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Background: Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that functional LGI1 is secreted by excitatory neurons, GABAergic interneurons, and astrocytes, and regulates AMPA-type glutamate receptor-mediated synaptic transmission by binding ADAM22 and ADAM23. However, > 40 LGI1 mutations have been reported in familial ADLTE patients, more than half of which are secretion-defective. How these secretion-defective LGI1 mutations lead to epilepsy is unknown. Results: We identified a novel secretion-defective LGI1 mutation from a Chinese ADLTE family, LGI1-W183R. We specifically expressed mutant LGI1W183R in excitatory neurons lacking natural LGI1, and found that this mutation downregulated Kv1.1 activity, led to neuronal hyperexcitability and irregular spiking, and increased epilepsy susceptibility in mice. Further analysis revealed that restoring Kv1.1 in excitatory neurons rescued the defect of spiking capacity, improved epilepsy susceptibility, and prolonged the life-span of mice. Conclusions: These results describe a role of secretion-defective LGI1 in maintaining neuronal excitability and reveal a new mechanism in the pathology of LGI1 mutation-related epilepsy. [ABSTRACT FROM AUTHOR]

Background: The active components of Dracocephalum moldavica L. (TFDM) can inhibit myocardial ischemia by inhibiting oxidative stress. However, the effects of TFDM on astrocytes have not been investigated in vitro. The current study aimed to explore whether TFDM protects astrocytes against H2O2-induced apoptosis through a mitochondria-dependent pathway. Methods: The human glioma cell line U87 was used to investigate the ability of TFDM to protect astrocytes against H2O2-induced apoptosis. The cell counting kit-8 assay and flow cytometry were used to detect cell viability, apoptosis, MMP, Ca2+ influx and reactive oxygen species (ROS). Lactate dehydrogenase (LDH) and malonic dialdehyde (MDA) levels were measured by ELISA. In addition, protein and mRNA expression changes were detected by Western blotting and qRT-PCR. Results: TFDM (0.78~200 μg/ml) had limited cytotoxic effects on the viability of U87 cells. Compared with the model group (treated with H2O2 only), cells treated with medium- and high-dose TFDM exhibited reduced MDA concentrations (P < 0.05) and ROS production (P < 0.05) and decreased MMP (P < 0.05) and reduced apoptosis (P < 0.05). The percentage of annexin V-FITC-stained cells was markedly suppressed by TFDM, confirming its anti-apoptotic properties. WB results showed that protein expression of Bcl-2-associated X protein (BAX), Caspase-3, Caspase-9, Caspase-12, and B-cell leukemia/lymphoma 2 (Bcl2) was reduced in the TFDM group compared with that in the model group (P < 0.05) and that expression of these proteins was normalized by TFDM treatment in a dose-dependent manner. According to RT-qPCR results, TFDM pretreatment resulted in reduced mRNA expression of BAX, Caspase-9, Caspase-12, p38MAPK, and CaMKII and increased mRNA expression of mTOR compared with the model group. Conclusions: The current study revealed the protective effects of TFDM on U87 cells under oxidative stress conditions through the inhibition of a mitochondria-dependent pathway that is associated with the CaMKII/P38MAPK/ERK1/2 and PI3K/AKT/mTOR pathways. [ABSTRACT FROM AUTHOR]

Background: No treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain.Methods: The DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators.Discussion: This trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019. [ABSTRACT FROM AUTHOR]

Background: Total knee arthroplasty (TKA) is gradually regarded as an effective choice for end-stage osteoarthritis or rheumatic arthritis. In the past, the management of tranexamic acid (TXA) using intravenous injection or topical application has been extensively researched. However, several studies have reported that oral TXA has an effect on blood loss. Therefore, a meta-analysis should be performed to determine whether oral TXA helps to prevent blood loss. Methods: Randomized controlled trials or retrospective cohort studies about relevant studies were searched in PubMed (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL, April 2017). Six studies that compared oral TXA to non-TXA were included in our meta-analysis. Meta-analyses (PRISMA) guidelines, the Cochrane Handbook, and the Jadad scale were used to evaluate the included studies and the results to ensure that the meta-analysis was viable. Results: In accordance with inclusion and exclusion, six studies with 2553 patients (oral TXA = 1386, without TXA = 1167) were eligible and accepted into this meta-analysis. Pooled data indicated that the oral TXA group was effective compared to the without TXA group in terms of hemoglobin (Hb) drop (P < 0.05), blood loss at 24 h (P < 0.05), total blood loss (P < 0.05), and the transfusion rate (P < 0.05). No significant differences were found in the length of hospital stay (P = 0.96) and complications (P = 0.39). Conclusion: Compared to the non-TXA group, the oral TXA group showed effects of blood sparing. Considering the cost and effectiveness, oral TXA is useful for TKA. [ABSTRACT FROM AUTHOR]

Background: Small trials suggest that levosimendan is associated with a favorable outcome in patients undergoing cardiac surgery. However, recently published larger-scale trials did not provide evidence for a similar benefit from levosimendan. We performed a meta-analysis to assess the survival benefits of levosimendan in patients undergoing cardiac surgery and to investigate its effects in subgroups of patients with preoperative low-ejection fraction (EF).Methods: We identified randomized clinical trials through 20 April 2017 that investigated levosimendan therapy versus control in patients undergoing cardiac surgery. Individual patient data from each study were compiled. Meta-analyses were performed for primary outcomes, secondary outcomes and serious adverse events, and subgroup analyses according to the preoperative EF of enrolled patients were also conducted. The risk of bias was assessed using the Cochrane risk-of-bias tool.Results: Seventeen studies involving a total of 2756 patients were included. Levosimendan therapy was associated with a significant reduction in 30-day mortality (RR 0.67; 95% CI, 0.49 to 0.93; p = 0.02) and reduced the risk of death in single-center trials (RR 0.49; 95% CI, 0.30 to 0.79; p = 0.004) and in subgroup trials of inferior quality (RR 0.39; 95% CI, 0.17 to 0.92; p = 0.02); however, in multicenter and in high-quality subgroup-analysis trials, no significant difference in mortality was observed between patients who received levosimendan therapy and controls (p > 0.05). However, in high-quality subgroup trials, levosimendan therapy was associated with reduced mortality in patients in a preoperative low-EF subgroup (RR 0.58; 95% CI, 0.38 to 0.88; p = 0.01). Similarly, only patients in the preoperative low-EF subgroup benefited in terms of reduced risk of renal replacement therapy (RR 0.54; 95% CI, 0.34 to 0.85; p = 0.007). Furthermore, levosimendan therapy was associated with a significant reduction in intensive care unit (ICU) length of stay (MDR -17.19; 95% CI, -34.43 to -2.94; p = 0.02).Conclusions: In patients undergoing cardiac surgery, the benefit of levosimendan in terms of survival was not shown in multicenter or in high-quality trials; however, levosimendan therapy was associated with reduced mortality in patients with preoperative ventricular systolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: T regulatory cell (Treg) plays a critical role in respiratory allergy and allergen-specific immunotherapy (SIT), and γδ T cells might participate in mediating Treg quantity and/or function in some immunological diseases. To further characterize whether γδ T cells could influence Treg in allergic rhinitis (AR) and SIT, we investigated the expression pattern of Treg's Foxp3 gene and γδ T cell receptor (TCR) Vγ subfamily genes in peripheral blood mononuclear cells (PBMCs) of AR patients before and after SIT.Methods: Eighteen AR patients undergoing effective SIT with house dust mite extract for one year were recruited. Visual Analogue Scale (VAS) was applied to evaluate the severity. Immunofluorescence quantification analysis was performed to determine the serum specific IgE (sIgE) content. Real-time PCR was used to detect the expression levels of Foxp3 and TCR Vγ subfamilies. Ten healthy volunteers were recruited as the controls.Results: Nasal uni-VAS score after SIT was significantly lower than that before SIT, while serum sIgE content was similar before and after SIT. Expression levels of Foxp3 and TCR Vγ subfamilies in AR patients before treatment were significantly lower than those in healthy subjects. Expression levels of VγI and II were similar before and after SIT, while expression levels of Foxp3 and VγIII after SIT were significantly higher than those before. Before SIT, the significant positive correlation was observed between expression levels of Foxp3 and VγI, II, III, while negative correlation was observed between Foxp3, VγIII and VAS. After SIT, the significant positive correlation between expression levels of Foxp3 and VγIII and negative correlation between Foxp3, VγIII and VAS were observed.Conclusions: Treg and Vγ subfamily T cells were in a dynamic equilibrium in AR patients before and after effective immunotherapy for one year. The early improvement of symptoms following immunotherapy might be independent of the serum sIgE content in AR patients, but associated with the reconstitution of T cell immunity. [ABSTRACT FROM AUTHOR]

Background and Aim: Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients.Methods: Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM).Results: 21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn's index and serum DAK protein.Conclusions: The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients. [ABSTRACT FROM AUTHOR]

Background: Total knee arthroplasty (TKA) is gradually regarded as an effective choice for end-stage osteoarthritis or rheumatic arthritis. In the past, the management of tranexamic acid (TXA) using intravenous injection or topical application has been extensively researched. However, several studies have reported that oral TXA has an effect on blood loss. Therefore, a meta-analysis should be performed to determine whether oral TXA helps to prevent blood loss., Methods: Randomized controlled trials or retrospective cohort studies about relevant studies were searched in PubMed (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL, April 2017). Six studies that compared oral TXA to non-TXA were included in our meta-analysis. Meta-analyses (PRISMA) guidelines, the Cochrane Handbook, and the Jadad scale were used to evaluate the included studies and the results to ensure that the meta-analysis was viable., Results: In accordance with inclusion and exclusion, six studies with 2553 patients (oral TXA = 1386, without TXA = 1167) were eligible and accepted into this meta-analysis. Pooled data indicated that the oral TXA group was effective compared to the without TXA group in terms of hemoglobin (Hb) drop (P < 0.05), blood loss at 24 h (P < 0.05), total blood loss (P < 0.05), and the transfusion rate (P < 0.05). No significant differences were found in the length of hospital stay (P = 0.96) and complications (P = 0.39)., Conclusion: Compared to the non-TXA group, the oral TXA group showed effects of blood sparing. Considering the cost and effectiveness, oral TXA is useful for TKA.

Background: In the past decade, the carbapenemase-producing Enterobacteriaceae (CPE) have been reported worldwide. Emergence of carbapenemase-producing strains among Enterobacteriaceae has been a challenge for treatment of clinical infection. The present study was undertaken to investigate the characteristics of carbapenem-resistant Klebsiella pneumoniae recovered from an outbreak that affected 17 neonatal patients in neonatal intensive care unit (NICU) of Kunming City Maternal and Child health Hospital, which is located in the Kunming city in far southwest of China., Methods: Minimum inhibitory concentrations (MICs) for antimicrobial agents were determined according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI); Modified Hodge test and Carba-NP test were preformed to identified the phenotypes of carbapenemases producing; To determine whether carbapenem resistance was transferable, a conjugation experiment was carried out in mixed broth cultures; Resistant genes were detected by using PCR and sequencing; Plasmids were typed by PCR-based replicon typing method; Clone relationships were analyzed by using multilocus-sequence typing (MLST) and pulsed field gel electrophoresis (PFGE)., Results: Eighteen highly carbapenem-resistant Klebsiella pneumoniae were isolated from patients in NICU and one carbapenem-resistant K. pneumoniae isolate was detected in incubator water. All these isolates harbored bla NDM-1. Moreover, other resistance genes, viz., bla IMP-4 , bla SHV-1 , bla TEM-1 , bla CTX-M-15 , qnrS1, qnrB4, and aacA4 were detected. The bla NDM-1 gene was located on a ca. 50 kb IncFI type plasmid. PFGE analysis showed that NDM-1-producing K. pneumoniae were clonally related and MLST assigned them to sequence type 105., Conclusions: NDM-1 producing strains present in the hospital environment pose a potential risk and the incubator water may act as a diffusion reservoir of NDM-1- producing bacteria. Nosocomial surveillance system should play a more important role in the infection control to limit the spread of these pathogens.