Effects of tumor derived exosomes on T cells markers expression

Abstract Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN- expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Resumo Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas os verdadeiros representantes das células-mãe modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN- em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Effects of tumor derived exosomes on T cells markers expression / Efeitos de exossomos derivados de tumor na expressão de marcadores de células T

Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas ­ os verdadeiros representantes das células-mãe ­ modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India

Purpose: The second wave of coronavirus disease 2019 (COVID?19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino?orbital?cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio?chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital?based study included all in?patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin?6 (IL?6), C?reactive protein (CRP), and D?dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty?two (89.4%) had pre?existing diabetes, and five (10.6%) had steroid?induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL?6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL?6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL?6 levels are best associated with survival

Recent advances in preclinical research of renal xenotransplantation and selection of potential recipients in the future / 中华器官移植杂志

After continuous efforts from generations of transplant surgeons, kidney transplantation (KT) has become an optimal treatment for end-stage renal disease.However, an imbalance between supply and demand of organs has always restricted the development of KT.For this clinical dilemma, xenotransplantation is expected to become one practical alternative for alleviating organ shortage.This review summarized recent literature reports of kidney xenotransplantation and the latest cases of pig-to-human kidney and heart transplantations.Also clinical transformations and applications of kidney xenotransplantation were discussed.

The mediating effect of impact of event and thought suppression between childhood abuse experience and suicide attitude among male prisoners / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between childhood abuse experience and suicide attitude among male prisoners, and the mediating effect of impact of event and thought suppression.Methods:Totally 370 male prisoners were tested by personal report of childhood abuse(PRCA), impact of event scale(IES), white bear suppression inventory(WBSI) and suicide attitude inventory(SAI). SPSS 22.0 was used for correlation analysis, regression analysis and other statistical analysis.Results:The scores of PRCA, IES, WBSI and SAI were (2.60±0.62), (2.69±0.62), (2.83±0.79), (3.06±0.61), respectively.There were significant differences in the scores of PRCA, IES and WBSI among different suicide attitude groups( F=42.69, 51.06, 78.76, all P<0.01). After controlling age variables, positive correlation was observed between PRCA, IES, WBSI and SAI ( r=0.38-0.76, all P<0.01). Impact of event and thought suppression played a mediating role in the relationship between childhood abuse experience and suicide attitude among male prisoners.The mediating effect included three paths: one was the single mediating effect of impact of event, the other was the single mediating effect of thought suppression and the third was the chain mediating effect of impact of event and thought suppression, and the effect values were 0.29, 0.23 and 0.05, respectively. Conclusion:Childhood abuse experience not only directly influences male prisoners' suicide attitude, but also indirectly influences their suicide attitude through the mediating effects of impact of event and thought suppression.

Cost-effectiveness analysis of long-acting versus short-acting recombinant human granulocyte stimulating factor in the treatment of III° and IV° bone marrow suppression after chemotherapy / 中国基层医药

Objective:To investigate the cost-effectiveness of long-acting versus short-acting recombinant human granulocyte stimulating factor in the treatment of III° and IV° bone marrow suppression after chemotherapy. Methods:The data of patients who presented with III and IV° bone marrow suppression after chemotherapy and received treatment with recombinant human granulocyte stimulating factor from January 2018 to December 2019 were collected. These patients were divided into the short-acting recombinant human granulocyte stimulating factor group (rhG-CSF group) and the long-acting recombinant human granulocyte stimulating factor group (PEG-rhG-CSF group) group. Clinical efficacy, the incidence of adverse reactions, and cost-effectiveness were compared between the two groups.Results:There were 88 patients, aged (63.97 ± 11.64) years, in the rhG-CSF group. There were 80 patients, aged (63.26 ± 9.09) years in the PEG-rhG-CSF group. There was no significant difference in baseline data between the two groups ( P > 0.05). Total response rate was 72.72% (64/88) in the rhG-CSF group and 78.75% (63/80) in the PEG-rhG-CSF group ( χ2 = 0.82, P = 0.360). The incidence of related adverse reactions was 7.95% (7/88) and 7.5% (6/80) in the rhG-CSF and PEG-rhG-CSF groups respectively ( χ2 = 0.01, P = 0.910). The average cost was (124.88 ± 113.07) yuan and (3 159.04 ± 505.05) yuan in the rhG-CSF and PEG-rhG-CSF groups respectively ( t = 51.68, P < 0.01). The cost-effectiveness ratio was 1.55 and 40.11 in the rhG-CSF and PEG-rhG-CSF groups respectively. Taking the rhG-CSF group as a reference, the incremental cost-effectiveness ratio in the PEG-rhG-CSF group was 505.13. Conclusion:Long-acting and short-acting recombinant human granulocyte stimulating factors have similar curative effects and related adverse reactions in the treatment of III° and IV°bone marrow suppression after chemotherapy. The cost-effectiveness ratio of the rhG-CSF group is lower than that of the PEG-rhG-CSF group. Appropriate treatment schemes for increasing white blood cell levels should be selected based on the individual situation of the patient.

Differential diagnosis of brucellar spondylitis and tuberculous spondylitis based on FS-T2WI sequence combined with machine learning / 中华地方病学杂志

Objective:To investigate the performance of a predictive model based on fat suppression (FS)-T2WI sequence combined with machine learning in the differential diagnosis of brucellar spondylitis (BS) and tuberculous spondylitis (TS).Methods:The clinical and imaging data of 74 patients with BS and 81 patients with TS diagnosed clinically or pathologically in the First Affiliated Hospital of Xinjiang Medical University from January 2017 to January 2022 were retrospectively analyzed, and all patients underwent spinal magnetic resonance imaging (MRI) examination before treatment. Patients were randomly divided into a training group ( n = 123) and a testing group ( n = 32) in an 8 ∶ 2 allocation ratio, and radiomics feature extraction and dimensionality reduction analysis were performed on FS-T2WI sequence images. Four machine learning algorithms, including K-nearest neighbor (KNN), support vector machine (SVM), random forest (RF) and logistic regression (LR), were used to construct a radiomics model, and receiver operating characteristic (ROC) curve was used to analyze the differential diagnostic performance of each model for BS and TS. Results:A total of 1 409 radiomics features were extracted, and 7 related features were screened and included for identification of BS and TS, among which the Maximum2DDiameterColumn feature value showed a strong correlation, and there was a statistically significant difference between BS and TS patients ( P < 0.001). In the testing group, the area under the ROC curve (AUC) value of the SVM model for identifying BS and TS was 0.886, with a sensitivity of 0.53, a specificity of 0.88, and a diagnostic accuracy of 0.81; in the training group, the AUC value of the SVM model for identifying BS and TS was 0.811, the sensitivity was 0.68, the specificity was 0.72, and the diagnostic accuracy of the model was 0.78. Conclusion:The prediction model based on FS-T2WI sequence combined with machine learning can be used to identify BS and TS, and the diagnostic performance of SVM model is prominent and stable.

Relationship between emotional exhaustion and work stress, thought suppression, difficulties in emotion regulation in clinical nurses / 中国职业医学

Objective To explore the current status of emotional exhaustion among clinical nurses and its relationship with work stress, thought suppression, difficulties in emotion regulation. Methods A totally of 1 159 clinical nurses from 10 cities in Henan Province and Fujian Province were enrolled as the research subjects using grabbing random balls method. And their status of work stress, thought suppression, difficulties in emotion regulation and emotional exhaustion were investigated by Depression-Anxiety-Stress Scale, White Bear Suppression Inventory, Brief Version of the Difficulties in Emotion Regulation Scale and Emotional Exhaustion Scale. Results The scores for work stress, thought suppression, difficulties in emotion regulation, emotional exhaustion were (23.5±3.8), (47.4±6.5), (54.1±7.2), (11.7±4.2), respectively. Among them, 40.0% of nurses experienced emotional exhaustion. Bootstrap analysis results showed that work stress positively affected emotional exhaustion among clinical nurses [standardized partial regression coefficient (β)=0.42, 95% confidence intervals (CI)： 0.36-0.44］. Work stress affected emotional exhaustion through thought suppression (β=0.16, 95%CI： 0.14-0.20), difficulties in emotion regulation (β=0.16, 95%CI： 0.14-0.19), and the chain mediating role of thought suppression and difficulties in emotion regulation (β=0.07, 95%CI： 0.04-0.09). Conclusion Emotional exhaustion symptoms are prevalent among clinical nurses. Work stress directly and indirectly influences thought suppression, difficulties in emotion regulation and emotional exhaustion of nurses.

Exploring the protective mechanism of Tibetan medicine Potentilla anserine on cyclophosphamide-induced myelosuppression based on metabonomics technology / 药学学报

The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Expression and clinical significance of interferon regulatory factor 4 and soluble suppression of tumorigenesis 2 in conjunctival epithelial cells and tears of patients with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and clinical significance of interferon regulatory factor 4(IRF4)and soluble suppression of tumorigenesis 2(sST2)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: A total of 94 patients with dry eye who admitted to our hospital from January 2019 to December 2021 were selected as the dry eye group, and 97 physical examiners who underwent ophthalmic examination were selected as the control group at the same time. The conjunctival epithelial cells and tears of the subjects were collected, and the clinical indicators, including tear film break-up time(BUT), corneal fluorescein staining(CFS)score, and Schirmer Ⅰ test(SⅠt)were recorded. The levels of IRF4 and sST2 in conjunctival epithelial cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR), and the levels of IRF4 and sST2 in tears were detected by enzyme-linked immunosorbent assay(ELISA). Pearson method was used to analyze the correlation between IRF4 and sST2 levels in conjunctival epithelial cells and tears and clinical indicators of dry eye patients.RESULTS: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears in dry eye group before treatment were significantly higher than those in control group(P&#x003C;0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients at 4wk after treatment were significantly lower than those before treatment(P&#x003C;0.001). The BUT and SⅠt of dry eye patients increased significantly at 4wk after treatment, and the CFS score decreased significantly(P&#x003C;0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients before treatment were positively correlated with CFS score before treatment and negatively correlated with BUT and SⅠt before treatment(P&#x003C;0.001).CONCLUSION: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of patients with dry eye are increased, and are significantly correlated with BUT, SⅠt and CFS scores, which has potential to become a new therapeutic target for dry eye.

"Mulher, você não precisa disso": discursos em embate sobre a pílula e a supressão da menstruação / "Woman, you don't need this": Negotiation of discourses on the pill and menstrual suppression / "Mujer, no necesitas esto": Discursos en conflicto sobre la píldora y la supresión de la menstruación

Resumo O discurso médico do século XIX listava uma série de desordens físicas e mentais associadas aos órgãos reprodutivos das mulheres (Rohden, 2009). Um fenômeno corporal até hoje frequentemente construído como patológico é a menstruação (Vieira, 2002), para o qual existe uma ferramenta médica de intervenção amplamente empregada: a pílula anticoncepcional. Como o período menstrual é muitas vezes visto como um problema, sua interrupção por meio da ingestão contínua da pílula é recorrentemente propagada como a solução (Kissling, 2013). À luz dessas ideias, analiso como duas mulheres autoidentificadas como feministas negociam significados sobre a pílula, a menstruação e a supressão menstrual em entrevistas orais semiestruturadas. O objetivo do trabalho é investigar como sentidos biomédicos sobre o corpo feminino são discursivamente reificados, desafiados e corporificados.

Abstract Nineteenth century's medical discourse listed a series of physical and mental disorders caused by women's reproductive organs (Rohden, 2009). A bodily function that until nowadays has been frequently constructed as pathological is menstruation (Vieira, 2002), for which there is a widely employed medical tool of intervention: the contraceptive pill. As the period is often seen as a problem, its suppression through the uninterrupted use of the pill is recurrently advertised as the solution (Kissling, 2013). In light of these ideas, I analyse how two self-identified feminist women negotiate meanings around the pill, menstruation and menstrual suppression in semi-structured oral interviews. The purpose of the work is to investigate how biomedical meanings of the female body are discursively reified, challenged and embodied.

Resumen El discurso médico del siglo XIX enumeraba una serie de trastornos físicos y mentales asociados a los órganos reproductivos de la mujer (Rohden, 2009). Un fenómeno corporal que con frecuencia se interpreta como patológico es la menstruación (Vieira, 2002), para la cual existe una herramienta médica intervencionista ampliamente utilizada: la píldora anticonceptiva. Como el período menstrual a menudo se ve como un problema, su interrupción a través de la toma continua de la píldora se propaga recurrentemente como la solución (Kissling, 2013). A la luz de estas ideas, analizo cómo dos mujeres autoidentificadas como feministas negocian significados sobre la píldora, la menstruación y la supresión menstrual en entrevistas orales semiestructuradas. El objetivo de este trabajo es investigar cómo los significados biomédicos sobre el cuerpo femenino son materializados, cuestionados y encarnados discursivamente.

Factors associated with viral load suppression among human immunodeficiency virus (HIV) positive adolescents and young adults in Ngororero District, Rwanda

Background Optimal viral load suppression results from good adherence to treatment. The viral load suppression advantages include the reduction of virus transmission. In Rwanda, however, viral load suppression among adolescents and young adults has been proven relatively low than in other age groups. Objectives To assess the factors associated with viral load suppression among adolescent and young adults in Ngororero district, Rwanda. Methods A cross sectional study that included 151 adolescents and young adults aged from 15 to 24 years was conducted in Ngororero district. Data were entered in Epi-Info version 7 software and analyzed using STATA15. Results Females and males were 68% and 32% respectively. Sixty percent of the participants were aged20-24 years. Multivariable analysis revealed the factors associated with viral load suppression: Ubudehe category 2, P= 0.016, AOR = 6.6, CI [1.4, 31.1]; ubudehe category 3, P= 0.004, AOR = 8.9, CI [2.01,39.8]; spending between 5 to 9 years on ART, P= 0.022, AOR = 0.16 [CI0.03, 0.89;) and often forget to take medication, P= 0.011, AOR = 0.35, CI [0.13, 0.97.] Conclusion Viral load suppression among adolescents and young adults was low. Improving socio-economic conditions of adolescents and young adults, as well as provision of continuous counselling to them during their whole treatment life can improve significantly their adherence.

Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies / 浙江大学学报·医学版

Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.

Adaptive repetitive control of wrist tremor suppression based on functional electrical stimulation / 生物医学工程学杂志

Tremor is an involuntary and repetitive swinging movement of limb, which can be regarded as a periodic disturbance in tremor suppression system based on functional electrical stimulation (FES). Therefore, using repetitive controller to adjust the level and timing of FES applied to the corresponding muscles, so as to generate the muscle torque opposite to the tremor motion, is a feasible means of tremor suppression. At present, most repetitive control systems based on FES assume that tremor is a fixed single frequency signal, but in fact, tremor may be a multi-frequency signal and the tremor frequency also varies with time. In this paper, the tremor data of intention tremor patients are analyzed from the perspective of frequency, and an adaptive repetitive controller with internal model switching is proposed to suppress tremor signals with different frequencies. Simulation and experimental results show that the proposed adaptive repetitive controller based on parallel multiple internal models and series high-order internal model switching can suppress tremor by up to 84.98% on average, which is a significant improvement compared to the traditional single internal model repetitive controller and filter based feedback controller. Therefore, the adaptive repetitive control method based on FES proposed in this paper can effectively address the issue of wrist intention tremor in patients, and can offer valuable technical support for the rehabilitation of patients with subsequent motor dysfunction.

The clinical application of head-shaking test combined with head-shaking tilt suppression test in distinguishing between peripheral and central vertigo at bedside vs. examination room

Abstract Objectives: To investigate the clinical value of using Head-Shaking Test (HST) + Head-Shaking Tilt Suppression Test (HSTST) to distinguish between peripheral and central vertigo as well as to analyze the consistency of findings between tests at the bedside vs. in the examination room. Methods: We retrospectively analyzed patients who presented for central or peripheral vertigo from July 2019 to July 2021. The results were compared between HST and HST+HSTST. The concordance between bedside and examination room outcomes was analyzed. Results: Forty-seven (58.8%) patients in the peripheral vertigo group and 33 (41.2%) patients in the central vertigo group were included. In the peripheral group, 44 (both examination room and bedside: 93.6%) patients had horizontal Head-Shaking Nystagmus (hHSN), most of which were suppressed in HSTST. However, in the central group, most cases had perverted HSN (pHSN; examination room: 72.7%; bedside: 66.7%), which was seldomly suppressed in HSTST. The HST+HSTST showed a >20% higher specificity in identifying peripheral vertigo than HST alone. The bedside results were consistent with the examination room results using the kappa test (p< 0.001). Conclusions: Suppressed hHSN was a strong indicator of peripheral vertigo. Conversely, pHSN was more often seen in central vertigo, which was not readily suppressed in HSTST. The bedside results of HST+ HSTST yielded qualitative agreement with the tests in the examination room. HST+ HSTST could be used as reliable methods in the clinic to distinguish between peripheral and central vestibular disorders. Level of evidence: Level 3.

Respuesta inmune e inmunosupresión en pacientes con ventilación mecánica por infección por SARS-CoV-2 / Immune response and immune suppression in patients with mechanical ventilation secondary to SARS-CoV-2 infection / Resposta imune e imunossupressão em pacientes com ventilação mecânica devido à infecção por SARS-CoV-2

Resumen Introducción: La pandemia por SARS-CoV-2 ha inspirado intriga sobre la respuesta inmune a dicho virus, especialmente en pacientes graves con síndrome de dificultad respiratoria aguda (SDRA). Este estudio describe el comportamiento de la respuesta inmune, la inmunosupresión y sus desenlaces en los pacientes con ventilación mecánica (VM). Material y métodos: Cohorte prospectiva. Del 23 de marzo al 31 de diciembre de 2020 se recolectó información basal, parámetros ventilatorios, gasométricos y estudios de laboratorio de todos los pacientes mayores de 18 años que recibieron VM por COVID-19 con registros hasta el día 15 de VM. Se dividieron los grupos en pacientes vivos a los 90 días y defunciones. Resultados: Registramos 218 pacientes, con mortalidad de 23%. En el día 1 de VM, los pacientes no presentaron diferencias en conteos celulares o reactantes de fase aguda, excepto dímero D de 1,020 (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. En el análisis de regresión lineal de efectos mixtos se observaron diferencias cronológicas estadísticamente significativas en leucocitos y proteína C reactiva (PCR) concordante con la elevación de la presión de distensión alveolar (PDalv). No se encontró asociación con mortalidad en el uso de tocilizumab 2.20 (0.279-17.358) y corticosteroides 0.54 (0.229-1.273) en riesgos proporcionales de Cox al día 1 de VM. Durante los 15 días de VM los pacientes que fallecieron recibieron dosis más altas de corticosteroides, dosis mayores de 150 mg/día equivalente a prednisona se asocian a mortalidad. Conclusiones: Existe evolución cronológica similar en elevación de PCR, leucocitos y elevación de la PDalv, las cuales se explican por la disminución de la distensibilidad pulmonar estática (Cstat) y la presión positiva al final de la espiración total (PEEP total). El uso de tocilizumab no tuvo asociación con la mortalidad y dosis equivalentes a prednisona entre 100-150 mg/día se asocian a mejores resultados.

Abstract Introduction: The SARS-CoV-2 pandemic has inspired interest in the immune response to the virus, especially in severe patients with acute respiratory distress syndrome (ARDS). The study describes the behaviour of the immune response, immune suppression, and their results in patients under mechanical ventilation (MV). Material and methods: Prospective cohort. From March 23rd to December 31st, 2020, we recollected basal information, MV parameters, blood gas analysis and laboratory studies of all the patients over 18 years who received MV secondary to COVID-19. We registered 15 continuous days of MV. We divided the groups in patients alive at day 60 and deaths. Results: We included 218 patients with a mortality of 23%. In day 1 of MV, the patients didn't have any differences in cell counts or acute phase reactants, except for D Dimer (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. In mixed effects linear regressions, we found statistically significant chronological differences in C reactive protein (CPR) and leucocyte count, concordant with the elevation of the driving pressure (DP). In the Cox regression we found no association with tocilizumab and corticosteroids with mortality on day 1 of MV. Patients who died received higher doses of corticosteroids throughout the 15 days of MV, with doses equivalent to prednisone over 150 mg/day are associated with mortality. Conclusions: There is a similar chronological behaviour in the elevation of acute phase reactants and the elevation con DP with no elevation of Vt, which can be explained by the drop of total PEEP and Cstat. There was no association with the use of tocilizumab and mortality, and a dose of 100-150 mg/día of equivalent of prednisone was associated with better results.

Resumo Introdução: A pandemia de SARS-CoV-2 inspirou intrigas sobre a resposta imune ao referido vírus, especialmente em pacientes gravemente doentes com síndrome do desconforto respiratório do adulto (SDRA). Este estudo descreve o comportamento da resposta imune, imunossupressão e seus desfechos em pacientes em ventilação mecânica (VM). Material e métodos: Coorte prospectiva. De 23 de março a 31 de dezembro de 2020, foram coletadas informações basais, parâmetros ventilatórios e gasométricos e estudos laboratoriais de todos os pacientes maiores de 18 anos que receberam VM para COVID-19 com registros até o dia 15 de VM. Os grupos foram divididos em pacientes vivos em 90 dias e óbitos. Resultados: Registramos 218 pacientes, com mortalidade de 23%. No dia 1 de VM, os pacientes não apresentaram diferenças na contagem de células ou reagentes de fase aguda, exceto dimero D 1020 (705-1711) vs 1328 (940-2340) ng/dL p = 0.035. Na análise de regressão linear dos efeitos mistos, observam-se diferenças cronológicas estatisticamente significativas nos leucócitos e na proteína C reativa (PCR), consistentes com o aumento da pressão de distensão alveolar (PDalv). Não foi encontrada associação com mortalidade no uso de tocilizumab 2.20 (0.279-17.358) e corticoide 0.54 (0.229-1.273) nos riscos proporcionais de COX no 1o dia de VM. Durante os 15 dias de VM, os pacientes que foram a óbito receberam doses maiores de corticosteróides, doses a partir de 150 mg/dia equivalentes a prednisona estão associadas à mortalidade. Conclusões: Há evolução cronológica semelhante em PCR e leucócitos elevados e PDalv elevados, explicados pela diminuição da complacência pulmonar estática (Cstat) e da pressão positiva ao final da expiração total (PEEPtotal). O uso de tocilizumab não foi associado à mortalidade e doses equivalentes à prednisona entre 100-150 mg/dia estão associadas a melhores resultados.

Mild overexpression of a novel transcription factor Grainy head like-2 (Grhl2) elicits hybrid phenotype in human astrocytoma cells

The Grainy head like-2 (Grhl2) transcription factor plays a major role in embryonic and cancer development. The role of Grhl2 has been intensively studied in various cancers but not for brain cancer. Hence, in this study, we provide a preliminary understanding on the role of Grhl2 that regulate the transition of astrocytoma cells. The human A172 astrocytoma cell line, a mesenchymal cell characterized by mild overexpression of Grhl2 transcription factor, was used in this study. At first, the Grhl2 stably overexpressing A172 clones into three types i.e., Grhl2+ (mild), Grhl2++ (moderate) and Grhl2+++ (high) based on mRNA and protein expression levels of Grhl2 were characterized. Phenotypic characteristics of vector and Grhl2+ cells were observed using phase contrast microscopy. Quantitative PCR (qPCR), Western blot and immunofluorescence were used to detect the level of mesenchymal markers (N-cadherin/vimentin) and also epithelial markers (E-cadherin/ ?- catenin) in vector and Grhl2+ cells. The migration and invasion characteristics of vector and Grhl2+ cells were determined by scratch assay and Boyden chamber assay. Further, the Grhl2+ cells were characterized to determine the effect of temozolomide chemotherapy drug which were widely used in treating brain cancer. As expected, in phase contrast image, we observed the mesenchymal characteristic of A172 cells becomes hybrid phenotype i.e., mixture of mesenchymal (spindle-like fibroblast morphology) and epithelial (cobblestone like appearance) cells upon Grhl2 mild expression (Grhl2+) when compared to vector cells. Further, we found that there was a significant upregulation of E-cadherin at both mRNA and protein levels in Grhl2+ cells when compared to vector cells. There was a significant upregulation of ?-catenin, N-cadherin and vimentin at mRNA levels, but there was no significant upregulation at the protein levels in Grhl2+ cells compared to the vector cells. The migration and invasion were diminished in Grhl2+ cells when compared to the vector control cells. We observed that the Grhl2+ were sensitive to the temozolomide compared to the vector cells. This infers that the Grhl2+ cells were unable to attain complete transition of mesenchymal to epithelial state, and hence we categorized the Grhl2+ cells as hybrid phenotype. The results provide a better understanding of the largely unknown function of Grhl2 in human astrocytoma cells as tumor progression or suppression.

Correlation of serum ST2 levels with severity of diastolic dysfunction on echocardiography and findings on cardiac MRI in patients with heart failure with preserved ejection fraction

Objective: The aim of the present study was to find a correlation of serum Suppression of tumorigenicity 2 (ST2) levels with severity of diastolic dysfunction on echocardiography and cardiac magnetic resonance imaging (CMRI) in heart failure with preserved ejection fraction (HFpEF) patients. Methods: Fifty patients aged _x0001_18 years fulfilling diagnostic criteria for HFpEF were included. ST2 levels, 2D echocardiography and CMRI were performed. Left ventricular ejection fraction, E/A, Septal E/E’, left atrial volume index (LAVI), tricuspid regurgitation (TR), assessment of diastolic dysfunction, T1 mapping in milliseconds and late gadolinium enhancement (LGE) in percentage were noted. The primary outcome measure was to study correlation of ST2 levels with severity of diastolic dysfunction, whereas the secondary outcome measures were to study correlation of ST2 levels with native T1 mapping and LGE on CMRI. Results: ST2 levels showed statistically significant and positive correlation with E/E’ (r ¼ 0.837), peak TR velocity (r ¼ 0.373), LAVI (r ¼ 0.74), E/A (r ¼ 0.420), and T1 values in milliseconds (r ¼ 0.619). There was no statistically significant correlation between ST2 level and LGE in % (r ¼ 0.145). The median ST2 levels in patients with E/E’ > 14 and E/E’ 14 were 110.8 and 36.1 respectively (p-value < 0.05). The mean ST2 levels were significantly higher in patients who had diastolic dysfunction grade III (126.4) and New York Heart Association class IV (133.3). Conclusions: Evaluation of ST2 adds important information to support the diagnosis of left ventricular diastolic dysfunction in patients with HFpEF

Evaluation of Serum Interleukin-33 and Soluble Suppression of Tumorigenicity 2 (sST2) Receptors in Patients with and without Periodontal Disease

Context: Interleukin?33 and its receptor soluble suppression of tumorigenicity 2 (sST2) play an important role in inflammation and its role in periodontal disease is yet unclear. The role of both IL?33 and sST2 together in periodontal disease as biomarkers has never been studied. Aim: To assess the levels of IL?33 and sST2 in serum samples of patients with periodontitis and healthy subjects. Methods: A total of 71 subjects (30 healthy subjects and 41 patients with periodontal disease) were included in the cross?sectional study. Community Periodontal Index (CPI) was used to assess periodontal health by utilizing a mouth mirror and a CPI probe. Venous blood was collected and serum was separated. Serum levels of IL?33 and sST2 were determined by the enzyme?linked immunosorbent assay (ELISA) assay. Statistical Analysis: Graph Pad Prism 5 was used for statistical analysis. Mann Whitney test was applied to compare the two groups. Results: The level of IL?33 was not found to be elevated among healthy subjects and sST2 was found elevated among patients with periodontal disease. The serum concentration of IL?33 was found at 472 ± 114 pg/ml and 282 ± 77 pg/ml among healthy subjects and patients with periodontal disease respectively. Significantly higher values of sST2 at 28 ± 2 ng/ml were found among periodontal patients as compared to healthy subjects with values of 18 ± 1 ng/ml. No significant differences were noted between mild to moderate and severe periodontitis for IL?33 and sST2 between the two groups. Conclusion: This study shows alteration in serum levels of IL?33 and sST2 in periodontitis patients. IL?33 and sST2 may be potential inflammatory markers of periodontitis. Further studies are required on a large sample size for better understanding. This pilot study is the first to assess the serum levels of both IL?33 and sST2 together among patients with and without periodontal disease.

Syndrome of resistance to thyroid hormone and thyrotropin-secreting pituitary adenoma: Case series study / 中华内分泌代谢杂志

Objective:To outline clinical features in syndrome of resistance to thyroid hormone(RTH) and thyrotropin-secreting pituitary adenoma(TSH adenoma) based on a case series, and to assess the value of octreotide suppression test and high-dose dexamethasone suppression test(HDDST) in differentiating the two diseases.Methods:A total of 22 cases with RTH and TSH adenoma clinically diagnosed in Xiangya Hospital of Central South University from October 2010 to December 2021 were retrieved. The clinical characteristics of the two diseases and results to different tests were analyzed and summarized.Results:(1) The tumors in TSH adenoma patients were larger than those with RTH complicated with pituitary mass, which presented chiasmatic compression on images( P<0.05). (2) In octreotide suppression test, thyrotropin(TSH) inhibition rate in RTH patients was lower than that in TSH adenoma patients( P<0.05). In HDDST, TSH inhibition rate was higher in patients with RTH than in patients with TSH adenoma( P<0.05). (3) The TSH inhibition rate was calculated by receiver operating characteristic(ROC) curve. The sensitivity and specificity of octreotide suppression test were 91.9% and 55.6%, respectively, and the threshold value of TSH inhibition rate was 64.24%. The sensitivity and specificity of HDDST were 54.4% and 89.0%, respectively, and the threshold value of TSH inhibition rate was 65.73%.The combined sensitivity and specificity of the two tests were 77.8% and 90.9%, indicating better diagnostic value( P<0.05). Conclusions:The combination of octreotide suppression test and HDDST is of clinical value in differentiating RTH from TSH adenoma. TSH adenoma is more aggressive than that of pituitary adenoma with RTH.