An unusually high prevalence of allergic rhinitis at high altitudes in 6-7 year old children - An epidemiological study.

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6-7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6-7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2-38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8-21.6) (p < 0.001). Both areas studied had a greater prevalence of AR compared to international data. In both XB and DiQ, male gender, history of early antibiotic use, urban place of birth and place of residence, presence of smokers within the same household, family history of allergic diseases (such as atopic dermatitis), as well as higher parental educational level were all associated with a higher prevalence of AR (p < 0.05). In DiQ, the prevalence of AR in Han ethnicity was greater than that of ethnic minorities (p < 0.05). In XB, being a single child was associated with an increased prevalence of AR compared to those who had siblings (p < 0.05). Conclusion: Our study found that the prevalence of AR is relatively greater at higher altitudes. Genetic and environmental factors both play an important role in the pathogenesis of AR. While altitude may be an important environmental factor, confounding factors may include humidity, temperature and distribution pattern of common aeroallergens.

Whole-Genome Sequencing for Identifying Candidate Genes Related to the Special Phenotypes of the Taihu Dianzi Pigeon.

The Taihu Dianzi pigeon is a breed native to China, and its special piebalding, crest, and polydactyly phenotypes are the result of artificial and natural selection. Here, we analyzed the genetic differences among three kinds of pigeons with different phenotypes at the genomic level. A selective sweep was conducted based on the fixation index (FST) and nucleotide diversity (π) ratio, and the results revealed that MC1R was related to the formation of the distinctive piebalding of the Taihu Dianzi pigeon. Combined with the results of genome-wide association studies, we identified candidate genes associated with the crest (SMYD and STOX2) and polydactyly (SLC52A3 and ANGPT4). The candidate genes identified in this study and their variants may be useful for understanding the genetic mechanism underlying the special phenotypes of the Taihu Dianzi pigeon. This study provides new insights into the genetic factors that may influence the formation of the special piebalding, crest, and polydactyly characteristics in pigeons.

Engineering 0D/2D Architecture of Ni(OH)2 Nanoparticles on Covalent Organic Framework Nanosheets for Selective Visible-Light-Driven CO2 Reduction.

Low-dimensional materials serving as photocatalysts favor providing abundant unsaturated active sites and shortening the charge transport distance, but the high surface energy readily causes the aggregation that limits their application. Herein, it is demonstrated that 2D covalent organic framework (COF) TpBD nanosheets are effective in the dispersion and stabilization of 0D Ni(OH)2 . The COF precursor TpBD is synthesized from the Schiff base condensation of 1,3,5-triformylphloroglucinol (Tp) and benzidine (BD) and exfoliated into 2D nanosheets named BDNs via ultrasonication. The formation of highly dispersive 0D Ni(OH)2 on BDNs is reached under a mild weak basic condition, enabling robust active sites for CO2 adsorption/activation and rapid interface cascaded electron transport channels for the accumulation of long-lived photo-generated charges. The champion catalyst 30%Ni-BDNs effectively catalyze the CO2 to CO conversion under visible-light irradiation, offering a high CO evolution rate of 158.4 mmol g-1 h-1 and turnover frequency of 51 h-1 . By contrast, the counterpart photocatalyst, the bulk TpBD stabilized Ni(OH)2 , affords a much lower CO evolution rate and selectivity. This work demonstrates a new avenue to simultaneously construct efficient active sites and electron transport channels by coupling 0D metal hydroxides and 2D COF nanosheets for CO2 photoreduction.

Allergic Rhinitis as an Independent Risk Factor for Postoperative Recurrence of Children Chronic Sinusitis.

(1) Background: The recurrence rate of childhood recurrent sinusitis varies widely between 12% and 50%, with the postoperative recurrence risk factors remaining largely unidentified. We sought to enhance the understanding of chronic rhinosinusitis (CRS) via a retrospective observational childhood cohort. (2) Methods: The study recruited 125 cases. Demographic data and univariate and multivariate logistic regression analyses were conducted to investigate potential risk factors of childhood recurrent sinusitis following functional endoscopic sinus surgery (FESS). (3) Results: A postoperative recurrence rate of 21.6% was determined. Among the participants, 21 cases presented a history of allergic rhinitis (AR), with the remaining 104 cases being AR-free. A significantly heightened recurrence rate was noted in those bearing a history of AR compared to their counterparts devoid of such history (p < 0.000). The fully adjusted logistic regression model indicated a 21.04-fold increased risk of postoperative recurrence in childhood CRS bearing a history of AR compared to those without an AR history (p = 0.000), highlighting the history of AR as an independent risk factor for postoperative childhood recurrent sinusitis (p = 0.001); (4) Conclusions: The data implicate AR as an independent risk factor for postoperative childhood recurrent sinusitis.

Evaluation of Intralymphatic Immunotherapy in Allergic Rhinitis Patients: A Systematic Review and Meta-analysis.

Background: Intralymphatic immunotherapy (ILIT) is short-course administration of allergen-specific immunotherapy (AIT). This study is aimed at assessing the clinical efficacy and safety of ILIT in patients with allergic rhinitis (AR). Methods: MEDLINE, PUBMED, and Cochrane Library were used to conduct electronic searches for clinical trials comparing ILIT and placebo in patients with AR. The final search took place on August 24, 2022. Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias in the included studies. The outcomes included combined symptom and medication scores (CSMS), visual analog scale (VAS), allergic rhinoconjunctivitis quality of life (RQLQ), Skin-prick test (SPT), and adverse events (AEs). Data were synthesized as mean difference (MD)/standard mean difference (SMD) or risk difference (RD) and 95% confidence interval (CI). Results: Thirteen studies (454 participants) were included in this study. The ILIT group had better clinical improvement on the CSMS (random effects model, SMD-0.85, 95% CI [-1.58, -0.11], P = 0.02) and RQLQ (fixed-effects model, MD-0.42, 95% CI [0.69, 0.15], P = 0.003) than the placebo group. The booster injection was beneficial for CSMS (P < 0.0001), and the 4-week injection interval was superior to the 2-week injection period for improving VAS (P < 0.0001). Local swelling or erythema was the main AE following injection (random effects model, RD 0.16, 95% CI [0.05, 0.27], P = 0.005). Discussion. For individuals with AR, ILIT is safe and effective. ILIT alleviates clinical symptoms and reduces pharmaceutical consumption without causing severe AEs. However, the validity of this study is compromised by the substantial heterogeneity and risk of bias in the included researches. RegistrationCRD42022355329.

Evaluation of Meat Quality of Local Pigeon Varieties in China.

To evaluate the germplasm characteristics and nutritional value of Chinese native pigeon varieties, this study analyzed the nutrient composition of the meat of four Chinese native pigeon varieties and then compared them with those of the White King pigeon, which is the most commonly used in China. A total of 150 pigeons aged 28 d (squabs) of 5 breeds including Taihu pigeon, Shiqi pigeon, Ta-rim pigeon, Boot pigeon, and White King pigeon were selected for slaughter. The basic meat quality parameters and contents of conventional nutritional compositions, inosine acid, amino acids, and fatty acids were measured. The results showed that there were significant differences in flesh color (L*, b*), pH, and water loss rate of different breeds of suckling pigeons (p < 0.05). Compared with White King pigeons, four local breeds had dark breast meat and a low water loss rate. The protein contents of Taihu, Tarim, and Shiqi suckling pigeons were significantly higher than those of White King pigeons (p < 0.05). Taihu pigeons had the highest protein content, reaching 22.72%. The inosinic acid content of Tarim pigeons was the highest (1.31 mg/g) and was significantly higher than that of Shiqi pigeons, Boot pigeons, and White King pigeons (p < 0.05). There was no significant difference in the content of amino acids, the ratio of essential amino acids, and the ratio of umami amino acids in the meat of different breeds of pigeons (p > 0.05). The percentage of saturated fatty acids (SFAs) in the breast muscle of local breeding pigeons was significantly lower than that of White King pigeons (p < 0.05), and the percentages of lauric acid, palmitic acid, eicosanoic acid, and behenic acid in SFAs reached significant levels (p < 0.05). The content of eicosapentaenoic acid (EPA) in the meat of Taihu pigeons was significantly higher than that in other breeds. In conclusion, compared with the White King pigeon, the meat of local breed pigeons (Taihu pigeon, Shiqi pigeon, Tarim pigeon, and Boot pigeon) had dark flesh, good water retention, high protein and inosine contents, a high proportion of essential amino acids, and a low saturated fatty acid ratio. In addition, Taihu pigeons had the highest protein content (22.72%), monounsaturated fatty acids (44.58%), and EPA (0.47%) compared to other breeds.

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets.

Allergic rhinitis and asthma are common airway allergic diseases, the incidence of which has increased annually in recent years. The human body is frequently exposed to allergens and environmental irritants that trigger immune and inflammatory responses, resulting in altered gene expression. Mounting evidence suggested that epigenetic alterations were strongly associated with the progression and severity of allergic diseases. Noncoding RNAs (ncRNAs) are a class of transcribed RNA molecules that cannot be translated into polypeptides and consist of three major categories, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Previous studies showed that ncRNAs were involved in the physiopathological mechanisms of airway allergic diseases and contributed to their occurrence and development. This article reviews the current state of understanding of the role of noncoding RNAs in airway allergic diseases, highlights the limitations of recent studies, and outlines the prospects for further research to facilitate the clinical translation of noncoding RNAs as therapeutic targets and biomarkers.

Exosomes Derived hsa-miR-4669 as a Novel Biomarker for Early Predicting the Response of Subcutaneous Immunotherapy in Pediatric Allergic Rhinitis.

Purpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR. Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children. Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P<0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785). Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.

A Mobile-based Virtual Reality Speech Rehabilitation App for Patients With Aphasia After Stroke: Development and Pilot Usability Study.

BACKGROUND: Stroke has the highest disability-adjusted life-years lost in any disease, and approximately one-third of the patients get aphasia. Computers and tablets are innovative and aid in intensive treatments in speech rehabilitation for patients with aphasia. However, mechanical training limits the help to patients. OBJECTIVE: This study aims to provide a framework for an integrated virtual reality (VR) app to provide speech rehabilitation for patients with aphasia. METHODS: The content was generated through an in-depth literature review and discussion with experienced rehabilitation physicians and occupational therapists. We then conducted a 2-round Delphi study with 15 experts from hospitals and universities to rate the content using a 5-point Likert scale. The app was developed by an interdisciplinary team involving VR, medical science of rehabilitation, and therapeutic rehabilitation. Pilot usability testing of this novel app was conducted among 5 patients with aphasia, 5 healthy volunteers, 5 medical staff, and 2 VR experts. RESULTS: We designed 4 modules of speech rehabilitation: oral expression, auditory comprehension, cognition, and comprehensive application. Our VR-based interactive and intelligent app was developed to provide an alternative option for patients with aphasia. Pilot usability testing revealed user satisfaction with the app. CONCLUSIONS: This study designed and tested a novel VR-based app for speech rehabilitation specifically adapted to patients with aphasia. This will guide other studies to develop a similar program or intelligent system in a clinical setting.

Effectiveness of virtual reality-based interventions in rehabilitation management of breast cancer survivors: protocol of a systematic review and meta-analysis.

INTRODUCTION: Breast cancer is the leading cause of global cancer incidence and represents 11.7% of all new cancer cases. However, breast cancer survivors (BCS) suffer from many intense physical and psychological symptoms, functional deficits and adverse effects during and after treatment, significantly affecting their quality of life. Virtual reality (VR) technology uses computer technology to create an interactive three-dimensional world by visual, audio and touch simulation and is being used in breast cancer rehabilitation management. This paper reports on the protocol for a systematic review and meta-analysis exploring the efficacy of VR-based interventions in the rehabilitation management of BCS. METHODS AND ANALYSIS: This protocol for conducting a systematic review and meta-analysis was prepared according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Web of Science, PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials, CNKI, Wanfang, VIP and SinoMed will be used in the search. The search will include randomised controlled trials, quasi-experimental studies and case-controlled trials published in English and Chinese. Further, the risk of bias of the studies included in the systematic review and meta-analysis will be assessed using the Cochrane risk-of-bias tool. The statistical program Review Manager V.5.3 will be used in the meta-analysis. The I² test will be used to determine statistical heterogeneity among the included studies. ETHICS AND DISSEMINATION: Ethics approval will not be needed because the data to be used in this systematic review and meta-analysis will be extracted from published studies. The systematic review and meta-analysis will focus on whether VR-based interventions are effective in the rehabilitation management of BCS. It will be disseminated by publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021250727.

Endoscopic frontal recess anatomy directed by the drainage pathways using the connecting plates as landmarks.

PURPOSE: To investigate the anatomical features of frontal recess (FR) drainage, and the classification of FR cells and frontal sinus (FS). METHODS: Fifty sides from 30 adult cadaver heads were examined. FR cells and FS along the drainage pathways were dissected under 0° and 70° endoscopic views using unique connecting structures between the uncinate process and the ethmoid bulla as landmarks. RESULTS: Connecting plates between the uncinate process and the ethmoid bulla were discovered and termed medial suprainfundibular plate (MSIP), which were observed on each cadaver head, and lateral suprainfundibular plate (LSIP) on 92% (46/50) sides. Separated by MSIP, two drainage pathways were identified and named medial pathways of the FR (MPFR) medial to the MSIP and the lateral pathways of the FR (LPFR) in the lateral side. Different drainage pathways of the FS were confirmed, in which drained into the MPFR in 37 and into the LPFR in 13 of the cadaver sides. CONCLUSIONS: MSIP is the critical landmark for the recognition of MPFR, LPFR, and the classification of FR cells. The FR resection along LPFR and MPFR facilitated excellent exposure of FS.

Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling.

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling. Methods: We prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders. Results: Sixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ. Conclusion: Our discover-validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.

[Effect of "Buqi Yixue" needling on neurological function and nerve conduction velocity in patients with diabetic peripheral neuropathy].

OBJECTIVE: To observe the efficacy of "Buqi Yixue "needling on clinical symptoms, neurological function and nerve conduction velocity in patients with diabetic peripheral neuropathy. METHODS: Eighty-six patients with diabetic peripheral neuropathy numbness and pain were equally randomized into control group and treatment group. The patients of the control group received basic treatment and oral administration of Cilostazol (50 mg/time, 2 times/d) and Epalrestat (50 mg/time, 3 times/d). The patients of the treatment group received acupuncture stimulation of Danzhong (CV17), Qihai (CV6), Pishu (BL20), Quchi (LI11), etc., for 30 min, once every day, on the basic treatment. The treatment was conducted for 8 successive weeks. The scores of Traditional Chinese Medicine (TCM) symptoms, Toronto clinical scoring system (TCSS) and nerve conduction velocity (NCV) were detected before and after the treatment. RESULTS: After the treatment, the scores of TCM symptoms and TCSS were considerably decreased (P<0.05), and the NCV was significantly increased (P<0.05) in both groups compared with those of their own pre-treatment. The the-rapeutic effect of the treatment group was significantly superior to that of the control group in lowering the scores of TCM symptoms and TCSS, and in up-regulating the NCV (P<0.01). CONCLUSION: "Buqi Yixue" needling is effective in improving clinical symptoms and increasing NCV in patients with diabetic peripheral neuropathy.

Effects of Different Dietary Calcium Levels on the Performance, Egg Quality, and Albumen Transparency of Laying Pigeons.

In order to confirm the dietary calcium (Ca) requirement to keep a balance of the production performance and the albumen transparency, the study examined the effects of different dietary Ca levels on the production performance, egg quality, and albumen transparency of laying pigeons. 1080 pigeon pairs were randomly allocated into six treatment groups, each consisting of six replicates of 30 pigeon pairs per treatment. Ca levels of 0.60, 0.90, 1.20, 1.80, 2.40, and 3.00% were fed. The results showed that the laying rate, average egg weight, and feed to egg ratio were significantly influenced by Ca levels (p < 0.05). Albumen percentage, albumen height, Haugh unit, and eggshell thickness at 8 w and 16 w were significantly influenced by Ca levels (p < 0.05). The L*, a*, b*, and c* values of cooked albumen at 8 w and 16 w were all significantly influenced by Ca levels (p < 0.05). After 16 w of feeding different Ca levels, the percentage of transparent eggs had an early increasing and later decreasing trend. In conclusion, taking the transparency of pigeon eggs as an assessment index and considering production performance secondly, the optimal level of dietary Ca for laying White King pigeons is 0.90%.

Effect of willed movement training on neurorehabilitation after focal cerebral ischemia and on the neural plasticity-associated signaling pathway.

Neurorehabilitation training is a therapeutic intervention for the loss of neural function induced by focal cerebral ischemia, however, the effect varies depending on the neurorehabilitation exercises. Willed movement (WM) training is defined as task­oriented training, which increases enthusiasm of patients to accomplish a specific task. The current study was performed to the evaluate effect of WM training on neurorehabilitation following focal cerebral ischemia, and further investigate the influence on neural plasticity­associated signaling pathway. Sprague­Dawley rats following temporary middle cerebral artery occlusion (tMCAO) were randomly divided into four groups: tMCAO (no rehabilitation training), CR (control rehabilitation), EM (environmental modification) and WM groups. Rats in the CR group were forced to exercise (running) in a rotating wheel. In the WM group, food was used to entice rats to climb on a herringbone ladder. Herringbone ladders were also put into the cages of the rats in the CR and EM groups, however without the food attraction. WM group exhibited an improvement in neurobehavioral performance compared with other groups. TTC staining indicated an evident reduction in brain damage in the WM group. There were increased synaptic junctions following WM training, based on the observations of transmission election microscopy. Investigation of the molecular mechanism suggested that WM training conferred the greatest effect on stimulating the extracellular signal­related kinase (ERK)/cyclic adenosine monophosphate response element­binding protein 1 (CREB) pathway and glutamate receptor 2 (GluR2)/glutamate receptor interacting protein 1­associated protein 1 (GRASP­1)/protein interacting with C­kinase 1 (PICK1) cascades among groups. Collectively, the improvement of neurobehavioral performance by WM training following tMCAO is suggested to involve the ERK/CREB pathway and GluR2/GRASP­1/PICK1 cascades. The present study provided a preliminary foundation for future research on the therapeutic effect of WM training against stroke­induced neuron damage.

MiR-223/PAX6 Axis Regulates Glioblastoma Stem Cell Proliferation and the Chemo Resistance to TMZ via Regulating PI3K/Akt Pathway.

Chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the miR-223/paired box 6 (PAX6) pathway could increase the sensitivity of glioma to Temozolomide. An elevated level of miR-223 was observed in glioma tissues. Exogenous miR-223 promoted cell survival when exposed to Temozolomide (TMZ), while miR-223 inhibition could reverse this process. The RNA and protein levels of PAX6 were significantly decreased by exogenous miR-223, and the 3'-untranslated region of PAX6 was shown to be a target of miR-223. Besides, it has also been reported that PI3K/Akt signaling pathway is pivotal to regulate glioma growth and proliferation. In the present study, we revealed that miR-223/PAX6 axis regulated the growth, invasion, and chemo resistance of glioblastoma stem cells to TMZ via regulating PI3K/Akt signaling pathway, which present a novel potential therapy for intervention of glioblastoma. Taken together, our findings shed new light on the miR-223/PAX6 pathway in glioma and this pathway might modulate the sensitivity of glioma to TMZ via regulating PI3K/Akt signaling pathway. J. Cell. Biochem. 118: 3452-3461, 2017. © 2017 Wiley Periodicals, Inc.

STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats.

Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.

Effect Comparison of Both Iron Chelators on Outcomes, Iron Deposit, and Iron Transporters After Intracerebral Hemorrhage in Rats.

Iron overload plays a key role in brain injury after intracerebral hemorrhage (ICH). We explored the roles of ferric iron chelator-deferiprone (DFP)-and ferrous iron chelator-clioquinol (CQ)-in ICH rats through the outcomes, iron deposits, reactive oxygen species (ROS), brain water content, and related iron transporters. One hundred eight Sprague-Dawley rats received intra-striatal infusions of 0.5 U of type IV collagenase to establish ICH models. The rats were randomly assigned to the sham, vehicle, DFP, and CQ groups. We evaluated the outcomes, iron levels, brain water content, and ROS; meanwhile, immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) were utilized to determine ferritin, transferrin, transferrin receptor, divalent metal transport 1 (DMT1), and ferroportin at 48 and 72 h, 7 and 14 days after surgery. Our results showed ICH induced iron overload, brain edema, ROS formation, and neurological deficits. Both iron chelators decreased iron levels; CQ improved the neurological outcome, attenuated brain edema, and ROS production. DFP reduced iron contents but not brain water content and ROS generation. DFP failed to improve the outcome. ICH initiated endogenous iron chelators and transporters, both exogenous iron chelators enhanced expression of transferrin and transferrin receptor. CQ enhanced expression of ferroportin but not DMT1, while DFP enhanced expression of DMT1 but not ferroportin. Ferrous iron contributed to brain injury, and binding ferrous iron can modestly improve outcome after ICH in rats. The exogenous ferrous iron chelator possibly functioned via endogenous ferrous iron transporters on ICH. Therefore, ferrous iron may be a promising target for ICH in future.

Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats.

Early sitting, standing, and walking in conjunction with contemporary Bobath approach for stroke patients with severe motor deficit.

BACKGROUND: The commonly used therapeutic approach, the contemporary Bobath approach (CBA), is not sufficient to restore independent locomotion for individuals with severe motor deficit (SMD) after stroke. Therefore, we propose that the early sitting, standing, and walking in conjunction with the CBA (ECBA) be used to treat individuals with SMD after stroke. OBJECTIVE: To investigate whether ECBA may enhance mobility and balance in subjects with SMD after stroke. METHODS: Thirty-three men and 15 women, aged 60 to 74 years, with SMD after stroke were recruited for the study. CBA or ECBA was performed with the subjects 5 times per week in 50-minute sessions for 8 weeks. The Stroke Rehabilitation Assessment of Movement (STREAM) and the Berg Balance Scale were implemented before treatment and at 4 and 8 weeks after treatment, respectively. RESULTS: The STREAM scores indicated that ECBA was more efficient than the CBA intervention for lower extremity mobility, F(1, 46) = 24.0, P < .001, and basic mobility, F(1, 46) = 102.6, P < .001. Overall STREAM scores were higher in the ECBA group, F(1, 46) =24.1, P < .001, after 8 weeks of therapy. Balance scores of the ECBA subjects were higher than those of the CBA subjects after 8 weeks of therapy, F(1, 46) = 73.1, P < .001. However, there was no difference in upper extremity mobility between the 2 groups. CONCLUSION: ECBA is a valuable intervention to improve lower extremity mobility, basic mobility, and balance ability for individuals with SMD after stroke.