Contribution of small airway inflammation to the development of COPD.

BACKGROUND: Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD. METHODS: A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO50, FeNO200, and calculated CaNOdual. Both FeNO200 and CaNOdual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD. RESULTS: Exhaled NO levels (FnNO, FeNO50, FeNO200, and CaNOdual) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO50, FeNO200, and CaNOdual) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNOdual (AUC ROC = 0.707) in COPD. FeNO200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO50 and FeNO200. CONCLUSION: The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.

Dl-3-n-Butylphthalide Protects against Memory Deficits in Vascular Dementia Rats by Attenuating Pyroptosis via TLR-4/NF-κB Signaling Pathway.

INTRODUCTION: Inflammation is closely associated with the pathogenesis of vascular dementia (VD). Dl-3-n-butylphthalide (NBP) is a small molecule compound extracted from the seeds of Chinese celery, which have anti-inflammatory properties in animal models of acute ischemia and patients with stroke. In this experiment, we studied the protective effects of NBP in a rat model of VD induced by permanent bilateral occlusion of the common carotid arteries and investigated the role of the TLR-4/NF-κB inflammatory signaling pathway in the pathology of VD. METHODS: The Morris water maze test was used to evaluate cognitive deficits in the VD rats. Western blot, immunohistochemistry, and PCR analyses were used to analyze the molecular basis of the inflammatory response. RESULTS: NBP significantly improved the learning and memory ability of VD rats. With regard to the protective mechanism, the results showed that NBP significantly downregulated the relative expression of Cleaved Cas-1/Cas-1 and Cleaved GSDMD/GSDMD. Moreover, NBP decreased the levels of the TLR-4 and NF-κB (P65) protein and phosphorylation of P65 in the hippocampus of VD rats via the TLR-4/NF-κB signaling pathway. CONCLUSION: These findings demonstrate that NBP protects against memory deficits in permanent bilateral common carotid artery occlusion-induced VD rats by attenuating pyroptosis via the TLR-4/NF-κB signaling pathway.

SERPINA1 and plasminogen as novel biomarkers in obstetric antiphospholipid syndrome patients.

OBJECTIVES: To explore the potential biomarkers and mechanisms in obstetric antiphospholipid syndrome (OAPS) patients by placental proteomics. METHODS: Among 212 follow-up pregnancy patients based on the Chinese Rheumatism Data Center database (CRDC), we continuously recruited 30 pregnancy patients at the late stage of pregnancy for proteomics study. Fresh placental tissues were collected and 4D label-free technologies were used to analyse the placental proteome in patients. Bioinformatic analysis was applied to identify differentially expressed proteins (DEPs) and crucial pathways. Placental tissues were also stained with haematoxylin and eosin (H & E) for histological analysis. RESULTS: We collected 7 OAPS patients (33.85±1.57 years), 4 SAPS patients (34.25 ± 3.86 years), 8 SLE patients (30.38±2.56 years), and 11 healthy controls (31.45±3.01 years). All patients in the SAPS and OAPS group had adverse pregnancy history. A total of 7040 proteins containing at least one unique peptide were identified. There were 214 DEPs between the healthy group and the OAPS group, of which 82 proteins were upregulated and 132 proteins were downregulated in the OAPS group based on fold change ≥1.5 and p-values ≤0.05. We found that the complement and coagulation pathway played a significant role in OAPS patients. Several key proteins (C1Q, C4b, SERPINA1, plasminogen) highly expressed in placental tissues, that may serve as biomarkers for OAPS patients. CONCLUSIONS: The complement and coagulation pathway and related DEPs (SERPINA1 and plasminogen) were of crucial importance in OAPS patients.

Cerebral venous thrombosis (CVT) complicating tubercular meningitis.

BACKGROUND: Tuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further. METHODS: Among those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. "Tuberculous meningitis" and "cerebral venous thrombosis" were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition. RESULTS: Among 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent. CONCLUSIONS: CVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs.

Comparison of the efficacy and safety of rivaroxaban and low-molecular-weight heparin in Chinese lung cancer patients with nonhigh-risk pulmonary embolism.

BACKGROUND: Data that guide selection of differing anticoagulant regimens for specific cancer-associated venous thromboembolism (VTE) are lacking. We aimed to compare the efficacy and safety of rivaroxaban and low-molecular-weight heparin (LMWH) against nonhigh-risk pulmonary embolism (PE) in Chinese lung cancer patients. METHODS: Four hundred forty-six Chinese lung cancer patients with nonhigh-risk PE who initiated treatment with rivaroxaban or LMWH were identified from Zhongshan Hospital database from 2016 to 2020. The primary outcomes were the composite event of VTE recurrence or major bleeding, and all-cause mortality. The secondary outcomes were VTE recurrence, major bleeding and clinically relevant non-major bleeding (CRNMB). Propensity score matching was used to balance baseline covariates. We conducted sensitivity analysis by stabilized inverse probability of treatment weighting and competing risk analysis by a Fine and Gray subdistribution hazard model. RESULTS: In propensity score-matched cohorts, rivaroxaban was similar to LMWH in the risks of the composite outcome (hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.45-1.21; P = 0.22), VTE recurrence (HR, 0.69; 95% CI, 0.36-1.34; P = 0.28), major bleeding (HR, 0.79; 95% CI, 0.37-1.68; P = 0.54) and CRNMB (HR, 1.13; 95% CI, 0.62-2.09; P = 0.69). All-cause mortality was significantly lower in rivaroxaban group than LMWH group (HR, 0.52; 95% CI, 0.36-0.75; P < 0.001). The primary and secondary outcomes favored rivaroxaban over LMWH in all the subgroups expect for central PE and intermediate-risk PE. The sensitivity analysis yielded similar results, and competing risk analysis was in accordance with the primary findings. CONCLUSIONS: Rivaroxaban might be a promising alternative to LMWH as initial treatment for nonhigh-risk PE in lung cancer patients.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Thrombocytopenia in primary antiphospholipid syndrome: association with prognosis and clinical implications.

OBJECTIVES: Thrombocytopenia, a frequent clinical manifestation in patients with APS, could be an independent predictor of recurrent thrombotic, obstetric and severe extracriteria events. METHODS: This single-centre prospective study enrolled 218 consecutive patients diagnosed with primary APS between 2010 and 2021. Thrombocytopenia was defined as a platelet count less than 100 × 109/L. RESULTS: Our cohort included 74 (33.94%) patients with thrombocytopenia and 144 patients with a continuous normal platelet count. Comparison of baseline characteristics indicated that patients with thrombocytopenia had more visceral venous thromboses [10 (13.51%) vs 5(3.47%); P = 0.009] and extracriteria manifestations [mainly haemolytic anaemia; 20 (27.03%) vs 17 (11.81%); P = 0.007]. Hypocomplementemia was more likely among patients with thrombocytopenia [19 (25.68%) vs 16 (11.11%); P = 0.01]. The presence of aCL-IgG/IgM, anti-ß2-glycoprotein I and lupus anticoagulant were more frequently detected in patients with thrombocytopenia. In survival analysis, thrombotic, obstetric and severe extracriteria survival rates were significantly worse in patients with thrombocytopenia. In multivariate Cox regression, thrombocytopenia was an independent risk factor for all endpoint events, including thrombotic events [hazard ratio (HR) 2.93 (95% CI 1.31, 6.56), P = 0.009], pregnancy morbidity [HR 8.00 (95% CI 2.43, 26.37), P = 0.0006] and severe extracriteria events [HR 15.27 (95% CI 1.85, 125.98), P = 0.01]. CONCLUSION: Thrombocytopenia could identify primary APS patients at high risk of developing thrombotic events, pregnancy morbidity and severe extracriteria events.

Alternations in neural oscillation related to attention network reveal influence of indoor toluene on cognition at low concentration.

Despite accumulative literature reporting negative impacts of high-concentration toluene, cognitive effects of toluene at low concentration are still unclear. Twenty-two healthy college students were exposed in a closed environmental chamber to investigate the influence of indoor toluene on cognitive performance and brain activity. During each toluene exposure condition (0 ppb, 17.5 ppb, 35 ppb, and 70 ppb), attention network test and electroencephalogram (EEG) recording were synchronously performed after 4-hour toluene exposure. Characteristic neural oscillation patterns in three attention networks were compared between four groups. The statistical analyses indicated that short-term exposure to toluene had no significant impact on behavioral performance of attention network. However, there was a significant increase in the power of theta and alpha band of executive network and orienting network in the whole brain, especially in frontal region when exposed to toluene. Besides, no significant difference was observed in alerting network. The alternations in neural oscillation demonstrated that more effort was required to accomplish the same tasks when exposed to toluene. The present study revealed that short-term exposure to toluene affected brain activity of attention network even at low concentration, which provided a theoretical basis for the development of safer evaluation methods and standards in the future.

Gamma-aminobutyric acid (GABA) changes in the hippocampus and anterior cingulate cortex in patients with temporal lobe epilepsy.

PURPOSE: To explore the changes of gamma-aminobutyric acid (GABA) levels in the bilateral hippocampus and anterior cingulate cortex (ACC) of healthy control subjects and patients with temporal lobe epilepsy (TLE) and the correlation of GABA levels with the clinical symptoms by quantitative magnetic resonance spectroscopy (MRS). METHODS: N-acetylaspartate (NAA), creatine (Cr) as well as choline (Cho) and GABA levels in the bilateral hippocampus and ACC were measured in 40 patients with TLE and 26 healthy control (NC) subjects with quantitative Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS). The NAA/(Cho + Cr) and GABA/Cr ratios were compared between the NC and TLE groups. Comparisons were also made between the subgroups with lateralization (left TLE, right TLE and uncertain), short (<10 years) and longer (≥10 years) clinical seizure history (CSH), low (<1/month) and higher (≥1/month) seizure frequency (SF), with and without cognitive impairment (CI) in the patients with TLE, and by antiepileptic medications. Further analyses of the clinical information and metabolite ratios between the patients with TLE with and without CI were preformed. RESULTS: The GABA/Cr ratio was significantly decreased in the bilateral hippocampus (left: P = 0.028, right: P = 0.035), while the NAA/(Cho + Cr) ratio was decreased only in the right hippocampus (RH) (P = 0.004) in patients with TLE compared with that of the NCs. Whereas the NAA/(Cho + Cr) ratio showed a consistent decreasing trend in bilateral hippocampus during the CSH, it only showed a significant difference in the RH. The GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased in the short seizure history (<10 years) patients with TLE compared with NCs (left: P = 0.018, right: P = 0.012), whereas the long seizure history (≥10 years) patients with TLE showed no difference with the NCs. However, in the ACC, the GABA/Cr ratio of the CI group was significantly decreased compared with that of NCs (P = 0.015). Further analysis showed that the patients with TLE with CI had obvious atrophy of the gray matter volume (GMV) and total parenchymal brain volume (PBV); GABA/Cr ratio was decreased in ACC, but increased in bilateral hippocampus compared with that of the no cognitive impairment (NOCI) group. CONCLUSION: The GABA/Cr ratio was more valuable than the NAA/(Cho + Cr) ratio in evaluating the dynamic metabolite changes in patients with TLE. Importantly, the GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased at the early stage, but recovered to normal levels later. The decreased GABA/Cr ratio in the ACC might indicate more cerebral cortex was involved, resulting in more CI in patients with TLE.

Alterations in neural oscillations related to working memory deficit in temporal lobe epilepsy.

OBJECTIVE: Working memory (WM) is critical for higher level cognition, but the underlying neural mechanisms are not fully understood. Impaired WM affects routine daily activities and is observed in patients with temporal lobe epilepsy (TLE). This study investigated neural oscillations associated with different WM phases, to determine the specific neural activity linked with the phases of WM impairment. METHODS: Patients with TLE (n = 52) and healthy volunteers (n = 35) completed a WM task, during which 34-channel electroencephalogram signals were recorded. Characteristic neural oscillation patterns during each WM phase were compared between the 2 groups. RESULTS: Patients with TLE showed decreased theta power during the encoding phase of WM, which was associated with reduced accuracy in the WM task. Altered theta power in the frontal region of the brain during the encoding phase was associated with a longer reaction time. CONCLUSIONS: Alterations in theta oscillation are related to WM impairment in patients with TLE and may serve as an early marker for evaluating WM deficits. SIGNIFICANCE: This study provides an early marker for evaluating WM deficits in TLE.

The Downregulation of Truncated TrkB Receptors Modulated by MicroRNA-185 Activates Full-Length TrkB Signaling and Suppresses the Epileptiform Discharges in Cultured Hippocampal Neurons.

Epilepsy is a common neurological disorder characterised by occurrence of spontaneous recurrent epileptiform discharges (SREDs) in neurons. The cellular mechanisms that underlie epilepsy are known to be regulated by brain-derived neurotrophic factor. However, some studies show that tropomyosin-related kinase B (TrkB), which is the receptor for BDNF, plays an important role in the pathophysiology of epilepsy. Our previous research revealed that truncated TrkB receptors are upregulated in a rat hippocampal neuronal model of SREDs. In contrast, full-length TrkB receptors are downregulated. Furthermore, the activation of full-length TrkB signaling is suppressed by the overexpression of truncated TrkB. In this study, to regulate the expression of truncated TrkB receptor and full-length TrkB signaling, rno-miR-185-3p was transduced into the SREDs model. Then, the changes in the activity of L-type voltage-gated calcium channels (VGCCs) and in epileptiform discharges were investigated. Transduction of rno-miR-185-3p downregulated the expression of truncated TrkB and dramatically activated full-length TrkB signaling in the model. Next, we found that the activation of full-length TrkB signaling decreased the maximal Ca2+ current density in the model, delayed the steady-state activation and accelerated the inactivation of L-type VGCCs. Finally, the epileptiform discharges in the model could be impaired. Based on the above results, we suggest that the activation of full-length TrkB signaling may suppress the properties of L-type VGCCs, and thus ameliorate the epileptiform discharges in the model. The activation of full-length TrkB signaling may affect the inhibition of epilepsy. This provides a rationale for the activation of full-length TrkB signaling in preventive therapies.

Functional brain network mechanism of executive control dysfunction in temporal lobe epilepsy.

BACKGROUND: Executive control dysfunction is observed in a sizable number of patients with temporal lobe epilepsy (TLE). Neural oscillations in the theta band are increasingly recognized as having a crucial role in executive control network. The purpose of this study was to investigate the alterations in the theta band in executive control network and explore the functional brain network mechanisms of executive control dysfunction in TLE patients. METHODS: A total of 20 TLE patients and 20 matched healthy controls (HCs) were recruited in the present study. All participants were trained to perform the executive control task by attention network test while the scalp electroencephalogram (EEG) data were recorded. The resting state signals were collected from the EEG in the subjects with quiet and closed eyes conditions. Functional connectivity among EEGs in the executive control network and resting state network were respectively calculated. RESULTS: We found the significant executive control impairment in the TLE group. Compared to the HCs, the TLE group showed significantly weaker functional connectivity among EEGs in the executive control network. Moreover, in the TLE group, we found that the functional connectivity was significantly positively correlated with accuracy and negatively correlated with EC_effect. In addition, the functional connectivity of the executive control network was significantly higher than that of the resting state network in the HCs. In the TLE group, however, there was no significant change in functional connectivity strengths between the executive control network and resting state network. CONCLUSION: Our results indicate that the decreased functional connectivity in theta band may provide a potential mechanism for executive control deficits in TLE patients.

Isobaric tag for relative and absolute quantitation based quantitative proteomics reveals unique urinary protein profiles in patients with preeclampsia.

Preeclampsia (PE) is one of the most significant pregnancy-related hypertensive disorders. Currently, there are no useful markers to predict the onset of the condition in pregnant women. To provide further insights into the pathogenesis of PE and identify biomarkers of the condition, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomics coupled with 2-D LC-MS/MS, to analyze urinary protein profiles from 7 PE patients and 7 normotensive pregnant women. A total of 294 proteins were abnormally expressed in PE patients. Of these, 233 were significantly down-regulated and 61 proteins were significantly up-regulated. Bioinformatics analysis using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, found that the most differentially expressed proteins (DEPs) were involved in coagulation and complement pathways, the renin-angiotensin system and cell adhesion molecules (CAMs) pathways. We further validated three of the DEPs, including serotransferrin (TF) and complement factor B (CFB) by immunoblottingand serum paraoxonase/arylesterase 1 (PON1) by ELISA using 14 pairs of urine samples from PE patients and normal pregnant women. Taken together, our results provide the basis for further understanding the pathogenesis of PE and identifying predictive biomarkers.

High levels of circulating cell-free DNA are a biomarker of active SLE.

BACKGROUND: High levels of circulating cell-free DNA (cfDNA) have been reported in patients with inflammatory conditions. The aim of the study was to investigate the levels of cfDNA in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Comparative groups comprised 22 nonpregnant and 36 pregnant women with SLE (test groups) and 60 nonpregnant and 199 pregnant women with no history of SLE (control groups). The levels of cfDNA in plasma were quantitated by a fluorometric dsDNA assay. RESULTS: Compared to controls, the median levels of cfDNA were significantly higher in nonpregnant SLE patients (7.38 ng/mL vs 4.6 ng/mL, P = 0.033) and in pregnant SLE patients (7.65 ng/mL vs 5.25 ng/mL, P = 0.003). Based on SLE disease activity index (SLEDAI) scores, the median cfDNA levels were significantly higher in patients with active disease (4 < SLEDAI < 15) compared with patients with inactive disease (SLEDAI < 4) (13.58 ng/mL vs 6.72 ng/mL, P = 0.01). While there was a trend of increased cfDNA levels with higher SLEDAI scores (R2  = 0.3, P < 0.001), we found no association of increased cfDNA levels with nephritis, skin manifestations, multiorgan inflammations or with other inflammatory markers such as decreased C3 and C4 levels or increased anti-ds DNA antibodies. CONCLUSIONS: Our results suggest that in addition to classical SLE serological markers, measurement of circulating plasma cfDNA levels has potential as a useful biomarker for assessing SLE disease activity in patients and monitoring treatment.

An investigation of the characteristics of outpatients with epilepsy and antiepileptic drug utilization in a multicenter cross-sectional study in China.

OBJECTIVES: This study aimed to describe the distribution of seizure types, clinical characteristics, and antiepileptic drug (AED) utilization in patients with epilepsy visiting tertiary hospitals in China. METHODS: This was an observational, cross-sectional epidemiology study conducted at 11 tertiary hospitals across China from May 2014 to November 2014. A total of 1603 patients, of either sex or any age with confirmed diagnosis of epilepsy, visiting outpatient clinics at tertiary hospitals were screened and enrolled. Demographics, seizure types, frequency, etiologies, comorbidities, and current AED therapy were analyzed using descriptive statistics. RESULTS: Overall, the majority (n=1201; 74.9%) of patients were adults (16-59years of age), and the mean (SD) age was 27.5 (15.9) years. A total of 989 (61.7%) patients had partial seizures, and 653 (40.7%) had generalized seizures. The majority experienced monthly (n=663) or yearly (n=625) seizures, with 2.7seizures/month or 2.9seizures/year, respectively. The most commonly reported symptomatic etiologies were traumatic brain injury, encephalitis, and stroke, whereas the most common comorbidities were sleep disorder, headache, anxiety, and depression. Overall, monotherapy was used in 54.1% of patients, while 30.6% of patients used dual therapy. The most commonly prescribed monotherapy for patients with partial seizures was oxcarbazepine (25.9%), while that for patients with generalized seizures was valproic acid (38.9%), and the most common AED combination was valproic acid and lamotrigine. Overall, valproic acid was the most commonly prescribed AED as monotherapy and combination therapy. CONCLUSION: Findings from this study provide extensive information on clinical characteristics and utilization of AEDs in Chinese patients with epilepsy which may help physicians make well-informed clinical decisions.

Contribution of maternal copy number variations to false-positive fetal trisomies detected by noninvasive prenatal testing.

OBJECTIVE: The aim of the study was to determine the contribution and significance of maternal copy number variations (CNVs) to false-positive noninvasive prenatal testing (NIPT) trisomy results. METHODS: A total of 112 021 patients were referred for NIPT. Fetal aneuploidy testing was performed using low coverage massively parallel sequencing, and results reported as chromosome Z-scores. Copy number variation sequencing (CNV-Seq) was used to detect maternal DNA CNVs. RESULTS: Confirmatory amniocentesis and karyotyping of 563 of 781 patients (72%) receiving a positive trisomy result revealed 489 true and 74 false positives. In 6 of these 74 patients (8.1%), CNV-Seq revealed non-pathogenic maternal duplications (1.76-10.90 megabases) on the chromosome associated with the fetal trisomy. There was a strong correlation of higher Z-scores with increasing size of the maternal CNVs (R2 = 0.94). When the contribution of the maternal CNV-Seq reads to chromosome Z-scores were removed, all original Z-scores shifted to the normal range. CONCLUSIONS: Maternal CNVs can potentially contribute to a small but significant number of false-positive fetal trisomies detected by NIPT. To avoid unnecessary invasive procedures and better manage patients, we recommend that confirmatory maternal DNA sequencing is performed when the NIPT methodology used indicates a high risk of a maternal CNV. © 2017 John Wiley & Sons, Ltd.

The suppression of epileptiform discharges in cultured hippocampal neurons is regulated via alterations in full-length tropomyosin-related kinase type B receptors signalling activity.

Epilepsy is a common neurological disease. Understanding the mechanisms of epileptogenesis at the cellular and molecular levels may provide novel targets for preventing this disorder. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase type B (TrkB) are believed to be critical for epileptogenesis. Previous studies have revealed possible changes in the expression of full-length TrkB receptors (TrkB.FL) and truncated TrkB receptors (TrkB.T) in neurodegenerative disorders. In this study, we investigated alterations in TrkB receptor expression and TrkB signalling activity in a rat hippocampal neuronal model of spontaneous recurrent epileptiform discharges (SREDs) and the effects on the epileptiform discharges. To induce epileptiform discharges, we established a model with Mg(2+) -free treatment. We found a dramatic upregulation of TrkB.T and a decrease in TrkB.FL in the SREDs model. Calpain contributed to the downregulation of TrkB.FL. The upregulation of TrkB.T required transcription and translation activity. Furthermore, BDNF induced the activation of TrkB.FL signalling. However, TrkB.FL signalling was inhibited in the SREDs model. Although calpain inhibitors prevented a decrease in TrkB.FL, they did not restrain the downregulation of TrkB.FL signalling activity in the model. However, a SREDs model with a translation inhibitor prevented the increase in TrkB.T and re-activated TrkB.FL signalling activity. Finally, we used electrophysiology to observe that a downregulation of TrkB.T could relieve the representative epileptiform discharges in the model. These results, taken together, demonstrate that alterations in TrkB.FL signalling may be regulated via TrkB.T receptors. Upregulation of TrkB.FL signalling suppresses epileptiform discharges in the SREDs model.

Transcutaneous auricular vagus nerve stimulation improves working memory in temporal lobe epilepsy: A randomized double-blind study.

AIMS: This study investigated the impact of transcutaneous auricular vagus nerve stimulation (taVNS) on working memory (WM) in refractory temporal lobe epilepsy (rTLE) and the underlying mechanisms. METHODS: In this randomized double-blind study, 28 rTLE patients were subjected to an active or sham taVNS (a/s-taVNS) protocol for 20 weeks (a-taVNS group, n = 19; s-ta VNS group, n = 9). Patients performed visual WM tasks during stimulation and neural oscillations were simultaneously recorded by 19-channel electroencephalography. RESULTS: Compared with the baseline state, reaction time was significantly shorter after 20 weeks of taVNS in the a-taVNS group (p = 0.010), whereas no difference was observed in the s-taVNS group (p > 0.05). The power spectral density (PSD) of the theta frequency band in the Fz channel decreased significantly after a-taVNS during WM-encoding (p = 0.020), maintenance (p = 0.038), and retrieval (p = 0.039) phases, but not in the s-taVNS group (all p > 0.05). CONCLUSION: Neural oscillations during WM were altered by taVNS and WM performance was improved. Alterations in frontal midline theta oscillations may be a marker for the effect of taVNS on cognitive regulation.

The Impact of Different Smoking Behavior on Pulmonary Function and Pulmonary Hypertension Among Chinese Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD. Patients and Methods: Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH. Results: The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP. Conclusion: The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.

Performance validation of the 2023 American College of Rheumatology/European League Against Rheumatism antiphospholipid syndrome classification criteria in an antiphospholipid syndrome cohort.

BACKGROUND: The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. OBJECTIVES: To validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. METHODS: This was a single-center cohort study. Inclusion criteria aligned with the entry criteria of 2023 criteria. APS classification by "expert consensus panel" served as the gold standard. Sensitivity and specificity were compared between the 2023 and 2006 criteria. RESULTS: A total of 526 patients with a mean age of 38.55 ± 12.67 years were enrolled, of whom 366 (69.58%) were female and 182 (34.60%) had systemic lupus erythematosus (SLE). Among them, 407 (77.38%) patients were classified as APS by experts. The 2023 criteria demonstrated higher overall specificity than the 2006 criteria (0.983 vs 0.950), while sensitivity was relatively lower (0.818 vs 0.853). The sensitivity of the 2023 criteria improved for patients with SLE (0.860 vs 0.825), microvascular manifestations (0.867 vs 0.786), cardiac valve disease (0.903 vs 0.774), and thrombocytopenia (0.811 vs 0.790). Reduced sensitivity of the 2023 criteria was linked to the omission of certain microvascular manifestations, a stricter definition of pregnancy morbidity, and the exclusion of isolated thrombocytopenia and isolated IgM isotype antiphospholipid antibodies from meeting clinical and laboratory criteria, respectively. CONCLUSION: The 2023 criteria offer higher overall specificity and improved sensitivity in specific patient subsets, such as those with SLE, microvascular manifestations, cardiac valve disease, and thrombocytopenia when compared with the 2006 criteria.