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Aims/Introduction Women with excessive gestational weight gain (GWG) are at a higher risk for complications during pregnancy, such as preeclampsia. However, the association between excessive GWG and gestational diabetes mellitus (GDM) remains unclear. Materials and Methods We retrospectively reviewed 8,352 women from our obstetric database with singleton pregnancies who gave birth after 28 completed weeks of gestation between January 1, 2012, and December 31, 2016, excluding pregnancies complicated by fetal anomalies, fetal death, and overt diabetes. Diagnosis of GDM was based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups. We used two classification methods to define excessive GWG: a weight gain above the 90th percentile of the population, or exceeding the upper range recommended by the Institute of Medicine, stratified by pre‐pregnancy body mass index. Statistical analysis was performed using multiple logistic regression to determine the association between excessive GWG and the risk of GDM. Results Overall, 1,129 women (13.5%) were diagnosed with GDM. There was no difference in GWG between women with and without GDM in the first trimester and before GDM screening. Women with GDM had significantly less GWG in the second trimester, after GDM screening, and throughout the whole gestation than women without GDM. No correlation was found between excessive GWG in the first and second trimesters, before GDM screening, and the later development of GDM. Conclusions Our results indicate that excessive GWG prior to GDM screening is not associated with an increased risk of GDM. more...

Background The optimal first‐line approach for patients with symptomatic atrial fibrillation (AF) remains unclear. We compared the efficacy and safety of cryoballoon ablation (CBA) and antiarrhythmic drugs (AADs) in the initial management of symptomatic AF. Hypothesis CBA is superior to AAD as initial therapy for symptomatic AF. Methods We searched the EMBASE, PubMed, and Cochrane Library databases for randomized controlled trials (RCTs) that compared CBA with AAD as first‐line treatment for AF from the date of database establishment until March 18, 2021. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure of treatment effect. Results Three RCTs that enrolled 724 patients in total were included in this meta‐analysis. Majority of the patients were relatively young and had paroxysmal AF. CBA was associated with a significant reduction in the recurrence of atrial arrhythmia compared with AAD therapy, with low heterogeneity (RR, 0.59; 95% CI, 0.49–0.71; p more...

Background Bone disease causes short-term or long-term physical pain and disability. It is necessary to explore new drug for bone-related disease. This study aimed to explore the role and mechanism of Salidroside in promoting osteogenic differentiation of adipose-derived stromal cells (ADSCs). Methods ADSCs were isolated and treated with different dose of Salidroside. Cell count kit-8 (CCK-8) assay was performed to assess the cell viability of ADSCs. Then, ALP and ARS staining were conducted to assess the early and late osteogenic capacity of ADSCs, respectively. Then, differentially expressed genes were obtained by R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially expressed genes were further analyzed. The expression of OCN, COL1A1, RUNX2, WNT3A, and β-catenin were measured by real-time PCR and Western blot analysis. Last, β-catenin was silenced by small interfering RNA. Results Salidroside significantly increased the ADSCs viability at a dose-response manner. Moreover, Salidroside enhanced osteogenic capacity of ADSCs, which are identified by enhanced ALP activity and calcium deposition. A total of 543 differentially expressed genes were identified between normal and Salidroside-treated ADSCs. Among these differentially expressed genes, 345 genes were upregulated and 198 genes were downregulated. Differentially expressed genes enriched in the Wnt/β-catenin signaling pathway. Western blot assay indicated that Salidroside enhanced the WNT3A and β-catenin expression. Silencing β-catenin partially reversed the promotion effects of Salidroside. PCR and Western blot results further confirmed these results. Conclusion Salidroside promoted osteogenic differentiation of ADSCs through Wnt/β-catenin signaling pathway. more...

Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated. In this study, we found that FOXG1 plays an important role in the auditory degeneration process through regulation of macroautophagy/autophagy. Inhibition of FOXG1 decreased the autophagy activity and led to the accumulation of reactive oxygen species and subsequent apoptosis of cochlear hair cells. Recent clinical studies have found that aspirin plays important roles in the prevention and treatment of various diseases by regulating autophagy and mitochondria function. In this study, we found that aspirin increased the expression of FOXG1, which further activated autophagy and reduced the production of reactive oxygen species and inhibited apoptosis, and thus promoted the survival of mimetic aging HCs and HC-like OC-1 cells. This study demonstrates the regulatory function of the FOXG1 transcription factor through the autophagy pathway during hair cell degeneration in presbycusis, and it provides a new molecular approach for the treatment of age-related hearing loss. Abbreviations: AHL: age-related hearing loss; baf: bafilomycin A1; CD: common deletion; D-gal: D-galactose; GO: glucose oxidase; HC: hair cells; mtDNA: mitochondrial DNA; RAP: rapamycin; ROS: reactive oxygen species; TMRE: tetramethylrhodamine, ethyl ester more...

For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications. more...

Stroke is the second highest cause of death globally and a leading cause of not only physical disability but also cognitive. Approximately two-thirds of Ischemic Stroke patients, who represent the most common type of stroke are found to have mild deficits. Minor stroke, sometimes also referred to as “mild stroke”, is often defined in research studies as a National Institute of Health Stroke Scale (NIHSS) score of 5 or less, although, the cut point for NIHSS score or standardized criterion to define minor stroke has not been established. In the past, many studies have been focusing on the definition of the minor stroke to better stabilize the acute treatment guidelines, to predict the functional outcome, and also for early risk factors stratification. Different studies use different criteria or different cut-points of NIHSS scores to define minor stroke. Aside from indecision of acute management of minor stroke, many other questions have been raised regarding minor strokes, for example, the interaction of large vessel occlusion with minor stroke, the prevalence rate of depression, anxiety, cognitive dysfunction, chronic head after minor stroke, and so on. Finding a universal definition for minor stroke is the key to establish the guideline for management for this group of patients. However, the guidance of treatment of minor stroke is not the focus of this review. The review will focus on the deep comprehension of minor stroke characteristics, summarizing the new findings related to minor stroke, and highlight the essential points to consider for characterizing mild stroke symptoms for a new direction guide for future studies. more...

The trypsin-assisted extraction of polysaccharides from Allium cepa L. was optimized using the response surface methodology (RSM). The optimum extraction conditions were extraction temperature, ext... more...

Hitting SARS-CoV-2 in a new spot A key target for therapeutic antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the spike protein, a trimeric protein complex with each monomer comprising an S1 and an S2 domain that mediate binding to host cells and membrane fusion, respectively. In addition to the receptor binding domain (RBD), S1 has an N-terminal domain (NTD). In searching for neutralizing antibodies, there has been a focus on the RBD. Chi et al. isolated antibodies from 10 convalescent patients and identified an antibody that potently neutralizes the virus but does not bind the RBD. Cryo–electron microscopy revealed the epitope as the NTD. This NTD-targeting antibody may be useful to combine with RBD-targeting antibodies in therapeutic cocktails. Science , this issue p. 650 more...

Background. Hip fractures among older adults are a major public health concern worldwide. This study investigated the potential clinical factors that predict postoperative 1-year activities of daily living (ADL), quality of life (QoL), and mortality in Taiwanese older adults following hip fracture. Methods. This is a prospective cohort study enrolling older adults (≥60 years) who had undergone hip fracture surgery in a single medical center. The comprehensive clinical history of each patient was examined. QoL, ADL, and mortality events were recorded consecutively at 3, 6, and 12 months after operation. The multiple logistic regression model and the generalized estimating equation (GEE) were adopted to identify contributing factors for mortality and postoperative ADL and QoL prognosis, respectively. Results. Among 377 participants with hip fracture, 48 died within 1 year of the index operation. ADL and QoL considerably decreased at 3 months following hip surgery. Old age, high Charlson Comorbidity Index, and American Society of Anesthesiologists grading were crucial predictors for mortality at the 1-year follow-up. The generalized estimating equation analysis indicated that the length of postoperative follow-up time, serum albumin level, patient cognitive status, and handgrip strength were considerably associated with QoL and ADL recovery prognosis in the Taiwanese older adults following hip fracture. Conclusions. Hip fractures have long-lasting effects on the older adults. Our data imply several prognosis predicting parameters that may assist clinicians in accounting for an individual’s personalized risks in order to improve functional outcomes and reduce mortality. more...

Background One of the most common causes of acute cerebral infarction (ACI) is intracranial artery stenosis (ICAS). The goal of our study was to evaluate the accuracy of transcranial Doppler (TCD) compared with magnetic resonance angiography (MRA) for diagnosing ICAS in patients with ACI. Materials and Methods Consecutive patients presenting with ACI to the neurology department underwent both MRA and TCD examination within 6 hours of difference. To calculate the agreement between the results of MRA and TCD, kappa coefficient test was used. Sensitivity, specificity, and positive and negative TCD predictive values have been calculated in comparison with MRA. Results A total of 115 patients was included. There were 77 males (66.95%) and 38 females (33.04%). The mean age of patients was 68.32 ± 10.66 years (range 29–80). The agreement between TCD and MRA in detecting stenosis was 0.56 for anterior circulation artery (ACA), and 0.40 for posterior circulation artery. For the detection of ICAS, sensitivity, specificity, positive predictive value, and negative predictive values were 85.9, 90.0, 98.2, and 50.0% for anterior cerebral artery and 73.5, 86.7, 96.2, and 40.0% for posterior cerebral artery, respectively. Conclusions Moderate agreement of anterior circulation stenosis and fair agreement for posterior circulation stenosis was found between TCD and MRA in the evaluation of ICAS. In anterior circulation, the diagnostic accuracy of TCD is higher compared with the posterior circulation. more...

Purpose Laryngeal squamous-cell carcinoma (LSCC) is the second most common malignant tumor of head and neck squamous cell carcinoma. The study was aimed to identify key long non-coding RNAs (lncRNAs) biomarkers for LSCC. Methods Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between LSCC and adjacent tissues were obtained based on The Cancer Genome Atlas. DElncRNA-DEmRNAs co-expression and DElncRNA-nearby-target DEmRNA interaction networks were constructed. Receiver operating characteristic and survival analysis were performed. A published dataset were as used to validate the result of bioinformatics analysis. Results We obtained 1103 DEmRNAs and 306 DElncRNAs between LSCC and adjacent tissues. A total of 338 DElncRNA-DEmRNA co-expression pairs and 229 DElncRNA-nearby-target DEmRNA pairs were obtained. Ten DElncRNAs and six DEmRNAs has great diagnostic value for LSCC. HOXB9 has potential prognostic value for LSCC. The results of GSE84957 validation were generally consistent with our results. Conclusion Our study provided clues for understanding the mechanism and developing potential biomarkers for LSCC. more...

Background: Previous studies have shown conflicting results about the benefits of pretreatment with intravenous thrombolysis before endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) with large vessel occlusions (LVOs). This study aimed to investigate the clinical efficacy and safety of EVT alone vs. bridging therapy (BT) in patients with AIS with LVOs.Methods: A systematic review with meta-analysis of all available studies comparing clinical outcomes between BT and EVT alone was conducted by searching the National Center for Biotechnology Information/National Library of Medicine PubMed and Web of Science databases for relevant literature from database inception to October 20, 2020.Results: A total of 93 studies enrolling 45,190 patients were included in the present analysis. In both unadjusted and adjusted analyses, BT was associated with a higher likelihood of 90-day good outcome (crude odds ratio [cOR] 1.361, 95% confidence interval [CI] 1.234–1.502 and adjusted OR [aOR] 1.369, 95% CI 1.217–1.540) and successful reperfusion (cOR 1.271, 95% CI 1.149–1.406 and aOR 1.267, 95% CI 1.095–1.465) and lower odds of 90-day mortality (cOR 0.619, 95% CI 0.560–0.684 and aOR 0.718, 95% CI 0.594–0.868) than EVT alone. The two groups did not differ in the occurrence of symptomatic intracranial hemorrhage (sICH) (cOR 1.062, 95% CI 0.915–1.232 and aOR 1.20, 95% CI 0.95–1.47), 24-h early recovery (cOR 1.306, 95% CI 0.906–1.881 and aOR 1.46, 95% CI 0.46–2.19), and number of thrombectomy device passes ≤ 2 (aOR 1.466, 95% CI 0.983–2.185) after sensitivity analyses and adjustment for publication bias.Conclusions: BT provides more benefits than EVT alone in terms of clinical functional outcomes without compromising safety in AIS patients with LVOs. more...

BackgroundA reliable cancer biomarker will be critical for advanced colorectal cancer (CRC) therapeutic approaches since current treatments are limited to certain patient characteristics, such as age, sex, comorbidities and patients received self-expandable metal stents implantations. The association of epidermal growth factor-like domain 6 (EGFL6) with cancer development has been reported. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. MethodsAn anti-EGFL6 antibody was generated by phage display technology to investigate the potential therapeutic efficacy in CRC. Methylene blue staining was applied to investigate the EGFL6 expression in CRC patients and animal tissue. Protein and DNA level of EGFL6 expression as well as related pathway investigation were determined by western blot and quantitative real time PCR. Silence EGFL6 by siRNA transfection, transwell migration and invasion assay were performed to verify EGFL6 function. Student t test, Kruskal-Wallis test and multiple comparisons were used to statistical analysis results. ResultsSignificant EGFL6 expression was found in colon tissues from patients and spontaneous tumorigenesis mouse but not in normal tissue. Furthermore, we found EGFL6 could enhance cancer cell migration, invasion and proliferation in CRC via up-regulating ERK/ AKT pathway, as well as reducing ADAMTS1 and Snail expression. We also found EGFL6 regulates cell abilities through EGFR/αvβ3 integrin receptors. By conducting animal experiments, our anti-EGFL6 antibody, EGFL6-E5-IgG, showed tumor inhibition and anti-metastasis ability. Furthermore, no impact on angiogenesis and wound healing by using EGFL6-E5-IgG were observed. ConclusionsWe demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential cancer biomarker and therapeutic target worth further investigation. more...

Aberrant expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) has been frequently clarified in various cancers, however, its role in endometrial cancer (EC) has not been assessed in detail. This study aimed to investigate the biological role of B3GNT3 in EC and simply explored the detailed mechanism. The EC RNA-Seq dataset from TCGA database was applied to evaluate the expression of B3GNT3 and assess its role on prognostic value. HEC-1-A and KLE cell lines of EC were used to perform loss- and gain-of-function B3GNT3 assays respectively. Quantitative real-time PCR (qRT-PCR) and western blot were used to measure the mRNA and protein levels of indicated molecules respectively. Cell counting kit-8, clone formation tests, and Transwell assay served to determine the changes of proliferative, invasive and migratory abilities of EC cells after altering the expression of B3GNT3. B3GNT3 was found to be highly expressed in EC tissues compared to normal tissues according to the online public databases, which confirmed by the following qRT-PCR in 3 EC cell lines. Besides, high B3GNT3 expression presented a worse overall survival in EC patients as compared with low B3GNT3 expression group. Furthermore, functional experiments in vitro indicated that B3GNT3 could facilitate the cell growth, invasion and migration. Moreover, we found that downregulation of B3GNT3 significantly reduced the expression level of GTP-RhoA and GTP-RAC1, whereas upregulation of B3GNT3 presented the opposite results. The results of current study demonstrate that B3GNT3 acts as an oncogene that promotes EC cells growth, invasion and migration possibly through regulating the RhoA/RAC1 signaling pathway-related markers, suggesting that B3GNT3 may be a candidate biomarker for EC therapeutic intervention. more...

Background: Benign paroxysmal positional vertigo (BPPV) is a self-limiting and recurrent disease but the cost is considerable. The number of patients with BPPV increased significantly under the quarantine policy in Hangzhou. The unhealthy lifestyle risk factors of BPPV have not yet been investigated. Thus, the objective is to analyze whether an unhealthy lifestyle is a risk factor of BPPV.Methods: One hundred and sixty three patients with idiopathic BPPV aged 22–87 years (BPPV group), and 89 aged 23–92 years sex-matched control subjects (non-BPPV group) were enrolled in this study. All BPPV patients received a definitive diagnosis which excluded secondary BPPV. Non-BPPV cases excluded BPPV, sudden deafness, Meniere's disease, ear or craniofacial surgery, vestibular neuritis, and head trauma history. We obtained a blood lipids profile, serum uric acid, total bilirubin, and related diagnostic information through the electronic medical record system. To get the time of physical activities and recumbent positions, we asked the patient or their family from February 2020 to June 2020, and the rest of the patient's information was acquired by phone or WeChat.Data Analyses: The t-test or chi-squared test, univariate, and multiple logistic regression analyses were performed for the two groups. For each factor, odds ratios were calculated with 95% confidence intervals (CIs). Moreover, test equality of two or more receiver operating characteristic (ROC) analyses were applied to the physical activities, and recumbent position time; area under curve (AUC) measures were calculated with 95% CIs and compared with each other.Results: The BPPV group had unhealthy lifestyles such as poor physical activities, prolonged recumbent position time, and low rate of calcium or VD supplementation in univariate logistic regression analyses (P < 0.05). Poor physical activities and prolonged recumbent position time were independently associated with BPPV in multiple logistic regression models (OR = 18.92, 95% CI: 6.34–56.43, p = 0.00 and OR = 1.15, 95% CI: 1.01–1.33, p < 0.04). In the comparison of ROC curves of recumbent position time and physical activities in identifying BPPV, AUCs were 0.68 (0.61–0.74), and 0.68 (0.63–0.73), respectively.Conclusion: We conclude that poor physical activities and prolonged recumbent position time may be independent risk factors for BPPV patients, but hypertension, hyperuricemia, hyperlipidemia, hemoglobin, diabetes, serum bilirubin, CHD, and CI, may not be. more...

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials., A vaccine preventing infection and transmission of SARS-CoV-2 is needed. Here, Wu et al. generate an adenovirus-vector vaccine expressing SARS-CoV-2 spike protein and show that a single dose of mucosal vaccination protects mice and ferrets from infection and inhibits virus replication in the upper respiratory tract. more...

Introduction: Intracranial artery stenosis is the most common cause of acute ischemic stroke, especially among people in Asia. About its epidemiology, however little is understood. The goal of our research is to establish the prevalence of intracranial artery stenosis in patients with acute ischemic stroke in a tertiary care hospital. Methods: A descriptive cross-sectional study was done in 1006 acute ischemic stroke patients at Affiliated Zhongda Hospital, School of Medicine, Southeast University China from May 2018 to May 2019. Ethical approval was taken from the Ethical review committee of the institution. A convenient sampling method was done. Intracranial artery stenosis was diagnosed when evidence of acute ischemic stroke was found in the territory of approximately 2 50% stenosis identified by Transcranial Doppler ultrasound and confirmed by magnetic resonance angiography or computed tomography. Statistical analysis was done using the Statistical Package for the Social Sciences version 20. Results: The prevalence of intracranial artery stenosis was found in 331 (32.90%) patients at 95% Confidence interval (0.24-0.42%). Among 331 cases the anterior circulation artery stenosis was present on 201 (19.98%) patients, followed by posterior circulation artery stenosis on 80 (7.95%) patients, then anterior plus posterior circulation artery stenosis on 50 (4.97%) patients. Conclusions: Intracranial artery stenosis is one of the most causes of acute ischemic stroke in China. The proportion of anterior circulation artery stenosis was higher than that in the posterior circulation. more...

Background: Benign paroxysmal positional vertigo (BPPV) is self-limiting and recurrent but the cost is considerable. The recurrence of BPPV increased significantly under the quarantine policy in Hangzhou. The unhealthy lifestyle risk factors of the recurrence of BPPV have not yet been investigated. So, the objective is to analyze the unhealthy lifestyle risk factors of recurrent BPPV.Methods: A retrospective observational study was conducted in the Department of Neurology in Tongde Hospital of Zhejiang Province from December 2018 to March 2020. The study included 186 patients aged 23–86 years. All patients received the definitive diagnosis and canalith repositioning maneuvers (CRM) treatment and finally accomplished follow-up for one year. Demographic variables, potential recurrence risk factors, neurological examination, cranial computed tomography and lifestyle were assessed.Data Analyses: The t-test or chi-squared test was first performed for group comparison, then logistic regression analysis was performed to investigate the recurrence risk factors in all of the patients.Results: The 1-year recurrence rates of BPPV patients after reposition maneuvers were 36.02%, is significantly higher than other study especially in the first quarter of 2020 (38.8% of patients with BPPV recurrence). Logistic regression analysis shows that BPPV patients who was poor physical activities and prolonged recumbent position time have more recurrence risks. Poor physical activities (odds ratio =5.690, 95% confidence interval: 1.650-19.618, p Conclusion: We conclude that poor physical activities and prolonged recumbent position time may be independent risk factors for the recurrence of BPPV patients, but aging, Ménière’s disease, sudden deafness migraine, hypertension, hyperlipemia, diabetes, CHD, POCI, mental factors, and mental labor do not increase the recurrence risk. more...

The Astragalus membranaceus polysaccharides (APS) can improve immunity and enhance treatment reactions. This study analyzed the effects of effective antivascular endothelial growth factor (anti-VEGF) antibody production in mice treated with APS. After APS treatment, the serum of mice produced the antibody reactions that can cross-validate VEGF. The isolated single-chain fragment variable (scFv) antibodies could neutralize VEGF and inhibit in vivo tumor growth. Of the scFvs, scFv 4E can significantly compete the interaction of bevacizumab with VEGF. In cell experiments, scFv 4E effectively inhibited human umbilical vein endothelial cells induced by VEGF in vitro. In a matrix gel-assisted angiogenesis model, scFv 4E significantly inhibited angiogenesis reactions. In addition, in a xenograft model established in the colorectal cancer cell strain HCT116, scFv 4E treatment inhibited tumor growth by up to 52.7%. Finally, molecule docking was performed to simulate the complex interactions of scFv 4E and VEGF, the main driving forces of which involve the hydrophobic interactions and hydrogen bonds of Tyr108 and Tyr 109 of the complementarity-determining region H3 loop with VEGF. The results help in establishing antibody library with high diversity for selecting antibodies with specificity. In addition, this study indirectly expounded the correlations of APS enhancing immunity regulation in vivo. more...

Fibroblast growth factors (FGFs) and their receptors control various biological functions. Dysregulated FGF signaling has been implicated in the pathogenesis of human cancers. Aberrant activation o... more...

Objective: To compare the risk profiles for gestational diabetes mellitus (GDM) using a one-step and two-step screening method and diagnostic criteria. Materials and methods: A retrospective cohort study was conducted among women screened using Carpenter and Coustan's (C&C) criteria (two-step method) and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (one-step method). All deliveries after 28 weeks of gestation, except for pregnancies complicated by pre-pregnancy diabetes mellitus, were analyzed. Multiple logistic regression was used to assess the associations between GDM and various potential risk factors. Results: Risk factors for C&C-defined GDM were pre-pregnancy body mass index >24.2 kg/m2 (adjusted odds ratio [OR] 2.49, 95% confidence interval [CI] 1.92–3.23), maternal age at delivery >34 years (adjusted OR 2.46, 95% CI 1.96–3.09), history of fetal death (adjusted OR 2.56, 95% CI 1.37–4.78), and chronic hypertension (adjusted OR 3.66, 95% CI 1.50–8.91). In addition to these factors, conception assisted by reproductive technology (adjusted OR 1.64, 95% CI 1.19–2.25) and genetic amniocentesis (adjusted OR 1.19, 95% CI 1.03–1.38) were IADPSG-defined GDM risk factors. Conclusion: Risk factors for GDM differ with the diagnostic criteria used. This information is important when changing GDM screening strategies from the two-step approach to the one-step approach. Keywords: Assisted reproductive technology, Body mass index, Gestational diabetes mellitus, Risk factors more...

Objective To compare proposed new cutoff points for four obesity indicators—waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip ratio (WHR) and body mass index (BMI)—with their current cutoff points to determine which are better standards predicting 5-year incidence of hypertension (HT) and diabetes mellitus (DM) among premenopausal women. Design Data were obtained from the 2002 and 2007 Survey on the Prevalence of HT, Hyperglycemia and Hyperlipidemia in Taiwan conducted by the Ministry of Health and Welfare, Taiwan. Premenopausal women were grouped based on the proposed cutoff points versus reference cutoff points for obesity indicators. Participant A total of 1466 premenopausal women aged between 20 and 57 years old were recruited. Main outcome measure Five-year incidence of HT and DM. Results Our new obesity indicator cutoff points—WHtR 0.49, WC 74.7 cm, WHR 0.79 and BMI 22.3 kg/m2—were better predictors for 5-year HT incidence in premenopausal women compared with those of current standards, but were not significantly different for DM. Among the four obesity indicators, WHtR and WC were optimal for their 5-year predictive ability for HT and DM in premenopausal women. Conclusions To avoid too many cutoff points for practitioners to adopt and memorize, the proposed new cutoff points were recommended preferentially to prevent the incidence of HT and DM in premenopausal women. more...

Pollination dynamics was studied in a first-generation Platycladus orientalis (L.) Franco seed orchard with pedigree reconstruction using eight nuclear and four chloroplast SSRs. The pedigree reconstruction assigned 371 of 448 studied seeds to one of the orchard’s 192 candidate male parents and showed a high level of outcrossing and pollen contamination in the orchard’s seed crop. While the orchard’s seed population showed greater allelic richness compared with the parental population, a few alleles present in the parental population were missing in the seed crop. Additionally, we detected no significant correlation between male reproductive energy (pollen yield) and male reproductive success; however, uneven parental contribution was also observed. Pollen management practices were recommended to ensure the maintenance of genetic diversity in the seed crops and increase in genetic gain. more...

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P more...

Given the low substitution rate in plastomes, the polymorphic and codominant nature of chloroplast SSRs (cpSSRs) makes them ideal markers, complementing their nuclear counterpart. In Cupressaceae, cpSSRs are mostly paternally inherited, thus, they are useful in mating systems and pollen flow studies. Using e‐PCR, 92 SSR loci were identified across six Cupressaceae plastomes, and primers were designed for 26 loci with potential interspecific transferability. The 26 developed cpSSRs were polymorphic in four genera, Platycladus, Sabina, Juniperus, and Cupressus and are suitable for Cupressaceae molecular genetic studies and utilization. We genotyped 192 Platycladus orientalis samples from a core breeding population using 10 of the developed cpSSRs and 10 nuclear SSRs, and these individuals were identified with high confidence. The developed cpSSRs can be used in (1) a marker‐assisted breeding scheme, specifically when paternity identification is required, (2) population genetics investigations, and (3) biogeography of Cupressaceae and unraveling the genetic relationships between related species. more...

Background Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a protective mechanism for secondary inflammatory injury as well as a contributor to infection complications. Although stroke-induced hyperactivation of the sympathetic system is proved to facilitate SIDS, the involved endogenous factors and pathways are largely elusive. In this study, we aim to investigate the function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS. Methods Splenic ARRB2 expression and the sympathetic system activity were detected after establishing transient models of middle cerebral artery occlusion (MCAO). In addition, a correlation between ARRB2 expression and the sympathetic system activity was analyzed using a linear correlation analysis. Any SIDS reflected in monocyte dysfunction was investigated by measuring inflammatory cytokine secretion and neurological deficit scores and infarct volume were tested to assess neurological outcome. Further, ARRB2 expression in the monocytes was knocked down in vitro by siRNAs. Following the stimulation of noradrenaline and lipopolysaccharide, cytokine secretion and the nuclear factor-κB (NF-κB) pathway were evaluated to gain insight into the mechanisms related to the contribution of ARRB2 to adrenergic-induced monocyte dysfunction. Results Splenic ARRB2 expression was significantly increased after stroke and also showed a significant positive correlation with the sympathetic system activity. Stroke-induced monocyte dysfunction resulted in an increase of the interleukin-10 (IL-10) level as well as a decrease of the interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Also, blockade of adrenergic-activity significantly reversed these cytokine levels, and blockade of adrenergic-activity improved stroke-induced neurological results. However, the improved neurological results had no significant correlation with ARRB2 expression. Furthermore, the in vitro results showed that the deficiency of ARRB2 dramatically repealed adrenergic-induced monocyte dysfunction and the inhibition of NF-κB signaling phosphorylation activity. Conclusions ARRB2 is implicated in the sympathetic-triggered SIDS, in particular, monocyte dysfunction after stroke. Accordingly, ARRB2 may be a promising therapeutic target for the immunological management of stroke in a clinic. more...

BACKGROUND: Overweight/obesity is a substantial global public health concern, which can be caused by genetic factors and energy balance-related behaviors (EBRBs). If it occurs in children with congenital heart disease (CCHD), it can yield an extra burden on their health. Most studies on CCHD have taken place in Western societies, leaving Asian populations understudied, especially children. OBJECTIVE: We sought (1) to determine body mass index distribution among school-aged CCHD in Taiwan, (2) to ascertain whether the body mass index of CCHD differs from that of the general population, (3) to describe EBRBs in CCHD, and (4) to identify factors associated with underweight and overweight/obesity among CCHD. METHODS: In this cross-sectional study, 97 child-parent dyads (53.6% boys; mean age, 9.73 years; 25.8% moderate-to-severe heart conditions) were enrolled. Self-administered questionnaires were used to collect demographics, medical factors, food frequency, physical activity, and sedentary behaviors. Anthropometric measurements were taken in the hospital. Independent predictors of EBRBs and health conditions were calculated through logistic regression analysis. RESULTS: Among Taiwanese CCHD, 19.6% were underweight and 14.4% were overweight/obese. Children with moderate-to-severe heart defects were more often underweight. Body mass index did not differ between CCHD and children in the general population. More complex heart defects and asthma were associated with being underweight, whereas sedentary behaviors, cardiomegaly, and the New York Heart Association classification II to IV were associated with being overweight/obese. CONCLUSIONS: Sedentary lifestyle is seemingly the only EBRB correlated with being overweight. Physical activity programs for children may help prevent and treat overweight or obesity in Asian CCHD, similar to Western countries. ispartof: JOURNAL OF CARDIOVASCULAR NURSING vol:35 issue:3 pages:291-299 ispartof: location:United States status: published more...

Background and purpose MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the early stage of acute ischaemic stroke (AIS). The purpose of this study was to investigate the expression patterns of miRNAs in peripheral blood mononuclear cells (PBMCs) from AIS patients and further explore related molecular mechanisms in stroke-induced immunodeficiency syndrome (SIDS). Methods The miRNA expression patterns of PBMCs were detected by miRNA microarray and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in AIS patients and healthy controls. Bioinformatics methods and luciferase reporter assays were used to detect the downstream target genes. Following stimulation with lipopolysaccharide and interleukin-4, the expression of miR-4443, tumor necrosis factor receptor associated factor 4 (TRAF4) and the nuclear factor kappa B (NF-κB) pathway were evaluated. Furthermore, transfection with miR-4443 mimic or inhibitor in the monocytes was carried out to gain insight into the mechanisms in SIDS. Results Interleukin-10 in AIS patients was significantly higher than that of healthy controls. The miRNA microarray analysis and qRTPCR validation showed that only miR-4443 was upregulated expressed in PBMCs from AIS patients, especially in monocytes. miR-4443 was shown to directly interact with the 3' untranslated regions of TRAF4, resulting in suppression of TRAF4 protein expression. Furthermore, the expression of miR-4443 and TRAF4 was regulated by stimulation with lipopolysaccharide or interleukin-4. Additionally, overexpression of miR-4443 suppressed the TRAF4/Iκα/NF-κB signaling pathway to activate the expression of anti-inflammatory cytokines in monocytes. Conclusions The increased expression of miR-4443 induced monocyte dysfunction by targeting TRAF4, which may function as a crucial mediator in SIDS. more...

Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used d -galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways. more...

BACKGROUND The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector-target interactions by cytotoxic analysis and conjugate formation assay. RESULTS We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I- cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis. CONCLUSION In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector-target interaction. more...

Background and purpose The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months. Methods Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0–1; good outcome, mRS 0–2; and death, mRS 6). Results In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89–4.55) compared with patients with a TG/HDL-C ≥ 0.87. Conclusions A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS. more...

// Huan Wang 1 , Fu-Ling Yan 1 , Michael Cunningham 3 , Qi-Wen Deng 1 , Lei Zuo 1 , Fang-Lan Xing 1 , Lu-Hang Shi 2 , Shan-Shan Hu 2 , Ya Huang 2 1 Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China 2 School of Medicine, Southeast University, Nanjing, China 3 Public Health School of Southeast University, Nanjing, China Correspondence to: Fu-Ling Yan, email: yanfuling218@163.com Keywords: stroke, infection, immune, sympathetic pathway, HLA-DR Received: February 25, 2016 Accepted: June 30, 2016 Published: July 08, 2016 ABSTRACT Background: Evidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood. Results: SAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no-infection patients within 48h after stroke onset. NA significantly increased IL-10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing β-arrestin2 expression which reduced the activation of the NF-κB pathway. Propranolol reversed this effect of NA by reducing β-arrestin2 expression. Materials and Methods: A systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of β-arrestin2, NF-κB, IκBα and phosphor-IκBα were performed to assess the activation of the sympathetic pathway. Conclusion: IL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration. more...

Nasopharyngeal carcinoma (NPC) is one of the most malignant head and neck carcinomas with unique epidemiological features. In this study, we aimed to identify the novel NPC-related genes and biological pathways, shedding light on the potential molecular mechanisms of NPC. Based on Gene Expression Omnibus (GEO) database, an integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in NPC compared to normal control. The genes which were both differentially expressed and differentially methylated were identified. Functional annotation and protein–protein interaction (PPI) network construction were used to uncover biological functions of DEGs. Two DNA methylation and five gene expression datasets were incorporated. A total of 1074 genes were up-regulated and 939 genes were down-regulated in NPC were identified. A total of 719 differential methylation CpG sites (DMCs) including 1 hypermethylated sites and 718 hypomethylated sites were identified. Among which, 11 genes were both DEGs and DMGs in NPC. Pathways in cancer, p53 signaling pathway and Epstein–Barr virus infection were three pathways significantly enriched pathways in DEmRNAs of NPC. The PPI network of top 50 DEGs were consisted of 191 nodes and 191 edges. Our study was helpful to elucidate the underlying mechanism of NPC and provide clues for therapeutic methods. more...

Presbycusis is a sensorineural hearing loss caused by hearing system aging and degeneration. The clinical manifestations are progressive bilateral symmetrical hearing loss, and the hearing curve is mostly slope-shaped with high-frequency reduction, sometimes flat. The results of the second national sample survey of disabled persons (2006) showed that the total number of hearing and speech disability in China was 27.8 million, accounting for 34% of the total number of disabled people in China. Among them are people over 60 years old. There are 20.4541 million people with hearing disabilities. There are 9.49 million senile deaf patients, accounting for 34.1% of the total number of hearing disabilities. As society gradually becomes aging, the incidence of presbycusis is getting higher and higher. The study of its pathogenesis is of great significance for the diagnosis, treatment, and prevention of presbycusis. The rapid progress of molecular biology experimental technology has provided us with a new opportunity to fully understand and reveal the presbycusis. In the near future, early diagnosis of presbycusis-related genes and early prevention or delay of the occurrence and development of presbycusis will become a reality. more...

The human cluster of differentiation 19 (CD19) is highly expressed in most leukemia, rendering is a promising therapeutic target. In this study, we generated anti-CD19 single-chain variable fragments (scFv) from immunized chickens by phage display technology. After constructing a scFv antibody library with 2.5 × 10 more...

To understand the mechanism for inhibition of hepatitis B virus (HBV) infection is important. In this study, single-chain variable fragment (scFv) antibodies were generated and directed to the pre-S2 epitope of HBV surface antigen (HBsAg). These human scFvs were isolated from a person with history of HBV infection by phage display technology. An evaluation of panning efficiency revealed that the eluted phage titer was increased, indicating that specific clones were enriched after panning. Selected scFvs were characterized with the recombinant HBsAg through Western blotting and enzyme-linked immunosorbent assay to confirm the binding ability. Flow cytometry analysis and immunocytochemical staining revealed that one scFv, S17, could recognize endogenous HBsAg expressed on the HepG2215 cell membrane. Moreover, the binding affinity of scFv S17 to the pre-S2 epitope was determined to be 4.2 × 10-8 M. Two ion interactions were observed as the major driving forces for scFv S17 interacting with pre-S2 by performing a rational molecular docking analysis. This study provides insights into the structural basis to understand the interactions between an antibody and the pre-S2 epitope. The functional scFv format can potentially be used in future immunotherapeutic applications. more...

The cosmetic and functional deformities induced by thickened folds and furrows are the main complaints of patients in pachydermoperiostosis (PDP). However, traditional drug therapy only has a limited effect for its unclear genetic pathogenesis. Surgical treatment has now become one of the optimal strategies mainly aiming for its cosmetic improvement. Here we describe a comprehensive management of PDP approached with surgical procedure thereby showing markedly improved cosmetic outcome. Experientially, the surgical treatment of PDP is effective and may be preferentially recommended for PDP patients especially of severe degree. more...

Background: Studies suggest that brain-derived neurotrophic factor (BDNF) exerts effects on the neuronal function of hippocampal neurons and increases hippocampal mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, which causes depressive behaviors in rat or mouse. Here we focus on the change of serum MKP-1, BDNF, testosterone (T), and estradiol (E2) levels, in order to test the hypothesis that dysregulation of MKP-1, BDNF, T, and E2 are associated with depression in perimenopausal women. Methods: Women with depression, after meeting criteria in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, for mental and behaviural disorders and the 17-item Hamilton Depression Rating Scale (HDRS), were included in the study. Psychosocial data and blood samples were obtained from the subjects in the study, including 38 perimenopausal and 32 young women with depression, 26 healthy control perimenopausal women, and 34 young women. Results: Serum MKP-1 levels were higher and T was lower in the women with depression compared to controls (p more...

In previous study, we found that in order to prevent MS in women aged65 years, the cutoff points of obesity indicators should be lowered.To investigate whether our proposed cutoff points of obesity indicators predict the occurrence of hypertension (HT), diabetes mellitus (DM), and hyperlipidemia in premenopausal women with greater sensitivity and specificity compared to reference cutoff points of obesity that are currently being used.Using the database of the "2002 Survey on the Prevalence of Hypertension, Hyperglycemia and Hyperlipidemia in Taiwan" provided by the Bureau of Health Promotion, Taiwan as research material, data from 2270 premenopausal women aged 20-65 years were used for the analyses. The receiver-operating characteristic curves (ROC) of the body-mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were used to predict HT, DM, and hyperlipidemia.Obesity is not a good predictor of the occurrence of hyperlipidemia in premenopausal women aged65 years. However, our proposed cutoff points had greater sensitivity and specificity than did the reference cutoff points. To prevent the risk of HT and DM in premenopausal women, the cutoff points of obesity indicators should be reduced. The proposed values are as follows: a WHR of 0.79; a WC of 74.7 cm; a WHtR of 0.49; and a BMI of 22.3 kg/m(2). more...

Essential thrombocythemia (ET) is characterized by thrombotic and hemorrhagic events. The association of clinical characteristics of Chinese ET patients and additional sex combs like 1 (ASXL1) mutations in these patients has remained to be elucidated. In the present study, 72 newly diagnosed Chinese ET patients were enrolled to determine ASXL1 mutations. Mutations in ASXL1, Janus kinase (JAK)2, calreticulin (CALR) and myeloproliferative leukemia (MPL) genes were detected using Sanger sequencing, and data were statistically analyzed. The frequencies of ASXL1, JAK2 V617F, CALR and MPL W515 mutations in ET patients were 19.4% (14/72), 29.2% (21/72), 31.9% (23/72) and 0% (0/72), respectively. Of note, 28 ET patients (38.9%) were negative for JAK2, CALR and MPL mutations; these patients were classified as triple-negative (TN). The frequency of ASXL1 mutations in patients with JAK2 V617F, CALR and TN mutations was 23.8% (5/21), 21.7% (5/23) and 14.3% (4/28), respectively. ASXL1-mutant patients exhibited significant propensities for thrombotic events compared with the ASXL1 wild-type (wt) cohort (42.9 vs. 12.1%; P=0.021). In addition, JAK2 V617F-mutant patients had a higher mean age compared with CALR-mutant (64.76 vs. 52.96 years; P=0.008) or TN patients (64.76 vs. 51.14 years; P=0.002). Furthermore, more white blood cells in the peripheral blood (PB) were observed in JAK2 V617F-mutant patients compared with those in TN patients (12.40 vs. 8.20×109/l; P=0.02). In addition, CALR-mutant patients exhibited more platelets (PLT) in PB than JAK2 V617F-mutant patients (787.91 vs. 562.17×109/l; P=0.047). TN patients had a significantly lower incidence of clinical symptoms, including dizziness, palpitation and chest congestion compared with CALR- or JAK2 V617F-mutant patients (14.1 vs. 39.1%; P=0.043 and 14.1 vs. 38.1%; P=0.050). No significant difference in progression-free survival was observed between ASXL1-mutant and ASXL1-wt patients (P=0.590). In conclusion, ASXL1-mutant ET patients are prone to experiencing thrombotic events. There was no significant difference in the occurrence of thrombotic events among CARL-mutant, JAK2 V617F-mutant and TN patients. Furthermore, ASXL1-mutant/TN patients exhibited a higher number of PLT than ASXL1/JAK2 V617F-double mutant patients. Therefore, ASXL1 mutations may be a risk factor for the occurrence of thrombotic events in ET patients. more...

Objective To observe the effect of complex reinforcing-reducing manipulations of acupuncture on flexion and extension angles of hip and knee in patients after surgical treatment of gluteus maximus contracture. more...

The aim of the present study was to investigate the key genes, miRNAs and pathways in hypopharyngeal squamous cell carcinoma (HPSCC) and to elucidate the mechanisms underlying HPSCC development. The gene and microRNA (miRNA) expression profiles of HPSCC tissues and adjacent normal tissues from three subjects were obtained. Differentially expressed genes (DEGs) and differentially expressed miRNAs were identified in HPSCC. Functional annotation and protein-protein interaction (PPI) network were conducted to elucidate the biological functions of DEGs. A total of 160 DEGs (16 upregulated and 144 downregulated genes) and 79 differentially expressed miRNAs (48 upregulated and 31 downregulated miRNAs) were identified in HPSCC. The deregulated genes were significantly involved in spliceosome, cell cycle and RNA degradation. In the PPI network, S-phase kinase associated protein 1 (SKP1), non-POU domain containing octamer binding (NONO) and zinc activated ion channel (ZACN) were identified as hub proteins. On the whole, the present study may help to gain a comprehensive understanding of tumorigenesis in HPSCC and provide valuable information for early diagnosis and drug design of HPSCC in future research. more...

To observe the effect of reinforcing and reducing manipulation by breathing on yin and yang meridian points for motor function of knee joints in patients with ischemic stroke. A total of 60 ischemic stroke cases were randomly allocated into an observation group and a control group, 30 in each group. Other than basic and conventional rehabilitation therapies, cases in the observation group were treated with reinforcing and reducing manipulation on yin and yang meridians points for a period of 8 weeks; whereas cases in the control group only received the same basic and conventional rehabilitation therapy as that in the observation group. Then the knee joint energy, support moment and shaking moment were compared between the two groups before treatment, and after 4-week and 8-week treatment respectively. Before treatment, there were no between-group significant differences in knee joint energy, support moment and shaking moment (all P>0.05). After treatment, the knee joint energy, support moment and shaking moment in both groups were significantly improved (P more...

Recombinant human interferon-omega (rhIFN-omega) exhibits a potent antiviral activity. Because of poor pharmacokinetics (PK) of rhIEN-omega, frequent dosing of rhIFN-omega is necessitated to achieve the sustained antiviral efficacy. PEGylation can efficiently improve the PK of rhIFN-omega while substantially decrease its bioactivity. The structure, antiviral activity and PK of the PEGylated rhIEN-omega were measured to establish their relationship with PEGylation sites, polyethylene glycol (PEG) mass and PEG structure. Accordingly, N-terminus and the lysine residues were selected as the PEGylation sites. PEGs with M-w of 20 kDa and 40 kDa were used to investigate the effect of PEG mass. Linear and branched PEGs were used to investigate the effect of PEG structure. PEGylation decreased the antiviral activity of rhIEN-omega and improved its PK. The PEGylation sites determine the bioactivity of the PEGylated rhIFN-omega and the conjugated PEG mass determines the PK. N-terminally PEGylated rhIFN-omega with 40 kDa linear PEG maintains 21.7% of the rhIFN-omega antiviral activity with a half-life of 139.6 h. Thus, N-terminally PEGylated rhIFN-omega with linear 40 kDa PEG is a potential antiviral agent for long-acting treatment of the viral diseases. (C) 2014 Elsevier B.V. All rights reserved. more...

Objective We observed the clinical effect of massage in treating chronic persistent pediatric asthma and the changes in expression of TLR1, TLR2, and TLR4 on macrophages. Methods One hundred sixty pediatric patients with persistent chronic asthma were collected, and divided into treatment and control groups of 80 each in strict accordance with the principle of random allocation. The patients in the control group received general nebulizer therapy, and the patients in the treatment group received infantile massage. Both groups of patients were observed for 3 months with respect to the following indicators: the frequency of asthmatic attacks; the frequency of respiratory tract infections (RTIs); C-ACT rating; and the PEF% of peripheral blood (PB) before and after treatment to detect macrophage TLR1, TLR2, and TLR4. Results After treatment, the frequency of asthmatic attacks, frequency of RTIs, C-ACT rating, and the PEF% and macrophage TLR1, TLR2, and TLR4 expression of fluorescence intensity in the treatment group showed a statistically significant increase when compared with the control group (*P Conclusion Pediatric massage can improve the clinical symptoms of pediatric asthma by up-regulating the expression of macrophage TLR1, TLR2, and TLR4. more...