The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Integrating plasma exosomal miRNAs, ultrasound radiomics and tPSA for the diagnosis and prediction of early prostate cancer: a multi-center study.

INTRODUCTION: This multi-center study aims to explore the roles of plasma exosomal microRNAs (miRNAs), ultrasound (US) radiomics, and total prostate-specific antigen (tPSA) levels in early prostate cancer detection. METHODS: We analyzed the publicly available dataset GSE112264 to identify the differentially expressed miRNAs associated with prostate cancer. Then, PyRadiomics was used to extract image features, and least absolute shrinkage and selection operator (LASSO) was used to screen the data. Subsequently, according to strict inclusion and exclusion criteria, the internal dataset (n = 199) was used to construct a diagnostic model, and the receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), and DeLong test were used to evaluate its diagnostic performance. Finally, we used an external dataset (n = 158) for further validation. RESULTS: The number of features extracted by PyRadiomics was 851, and the number of features screened by LASSO was 23. We combined the hsa-miR-320c, hsa-miR-944, radiomics, and tPSA features to construct a joint model. The area under the ROC curve of the combined model was 0.935. In the internal validation, the area under the curve (AUC) of the training set was 0.943, and the AUC of the test set was 0.946. The AUC of the external data set was 0.910. The calibration curve and decision curve were consistent with the performance of the combined model. There was a significant difference in the prediction ability between the combined prediction model and the single index prediction model, indicating the high credibility and accuracy of the combined model in predicting PCa. CONCLUSIONS: The combined prediction model, consisting of plasma exosomal miRNAs (hsa-miR-320c and hsa-miR-944), US radiomics, and clinical tPSA, can be utilized for the early diagnosis of prostate cancer.

The influence of PD-L1 expression levels on the efficacy of combination therapy in thymic epithelial tumors.

BACKGROUND: The significant expression of PD-L1 in thymic epithelial tumors (TETs) has been confirmed, and immunotherapy and its combination therapy have been effective in TETs. However, there is no present evidence that the expression levels of PD-L1 affects the efficacy of combination therapy. Our study aimed to shed light on this relationship. METHODS: Patients with thymic epithelial tumors (TETs) from multicenter hospitals were retrospectively identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) in 22 patients were included. We divided the patients the 22 patients with PD-L1 test into three levels (high expression, low expression and no expression) and analyzed the relationship between the levels of PD-L1 expression and the efficacy of combination therapy. RESULTS: Combination therapy showed an effective benefit in 22 patients with TETs, the median PFS (mPFS) was 16 months (95% CI: 8.5-23.5) and the median OS (mOS) was 38 months (95% CI: 21.5-54.5). Cox-regressive analysis found whether PD-L1 expression affected the PFS of patients (p = 0.017). Among the patients with PD-L1 expression, the levels of expression were correlated with curative effect (Kruskal-Wallis test, PFS: P = 0.012; OS: P = 0.01), and high expression group was along with better efficacy than low expression (Wilcoxon test, P = 0.01). Moreover, in 17 patients treated with immunotherapy combined with chemotherapy, the expression of PD-L1 was also associated with efficacy (Kruskal-Wallis test, p = 0.021). CONCLUSIONS: PD-L1 expression affects the PFS of patients. High expression of PD-L1 patients with TETs responded better to combination therapy, which could provide a therapeutic option in clinic. Besides, other targeted treatments should be considered.

Association between preoperative anemia optimization and major complications after non-cardiac surgery: a retrospective analysis.

BACKGROUND: Anemia is common in the preoperative setting and associated with increased postoperative complications and mortality. However, it is unclear if preoperative anemia optimization reduces postoperative complications. We aimed to assess the association between preoperative anemia optimization and a composite endpoint of major cardiovascular, renal, and pulmonary complications and all-cause mortality within 30 days after noncardiac surgery in adult patients. METHODS: In this retrospective analysis preoperative anemia was defined as hemoglobin concentration below 12.0 g.dl-1 in women and 13.0 g.dl-1 in men within 6 months before surgery. A propensity score-based generalized estimating equation analysis was used to determine the association between preoperative anemia optimization and the primary outcome. Moreover, mediation analysis was conducted to investigate whether intraoperative red blood cell transfusion or duration of intraoperative hypotension were mediators of the relation between anemia optimization and the primary outcome. RESULTS: Fifty-seven hundred anemia optimized, and 8721 non-optimized patients met study criteria. The proportion of patients having any component of the composite of major complications and all-cause mortality was 21.5% in the anemia-optimized versus 18.0% in the non-optimized, with confounder-adjusted odds ratio estimate of 0.99 (95% CI 0.86‒1.15) for anemia optimization versus non-optimization, p = 0.90. Intraoperative red blood cell transfusion had a minor mediation effect on the relationship between preoperative anemia optimization and the primary outcome, whereas duration of intraoperative hypotension was not found to be a mediator. CONCLUSION: Preoperative anemia optimization did not appear to be associated with a composite outcome of major in-hospital postoperative cardiovascular, renal, and pulmonary complications and all-cause in-hospital mortality.

Comparative genomic analysis of Sanghuangporus sanghuang with other Hymenochaetaceae species.

Sanghuangporus sanghuang is a medicinal macrofungus with antioxidant and antitumor activities, and it is enriched with secondary metabolites such as polysaccharides, terpenes, polyphenols, and styrylpyrone compounds. To explore the putative core genes and gene clusters involved in sanghuang biosynthesis, we sequenced and assembled a 40.5-Mb genome of S. sanghuang (SH1 strain). Using antiSMASH, local BLAST, and NCBI comparison, 12 terpene synthases (TPSs), 1 non-ribosomal peptide synthase, and five polyketide synthases (PKSs) were identified in SH1. Combining the transcriptome analysis with liquid chromatography mass spectrometry-ion trap-time of flight analysis, we determined that ShPKS1, one phenylalanine aminolyase (ShPAL), and one P450 monooxygenase (ShC4H1) were associated with hispidin biosynthesis. Structural domain comparison indicated that ShPKS2 and ShPKS3 are involved in the biosynthesis of orsellinic acid and 2-hydroxy-6-methylbenzoic acid, respectively. Furthermore, comparative genomic analysis of SH1 with 14 other fungi from the Hymenochaetaceae family showed variation in the number of TPSs among different genomes, with Coniferiporia weirii exhibiting only 9 TPSs and Inonotus obliquus having 20. The number of TPSs also differed among the genomes of three strains of S. sanghuang, namely Kangneng (16), MS2 (9), and SH1 (12). The type and number of PKSs also varied among species and even strains, ranging from two PKSs in Pyrrhoderma noxium to five PKSs in S. sanghuang SH1. Among the three strains of S. sanghuang, both the structural domains and the number of PKSs in strains MS2 and SH1 were consistent, whereas strain Kangneng exhibited only four PKSs and lacked the PKS with the structural domain KS-AT-DH-KR-ACP. Additionally, Sanghuangporus species exhibited more similar PKSs to Inonotus, with higher gene similarity around five PKSs, while showing differences from those of other fungi in the same family, including Phellinus lamaoensis. This result supports the independent taxonomic significance of the genus Sanghuangporus to some extent.

Association between preoperative anemia optimization and major complications after non-cardiac surgery: a retrospective analysis

Abstract Background: Anemia is common in the preoperative setting and associated with increased postoperative complications and mortality. However, it is unclear if preoperative anemia optimization reduces postoperative complications. We aimed to assess the association between preoperative anemia optimization and a composite endpoint of major cardiovascular, renal, and pulmonary complications and all-cause mortality within 30 days after noncardiac surgery in adult patients. Methods: In this retrospective analysis preoperative anemia was defined as hemoglobin concentration below 12.0 g.dl−1 in women and 13.0 g.dl−1 in men within 6 months before surgery. A propensity score-based generalized estimating equation analysis was used to determine the association between preoperative anemia optimization and the primary outcome. Moreover, mediation analysis was conducted to investigate whether intraoperative red blood cell transfusion or duration of intraoperative hypotension were mediators of the relation between anemia optimization and the primary outcome. Results: Fifty-seven hundred anemia optimized, and 8721 non-optimized patients met study criteria. The proportion of patients having any component of the composite of major complications and all-cause mortality was 21.5% in the anemia-optimized versus 18.0% in the non-optimized, with confounder-adjusted odds ratio estimate of 0.99 (95% CI 0.86-1.15) for anemia optimization versus non-optimization, p = 0.90. Intraoperative red blood cell transfusion had a minor mediation effect on the relationship between preoperative anemia optimization and the primary outcome, whereas duration of intraoperative hypotension was not found to be a mediator. Conclusion: Preoperative anemia optimization did not appear to be associated with a composite outcome of major in-hospital postoperative cardiovascular, renal, and pulmonary complications and all-cause in-hospital mortality.

The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT.

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Metformin Disrupts Signaling and Metabolism in Fetal Hepatocytes.

Metformin is used by women during pregnancy to manage diabetes and crosses the placenta, yet its effects on the fetus are unclear. We show that the liver is a site of metformin action in fetal sheep and macaques, given relatively abundant OCT1 transporter expression and hepatic uptake following metformin infusion into fetal sheep. To determine the effects of metformin action, we performed studies in primary hepatocytes from fetal sheep, fetal macaques, and juvenile macaques. Metformin increases AMP-activated protein kinase (AMPK) signaling, decreases mammalian target of rapamycin (mTOR) signaling, and decreases glucose production in fetal and juvenile hepatocytes. Metformin also decreases oxygen consumption in fetal hepatocytes. Unique to fetal hepatocytes, metformin activates stress pathways (e.g., increased PGC1A gene expression, NRF-2 protein abundance, and phosphorylation of eIF2α and CREB proteins) alongside perturbations in hepatokine expression (e.g., increased growth/differentiation factor 15 [GDF15] and fibroblast growth factor 21 [FGF21] expression and decreased insulin-like growth factor 2 [IGF2] expression). Similarly, in liver tissue from sheep fetuses infused with metformin in vivo, AMPK phosphorylation, NRF-2 protein, and PGC1A expression are increased. These results demonstrate disruption of signaling and metabolism, induction of stress, and alterations in hepatokine expression in association with metformin exposure in fetal hepatocytes. ARTICLE HIGHLIGHTS: The major metformin uptake transporter OCT1 is expressed in the fetal liver, and fetal hepatic uptake of metformin is observed in vivo. Metformin activates AMPK, reduces glucose production, and decreases oxygen consumption in fetal hepatocytes, demonstrating similar effects as in juvenile hepatocytes. Unique to fetal hepatocytes, metformin activates metabolic stress pathways and alters the expression of secreted growth factors and hepatokines. Disruption of signaling and metabolism with increased stress pathways and reduced anabolic pathways by metformin in the fetal liver may underlie reduced growth in fetuses exposed to metformin.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1.

OBJECTIVE: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. METHOD: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. RESULT: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3'UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. CONCLUSION: Serum miRNA-122 increased significantly after ACI, which may be a diagnostic marker of ACI. miRNA-122 may be involved in the pathological process of ACI and is related to the degree of neurological impairment and short-term prognosis in patients with ACI. miRNA-122 may play a regulatory role in ACI by inhibiting cell proliferation, increasing apoptosis, and inhibiting vascular endothelial cell regeneration through the CCNG1 channel.

Computer-aided diagnosis system versus conventional reading system in low-dose (< 2 mSv) computed tomography: comparative study for patients at risk of lung cancer

ABSTRACT BACKGROUND: Computer-aided diagnosis in low-dose (≤ 3 mSv) computed tomography (CT) is a potential screening tool for lung nodules, with quality interpretation and less inter-observer variability among readers. Therefore, we aimed to determine the screening potential of CT using a radiation dose that does not exceed 2 mSv. OBJECTIVE: We aimed to compare the diagnostic parameters of low-dose (< 2 mSv) CT interpretation results using a computer-aided diagnosis system for lung cancer screening with those of a conventional reading system used by radiologists. DESIGN AND SETTING: We conducted a comparative study of chest CT images for lung cancer screening at three private institutions. METHODS: A database of low-dose (< 2 mSv) chest CT images of patients at risk of lung cancer was viewed with the conventional reading system (301 patients and 226 nodules) or computer-aided diagnosis system without any subsequent radiologist review (944 patients and 1,048 nodules). RESULTS: The numbers of detected and solid nodules per patient (both P < 0.0001) were higher using the computer-aided diagnosis system than those using the conventional reading system. The nodule size was reported as the maximum size in any plane in the computer-aided diagnosis system. Higher numbers of patients (102 [11%] versus 20 [7%], P = 0.0345) and nodules (154 [15%] versus 17 [8%], P = 0.0035) were diagnosed with cancer using the computer-aided diagnosis system. CONCLUSIONS: The computer-aided diagnosis system facilitates the diagnosis of cancerous nodules, especially solid nodules, in low-dose (< 2 mSv) CT among patients at risk for lung cancer.

Frequently mutated genes in predicting the relapse of stage I lung adenocarcinoma.

PURPOSE: Approximately, 45-65% stage I non-small cell lung cancer (NSCLC) patients with surgical resection relapse within 5 years. Therefore, it is urgent to identify the predictors involved in the relapse of stage I NSCLC. METHODS/PATIENTS: Targeted sequencing was used to examine the mutation of tumor tissues and matched adjacent normal tissues from 35 patients with stage I lung adenocarcinoma (LUAD). Then, tissue microarrays containing tumor tissues from 149 stage I LUAD patients were used to assess protein expression of frequently mutated genes by immunohistochemistry. COX regression model was used to evaluate the impacts of frequently mutated genes and their protein expression on relapse-free survival (RFS) in stage I LUAD. RESULTS AND CONCLUSIONS: Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15-1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54-6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance.

The differences between modern modes of biathlon training at the olympic winter games / As diferenças entre os modos modernos de treinamento de biatlo nos jogos olímpicos de inverno / Las diferencias entre las modalidades modernas de entrenamiento de biatlón en los juegos olímpicos de invierno

ABSTRACT Introduction The biathlon is a snow sport that combines cross-country skiing and shooting, originating in Scandinavia. It requires athletes to not only have the ability to glide quickly over long distances but also to have the ability to shoot quickly and accurately. There is little research on biathlon characteristics and analysis of influencing factors and training strategies in China. Objective This study analyzes modern biathlon athletes' specific explosive power, endurance and training effects at the Winter Olympics. Methods Twenty biathlon athletes were selected as research volunteers. Physiological and biochemical indicators of the athletes were experimentally tested after training. Results There was a correlation between maximum speed and the height of the athletes' double stand test (SD) (p < 0.05). The heavier athletes skied relatively faster. However, the excessive body fat rate is not conducive to maintaining high-intensity skiing in the long term. The athletes' VO2max was closely related to their skiing performance and shot hit percentage (p < 0.05). Conclusion Maintaining gun ski training can positively improve the competitive level of world-class biathletes. The athlete's muscles have a solid ability to generate high mechanical power in a short time. It is beneficial to take advantage of a favorable position after the start of the competition. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O biatlo é um esporte de neve que combina esqui entre as montanhas e tiro, originário da Escandinávia. Requer que os atletas não só tenham a capacidade de deslizar rapidamente por longas distâncias, mas também que tenham a capacidade de atirar com rapidez e precisão. Existem poucas pesquisas sobre características do biatlo e análises de fatores de influência e estratégias de treinamento na China. Objetivo Este estudo analisa o poder explosivo específico, a resistência e os efeitos do treinamento dos atletas modernos de biatlo nos Jogos Olímpicos de Inverno. Métodos Selecionou-se 20 atletas de biatlo como voluntários de pesquisa. Os indicadores fisiológicos e bioquímicos dos atletas foram testados experimentalmente após o treinamento. Resultados Houve uma correlação entre a velocidade máxima e a altura do teste de duplo suporte (DP) dos atletas (p < 0,05). Os atletas mais pesados esquiam relativamente mais rápido. Porém a taxa excessiva de gordura corporal não é propícia para manter o esqui de alta intensidade a longo prazo. O VO2max dos atletas mostrou-se intimamente relacionado com seu desempenho de esqui e porcentagem de acertos no tiro (p < 0,05). Conclusão A manutenção do treinamento de esqui com armas pode desempenhar um papel positivo na melhoria do nível competitivo dos biatletas de classe mundial. Os músculos do atleta têm uma sólida capacidade de gerar alta potência mecânica em um curto período de tempo. É benéfico aproveitar uma posição favorável após o início da competição.Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El biatlón es un deporte de nieve que combina el esquí entre las montañas y el tiro, originario de Escandinavia. Requiere que los atletas no sólo tengan la capacidad de deslizarse rápidamente por largas distancias, sino también la capacidad de disparar con velocidad y precisión. Hay poca investigación sobre las características del biatlón y el análisis de los factores que influyen y las estrategias de entrenamiento en China. Objetivo Este estudio analiza la potencia explosiva específica, la resistencia y los efectos del entrenamiento de los atletas de biatlón moderno en los Juegos Olímpicos de Invierno. Métodos Se seleccionaron veinte atletas de biatlón como voluntarios para la investigación. Los indicadores fisiológicos y bioquímicos de los atletas fueron comprobados experimentalmente después del entrenamiento. Resultados Hubo una correlación entre la velocidad máxima y la altura de la prueba de doble apoyo (DP) de los atletas (p < 0,05). Los atletas más pesados esquiaron relativamente más rápido. Sin embargo, la excesiva tasa de grasa corporal no es propicia para mantener el esquí de alta intensidad a largo plazo. Se demostró que el VO2max de los atletas estaba estrechamente relacionado con su rendimiento en el esquí y el porcentaje de aciertos en el tiro (p < 0,05). Conclusión El mantenimiento del entrenamiento de esquí de pistola puede desempeñar un papel positivo en la mejora del nivel competitivo de los biatletas de categoría mundial. Los músculos del atleta tienen una sólida capacidad para generar una gran potencia mecánica en un corto período de tiempo. Es beneficioso aprovechar una posición favorable tras el inicio de la competición. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Muscle strength coordination training for athletes in mountaineering sports / Treinamento de coordenação da força muscular dos atletas em esportes de montanhismo / Entrenamiento de la coordinación de la fuerza muscular de los atletas de deportes de montaña

ABSTRACT Introduction Rock climbing is a physical activity that requires excellent physical conditioning. In addition to improving physical fitness and motor coordination, rock climbing requires constant improvements in muscle coordination skill training to enhance its modern tactics. Objective Explore the muscular coordination skill training of rock climbers. Methods A random sample of 8 athletes were assigned to the experiment involving the measurement of athletes' body composition, serum creatine kinase and blood urea levels, and other biomarkers collected before and after the trial. Results There was a significant negative correlation between dynamic balance and motor coordination ability after training in extreme rock climbing sports. On the second day after the rock climbing exercise, the volunteers' body weight and fat content significantly reduced, and the concentration of creatine kinase (CK) and blood urea (BU) increased significantly. Conclusion The exploration of extreme sports' effect on improving athletes' muscle coordination ability showed that strength and coordination should be enhanced in rock climbing. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A escalada em rocha é uma atividade física que exige excelente condicionamento físico. Além de melhorar a aptidão física e a coordenação motora, a escalada requer aperfeiçoamentos constantes no treinamento de habilidade em coordenação muscular para aprimoramento de suas táticas modernas. Objetivo Explorar o treinamento da capacidade de coordenação muscular de escaladores em rocha. Métodos Uma amostragem aleatória composta de 8 atletas foi designada para o experimento envolvendo a mensuração da composição corporal dos atletas, níveis séricos de creatina quinase e ureia sanguínea além de outros biomarcadores coletados antes e após o ensaio. Resultados Houve uma correlação negativa significativa entre o equilíbrio dinâmico e a capacidade de coordenação motora após o treinamento em esportes radicais de escalada em rocha. No segundo dia após o exercício de escalada em rocha, o peso corporal e o conteúdo de gordura dos voluntários mostrou uma redução significativa, e a concentração de creatina quinase (CK) e ureia sanguínea (BU) aumentaram significativamente. Conclusão A exploração do efeito dos esportes radicais na melhoria da capacidade de coordenação muscular dos atletas evidenciou que a força e a coordenação devem ser reforçadas no processo de escalada em rocha. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La escalada en roca es una actividad física que exige una excelente condición física. Además de mejorar la forma física y la coordinación motriz, la escalada requiere una mejora constante en el entrenamiento de las habilidades de coordinación muscular para optimizar su táctica moderna. Objetivo Explorar el entrenamiento de las habilidades de coordinación muscular de los escaladores de roca. Métodos Se asignó una muestra aleatoria compuesta por 8 atletas al experimento que incluía la medición de la composición corporal de los atletas, los niveles de creatina quinasa sérica y de urea en sangre, además de otros biomarcadores recogidos antes y después de la prueba. Resultados Se observó una correlación negativa significativa entre el equilibrio dinámico y la capacidad de coordinación motriz tras el entrenamiento en deportes extremos de escalada. El segundo día después del ejercicio de escalada en roca, el peso corporal y el contenido de grasa de los voluntarios mostraron una reducción significativa, y la concentración de creatina quinasa (CK) y de urea en sangre (BU) aumentó significativamente. Conclusión La exploración del efecto de los deportes extremos en la mejora de la capacidad de coordinación muscular de los atletas puso de manifiesto que la fuerza y la coordinación deben mejorarse en el proceso de escalada en roca. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122.

Computer-aided diagnosis system versus conventional reading system in low-dose (< 2 mSv) computed tomography: comparative study for patients at risk of lung cancer.

BACKGROUND: Computer-aided diagnosis in low-dose (≤ 3 mSv) computed tomography (CT) is a potential screening tool for lung nodules, with quality interpretation and less inter-observer variability among readers. Therefore, we aimed to determine the screening potential of CT using a radiation dose that does not exceed 2 mSv. OBJECTIVE: We aimed to compare the diagnostic parameters of low-dose (< 2 mSv) CT interpretation results using a computer-aided diagnosis system for lung cancer screening with those of a conventional reading system used by radiologists. DESIGN AND SETTING: We conducted a comparative study of chest CT images for lung cancer screening at three private institutions. METHODS: A database of low-dose (< 2 mSv) chest CT images of patients at risk of lung cancer was viewed with the conventional reading system (301 patients and 226 nodules) or computer-aided diagnosis system without any subsequent radiologist review (944 patients and 1,048 nodules). RESULTS: The numbers of detected and solid nodules per patient (both P < 0.0001) were higher using the computer-aided diagnosis system than those using the conventional reading system. The nodule size was reported as the maximum size in any plane in the computer-aided diagnosis system. Higher numbers of patients (102 [11%] versus 20 [7%], P = 0.0345) and nodules (154 [15%] versus 17 [8%], P = 0.0035) were diagnosed with cancer using the computer-aided diagnosis system. CONCLUSIONS: The computer-aided diagnosis system facilitates the diagnosis of cancerous nodules, especially solid nodules, in low-dose (< 2 mSv) CT among patients at risk for lung cancer.

Characteristics and Treatment Outcomes of Pediatric Langerhans Cell Histiocytosis with Thymic Involvement.

OBJECTIVE: To evaluate the characteristics and treatment outcomes of patients with pediatric Langerhans cell histiocytosis (LCH) with thymic involvement. STUDY DESIGN: We retrospectively described the clinical, biological, and imaging characteristics of a series of 19 patients with pediatric LCH with thymic involvement in our center between September 2016 and December 2019. We further analyzed the treatment response and outcomes of patients treated with chemotherapy or targeted therapy. RESULTS: Thymic involvement was found in 4.4% of a 433-consecutive pediatric LCH cohort; all LCH-thymic involvement presented with multisystem disease. Patients with thymic involvement were typically younger, harboring more lung and thyroid involvement and less bone involvement than those without thymic involvement. Most patients with thymic involvement had alteration of immunocompetence with decreased numbers of T-lymphocyte subsets and immunoglobulin G levels. Overall, 47.1% of patients demonstrated a response after 6 weeks of induction therapy, and 92.3% of the patients who did not respond to the first-line treatment had resolution of thymus after the second-line and/or targeted therapy. The progression/relapse rate showed no difference between patients who shifted to second-line therapy and those to dabrafenib (33.3% vs 25%, P = 1.000). The survival for patients with thymic involvement did not differ from those without thymic involvement. More patients treated with second-line chemotherapy had severe adverse events than those given dabrafenib (88.9% vs 0, P < .001). CONCLUSIONS: Thymic involvement was observed rarely in LCH and had specific clinical characteristics. Chemotherapy could resolve most thymic lesions, and BRAF inhibitors might provide a promising treatment option with less toxicity for infants with BRAF-V600E mutation. TRIAL REGISTRATION: http://www.chictr.org.cn, identifier: ChiCTR2000030457 (BCH-LCH 2014 study); ChiCTR2000032844 (dabrafenib study).

The long-term outcomes of posterior nasal neurectomy with or without pharyngeal neurectomy in patients with allergic rhinitis: a randomized controlled trial.

INTRODUCTION: Allergic rhinitis is a form of IgE mediated inflammation of the nasal mucosa in response to specific allergens, resulting in typical symptoms. OBJECTIVES: This study was designed with the primary goal of comparing the clinical efficacy of posterior nasal neurectomy with or without pharyngeal neurectomy for the treatment of moderate-to-severe perennial allergic rhinitis. Secondary study aims included a comparison of the severity of comorbidities, including chronic cough and asthma, between patients in these two surgical treatment groups. METHODS: A total of 52 patients were enrolled in this randomized controlled trial and were assigned to either the control group (posterior nasal neurectomy) or the experimental group (posterior nasal neurectomy + pharyngeal neurectomy). The visual analog scale and rhinoconjunctivitis quality of life questionnaire were used to compare the differences in patient symptoms between baseline and 6-, 12-, and 24-months post-treatment. In addition, patient cough and asthma symptoms were monitored during follow-up via visual analog scale and asthma control test respectively. RESULTS: No significant differences in preoperative scores were evident between groups (p > 0.05). At 6-months post-treatment, there were significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, and asthma control test scores relative to baseline values in experimental group and control group patients (p < 0.05), and this remained true upon 12- and 24-month follow-up. No significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, or asthma control test scores were observed between the two treatment groups at any postoperative follow-up time point (p > 0.05), while coughing severity was found to be significantly reduced in the experimental group relative to the control group (p < 0.05). CONCLUSION: posterior nasal neurectomy can be safely implemented with or without pharyngeal neurectomy in order to effectively treat allergic rhinitis. Combined posterior nasal neurectomy and pharyngeal neurectomy treatment may offer greater value than posterior nasal neurectomy alone for the treatment of allergic rhinitis patients with chronic cough.

Unusual polymethylene-interrupted, Δ5 monounsaturated and omega-3 fatty acids in sea urchin (Arbacia punctulata) from the Gulf of Mexico identified by solvent mediated covalent adduct chemical ionization mass spectrometry.

Sea urchin (class Echinoidea) gonads are a prized delicacy in Japan and many other world cultures. The complexity of its fatty acid (FA) profile, particularly minor FA, presents a formidable analytical challenge. We applied solvent mediated (SM) covalent adduct chemical ionization (CACI) tandem mass spectrometry to comprehensive de novo structural and quantitative characterization of the FA profile of Gulf of Mexico Atlantic sea urchin (Arbacia punctulata). >100 FA were detected including many with unusual double bond structure. Gulf sea urchin gonad lipids are rich in Δ5 monounsaturated FA 20:1(5Z) at 2.7% and the polymethylene-interrupted (PMI) diene 20:2(5Z,11Z) at 4.9%, as well as common omega-3 eicosapentaenoic acid (EPA; 5Z, 8Z, 11Z, 14Z, 17Z) at 9.8%±3.1% and arachidonic acid (AA; 5Z, 8Z, 11Z, 14Z) at 6.1%±2.1%. We propose plausible desaturation/elongation-based biochemical pathways for the endogenous production of unusual unsaturates. Unusual unsaturates may modify mammalian signaling and present novel bioactivities.

The hatching of cereal cyst nematode (Heterodera avenae) in response to different inorganic ions

Cereal cyst nematode is a major pest of small grain cereals, which causes huge yield losses to crops in China and other parts of the world. In this study, the effects of five inorganic ion concentrations on egg hatching of Heterodera avenae were studied. Results revealed that ZnCl2 and FeCl3 promoted hatching of induced and natural diapausing eggs. The cumulative hatching rates of eggs were 49 % and 13 % at 30 mM ZnCl2 and 10 mM FeCl3, respectively, which were higher than those of other treatments. The hatching ability promoted by ZnCl2 is greater than by FeCl3. Diapause induced eggs in ZnCl2 continued to hatch after 10 days; however, those in FeCl3 mainly hatched in the first two weeks. ZnCl2 had obvious stimulating effects on the hatching of natural diapause and non­diapause free eggs at 15 and 30 mM concentrations. FeCl3 promoted the hatching of natural diapause eggs; howevr, it inhibited hatching of non­diapause free eggs. Conversely, different concentrations of inorganic ions did not have any stimulatory effect on white female eggs. In the nematode life cycle, hatching is the critical stage because juveniles may be infected. The results of this study provide useful information the use of new fertilizers (including promoted hatching inorganic ions) applied before planting for controlling nematode diseases caused by H. avenae.(AU)