Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma. decades Thus needed However anlotinibmediated mediated unclear assays experiments ATG silencing cytoskeleton expression Furthermore addition Y27632 Y 27632 Y-2763 epithelialmesenchymal epithelial mesenchymal EMT. . (EMT) Mechanistically anlotinibinduced vivo inhibitors Y2763 2763 Y-276 (EMT Y276 276 Y-27 Y27 27 Y-2 Y2 2 Y-

Abstract Background stewart-treves syndrome (STS) is an angiosarcoma associated with chronic lymphedema. Objectives This article analyses the characteristics of twenty-two patients and proposes active intervention in lymphedema and the early diagnosis of STS. Methods Twenty-two patients with STS were diagnosed at the centre over an 11-year period. Clinical manifestations, a series of conventional analyses, and histopathology were used to study these cases retrospectively. Results The age range of 22 patients with STS was 15 to 78 years. The main clinical manifestations included multiple skin and subcutaneous nodules and scattered red or purplish-red rashes in the lymphoedematous limbs. These patients often showed clinical symptoms such as lymphedema, weakness, emaciation, pain, mass, lymphadenopathy and so on. The positive rates of ultrasonography, MRI and radionuclide imaging were 66.7% (6/9), 92.3% (12/13) and 18.2% (2/11), respectively. The main points regarding active intervention in lymphedema and early diagnosis of STS were summarized. Study limitations Since this was a retrospective study, the main points summarized by the author need to be further quantified in clinical work to guide the diagnosis of this kind of disease more conveniently. In addition, further clinical trials are needed to evaluate the role of lymphedema in the occurrence and development of malignant tumors. Conclusions STS can appear in lymphoedematous tissue many years after lymphedema onset. To avoid delays in the diagnosis and therapy of STS, physicians should actively look for signs or symptoms of malignant lymphedema during the follow-up period and promptly manage patients developing problems. stewarttreves stewart treves (STS twentytwo twenty two Twentytwo Twenty 11year year 11 retrospectively 2 1 7 purplishred purplish limbs weakness emaciation pain mass on ultrasonography 667 66 66.7 6/9, 69 6/9 , 6 9 (6/9) 923 92 3 92.3 12/13 1213 12 13 (12/13 182 18 18.2 2/11, 211 2/11 (2/11) respectively conveniently addition tumors onset followup follow up problems 66. 6/ (6/9 92. 12/1 121 (12/1 18. 21 2/1 (2/11 (6/ 12/ (12/ 2/ (2/1 (6 (12 (2/ ( (1 (2

RESUMO Introdução A ginástica aeróbica feminina é uma competição altamente artística e a análise de suas dificuldades é fundamental. Objetivo Este trabalho analisa a dificuldade dos movimentos da ginástica aeróbica feminina. Este estudo visa explorar as características coreográficas da dificuldade dos movimentos e avaliar as suas dificuldades. Métodos Várias atletas de aeróbica feminina são selecionadas como voluntárias para a pesquisa. Os pontos de vídeo da ginástica aeróbica feminina são classificados, agrupados, pontuados, tem suas ações combinadas, gravadas e organizadas. São utilizadas estatísticas matemáticas para analisar a dificuldade dos movimentos da aeróbica. Resultados O fator de dificuldade é o melhor critério de pontuação quantitativa para julgar os resultados da competição. A maior frequência no Grupo B foi a combinação de perna dividida em ângulo reto para suportar o giro de 720°. A mais alta frequência no Grupo C foi a transformação em tesoura de 180°. A mais alta frequência no Grupo D foi a divisão vertical sem suporte. A escolha da pontuação da dificuldade do projeto de cinco pessoas tende a ser estável e alta. Conclusão Os tipos de transição do espaço de ação de dificuldade na competição da equipe de aeróbica feminina são B-C-B, B-C-A, B, A. A pontuação da dificuldade da competição da equipe de aeróbica feminina foi significativamente correlacionada com a pontuação final. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction Feminine aerobic gymnastics is a highly artistic competition, and analyzing its difficulties is fundamental. Objective This work analyzes the difficulty of the movements of feminine aerobic gymnastics. This study aims to explore the choreographic characteristics of the difficulty of the movements and evaluate their difficulties. Methods Several female aerobics athletes are selected as volunteers for the research. The women’s aerobic gymnastics video points are classified, grouped, scored, and their actions combined, recorded, and organized. Mathematical statistics are used to analyze the difficulty of aerobics movements. Results The difficulty factor is the best quantitative scoring criterion to judge the competition results. The highest frequency in Group B was the right-angle split leg combination to support the 720° twist. The highest frequency in Group C was the 180° scissor transformation. The highest frequency in Group D was the unsupported vertical split. The five-person project difficulty score choice tended to be stable and high. Conclusion The transition types of difficulty action space in the competition of the women’s aerobics team are B-C-B, B-C-A, B, A. The difficulty score of the women’s aerobics team competition was significantly correlated with the final score. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

RESUMEN Introducción La gimnasia aeróbica femenina es una competición altamente artística y el análisis de sus dificultades es fundamental. Objetivo Este trabajo analiza la dificultad de los movimientos de la gimnasia aeróbica femenina. Este estudio pretende explorar las características coreográficas de la dificultad de los movimientos y evaluar sus dificultades. Métodos Se seleccionan varias atletas de aeróbic como voluntarias para la investigación. Los puntos de vídeo de la gimnasia aeróbica femenina se clasifican, se agrupan, se puntúan, se combinan sus acciones, se graban y se organizan. Se utilizan estadísticas matemáticas para analizar la dificultad de los movimientos aeróbicos. Resultados El factor de dificultad es el mejor criterio de puntuación cuantitativa para juzgar los resultados del concurso. La frecuencia más alta en el Grupo B fue la combinación de pierna dividida en ángulo recto para soportar el giro de 720°. La mayor frecuencia en el Grupo C fue la transformación en tijera de 180º. La frecuencia más alta en el Grupo D fue la división vertical sin apoyo. La elección de la puntuación de dificultad del proyecto de cinco personas tendió a ser estable y alta. Conclusión Los tipos de transición del espacio de acción de dificultad en la competición del equipo de aeróbic femenino son B-C-B, B-C-A, B, A. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars. 919 91 9 >91.9 nonsyndromic non syndromic genes PAX genotypephenotype genotype phenotype 2 China (China 201 2021 wholeexome whole exome WES (WES SWISSMODEL SWISS MODEL threedimensional three dimensional proteins reference NM_001372076.1 NM0013720761 NM 001372076 1 c1010CA cCA c 1010C A C p.T337K pT337K pTK p T337K T K (p.T337K c330331insGT cinsGT 330 331insGT insGT p.D113Afs*9 pD113Afs9 pDAfs D113Afs D Afs (p.D113Afs*9 then molars >91. 20 202 NM_001372076. NM001372076 00137207 CA pT TK 33 p.D113Afs* pD pD113Afs DAfs (p.D113Afs* >91 NM_001372076 NM00137207 0013720 3 p.D113Afs (p.D113Afs >9 NM_00137207 NM0013720 001372 > NM_0013720 NM001372 00137 NM_001372 NM00137 0013 NM_00137 NM0013 001 NM_0013 NM001 00 NM_001 NM00 0 NM_00 NM0 NM_0 NM_

Abstract To explore the emergency care method for patients suffering from acute cerebral infarction with hypertension and diabetes and its clinical effects. A total of 80 patients were selected, and were divided into the observation group and control group. The patients in the control group were given the routine emergency care, while the patients in the observation group were give the comprehensive emergency care, and the effects of clinical care of the patients in the two groups were compared. After receiving the comprehensive emergency care, the mortality rate, disability rate, recurrence rate, rescuing time, emergency triage time and NIHSS score of patients in observation group were lower than those of control group, and the differences between the two groups were of statistical significance (P < 0.05). Giving patients suffering from acute cerebral infarction with hypertension and diabetes the comprehensive emergency care could not only save the lives of patients effectively and rapidly, reducing the mortality rate, disability rate and recurrence rate, but also effectively shorten the rescue time and clinic time of the patients, reduce the degree of neurologic impairment caused to the patients. Therefore, comprehensive emergency care is worth promoting in clinical practice.

Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

ABSTRACT Objective: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. Materials and Methods: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. Results: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. Conclusion: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen.

This study aimed to evaluate the effect of a newly designed intensive caregiver education program (ICEP) on reducing cognitive impairment, anxiety, and depression in acute ischemic stroke (AIS) patients. One hundred and ninety-six AIS patients were divided into ICEP group and Control group in a 1:1 ratio using blocked randomization method. In the ICEP group, the caregivers received ICEP, while in the Control group caregivers received usual education and guidance. All patients received conventional rehabilitation treatment. Cognitive impairment (assessed by Mini Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score), anxiety (assessed by Hospital Anxiety and Depression Scale (HADS)-A score and Self-rating Anxiety Scale (SAS) score), and depression (assessed by HADS-D score and Self-rating Depression Scale (SDS) score) were assessed at baseline (M0), 3 months (M3), 6 months (M6), and 12 months (M12). Cognitive impairment score at M12 and cognitive impairment score change (M12–M0) were increased, while cognitive impairment rate at M12 was reduced in the ICEP group compared with the Control group. Anxiety score change (M12–M0), anxiety score at M12, and anxiety rate at M12 were decreased in the ICEP group compared with the Control group. Depression score change (M12–M0), depression score at M12, and depression rate at M12 were lower in the ICEP group compared with the Control group. Further subgroup analysis based on baseline features also provided similar results. In conclusion, ICEP effectively reduced cognitive impairment, anxiety, and depression in AIS patients.

Abstract Purpose: To investigate the effect of mesenteric lymph drainage on the spleen injury and the expressions of inflammatory cytokines in splenic tissue in mice following hemorrhagic shock. Methods: Male C57 mice were randomly divided into the sham shock, shock and shock+drainage groups. The mice in both shock and shock+drainage groups suffered femoral artery bleeding, maintained mean arterial pressure (MAP) of 40±2 mmHg for 90 min, and were resuscitated. And mesenteric lymph drainage was performed in the shock+drainage group at the time of resuscitation. After three hours of resuscitation, the splenic tissues were harvested for the histological observation and protein and mRNA expression analysis of cytokines. Results: The spleen in the shock group revealed a significantly structural damage and increased mRNA expressions of MyD88 and TRAF6 and protein expressions of TIPE2, MyD88, TRIF and TRAF3 compared to the sham group. By contrast, the splenic pathological injury in the shock+drainage group was alleviated significantly, and the mRNA and protein expressions of TIPE2, MyD88, TRIF, TRAF3 and TRAF6 were significantly lower than those in the shock group. Conclusion: These results indicate that post-hemorrhagic shock mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and the expressions of inflammatory cytokines.