome who attended Department of Neurology,The First Affiliated Hospital of Air Force Medical University,from December 2019 to March 2023. Clinical phenotype,electrophysiological characteristics,treatment methods and prognosis were analyzed. Results All four patients with anti-GAD65 antibody-associated stiff-person syndrome were female,with an age of 49-74 years,and delayed diagnosis(1-7 years) was observed in all four patients. Among the four patients,one had epilepsy,one had cerebellar ataxia,one had type 1 diabetes,and three had Hashimoto's thyroiditis. In the acute stage of the disease,one patient received high-dose hormone shock therapy,one received human immunoglobulin therapy,and two received low-dose hormone. As for long-term immunotherapy,three patients were given mycophenolate mofetil,and one patient was given regular infusion of human immunoglobulin. All four patients showed response to clonazepam and immunoregulatory therapy. Conclusion Anti-GAD65 antibody-associated stiff-person syndrome is often observed in middle-aged and elderly women,with delayed diagnosis in most cases. Patients may also have other clinical phenotypes and autoimmune diseases,and typical discharge of motor unit potential often exits in axial muscles. Clonazepam and immunotherapy are effective treatment methods for this disease.

The postictal generalized EEG suppression and its significance in sudden unexpected death in epilepsy / 中国神经精神疾病杂志

Sudden unexpected death in epilepsy(SUDEP)is the leading cause of accidental death in epileptic patients.The postictal generalized EEG suppression(PGES)is related to SUDEP.The age,seizure type,tonic seizure/tonic muscle contraction,ictal and post-ictal respiratory dysfunction and autonomic dysregulation is associated with PGES with significant individual variation.Progressive slowing of clonic phase(PSCP)in generalized tonic-clonic seizures(GTCS)is an independent predictor of the onset and prolongation of PGES.

The correlation between serum vitamin D and the risk of pre-eclampsia in the early, middle and late stages of pregnancy / 中国医师进修杂志

Objective:To investigate the correlation between serum vitamin D and the risk of pre-eclampsia at the early, middle and late stages of pregnancy.Methods:Pregnant women who registered and delivered in Electric Power Teaching Hospital of Capital Medical University from August 2020 to July 2021 were included. Pregnant women with pre-eclampsia during pregnancy were selected as the case group (150 cases), while pregnant women without any complications after delivery were selected as the control group (600 cases) according to the 1∶4 matching principle (age, pre-pregnancy body mass index and last menstruation). The levels of serum vitamin D in differences stages of pregnancy between the two groups were compared. Logistic regression model was used to analyze the association between serum vitamin D levels and the risk of pre-eclampsia.Results:The levels of serum vitamin D at the early, middle and late stages of pregnancy in the case group were lower than those in the control group: (14.32 ± 3.61) μg/L vs. (18.78 ± 4.73) μg/L, (15.06 ± 3.12) μg/L vs. (19.88 ± 4.25) μg/L, (16.04 ± 3.51) μg/L vs. (22.04 ± 5.63) μg/L, there were statistical differences ( P<0.05). Taking pregnant women with adequate serum Vitamin D as a reference, and adjusting for confounding factors such as gain weight and primipara, the risk of pre-eclampsia in early stages pregnant women with serum Vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR and 95% CI were 4.84(1.25 -31.42), 3.09(1.12 - 8.96), 1.48(1.12 - 13.05); the risk of pre-eclampsia in middle stages pregnant women with serum vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR(95% CI) were 4.43(1.23 - 13.55), 2.22(1.05 - 6.78), 1.12(0.45 - 7.73); the risk of pre-eclampsia in late stages pregnant women with serum vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR(95% CI) were 2.13(1.12 - 8.64), 1.76(1.02 - 4.98), 1.22(0.72 - 3.94). Conclusions:The level of serum vitamin D is associated with the risk of pre-eclampsia in pregnant women in the early, middle and late stages of pregnancy, and the risk of pre-eclampsia is significantly increase when the level of serum vitamin D is severely deficient or deficient during pregnancy.

Opinions on the nomenclature of familial cortical myoclonic tremor with epilepsy / 中华神经科杂志

Familial cortical myoclonic tremor with epilepsy (FCMTE) is a rare neurological disorder. There were more than 10 different terms of disease name in domestic and international published articles by searching FCMTE from PubMed and Wanfang database (from 1990 to 2022), which indicated the different understanding of the disease. It is necessary to discuss the correct and consentaneous name of the disease to facilitate the professional investigation in the future. The name evolution of FCMTE and the author′s views are described in this article.

The clinical and neuroelectrophysiological characteristics of patients with sudden unexpected death in epilepsy / 中华神经科杂志

Objective:To investigate the clinical and electrophysiological characteristics of patients with sudden unexpected death of epilepsy (SUDEP).Methods:Using "epilepsy" as the keyword, the relevant cases entered from October 2011 to March 2012 were searched in the database of the Electroencephalogram (EEG) Monitoring Center, Xijing Hospital, the Air Force Military Medical University. Telephone follow-up was conducted for all confirmed epilepsy patients, and for the death cases confirmed by telephone follow-up, the patients identified as consistent with SUDEP diagnosis were included in this study based on their past medical history, clinical data, death details, etc, and their clinical and neuroelectrophysiological characteristics were summarized and analyzed.Results:Among the 1 232 patients who underwent 24-hour video-EEG monitoring during the study period, 354 patients were successfully followed up by telephone interview, of whom 17 patients were died (4.8%), 12 individuals met the diagnosis of SUDEP (7 men, 5 women). The duration of the disease in 9 patients exceeded 10 years. Eight cases presented with focal-bilateral tonic clonic seizures. Nine patients were treated with anti-seizure drug monotherapy. All the 24-hour video EEG of 12 patients were abnormal. There were 8 occasions when the EEG occipital α background rhythm slowed down compared with the standard frequency of peers or was dominated by slow waves. Interictal epileptic discharge (IED) located in temporal lobe were found in 12 EEG records, of which 9 EEG records were found with frontal IED. One of the 12 cases received 24-hour video EEG twice within 6 years, and his EEG background rhythm was significantly slower and the IED region was expanded compared with the first EEG record. At the third year after reexamination of EEG, SUDEP developed in this patient.Conclusions:SUDEP patients have a long course of disease and bilateral tonic-clonic seizure. The interictal EEG shows occipital slow α activity and temporofrontal epileptiform discharges, which may increase the risk of SUDEP.

Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice

Equitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant.

Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants

The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.

Predictive value of systemic inflammation response index before treatment for pathological complete response in patients with breast cancer undergoing neoadjuvant chemotherapy / 国际肿瘤学杂志

Objective:To investigate the predictive value of systemic inflammation response index (SIRI) before treatment for pathological complete response (pCR) in patients with breast cancer undergoing neoadjuvant chemotherapy.Methods:The clinicopathological data of 119 patients with primary breast cancer undergoing neoadjuvant chemotherapy and subsequent breast-conserving or modified radical surgery from Cangzhou Central Hospital of Hebei Province between January 2010 to March 2020 were retrospectively analyzed, and patients were divided into pCR group ( n=19) and non-pCR group ( n=100) based on postoperative pathology. The SIRI before treatment between the two groups was compared. The patients were divided into SIRI≤0.25 ( n=10) , 0.26-0.50 ( n=42) , 0.51-0.75 ( n=29) , 0.76-1.00 ( n=19) , and >1.00 ( n=19) groups according the SIRI before treatment, and the pCR ratios of the five groups were compared. Spearman correlation analysis was applied to evaluate the relationship between SIRI before treatment and pCR, logistic regression analysis was used to identify the influencing factors of pCR for neoadjuvant chemotherapy in breast cancer patients, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI before treatment for pCR of neoadjuvant chemotherapy in breast cancer patients. Results:Tumor size ( Z=2.26, P=0.024) , axillary lymph node metastasis ( χ2=5.73, P=0.017) , human epidermal growth factor receptor-2 (HER-2) ( χ2=8.77, P=0.003) , Ki-67 ( Z=2.68, P=0.007) , cytological nuclear grade ( χ2=5.08, P=0.024) , neutrophil count before treatment ( Z=2.44, P=0.015) , monocyte/lymphocyte ratio before treatment ( Z=3.04, P=0.002) , and SIRI before treatment ( Z=3.29, P=0.001) had statistical differences between the pCR and non-pCR groups. The pCR ratios were 50% (5/10) in the SIRI ≤0.25 group, 21% (9/42) in the 0.26-0.50 group, 10% (3/29) in the 0.51-0.75 group, 11% (2/19) in the 0.76-1.00 group, and 0 (0/19) in the >1.00 group, with a statistic difference ( χ2=14.28, P=0.006) . SIRI before treatment was negatively related with pCR ( r=-0.30, P=0.001) . Univariate logistic regression analysis showed that tumor size ( OR=0.50, 95% CI: 0.28-0.89, P=0.019) , axillary lymph node metastasis ( OR=5.43, 95% CI: 1.19-24.83, P=0.029) , HER-2 ( OR=7.54, 95% CI: 1.65-34.36, P=0.009) , Ki-67 ( OR=1.03, 95% CI: 1.01-1.05, P=0.008) , cytological nuclear grade ( OR=0.20, 95% CI: 0.04-0.92, P=0.038) , neutrophil count before treatment ( OR=0.54, 95% CI: 0.32-0.92, P=0.023) , monocyte/lymphocyte ratio before treatment ( OR=0.00, 95% CI: 0.00-0.01, P=0.007) , and SIRI before treatment ( OR=0.03, 95% CI: 0.00-0.37, P=0.007) were influencing factors for pCR of neoadjuvant chemotherapy in breast cancer patients. Multivariate logistic regression analysis confirmed that tumor size ( OR=0.31, 95% CI: 0.14-0.72, P=0.007) , axillary lymph node metastasis ( OR=10.97, 95% CI: 1.35-89.61, P=0.025) , HER-2 ( OR=6.47, 95% CI: 1.18-35.65, P=0.032) , Ki-67 ( OR=1.04, 95% CI: 1.00-1.07, P=0.029) , cytological nuclear grade ( OR=7.87, 95% CI: 1.01-61.35, P=0.049) , and SIRI before treatment ( OR=0.03, 95% CI: 0.00-0.58, P=0.020) were independent influencing factors for pCR of neoadjuvant chemotherapy in breast cancer patients. The ROC curve showed that the area under the curve of SIRI before treatment for predicting pCR was 0.74 (95% CI: 0.65-0.82) , sensitivity was 68.0%, and specificity was 75.3%. The area under the curve of monocyte/lymphocyte ratio before treatment for predicting pCR was 0.72 (95% CI: 0.63-0.80) , sensitivity was 48.0%, and specificity was 84.2%. The area under the curve of neutrophil count before treatment for predicting pCR was 0.68 (95% CI: 0.59-0.76) , sensitivity was 61.0%, and specificity was 83.7%. Conclusion:SIRI before treatment may serve as a marker for predicting pCR in patients with breast cancer undergoing neoadjuvant chemotherapy, patients with low SIRI are more likely to obtain pCR.

A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes mimicking migraine attacks with visual aura / 中国医师杂志

Objective:To study the case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) which mimic migraine attacks with visual aura, to analyze the clinical features, and to recognize the nature of headache.Methods:The clinical features, image data and video electroencephalogram (EEG) of a suspected patient with MELAS were analyzed. Genomic DNA of mitochondria was extracted from blood and the next generation sequencing was performed to explore the mutation of genes about MELAS.Results:The patient was adolescent-onset, and presented with migraine-like attacks with visual aura, epileptic seizures, stroke-like episodes and hyperlactemia. Brain images suggested basal ganglia calcification, reversible left occipital cortex infarction and abnormal lactic acid peaks in both occipital cortex. Video EEG suggested abnormal adolescent EEG. Mitochondrial DNA sequencing showed that MT-TL1 gene had m. 3243A>G pathogenic mutation.Conclusions:There are a variety of clinical manifestations in MELAS, and migraine-like attacks with visual aura as initial symptoms may be manifestations of occipital lobe epilepsy. Clinicians should avoid confusing the diagnosis of migraine with visual aura, occipital epilepsy and MELAS, in order to make rational clinical decisions.

Interpretation of diagnostic criteria related to epilepsy and migraine / 中华神经科杂志

The concepts and diagnostic criteria such as "migralepsy" and "ictal epileptic headache" have been proposed by International Headache Society in succession, and have been widely used in clinical practice. However, the authors believe that these diagnostic criteria are worth discussing. Headache can be a symptom of epileptic seizures, or be a state after seizures. Migraine and epilepsy can be comorbid, while migralepsy may be a form of focal epilepsy essentially from the professional perspectives of epilepsy. All medical points of views and thoughts need to be focused, so the sub-professional groups of epilepsy and headache should strengthen the dialogue and consultation, in order to formulate the diagnostic criteria of epilepsy and migraine scientifically.

Clinical and electrophysiological study of sleep-related hypermotor epilepsy during rapid eye movement sleep / 中华神经科杂志

Objective:To explore the electro-clinical characteristics of sleep-related hypermotor epilepsy (SHE) in rapid eye movement (REM) stage.Methods:Five patients of SHE in REM stage were studied and followed up in the Electroencephalogram Monitoring Center, Department of Neurology, Xijing Hospital, the Air Force Military Medical University, from January 2016 to August 2021.Results:Among the 5 patients, there are 3 male patients, aged 21 to 46 years. A total of 23 seizures were monitored in 5 patients, of which 22 occurred in REM sleep and 1 occurred in non-REM Ⅲ sleep. Each attack lasted from 30 seconds to 1 minute, and was manifested as "hyperkinetic attack" during sleep, with or without disturbance of consciousness. There were no obvious abnormalities in electroencephalography during 13 attacks, with the focal sharp slow waves or slow waves during 9 attacks, and the focal slow waves occurrence at the end of the 10 attacks.Conclusion:Most of the hypermotor epileptic seizures in REM stage started from awakening reaction, and the interictal discharges occured in waking and non-REM sleep stage, which is necessary to distinguish from the REM sleep behavior disorder.

Clinical and electro-physiological characteristics of reflex epilepsy induced by thinking activities / 中华神经科杂志

Objective:To explore the clinical and electro-physiological characteristics of reflex epilepsy induced by thinking activities.Methods:Five patients of reflex epilepsy induced by thinking activities during electroencephalogram (EEG) monitoring in the EEG Monitoring Center, Department of Neurology, Xijing Hospital,the Air Force Military Medical University from January 2017 to September 2019 were studied and followed up.Results:All the 5 patients are male, aged 14 to 33 years, with the disease course of 3 to 9 years and the follow-up of 1 to 4 years. The myoclonic jerks, spasms seizure and generalized tonic and clonic seizure occured to the 5 patients. The EEG background of low amplitude alpha rhythm was recorded in the 5 patiens. The ictal-EEG of 2 cases showed the spike wave or spike slow complex waves in the central, parietal area, and the ictal-EEG of 1 case showed the generalized spike-wave discharge. There were no seizures occuring to the 2 cases during video-electroencephalography monitoring. There were no abnormalities in cranial magnetic resonance imaging. The arterial spin labeling of 2 cases suggested that the right cerebral hemisphere cerebral blood flow was lower than contralateral. Antiseizure drugs (levetiracetam in 4 cases and levetiracetam+magnesium valproate in 1 case) were administered, 4 cases were seizure free and 1 case was uncontrolled.Conclusions:The reflex epilepsy induced by thinking activities is common in young men, and the EEG background with low amplitude alpha rhythm may be the characteristic of the reflex epilepsy induced by thinking activities. The levetiracetam may be the good choice for the reflex epilepsy induced by thinking activities and the prognosis of reflex epilepsy induced by thinking activities is good.

Establishment of random forest model and its predictive value for pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy / 肿瘤研究与临床

Objective:To investigate the predictive value of established random forest model for pathologic complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy.Methods:The clinicopathologic data of 142 primary breast cancer patients undergoing breast-conserving surgery or modified radical mastectomy after neoadjuvant chemotherapy from Cangzhou Central Hospital between January 2010 and October 2021 were retrospectively analyzed. Histologically, breast and axillary lymph node without residual infiltrated tumors was treated as pCR. The patients were divided into pCR group (23 cases) and non-pCR group (119 cases) according to whether patients achieved pCR or not, and the differences of clinicopathologic data between the two groups were compared. The risk factors affecting pCR were identified by using logistic regression analysis, random forest model was established by using random forest function of R statistical software, and Gini index of random forest algorithmic was used to order the importance of variables. The receiver operating characteristic (ROC) curve was used to assess the value of random forest model in predicting the efficacy of neoadjuvant chemotherapy.Results:The overall pCR ratio after neoadjuvant chemotherapy was 16.20% (23/142). The proportion of tumor diameter ≤5 cm, negative axillary lymph node, negative human epidermal growth factor receptor 2 (HER2), Ki-67 positive index >20%, histological grade 2, and neoadjuvant chemotherapy regimens including targeted therapy in pCR group was higher than that in non-pCR group, and the difference was statistically significant (all P < 0.05). Univariate logistic regression analysis showed that tumor diameter, axillary lymph node, HER2, Ki-67, histological grade, and neoadjuvant chemotherapy regimens were related with pCR (all P < 0.05). Multivariate logistic regression analysis showed that tumor diameter >5 cm ( OR = 5.85, 95% CI 1.28-26.67, P = 0.022), positive axillary lymph node ( OR = 11.22, 95% CI 1.84-68.42, P = 0.009), positive HER2 ( OR = 7.35, 95% CI 1.45-37.26, P = 0.016), Ki-67 positive index ≤20% ( OR = 1.03, 95% CI 1.01-1.06, P = 0.017), histological grade 3 ( OR = 7.37, 95% CI 1.24-43.86, P = 0.028), and non-targeted therapy ( OR = 0.02, 95% CI 0.00-0.25, P = 0.003) were independent risk factors of pCR. Random forest algorithm showed that the importance order of risk factors of pCR was successively Ki-67 low expression, positive axillary lymph node, tumor diameter >5 cm, positive HER2, non-targeted therapy and histological grade 3. The area under the ROC curve of random forest model for predicting pCR was 0.84 (95% CI 0.74-0.93); the sensitivity was 87.0% and specificity was 72.3% when the optimal cut-off value was 0.88. Conclusions:Low expression of Ki-67, positive axillary lymph node, tumor diameter >5cm, positive HER2, non-targeted therapy and histological grade 3 are risk factors of pCR in breast cancer patients after neoadjuvant chemotheapy. Random forest model helps to predict pCR in breast cancer patients after neoadjuvant chemotheapy.

Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial

BackgroundProduction of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. MethodsThis phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 {micro}g{+/-}CpG1018 (a toll-like receptor 9 agonist), 3 {micro}g{+/-}CpG1018, 10 {micro}g, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). FindingsBetween March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5{middle dot}7% to 17{middle dot}1% among vaccine groups and was 2{middle dot}9% in controls; there was no vaccine-related serious adverse event. The 10 {micro}g formulations immunogenicity ranked best, followed by 3 {micro}g+CpG1018, 3 {micro}g, 1 {micro}g+CpG1018, and 1 {micro}g formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122{middle dot}23 IU/mL (1 {micro}g, 95% CI 86{middle dot}40-172{middle dot}91) to 474{middle dot}35 IU/mL (10 {micro}g, 95% CI 320{middle dot}90-701{middle dot}19), with 93{middle dot}9% to 100% of vaccine groups attaining a [≥]4-fold increase over baseline. InterpretationNDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 {micro}g and 3 {micro}g+CpG1018 formulations advanced to phase 2. FundingNational Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA)

A Newcastle disease virus-vector expressing a prefusion-stabilized spike protein of SARS-CoV-2 induces protective immune responses against prototype virus and variants of concern in mice and hamsters

Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.

Research on the electro-clinical aspects of epilepsy patients with breach rhythm / 中华神经科杂志

Objective:To investigate the clinical characteristics and electroencephalogram (EEG) of epilepsy patients with breach rhythm, improve clinical understanding of breach rhythm and avoid over-interpretation.Methods:Twelve epilepsy patients with breach rhythm who visited the Department of Neurology, Xijing Hospital, the Air Force Military Medical University from January 2016 to January 2017 were collected retrospectively. The clinical data, including etiology, clinical manifestations, EEG features and prognosis were summarized, and outpatient and telephone follow-up was performed for at least three years.Results:The clinical data of 12 patients with epilepsy with breach rhythm were collected, including eight males and four females, aged 36-78 years. After analysis, it was found that brain trauma was the most common cause of breach rhythm. Among them, two cases of skull defect were not repaired, eight cases were repaired with skull titanium mesh, one case was repaired with skull polymethylmethacrylate, and one case was repaired with skull polyetheretherketone. The distribution of the breach rhythm in 12 patients was consistent with the abnormal area of the skull. The breach rhythm can be expressed as high amplitude and fast frequency, or low amplitude and slow frequency and appear individually (similar to sharp waves, spikes). On the basis of pleomorphic slow waves, 10 patients were mixed with sharp waves and spike waves, and imaging confirmed that they had brain damage in corresponding parts. All of the 12 patients had a history of seizures, with tonic-clonic seizures and (or) focal seizures being the most common. Three patients with breach rhythm had no clinical seizures for more than five years, and had been taking antiepileptic drugs for epileptic spikes on EEG, and they were given reduction and discontinuation of the drugs and were seizure-free for three years during follow up.Conclusions:Skull repair is a common cause of breach rhythm, and repair materials with different resistances cause different waveforms and frequencies. Breach rhythm, epileptiform discharge and other pathological slow-wave activities can exist at the same time. Breach rhythm is a benign variant phenomenon which needs no special treatment.

A case report of lamotrigine related recurrent cough / 中华神经科杂志

The cough related with lamotrigine in a patient with epilepsy was analyzed and summarized. According to the criteria of adverse drug reaction, the cough of the patient was the certain adverse reaction of lamotrigine. It is necessary to realize cough is an adverse reaction of lamotrigine, which is helpful to avoid the misdiagnosis and mistreatment of cough.