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Background : Cardiogenic shock (CS) is the leading cause of the death in patients with ST elevation myocardial infarction (STEMI). Thyroid dysfunction is related to prognosis of patients with myocardial infarction. Hence, the aim of this study is to explore the relationship between thyroid hormones (free triiodothyronine [FT3] and free thyroxine [FT4]) and CS. Method : A total of 1270 patients with STEMI treated with percutaneous coronary intervention (PCI) were consecutively enrolled in our study. Patients were classified into two groups according to with or without CS during hospitalization. Stepwise multivariate logistic analysis was conducted to investigate the association of thyroid hormones and CS. Restricted cubic spline method was employed to further explore relationship between CS and thyroid hormones. Results : Patients who developed CS (n=103) had lower FT3 and higher FT4 on admission. The stepwise logistic analysis showed both FT3 (P=0.038) and FT4 (P=0.024) were independently related to CS. Restricted cubic splines indicated that lower FT3 ( 1.25 ng/dl) was correlated with higher prevalence of CS. Over 2.5 years’ follow-up, patients (n=294) with low FT3 ( =0.88 ng/dl) had the highest all-cause mortality (18.2%), whereas patients (n=293) with high FT3 and low FT4 had the lowest all-cause mortality (3.8%) (P for trend Conclusions : Both FT3 and FT4 are independently associated with in-hospital CS development in patients with STEMI treated with PCI. Patients with lower range of FT3 and upper range of FT4 had the worst outcomes in a long-term follow-up.

Objective: To investigate the influence of liver function damage in patients with hepatocellular carcinoma (HCC) after microwave ablation (MWA) on the prognosis and to establish an algorithm to predict liver function damage.Methods: This is a retrospective study. A total of 745 patients were enrolled and classified into the modeling group and the validation group. The risk factors of liver function damage were analyzed by using logistic regression model. The β coefficients derived from a logistic analysis were used to calculate the risk score. Diagnostic accuracy based on risk score was assessed by the area under the curve (AUC).Results: 69 patients in the modeling group suffered from liver function damage. The 1-,3-,5- and 7-year progression free survival were 69.4%, 37.2%, 22.6% and 12.4% for patients without liver function damage and 69.5%, 33.0%, 14.4% and 0% for patients with liver function damage, respectively (P = 0.537). The 1-, 3-, 5- and 7-year overall survival were 94.3%, 75.9%, 61.5% and 54.5% for patients without liver function damage and 81.3%, 57.1%, 42.7% and 42.7% for those with liver function damage (P = 0.004), respectively. The AUC of the risk score for predicting liver function damage was 0.798 for the modeling group and 0.832 for the validation group. The sensitivity and specificity of the risk score to identify liver function damage was 65.2%, 84.4% in the modeling group and 60.6%, 88.3% in the validation group, respectively.Conclusion: Liver function damage after MWA is unfavorable the long-term prognosis. The prediction algorithm based on five risk factors is robust and can be used to predict possible liver function damage.

Epilepsy is a neurological disease, and the location of a lesion before neurosurgery or invasive intracranial electroencephalography (iEEG) surgery using intracranial electrodes is often very challenging. The high-frequency oscillation (HFOs) mode in MEG signal can now be used to detect lesions. Due to the time-consuming and error-prone operation of HFOs detection, an automatic HFOs detector with high accuracy is very necessary in modern medicine. Therefore, an optimized capsule neural network was used, and a MEG (magnetoencephalograph) HFOs detector based on MEGNet was proposed to facilitate the clinical detection of HFOs. To the best of our knowledge, this is the first time that a neural network has been used to detect HFOs in MEG. After optimized configuration, the accuracy, precision, recall, and F1-score of the proposed detector reached 94%, 95%, 94%, and 94%, which were better than other classical machine learning models. In addition, we used the k-fold cross-validation scheme to test the performance consistency of the model. The distribution of various performance indicators shows that our model is robust.

BACKGROUND: As one of the main malignant tumors, breast cancer remains a worldwide public health issue. Here, we aimed to analyze the effects of breast-conserving surgery (BCS) combined with sentinel lymph node biopsy (SLNB) and axillary preservation on the recurrence, metastasis, complications, and cosmetic results of early breast cancer patients (BCPs). METHODS: The clinical data of 143 BCPs admitted to our hospital from January 2017 to January 2019 were collected retrospectively, and all patients were female. Patients (76 cases) undergoing BCS combined with SLNB and axillary preservation treatment were set as the combined group, and 67 cases undergoing traditional modified radical surgery were set as the control group. After the perioperative conditions of patients in the two groups were compared, the patients were followed up for 14 months to record information on the quality of life, recurrence, metastasis, complications, and cosmetic results. RESULTS: The operation time, intraoperative blood loss, and extubation time of the combined group were significantly less than the control group (P0.05); the incidence of postoperative complications was 14.92% in the control group, which was significantly higher than the incidence of 3.94% of the combined group (P

Objectives: This study aimed to systematically evaluate the effects of constraint-induced aphasia therapy (CIAT) for aphasic patients reported by randomized controlled trials. Methods: Relevant randomized controlled trials were retrieved from 11 electronic databases. A methodological quality assessment was conducted in accordance with the Cochrane Handbook, and meta-analyses were performed by using RevMan 5.2. A descriptive analysis was conducted when the included trials were not suitable for a meta-analysis. Results: A total of 12 trials were included. A statistically significant group difference was shown from the meta-analysis in the results measured by the Western Aphasia Battery (random-effects model, MD = 1.23, 95% CI = 0.31 to 2.14, P 0.05) and Aachen Aphasia Test (fixed-effects model, MD = −1.11, 95% CI = −4.49 to 2.27, P > 0.05). The descriptive analysis showed positive results in language performances of naming, repetition, and comprehension. Conclusion: This systematic review indicated that CIAT was efficient for improving language performance with regard to naming, comprehension, repetition, written language, and oral language based on the current evidence. And this review provides some meaningful guides for clinical practice: expand the therapy duration to 2 or 3 h per day, focus on naming, and choose the best assessment tool. It also indicates a need for more rigorous, large-scale, and high-quality trials in the future.

Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations (HFOs, > 80 Hz) and the epileptogenic zone, suggesting that HFOs can be a potential biomarker of epileptogenicity and epileptogenesis. This consensus includes the definition and standard detection techniques of HFOs, the localizing value of pathological HFOs for epileptic foci, and different ways to distinguish physiological from epileptic HFOs. The latest clinical applications of HFOs in epilepsy and the related findings are also discussed. HFOs will advance our understanding of the pathophysiology of epilepsy.

In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907-910, 2020.

Background Migraine is a common and disabling primary headache, which is associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study aimed to investigate the neural network during neutral, positive, and negative emotional stimuli in the migraine patients. Methods A total of 24 migraine patients and 24 age- and sex-matching healthy controls were enrolled in this study. Neuromagnetic brain activity was recorded using a whole-head magnetoencephalography (MEG) system upon exposure to human facial expression stimuli. MEG data were analyzed in multi-frequency ranges from 1 to 100 Hz. Results The migraine patients exhibited a significant enhancement in the effective connectivity from the prefrontal lobe to the temporal cortex during the negative emotional stimuli in the gamma frequency (30–90 Hz). Graph theory analysis revealed that the migraine patients had an increased degree and clustering coefficient of connectivity in the delta frequency range (1–4 Hz) upon exposure to positive emotional stimuli and an increased degree of connectivity in the delta frequency range (1–4 Hz) upon exposure to negative emotional stimuli. Clinical correlation analysis showed that the history, attack frequency, duration, and neuropsychological scales of the migraine patients had a negative correlation with the network parameters in certain frequency ranges. Conclusions The results suggested that the individuals with migraine showed deviant effective connectivity in viewing the human facial expressions in multi-frequencies. The prefrontal-temporal pathway might be related to the altered negative emotional modulation in migraine. These findings suggested that migraine might be characterized by more universal altered cerebral processing of negative stimuli. Since the significant result in this study was frequency-specific, more independent replicative studies are needed to confirm these results, and to elucidate the neurocircuitry underlying the association between migraine and emotional conditions.

Multiple myeloma is a heterogeneous plasma cell malignancy that remains incurable because of the tendency of relapse for most patients. Survival outcomes may vary widely due to patient and disease variables; therefore, it is necessary to establish a more accurate prognostic model to improve prognostic precision and guide clinical therapy. Here, we developed a risk score model based on myeloma gene expression profiles from three independent datasets: GSE6477, GSE13591, and GSE24080. In this model, highly survival-associated five genes, including EPAS1, ERC2, PRC1, CSGALNACT1, and CCND1, are selected by using the least absolute shrinkage and selection operator (Lasso) regression and univariate and multivariate Cox regression analyses. At last, we analyzed three validation datasets (including GSE2658, GSE136337, and MMRF datasets) to examine the prognostic efficacy of this model by dividing patients into high-risk and low-risk groups based on the median risk score. The results indicated that the survival of patients in low-risk group was greatly prolonged compared with their counterparts in the high-risk group. Therefore, the five-gene risk score model could increase the accuracy of risk stratification and provide effective prediction for the prognosis of patients and instruction for individualized clinical treatment.

Immune checkpoint inhibitors (ICIs) have made breakthrough progress in the treatment of various malignant tumors. However, only some patients receiving ICIs obtain long-lasting clinical effects, and some patients still do not achieve remission. Improving the treatment benefits of this part of the population has become a concern of clinicians. IL-1 signaling plays an important role in the tumor microenvironment (TME). However, the relationship between the IL-1 signaling mutation status and the prognosis of colon adenocarcinoma (COAD) patients receiving ICIs has not been reported. We downloaded the data of a COAD cohort receiving ICIs, including prognostic data and mutation data. Additionally, we downloaded the data of a COAD cohort from The Cancer Genome Atlas (TCGA) database, including clinical data, expression data and mutation data. Gene set enrichment analysis (GSEA) was used to assess differences in the activity of some key physiological pathways between the IL-1 signaling mutated-type (IL-1-MT) and IL-1 signaling wild-type (IL-1-WT) groups. The CIBERSORT algorithm was used to evaluate the contents of immune cells in the TME of COAD patients. The multivariate Cox regression model results suggested that IL-1-MT can be used as an independent predictor of a better prognosis in COAD patients receiving ICIs (P = 0.03, HR = 0.269, 95% CI: 0.082-0.883). Additionally, IL-1-MT COAD patients had significantly longer overall survival (OS) (log-rank P = 0.015). CIBERSORT analysis showed that the IL-1-MT group had high infiltration levels of activated dendritic cells (DCs), M1 macrophages, neutrophils, activated natural killer (NK) cells, activated CD4+ memory T cells and CD8+ T cells. Similarly, the IL-1-MT group had significantly upregulated immunogenicity, including in terms of the tumor mutation burden (TMB), neoantigen load (NAL) and number of mutations in DNA damage repair (DDR) signaling. GSEA showed that the IL-1-MT group was highly enriched in the immune response and proinflammatory mediators. Additionally, the expression levels of immune-related genes, immune checkpoint molecules and immune-related signatures were significantly higher in the IL-1-MT group than in the IL-1-WT group. IL-1-MT may be an independent predictor of a good prognosis in COAD patients receiving ICIs, with significantly longer OS in IL-1-MT COAD patients. Additionally, IL-1-MT was associated with significantly increased immunogenicity, activated immune cell and inflammatory mediator levels and immune response-related scores.

Background: The coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) has been identified as the main predictor of prognosis. However, the association of lipoprotein(a) [Lp(a)], a well-established proatherogenic factor, with atherosclerotic burden in patients with STEMI is unclear.Methods: In total, 1,359 patients who underwent percutaneous coronary intervention (PCI) for STEMI were included in analyses. Three prespecified models with adjustment for demographic parameters and risk factors were evaluated. Generalized additive models and restricted cubic spline analyses were used to assess the relationships of Lp(a) with Gensini scores and the no-reflow phenomenon. Kaplan–Meier curves were generated to explore the predictive value of Lp(a) for long-term all-cause mortality. Furthermore, mRNA expression levels of LPA in different groups were compared using the GEO database.Results: Patients in the highest tertile according to Lp(a) levels had an increased incidence of heart failure during hospitalization. Furthermore, patients with high levels of Lp(a) (>19.1 mg/dL) had sharply increased risks for a higher Gensini score (Pfor trend = 0.03) and no-reflow (Pfor trend = 0.002) after adjustment for demographic parameters and risk factors. During a median follow-up of 930 days, 132 deaths (9.95%) were registered. Patients with high levels of Lp(a) (>19.1 mg/dL) had the worst long-term prognosis (Pfor trend < 0.0001). In a subgroup analysis, patients with higher Lp(a) still had the highest all-cause mortality. Additionally, the mRNA expression levels of LPA in patients with STEMI with lower cardiac function were higher than those in other groups (P = 0.003). A higher coronary atherosclerotic burden was correlated with higher LPA expression (P = 0.01).Conclusion: This study provides the first evidence that Lp(a) (at both the protein and mRNA levels) is independently associated with coronary atherosclerotic lesions and prognosis in patients with STEMI treated with PCI.Clinical Trial Registration:http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900028516.

BACKGROUND: To explore the diagnostic value of epidermal growth factor receptor (EGFR) and structural maintenance of chromosome protein 4 (SMC4) for triple-negative breast cancer. METHODS: A total of 213 breast cancer patients were selected and divided into triple-negative breast cancer (100 cases) and non-triple-negative breast cancer (113 cases) according to the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Patient information including age, body mass index (BMI), smoking history, drinking history, menopause, tumor classification, lymph node metastasis, distant metastasis, clinical stage, and EGFR and SMC4 expression were collected for all subjects. Logistic regression analysis was then used to evaluate the risk factors for triple-negative breast cancer. The ROC curve was also used to evaluate the clinical value of EGFR and SMC4 in the diagnosis of triple-negative breast cancer. RESULTS: Logistic regression analysis showed that high expression of SMC4 and high expression of EGFR were both risk factors for triple-negative breast cancer, with an odds ratio (OR) of 1.72 and 1.56, respectively (both P

Background: Spectral-Domain Optical coherence tomography (SD-OCT) provides non-invasive, high speed, high resolution, three-dimensional cross-section imaging of macula. This study was aimed to investigate the diagnostic value of multimodal imaging technique of three-dimension (3D) optical coherence tomography (OCT) (3D-OCT) for diagnosis and characterizing of acute central serous chorioretinopathy (CSC). Methods: The 3D-OCT examinations of 82 cases of acute CSC were performed on the macular area, and the image characteristics were analyzed. Our study included a total of 87 eyes from 82 cases of CSC patients, 67 males and 15 females, aged 27 to 56 years, mean age 42.89±7.80 years old.Results: According to B-scan images, 87 (100%) eyes had ERD, 38 (44%) eyes had bulge of RPE, 36 (41%) eyes had PED, 8 (9%) eyes had membrane -like structure, 2 (2%) eyes had subretinal dot-like precipitates, 1 (1%) eyes had focal choroidal excavation (FCE), and 1 (1%) eye had fluctuation of internal limiting membrane (FI). In ILM-RPE thickness map, all eyes had a round or round like regular uniform domes. Total of 57 (66%) domes were limited in exam area and 30 (44%) domes beyond the scope of this examination and only part of the dome could be observed. In the Shadowgram image, all eyes had a round or round like black figure that correspond with domes In ILM-RPE thickness map. In RPE surface, 76(87%) eyes had a shallow plate depression, 71(82%) had small focal uplift and 1 (1%) eye had a focal concave.Conclusions: In OCT ILM-RPE thickness map, Shadowgram, and RPE surface, acute CSC had special images and can be helpful for diagnosis and difference diagnosis.Trial registration: Not applicable.

Summary Objective To preliminarily explore death risk factors in primary melanoma patients. Method Competing risk model analysis was used using a large sample public cohort and Cox proportional hazard model was compared. Result In the competing risk model analysis, age, gender, ethnicity, stage, site, TMN stage and metastases were the independent risk factors of single primary melanoma (SPM) death. T stage had a particularly important impact on SPM death. T2 stage had a 3.212 times greater risk of interest event than T1 stage [hazard ratio (HR) = 3.212, 95%CI: 2.994–3.446], T3 stage was 5.747 times greater than that T1 stage (HR = 5.747, 95%CI: 5.337–6.187) and T4 stage had a 7.086 times than T1 stage (HR = 7.086, 95%CI: 6.514–7.708). Gender, ethnicity, stage, site, T stage and brain and liver metastases were the independent risk factors of multiple primary melanoma (MPM) death. When some groups had a very high death rate or the reference group had a very low death rate in competing events, the results of Cox proportional hazard model may not be as accurate as the results obtained by fine-Gray regression model. Conclusion Early diagnosis and therapy, and prevention of tumor progression and metastases of primary melanoma patients are important measures to improve its prognosis and survival.

Background Extreme delta brush (EDB) is considered a potential marker for anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. The brain regions involved in EDB are unclear. Case presentation A 16-year-old woman with anti-NMDAR encephalitis who was experiencing psychosis was admitted. Electroencephalography (EEG) and magnetoencephalography (MEG) were used to analyze EDB in the patient. EDB on EEG could be disturbed by opening and closing the eyes, by occipital alpha rhythms and by sleep-wake cycles. The MEG results showed beta activity originating from bilateral superior parietal lobes. However, the delta wave originated from bilateral superior temporal gyri, the right middle temporal gyrus, the right inferior frontal gyrus, and the left inferior parietal lobe. Conclusions Delta wave and beta activity might originate from different brain regions. Beta activity might be transmitted forward to the frontotemporal lobe and superimposed with delta activity to form EDB on EEG.

The aim of this article is to introduce the recent advance on the studies of fungal keratitis published over past 5 years. We performed literature review of articles published on PubMed, Google Scholar, CNKI and Web of Science relevant to the diagnosis, pathogenesis and novel treatment of fungal keratitis. Excessive inflammation can lead to stromal damage and corneal opacification, hence the research on immune mechanism provides many potential therapeutic targets for fungal keratitis. Many researchers discussed the importance of earlier definitive diagnosis and were trying to find rapid and accurate diagnostic methods of pathogens. Develop new drug delivery systems and new routes of administration with better corneal penetration, prolonged ocular residence time, and better mucoadhesive properties is also one of the research hotspots. Additionally, many novel therapeutic agents and methods have been gradually applied in clinical ophthalmology. The diagnosis and treatment of fungal keratitis are still a challenge for ophthalmologist, and many researches provide new methods to conquer these problems.

Introduction This study was aimed to explore the relationship between neural network changes in newly diagnosed children with Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) and cognitive impairment. Methods Children's cognition was evaluated using the Wechsler Intelligence Scale for Children‐Fourth Edition (WISC‐IV). Magnetoencephalographic (MEG) data of 18 healthy children and 22 BECTS patients were recorded in order to construct a functional connectivity (FC) network, which was quantified by graph theory (GT). Results The mean age of the control group was 7.94 ± 1.89 years, and the mean age of BECTS patients was 8.14 ± 1.73 years. Our results show that the WISC‐IV index scores in the BECTS group were significantly lower than those in the control group. Besides, the FC network pattern of BECTS patients changed significantly in the 12–30, 30–80, and 250–500 Hz frequency band. The local functional connections between posterior cingulate cortex (PCC) and frontal lobe varied significantly in 12–30, 80–250, and 250–500 Hz. Our GT analysis shows that the connection strength of BECTS patients increases significantly in the 12–30 Hz frequency band, the path length decreases significantly in the 12–30 Hz and 30–80 Hz frequency bands, with the clustering coefficient decreasing significantly in the 12–30 Hz, 30–80 Hz, and 250–500 Hz frequency bands. Correlation analysis showed that the full‐scale IQ (FSIQ) was positively correlated with the 12–30 Hz clustering coefficient, verbal comprehension index (VCI) was positively correlated with the 250–500 Hz clustering coefficient, perceptual reasoning index (PRI) was positively correlated with the 12–30 Hz clustering coefficient, and perceptual reasoning index (PSI) was negatively correlated with the 12–30 Hz path length. Conclusion There is a trend of cognitive impairment in patients with early BECTS. This trend of cognitive impairment in early BECTS children may be related to the changes in the FC network pattern., BECTS patients have a certain degree of cognitive dysfunction in the early stage of the disease. The functional connections of patients with early BECTS showed unbalanced brain topology, and the brain network pattern was tending to be randomized. This trend of cognitive decline in early BECTS children may be related to the change of FC network patterns.

The giant cell tumor of tendon sheath (GCTTS) is a benign lesion most commonly attached to the tendons and bones of the fingers, hands, and wrists. The involvement of GCTTS to the foot is uncommon. The GCTTS invading tarsal bones and intertarsal joints is not described yet, and the appropriate diagnosis and treatment remain unclear. We report a case of GCTTS with the involvement of tarsal bones and intertarsal joint. Computed tomography scan and magnetic resonance imaging were used to further diagnose and evaluate the quality and range of tumor. The patient was treated with surgical excision of the tumor without application of bone graft. After adequate clearance of the tumor, the patient returned to an asymptomatic walk in 3 months. No malfunction, fracture, or tumor recurrence was found in 2-years follow-up. This report includes clinical, radiologic, histologic diagnostic, and surgical challenges in an unexpected lesion and a review of the literature.

The branched-chain amino acids (BCAA) play an important role in muscle energy metabolism, and Kruppel-like factor 15 (KLF15) is an essential regulator of BCAA metabolism in muscle under nutritional deficiency. In this study, we analyzed the effect of normal feeding (starvation for 0 day), starvation for 3, 7, 10, 15 days, and refeeding for 7 days after 15 days of starvation on the expression of KLF15 and BCAA metabolism in muscle of Chinese soft-shelled turtles by a fasting-refeeding trial. The results showed that the level of KLF15 transcription was increased first and then decreased in muscle during short-term starvation, and the protein level was gradually increased. Both the mRNA and protein level of the KLF15 returned to normal feeding level after refeeding for 7 days. The changing trend of the activities of branched-chain aminotransferase (BCAT) and alanine aminotransferase (ALT) was consistent to that of KLF15 mRNA, but at the transcription level, the expression of BCAT mRNA was consistent with the change of enzyme activity as well as ALT continued to increase in muscle under starvation. In addition, BCAA content showed a trend that decreased first and then increased under starvation, while the alanine (Ala) was the contrary. The above results indicated that the regulatory role of KLF15 in BCAA catabolism of muscle in Chinese soft-shelled turtles under nutritional deficiency, which might be activated the catabolism of BCAA in muscle to provide energy and maintain the homeostasis by KLF15-BACC signaling axis.

Intracranial studies provide solid evidence that high-frequency brain signals are a new biomarker for epilepsy. Unfortunately, epileptic (pathological) high-frequency signals can be intermingled with physiological high-frequency signals making these signals difficult to differentiate. Recent success in non-invasive detection of high-frequency brain signals opens a new avenue for distinguishing pathological from physiological high-frequency signals. The objective of the present study is to characterize pathological and physiological high-frequency signals at source levels by using kurtosis and skewness analyses. Twenty-three children with medically intractable epilepsy and age-/gender-matched healthy controls were studied using magnetoencephalography. Magnetoencephalographic data in three frequency bands, which included 2–80 Hz (the conventional low-frequency signals), 80–250 Hz (ripples) and 250–600 Hz (fast ripples), were analysed. The kurtosis and skewness of virtual electrode signals in eight brain regions, which included left/right frontal, temporal, parietal and occipital cortices, were calculated and analysed. Differences between epilepsy and controls were quantitatively compared for each cerebral lobe in each frequency band in terms of kurtosis and skewness measurements. Virtual electrode signals from clinical epileptogenic zones and brain areas outside of the epileptogenic zones were also compared with kurtosis and skewness analyses. Compared to controls, patients with epilepsy showed significant elevation in kurtosis and skewness of virtual electrode signals. The spatial and frequency patterns of the kurtosis and skewness of virtual electrode signals among the eight cerebral lobes in three frequency bands were also significantly different from that of the controls (2–80 Hz, P, This study demonstrated a new way to identify and classify high-frequency brain signals in epilepsy by measuring the kurtosis and skewness of virtual electrode waveforms computed with magnetoencephalography. The results revealed that epileptic high-frequency brain signals were characterized with elevation of kurtosis and highly localized to epileptogenic zones., Graphical Abstract Graphical Abstract

Cochlear implants (CI) are widely used in children and adults to restore hearing function. However, CI outcomes are vary widely. The affected factors have not been well understood. It is well known that the right and left hemispheres play different roles in auditory perception in adult normal hearing listeners. It is unknown how the implantation side may affect the outcomes of CIs. In this study, the effect of the implantation side on how the brain processes frequency changes within a sound was examined in 12 right-handed adult CI users. The outcomes of CIs were assessed with behaviorally measured frequency change detection threshold (FCDT), which has been reported to significantly affect CI speech performance. The brain activation and regions were also examined using acoustic change complex (ACC, a type of cortical potential evoked by acoustic changes within a stimulus), on which the waveform analysis and the standardized low-resolution brain electromagnetic tomography (sLORETA) were performed. CI users showed activation in the temporal lobe and non-temporal areas, such as the frontal lobe. Right-ear CIs could more efficiently activate the contralateral hemisphere compared to left-ear CIs. For right-ear CIs, the increased activation in the contralateral temporal lobe together with the decreased activation in the contralateral frontal lobe was correlated with good performance of frequency change detection (lower FCDTs). Such a trend was not found in left-ear CIs. These results suggest that the implantation side may significantly affect neuroplasticity patterns in adults.

OBJECTIVE The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)-functional magnetic resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response. METHODS Sixteen children with newly diagnosed and drug-naive CAE had 31 typical absence seizures during EEG-fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event-related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG-effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)-treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response. RESULTS Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P

Leprosy is also known as Hansen disease, as in some countries the diagnosis of leprosy carries a negative stigma and patients fear being shunned as outcasts. Presently, leprosy is primarily limited to specific geographical regions in resource-poor countries. As a result, there is increased difficulty for the younger generation of physicians today to correctly identify leprosy due to a lack of exposure and a low-index of suspicion, particularly in developed countries. In this case, the indurated lesions over the face demonstrated a preference for the outer lateral aspects over the maxillary areas, the nose bridge, and the pinna of the ears consistent with the organism’s preference for cooler regions of the body. This was also evident in the other skin lesions affecting the more acral regions of the limbs in the early stage of disease progression. There is a need to keep this infective condition as an alternate diagnosis to all unusual cutaneous lesions.

Background: Patients with relapsed/refractory acute myeloid leukemia (AML) have poor outcomes and high levels of healthcare utilization at end of life. Palliative care remains underused in this population despite the high symptom burden. Questions remain regarding how best to integrate palliative care for high risk hematology patients. Prior implementation of standardized palliative care consultation triggers on an inpatient solid tumor service led to increased palliative care consultations and decreased healthcare utilization (Adelson et al, JOP 2017). We conducted a prospective cohort study evaluating standardized palliative care consultation triggers for patients admitted to a tertiary academic center with advanced AML. Method: Trigger criteria were developed for hospitalized patients with hematologic malignancies on the inpatient hematology floors at Smilow Cancer Hospital and included: 1) persistent disease after ≥ 2 lines of therapy, 2) length of stay (LOS) >7 days for symptom management, 3) Eastern Cooperative Oncology Group (ECOG) performance status > 2, and 4) refractory graft versus host disease (GVHD) after ≥ 3 lines of therapy. Patients with relapsed/refractory AML were included if they met criteria #1. A palliative care nurse coordinator performed chart review of admitted patients 1-2 times per week from June to December 2020 and contacted the primary team when a patient met eligibility. Patient characteristics and healthcare outcomes were compared with patients with AML meeting criteria #1 admitted pre-intervention (June to December 2019) using Fisher t-tests. Results: A total of 110 admitted patients with advanced AML met eligibility criteria #1 (64 pre-intervention and 46 post-intervention). Baseline patient and disease characteristics were similar, including mean age at admission (60.4 vs 60.9 years, p=0.848), gender (64% vs 59% male, p=0.691), prior transplant (56% vs 52%, p=0.702), and AML risk stratification (67% vs 78% adverse risk, p=0.283). In the post-intervention group, 61% of eligible patients were screened. Of the screened patients, 54% received a palliative care consult, 18% were declined by the primary team, 14% were marked as not eligible, and 14% did not have a palliative care consult with reason unspecified. Within the same admission, there was a significant increase in advance care planning and/or advanced directive documentation post-intervention (13% vs 28%, p=0.049). There was no differences in pre- and post-intervention groups in time to palliative care consult from admission (7.2 vs 4.9 days, p=0.245), LOS (12.13 vs 12.33 days, p=0.941), 30-day readmissions (52% vs 39%, p=0.246), critical/intermediate care escalation (22% vs 13%, p=0.318) during the same admission. By July 2021, 92% of the pre-intervention patients and 57% of the post-intervention patients were deceased. Of the deceased patients, there was no differences in pre- and post-intervention groups in blood transfusions (100% vs 96%, p=0.306) or hospice enrollment (46% vs 62%, p=0.157) within 14 days of death. There was also no significant differences in pre- and post-intervention groups in non-palliative anti-neoplastic therapy use (37% vs 38%, p=0.999), hospital admissions (95% vs 88% p=0.364), or critical/intermediate care escalation (51% vs 38%, p=0.350) within 30 days of death. Conclusion: A trigger-based palliative care referral intervention is feasible and doubled palliative care use in patients with relapsed/refractory AML. Our intervention was associated with increased advance care planning documentation during the admission. There were directional changes in other healthcare measures, including decreased time to palliative care consult and escalation of care, as well as increased hospice enrollment. These differences, however, were not statistically significant due to the small sample size. The significant healthcare use likely reflected high symptom burden at end of life, associated with transfusions and admissions for infection and symptom management. More research is needed to determine how best to support these patients at end of life. Of note, our intervention period occurred during the COVID-19 pandemic, which may have impacted threshold for inpatient admissions and the inpatient census. Disclosures Adelson: Carrum Health: Other: Stock; Abbvie: Consultancy; Roche/Genentech: Consultancy, Honoraria, Patents & Royalties, Research Funding; Heron: Consultancy; Celgene: Consultancy. Prebet: BMS: Research Funding; BMS, Curios, Daichi: Consultancy.

Objective Rolandic epilepsy (RE) is one of the most common forms of epilepsy syndromes in children. The condition is usually accompanied with either unilateral or bilateral centrotemporal epileptic discharge. Despite the term “benign”, many studies have reported that children with benign epilepsy with centrotemporal spikes (BECTS) display a range of pervasive cognitive difficulties. In addition, existing research suggests that unilateral and bilateral centrotemporal spikes may affect cognition through different mechanisms. Consequently, the present study aimed to investigate cognitive impairment and the resting-state network topology of children with benign epilepsy with unilateral centrotemporal spikes (U-BECTS) and with bilateral centrotemporal spikes (B-BECTS). Methods This study recruited 14 children with U-BECTS and 14 with B-BECTS. Thereafter, cognition was assessed in 28 children with BECTS and 14 healthy controls, using the fourth edition of the Wechsler Intelligence Scale (WISC-IV). Additionally, the functional network of the brain was constructed through magnetoencephalography (MEG) to record the resting-state brain magnetic signals of the brain and by computing virtual sensor waveforms at the source level. Moreover, graph theory (GT) analysis was used to assess the properties of the brain network. Results Children in the B-BECTS group had an earlier onset of epilepsy compared to those in the U-BECTS category. In addition, both the B-BECTS and U-BECTS groups had lower Full Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), and Working Memory Index (WMI) scores, compared to the healthy controls although only children in the B-BECTS category had lower Perceptual Reasoning Index (PRI) scores. The results also showed that both BECTS groups had increased frontal cortex connectivity in specific frequency bands. Notably, children with B-BECTS showed a more disorderly and randomized network in the 1–4-Hz and 80–250-Hz frequency bands. Moreover, GT analysis showed that children with B-BECTS had lower clustering coefficient and characteristic path length in the 80–250-Hz frequency bands and higher connection strength in the 4–8-Hz frequency bands. On the other hand, the U-BECTS group had a higher clustering coefficient in the 8–12-Hz frequency bands, compared to the healthy controls. Correlation analysis revealed that there were negative correlations between network parameters, clinical characteristics, and neuropsychological data in the U-BECTS category. Conclusion The findings revealed that children with BECTS display a diffuse early cognitive deficit. In addition, resting-state suboptimal network topology may be the mechanism of cognitive impairment in children with BECTS. The study also showed that and children with B-BECTS may be at a higher risk of cognitive impairment.

224 Background: Patients with relapsed/refractory acute myeloid leukemia (AML) have poor outcomes and high levels of healthcare use at end of life. Palliative care remains underused in hematology and questions remain on how best to integrate palliative care for high-risk patients. We conducted a prospective cohort study evaluating palliative care consultation triggers for patients admitted to a tertiary academic center with advanced AML. Methods: Criteria were developed for all hospitalized patients with hematologic malignancy on the inpatient hematology floors and included: 1) persistent disease after ≥ 2 lines of therapy, 2) length of stay (LOS) > 7 days for symptom management, 3) ECOG performance status > 2, and 4) refractory GVHD ≥ 3 lines of therapy. Patients with relapsed/refractory AML were included if they met criteria 1. A nurse coordinator performed chart review of admitted patients 1-2 times/week from June to December 2020 on the inpatient hematology floor at Smilow Cancer Hospital and contacted the primary team when patients met eligibility. Patient characteristics and healthcare outcomes were compared with patients with AML meeting criteria 1 admitted pre-intervention (June to December 2019) using Fisher t-tests. Results: A total 110 admitted patients were eligible (64 pre-intervention and 46 post-intervention). Baseline patient and disease characteristics were similar, including mean age at admission (60.4 vs 60.9 years, p = 0.848), gender (64% vs 59% male, p = 0.691), prior transplant (56% vs 52%, p = 0.702), and AML risk stratification (67% vs 78% adverse risk, p = 0.283). In the post-intervention group, 61% of eligible patients were screened. Of the screened patients, 54% received a palliative care consult, 18% were declined by the primary team, 14% were marked as not eligible, and 14% did not have consult with reason unspecified. Overall, palliative care consults increased in the post-intervention group (22% vs 43%, p = 0.021). There was a significant increase in advance care planning and/or advanced directive documentation post-intervention (13% vs 28%, p = 0.049). There was no differences in pre- and post-intervention groups in LOS (12.13 vs 12.33 days, p = 0.941), 30-day readmissions (52% vs 39%, p = 0.557), critical/intermediate care escalation (22% vs 13%, p = 0.318) and non-palliative chemotherapy post-discharge (48% vs 39%, p = 0.246). Conclusions: A triggered palliative care referral intervention is feasible and doubled palliative care use in patients with relapsed/refractory AML, a group with high mortality and high healthcare utilization. Our intervention improved documentation of advance care planning. Although there were directional reductions in other healthcare use measures, the differences were not statistically significant, likely from the small sample sizes leading to the study being underpowered.

79 Background: Patient-trial matching is a critical step in clinical research recruitment that requires extensive review of clinical data and trial requirements. Prescreening, defined as identifying potentially eligible patients using select eligibility criteria, may streamline the process and increase study enrollment. We describe the real-world experience of implementing a standardized, universal clinical research prescreening protocol within a VA cancer center and its impact on research enrollment. Methods: An IRB approved prescreening protocol was implemented at the VACT Cancer Center in March 2017. All patients with a suspected or confirmed diagnosis of cancer are identified through tumor boards, oncology consults, and clinic lists. Research coordinators perform chart review and manually enter patient demographics, cancer type and stage, and treatment history into a REDCap (Research Electronic Data Capture) database. All clinical trials and their eligibility criteria are also entered into REDCap and updated regularly. REDCap generates real time lists of potential research studies for each patient based on his/her recorded data. The primary oncologist is alerted to a patient’s potential eligibility prior to upcoming clinic visits and thus can plan to discuss clinical research enrollment as appropriate. Results: From March 2017 to December 2020, a total of 2548 unique patients were prescreened into REDCAP. The mean age was 71.5 years, 97.5% were male, and 15.5% were African American. 32.57 % patients had genitourinary cancer, 17.15% had lung cancer, and 46.15% were undergoing malignancy workup. 1412 patients were potentially eligible after prescreening and 556 patients were ultimately enrolled in studies. The number of patients enrolled on therapeutic clinical trials increased after the implementation of the prescreening protocol (35 in 2017, 64 in 2018, 78 in 2019, and 55 in 2020 despite the COVID19 pandemic). Biorepository study enrollment increased from 8 in 2019 to 15 in 2020. The prescreening protocol also enabled 200 patients to be enrolled onto a lung nodule liquid biopsy study from 2017 to 2019. Our prescreening process captured 98.57% of lung cancer patients entered into the cancer registry during the same time period. Conclusions: Universal prescreening streamlined research recruitment operations and was associated with yearly increases in clinical research enrollment at a VA cancer center. Our protocol identified most new lung cancer patients, suggesting that, at least for this malignancy, potential study patients were not missed. The protocol was integral in our program becoming the top accruing VA site for NCI’s National Clinical Trial Network (NCTN) studies since 2019.

Purpose The purpose of this study was to determine whether retinal gap junctions (GJs) via connexin 36 (Cx36, mediating coupling of many retinal cell types) and horizontal cell (HC-HC) coupling, are involved in emmetropization. Methods Guinea pigs (3 weeks old) were monocularly form deprived (FD) or raised without FD (in normal visual [NV] environment) for 2 days or 4 weeks; alternatively, they wore a -4 D lens (hyperopic defocus [HD]) or 0 D lens for 2 days or 1 week. FD and NV eyes received daily subconjunctival injections of a nonspecific GJ-uncoupling agent, 18-β-Glycyrrhetinic Acid (18-β-GA). The amounts of total Cx36 and of phosphorylated Cx36 (P-Cx36; activated state that increases cell-cell coupling), in the inner and outer plexiform layers (IPLs and OPLs), were evaluated by quantitative immunofluorescence (IF), and HC-HC coupling was evaluated by cut-loading with neurobiotin. Results FD per se (excluding effect of light-attenuation) increased HC-HC coupling in OPL, whereas HD did not affect it. HD for 2 days or 1 week had no significant effect on retinal content of Cx36 or P-Cx36. FD for 4 weeks decreased the total amounts of Cx36 and P-Cx36, and the P-Cx36/Cx36 ratio, in the IPL. Subconjunctival 18-β-GA induced myopia in NV eyes and increased the myopic shifts in FD eyes, while reducing the amounts of Cx36 and P-Cx36 in both the IPL and OPL. Conclusions These results suggest that cell-cell coupling via GJs containing Cx36 (particularly those in the IPL) plays a role in emmetropization and form deprivation myopia (FDM) in mammals. Although both FD and 18-β-GA induced myopia, they had opposite effects on HC-HC coupling. These findings suggest that HC-HC coupling in the OPL might not play a significant role in emmetropization and myopia development.

Although cerebrovascular diseases have been considered as risk factors for cognitive decline and dementia, the associations between atherosclerosis and Alzheimer's disease (AD) have not been fully examined and remain controversial. The aim of this three-year prospective study was to investigate whether arotid artery atherosclerosis accelerates cognitive impairment in AD patients. The association of carotid intimal medial thickness (IMT) with prospective trajectories of cognitive function was assessed among 521 patients with light to moderate AD, and 437 AD patients were followed up annually for 3 years. Participants underwent initial carotid ultrasonography and repeated neuropsychological testing every year. Mixed-effects regression analyses were adjusted to estimate the effect of carotid IMT and other adjusting variables. The results of the present study indicated that carotid IMT was significantly associated with various measures of cognitive function. Furthermore, AD patients with higher carotid IMT values had a faster decline in cognitive scores in a variety of neuropsychological tests, particularly in verbal and non-verbal memory, semantic fluency and executive function. The present prospective study showed that carotid atherosclerosis is a predictive factor regarding the progression of cognitive impairment in AD patients, suggesting that early detection and treatment of vascular risk factors may prevent or at least postpone the evolution of the disease.

Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.

The critical role of lysine demethylase 4A (KDM4A), in regulating chromatin structure and consequently in driving cellular proliferation and oncogenesis has been the focus of recent studies. Non-small-cell lung cancer (NSCLC) patients with adenocarcinoma histology who were homozygous for KDM4A single nucleotide polymorphism (SNP)-A482 (rs586339) were recently shown to have significantly worse overall survival (OS) compared with patients with the wild-type or the heterozygous genotype at this locus (hazard ratio=1.68, P=0.042). In the current study, we investigated the association between the same polymorphism with OS in our Asian NSCLC-adenocarcinoma patients comprising Chinese (N=572), Malays (N=50), and Indians (N=22). KDM4A SNP-A482 genotype status was determined by Sanger sequencing. OS was calculated from the date of diagnosis to date of death or censored at the date of last follow-up. Kaplan-Meier analysis, log-rank test, and Cox regression methods were utilized to evaluate OS outcomes. KDM4A SNP-A482 had a minor allele (C) frequency of 18.8% and a major allele (A) frequency of 81.2% in our Asian NSCLC (adenocarcinoma) patients. However, the OS in our Asian NSCLC patients homozygous for KDM4A SNP-A482 was not significantly different from those who were wild type or heterozygous at this locus [CC vs. AA/AC: median OS (95% confidence interval): 40.2 (18.7-61.6) vs. 29.6 (26.9-32.3) months; P=0.858]. The results remained statistically nonsignificant even after adjustment for epidermal growth factor receptor mutational status, suggesting that KDM4A SNP-A482 does not significantly influence OS in Asian NSCLC patients.

Urolithiasis is a common disease with high recurrence rate. According to the record, the prevalence rate of urolithiasis is about 4–15% in Asia, Europe and America while the recurrence rate of urolithiasis is more than 50% after the treatment. The research done by the University of Chicago indicates that the presence of crystals in urine is an important factor of stone formation. Previous studies also conclude that the compound of crystals and stones are highly correlated. Therefore, it is important to analyze urine crystals accurately to prevent potential stone formation.

Introduction Most cochlear implant (CI) users have difficulty in listening tasks that rely strongly on perception of frequency changes (e.g., speech perception in noise, musical melody perception, etc.). Some previous studies using behavioral or subjective assessments have shown that short-term music training can benefit CI users’ perception of music and speech. Electroencephalographic (EEG) recordings may reveal the neural basis for music training benefits in CI users. Objective To examine the effects of short-term music training on CI hearing outcomes using a comprehensive test battery of subjective evaluation, behavioral tests, and EEG measures. Design Twelve adult CI users were recruited for a home-based music training program that focused on attentive listening to music genres and materials that have an emphasis on melody. The participants used a music streaming program (i.e., Pandora) downloaded onto personal electronic devices for training. The participants attentively listened to music through a direct audio cable or through Bluetooth streaming. The training schedule was 40 min/session/day, 5 days/week, for either 4 or 8 weeks. The pre-training and post-training tests included: hearing thresholds, Speech, Spatial and Qualities of Hearing Scale (SSQ12) questionnaire, psychoacoustic tests of frequency change detection threshold (FCDT), speech recognition tests (CNC words, AzBio sentences, and QuickSIN), and EEG responses to tones that contained different magnitudes of frequency changes. Results All participants except one finished the 4- or 8-week training, resulting in a dropout rate of 8.33%. Eleven participants performed all tests except for two who did not participate in EEG tests. Results showed a significant improvement in the FCDTs as well as performance on CNC and QuickSIN after training (p < 0.05), but no significant improvement in SSQ scores (p > 0.05). Results of the EEG tests showed larger post-training cortical auditory evoked potentials (CAEPs) in seven of the nine participants, suggesting a better cortical processing of both stimulus onset and within-stimulus frequency changes. Conclusion These preliminary data suggest that extensive, focused music listening can improve frequency perception and speech perception in CI users. Further studies that include a larger sample size and control groups are warranted to determine the efficacy of short-term music training in CI users.

Background Although altered neural networks have been demonstrated in recent MEG (magnetoencephalography) research in migraine patients during resting state, it is unknown whether this alteration can be detected in task-related networks. The present study aimed to investigate the abnormalities of the frequency-specific somatosensory-related network in migraine patients by using MEG. Methods Twenty-two migraineurs in the interictal phase and twenty-two sex- and age-matched healthy volunteers were studied using a whole-head magnetoencephalography (MEG) system. Electrical stimuli were delivered alternately to the median nerve on the right wrists of all subjects. MEG data were analyzed in a frequency range of 1–1000 Hz in multiple bands. Results The brain network patterns revealed that the patients with migraine exhibited remarkably increased functional connectivity in the high-frequency (250–1000 Hz) band between the sensory cortex and the frontal lobe. The results of quantitative analysis of graph theory showed that the patients had (1) an increased degree of connectivity in the theta (4–8 Hz), beta (13–30 Hz) and gamma (30–80 Hz) bands; (2) an increased connectivity strength in the beta (13–30 Hz) and gamma (30–80 Hz) bands; (3) an increased path length in the beta (13–30 Hz), gamma (30–80 Hz) and ripple (80–250 Hz) bands; and (4) an increased clustering coefficient in the theta (4–8 Hz), beta (13–30 Hz) and gamma (30–80 Hz) bands. Conclusions The results indicate that migraine is associated with aberrant connections from the somatosensory cortex to the frontal lobe. The frequency-specific increases in connectivity in terms of strength, path length and clustering coefficients support the notion that migraineurs have elevated cortical networks. This alteration in functional connectivity may be involved in somatosensory processing in migraine patients and may contribute to understanding migraine pathophysiology and to providing convincing evidence for a spatially targeted migraine therapy.

Objective The present study aimed to preliminary explore the abnormal neuromagnetic activation in female migraine patients between attacks using magnetoencephalography (MEG) and pattern reversed visual evoked magnetic fields (PR-VEFs). Methods A total of 17 female migraine subjects during the headache-free phase and 17 healthy controls (HC) were studied using a 275-channel magnetoencephalography (MEG) system. In this study, visual evoked magnetic fields (VEFs) were generated by a pattern-reversal check as the visual stimulus. The average of 100 VEFs was evolved by different half patterns were averaged and used to analyze waveform, spectrum, and source location within two frequency ranges (5–100 and 100–1000 Hz), respectively. Results In migraine subjects, the latency of second peak of VEFs (VIIs) showed significant prolongations when compared with HC. On the sensor level, the cortical spectral power in migraine subjects was similar to that of HC in the 5–100 Hz range and was lower in the 1000–1000 Hz range. There was a decrement of source strength in the visual cortex in migraine patients when compared to HC in both the 5–100 and 100–1000 Hz frequency range. Moreover, there was a similar odds of activation in 5–100 and 100–1000 Hz frequency ranges in the area beyond the primary visual cortex between the two groups. In addition, no correlation was observed between clinical data (intensity of headache, headache-history duration, the frequency of headaches) and MEG results. Conclusions The findings presented in the current study, suggested that interictal cortical activation following a visual stimulus was low in female migraine patients. The low pre-activation was detected in the visual cortex using VEF and MEG in both low and high-frequency band. Our results add to the existing evidence that cortical interictal excitability change may be relative to the pain-module mechanism in migraine brains. Thus, our data improved the apprehension of the cortical disorder of migraine in the high-frequency domain.

Purpose In guinea pigs, choroidal thickness (ChT) and choroidal blood perfusion (ChBP) simultaneously decrease in experimental myopia, and both increase during recovery. However, the causal relationship between ChBP and myopia requires further investigation. In this study, we examined the changes of ChBP with three different antimyopia treatments. We also actively increased ChBP to examine the direct effect on myopia development in guinea pigs. Methods Experiment 1: Guinea pigs wore occluders on the right eye for two weeks to induce form-deprivation myopia (FDM). Simultaneously they received daily antimyopia treatments: peribulbar injections of atropine or apomorphine or exposure to intense light. Experiment 2: The vasodilator prazosin was injected daily into the form-deprivation eyes to increase ChBP during the two-week induction of FDM. Other FDM animals received appropriate control treatments. Changes in refraction, axial length, ChBP, ChT, and hypoxia-labeled pimonidazole adducts in the sclera were measured. Results The antimyopia treatments atropine, apomorphine, and intense light all significantly inhibited myopia development and the decrease in ChBP. The treatments also reduced scleral hypoxia, as indicated by the decrease in hypoxic signals. Furthermore, actively increasing ChBP with prazosin inhibited the progression of myopia, as well as the increase in axial length and scleral hypoxia. Conclusions Our data strongly indicate that increased ChBP attenuates scleral hypoxia, and thereby inhibits the development of myopia. Thus ChBP may be a promising target for myopia retardation. As such, it can serve as an immediate predictor of myopia development as well as a long-term marker of it.

Our aim was to explore the pathophysiological mechanism of cognitive function changes in early untreated children with benign childhood epilepsy with centrotemporal spikes (BECTS).Magnetoencephalography (MEG) was performed in 33 children with BECTS and 18 healthy children. Wechsler Intelligence Scale for Children, fourth edition (WISC-IV) was used to divide children with BECTS into two groups. Normal cognitive function was defined as a full-scale intelligence quotient (FSIQ) of80, while decreased cognitive function was defined as a FSIQ of80. Accumulated source imaging was used to evaluate the neuromagnetic source activity in multifrequency bands.Of the 33 patients with early untreated BECTS, a total of 17 had a FSIQ of80 and 16 had FSIQ of80. The course of epilepsy and number of seizures in the FSIQ80 group were higher than that in the FSIQ80 group. Our MEG results showed that in the 4-8 Hz frequency band, both patient groups had inactivation of the posterior cingulate cortex (PCC) region compared with the healthy control group. In the 30-80 Hz frequency band, the FSIQ80 group showed inactivation of the PCC region compared with both the healthy control group and the FSIQ80 group. In the 80-250 Hz frequency band, the FSIQ80 group had inactivated of the medial frontal cortex (MFC) region compared with the healthy control group. In the 30-80 Hz frequency band, the strength of neuromagnetic source in patients with BECTS with FSIQ80 was higher than that in the FSIQ80 group and the healthy control group.The magnetic source inactivation of the MFC and PCC regions during the interictal time may be the reason for cognitive decline in early untreated children with BECTS. Children with BECTS with cognitive decline had a longer course of epilepsy and more seizures. The magnetic source localization in the 4-8 Hz frequency band may be a new imaging marker for the diagnosis of new BECTS.

The aim of this study is to quantitatively assess the resting-state brain activity in migraine patients during the headache-free phase with magnetoencephalography (MEG).A total of 25 migraine patients during the headache-free phase and 25 gender- and age-matched control patients were studied with a whole-head MEG system at eyes-closed resting-state. MEG data were analyzed in multifrequency range of 4-200Hz.In a regional cortex analysis, the spectral power of gamma oscillations in left frontal and left temporal regions was significantly increased in migraine patients as compared to controls (all p0.001), but no significant difference was found between the two groups for the global channels. Analyses of source location showed that there were significant differences in the distribution of gamma oscillation between migraine subjects and controls (p0.025).Migraine patients in resting-state had altered brain activities in spectral power value and source distribution that can be detected and analyzed by MEG.Abnormal brain activities in the left frontal and temporal regions may be involved in pain modulation and processing of migraine. These findings provide new insights into the possible mechanisms of migraine attacks.

As a low-affinity neurotrophins receptor, p75 neurotrophin receptor (p75NTR) is a transmembrane receptor involved in a diverse array of cellular responses, including apoptosis, survival, neurite outgrowth, migration, and cell cycle arrest, which may be related to some neurological disorders, such as Alzheimer's disease (AD), schizophrenia, major depressive disorder (MDD), posttraumatic stress disorder (PTSD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Indeed, a series of studies during the last decade has demonstrated that the p75NTR signaling plays key roles in most aspects of the neurological disorder diseases. In spite of the limited information available, this review still tried to summary the relationship between p75NTR and diverse neurological disorder diseases, and tried to further clarify the possible mechanism, which may provide a novel therapeutic target for the treatment of neurological disorders.

The present study was performed to determine the effect of high fat diet in lipid accumulation, oxidative stress and autophagy, and to explore the underlying molecular mechanism of high fat diet induced hepatic oxidative damage in Chinese softshell turtle. To this end, the control group were fed a normal fat diet (NFD, 6.38% lipid) and the experimental group were bred high fat diet (HFD, 13.89% lipid) for eight weeks. Lipid accumulation, oxidative stress and autophagy, as well as the mRNA expression of genes related to the antioxidant system were determined in the liver. Results showed that high fat diet not only exacerbated lipid accumulation in the liver and serum through increasing contents of triglyceride, total cholesterol and low-density lipoprotein and decreasing content of high-density lipoprotein, but also induced liver injury through increasing activities of alanine aminotransferase and aspartate aminotransferase in the serum. In addition, the experimental subject induced oxidative injury for the increase of reactive oxygen species, malondialdehyde and protein carbonyl contents and the reduction of glutathione contents, anti-superoxide anion capacity and catalase, total superoxide dismutase, glutathione peroxidase, glutathione-S transferase activities. Meanwhile, antioxidant-related signaling molecule expression were also decreased, which might attribute to regulate antioxidant-related signaling molecule. On top of that, it indicated promote the occurrence of liver autophagy via up-regulating expressions of AMP activated protein kinase, UNC-51-like kinase 1, Microtubule-associated proteins 1A/1B light chain 3 and down-regulating gene expression of mammalian target of rapamycin. In conclusion, high fat diet could enhance lipid accumulation in the liver and serum, lead to liver injury and oxidative damage, impair liver antioxidant capacity, regulate antioxidant-related signaling molecule expression and activate hepatic autophagy.

Here, we aimed to investigate brain activity in migraineurs in response to emotional stimulation. Magnetoencephalography (MEG) was used to examine 20 patients with episodic migraine (EM group), 15 patients with chronic migraine (CM group), and 35 healthy participants (control group). Neuromagnetic brain activity was elicited by emotional stimulation using photographs of facial expressions. We analyzed the latency and amplitude of M100 and M170 components and used Morlet wavelet and beamformers to analyze the spectral and spatial signatures of MEG signals in gamma band (30–100 Hz). We found that the timing and frequency of MEG activity differed across the three groups in response negative emotional stimuli. First, peak M170 amplitude was significantly lower in the CM group than in the control group. Second, compared with the control group, the average spectral power was significantly lower in the EM group and CM group at M100 and M170. Third, the average spectral powers of the M100 and M170 in the CM group were negatively correlated with either HAM-D scores or migraine attack frequency. No significant differences across groups was found for positive or neutral emotional stimuli. Furthermore, after negative emotional stimuli, the MEG source analysis demonstrated that the CM group showed a significantly higher percentage of amygdala activation than the control group for M100 and M170. Thus, during headache free phases, migraineurs have abnormal brain activity in the gamma band in response to negative emotional stimuli. Trial Registration: ChiCTR-RNC-17012599. Registered 7 September, 2017.

Objective To quantify the low- to high-frequency range of abnormal brain activities and assess the histopathologic and clinical correlation in patients with glioma. Methods Twenty-five patients with glioma and 20 healthy controls were examined with a magnetoencephalography (MEG) system. MEG data collected in 6 frequency bands, including 1–4 Hz, 4–8 Hz, 8–12 Hz, 12–30 Hz, 30–45 Hz, and 55–75 Hz, were analyzed by neuropathology to assess neuromagnetic signatures of glioma grade. Results Compared with controls, patients with glioma showed greatly altered brain activities in 4–8 Hz, 8–12 Hz, and 55–75 Hz. Magnetic source power of brain activities in 4–8 Hz and 55–75 Hz in patients with high-grade gliomas significantly differed from that in patients with low-grade gliomas. The magnitude of source power of brain activities in 4–8 Hz and 55–75 Hz had marked correlation with the grading of gliomas in histopathological analyses. Conclusions The degree of neuromagnetic source abnormality is a potential biomarker for noninvasive assessment of glioma grade. Because MEG tests can be performed noninvasively and preoperatively, MEG may play an important role in clinical biopsies and surgical planning for patients with brain gliomas in the future.

Childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, is usually treated with valproic acid (VPA) and lamotrigine (LTG) in China. This study aimed to investigate the ictal source locations and functional connectivity (FC) networks between the cortices and thalamus that are related to treatment response. Magnetoencephalography (MEG) data from 25 patients with CAE were recorded at 300 Hz and analyzed in 1–30 Hz frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. The FC networks between the cortices and thalamus were evaluated at the source level through a connectivity analysis. Treatment outcome was assessed after 36–66 months following MEG recording. The children with CAE were divided into LTG responder, LTG non-responder, VPA responder and VPA non-responder groups. The ictal source locations and cortico–thalamic FC networks were compared to the treatment response. The ictal source locations in the post-dorsal medial frontal cortex (post-DMFC, including the medial primary motor cortex and the supplementary sensorimotor area) were observed in all LTG non-responders but in all LTG responders. At 1–7 Hz, patients with fronto–thalamo–parietal/occipital (F–T–P/O) networks were older than those with fronto–thalamic (F–T) networks or other cortico–thalamic networks (p = 0.000). The duration of seizures in patients with F–T–P/O networks at 1–7 Hz was longer than that in patients with F–T networks or other cortico–thalamic networks (p = 0.001). The ictal post-DMFC source localizations suggest that children with CAE might experience initial LTG monotherapy failure. Moreover, the cortico–thalamo–cortical network is associated with age. Finally, the cortico–thalamo–cortical network consists of anterior and posterior cortices and might contribute to the maintenance of discharges.

Autophagy is a highly conserved pathway that permits recycling of nutrients within the cell and is rapidly upregulated during starvation or cell stress. Autophagy has been implicated in the pathophysiological process of warm ischemia-reperfusion injury in the rat lung. Cold ischemia (CI) preservation for lung transplantation also exhibits cell stress and nutrient deprivation, however, little is known with regard to the involvement of autophagy in this process. In the present study, CI preservation-induced autophagy and apoptosis was investigated in the lungs of Sprague Dawley rats. Sprague Dawley rat lungs were flushed and preserved at 4°C (i.e. CI) for various durations (0, 3, 6, 12 and 24 h). The levels of autophagy, autophagic cell death and apoptosis were measured at each time point following CI. The results revealed that autophagy was induced by CI preservation, which was initiated at 3 h, peaked at 6 h after CI and declined thereafter. Additionally, a coexistence of autophagic cell death and apoptosis was observed in rat lung tissues following prolonged CI. These findings demonstrate that autophagy is involved in the pathophysiological process of lung CI. Furthermore, autophagic cell death in addition to necrosis and apoptosis occurs following CI in the lung. CI preservation may therefore be a potential mechanism of lung injury during organ preservation prior to lung transplantation.

The relationship between physical activity (PA) and bone health is well known, but the role of lean mass (LM) and fat mass (FM) in this relationship remains uncertain. Therefore, the aim of this study was to examine the mediating effect of LM and FM on the relationship between PA and bone mineral density (BMD) in postmenopausal women.This cross-sectional study involved 282 postmenopausal women aged between 50 and 65 year, who were randomly selected from Hongqi community of Harbin City in China. PA was measured using an International PA Questionnaire. Body composition, BMD of the lumbar spine, hip, and total body were measured using dual-energy X-ray absorptiometry. Mediation analysis was performed to investigate the mediating effect of LM and FM on the relationship between PA and BMD.In partial correlation analysis, PA, LM, and FM were positively related to BMD. Positive correlation was found between PA and LM. There were significant differences in BMD between different categories of PA, but the differences disappeared after adjusting for LM. Mediation analysis showed that LM and FM played a mediating role in the relationship between PA and BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and 33.02%, respectively.LM and FM affected the relationship between PA and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.

Severe acute pancreatitis (SAP) is an acute inflammatory disease of the pancreas that involves various distant tissues and organs. This study aimed to investigate post-tissue injury repair by mesenchymal stem cells (MSCs) in a rat model of SAP. A total of 54 pathogen-free adult male SD rats were randomly assigned to the groups SAP, SAP + MSCs and sham-operated (SO). SAP was induced by 4% sodium taurocholate, and MSCs were injected via the dorsal penile vein 1 h later. The amylase activity, and tumor necrosis factor (TNF)-α and diamine oxidase (DAO) levels were measured with an enzyme-linked immunosorbent assay (ELISA), while the expression of aquaporin (AQP)-1 was evaluated by immunohistochemical staining. The pathological score of intestinal tissues was also compared among groups. Marked improvement in intestinal necrosis, villi shedding and infiltration of inflammatory cells was observed in the SAP + MSCs group compared to the SAP and SO groups. Amylase, TNF-α, and DAO levels were significantly increased in the SAP + MSCs group. The intestinal expression of AQP-1 was increased at 12 and 24 h post-MSC transplantation compared to the SO group. Rats of the SAP + MSCs group displayed higher pathological scores compared to the SAP group at all time points. Overall, these data showed that MSCs can inhibit systemic inflammation and reduce TNF-α release in a rat model of SAP-induced intestinal injury, suggesting that MSCs exert protective effects on the intestinal barrier during SAP.

To compare the effect of An’s Shaobei Injection (安氏芍倍注射液) with Xiaozhiling Injection (消痔灵注射液) in patients with internal hemorrhoids of grade I–III. This cohort study included 1,520 internal hemorrhoids patients with grade I–III who were scheduled for liquid injection treatment from July 2003 to July 2009. The cohort included patients who underwent either An’s Shaobei Injection treatment (the treatment group, 760 cases) or Xiaozhiling Injection treatment (the control group, 760 cases). All patients were followed up regularly for 3 years; the observing indices included anal function recovery and clinical response after operation. Among the 1,520 patients, 1,508 (99.2%) completed the 3-year follow-up. The efficacy rate was 97.5% in the treatment group, significantly higher than the control group (91.8%, P

The aim of this study was to investigate and analyse the caring attitude and behaviour of clinical nurses in terms of importance, competency and feasibility. The study used a survey design. Data were collected between January and June 2010. Two hundred and sixty clinical nurses were recruited. The caring attitude and behaviour of the nurses were assessed by using a translated version of the original Caring Nurse-Patient Interaction Scale-Short Scale. The subjects considered operative caring behaviour to be more important than expressive caring behaviour. The nurses felt more competent to practise operative caring behaviour in the clinic, and reported that such care was more feasible. The competency scores were positively correlated with age and work seniority. The feasibility scores for the clinical care dimension were positively correlated with age and work seniority. Nurses with a higher positional title had higher competency and feasibility scores. The results suggest that a rich life experience, accumulation of work experience and better competency might promote caring behaviour in nurses.