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Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "
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WWC1 regulates episodic learning and memory, and genetic nucleotide polymorphism of WWC1 is associated with neurodegenerative diseases such as Alzheimer's disease. However, the molecular mechanism through which WWC1 regulates neuronal function has not been fully elucidated. Here, we show that WWC1 and its paralogs (WWC2/3) bind directly to angiomotin (AMOT) family proteins (Motins), and recruit USP9X to deubiquitinate and stabilize Motins. Deletion of WWC genes in different cell types leads to reduced protein levels of Motins. In mice, neuron-specific deletion of Wwc1 and Wwc2 results in reduced expression of Motins and lower density of dendritic spines in the cortex and hippocampus, in association with impaired cognitive functions such as memory and learning. Interestingly, ectopic expression of AMOT partially rescues the neuronal phenotypes associated with Wwc1/2 deletion. Thus, WWC proteins modulate spinogenesis and cognition, at least in part, by regulating the protein stability of Motins.
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Angiomotinas , Aprendizaje , Ratones , Animales , Hipocampo/fisiología , Neuronas , Proteínas de Microfilamentos , CogniciónRESUMEN
The scaffolding protein angiomotin (AMOT) is indispensable for vertebrate embryonic angiogenesis. Here, we report that AMOT undergoes cleavage in the presence of lysophosphatidic acid (LPA), a lipid growth factor also involved in angiogenesis. AMOT cleavage is mediated by aspartic protease DNA damage-inducible 1 homolog 2 (DDI2), and the process is tightly regulated by a signaling axis including neurofibromin 2 (NF2), tankyrase 1/2 (TNKS1/2), and RING finger protein 146 (RNF146), which induce AMOT membrane localization, poly ADP ribosylation, and ubiquitination, respectively. In both zebrafish and mice, the genetic inactivation of AMOT cleavage regulators leads to defective angiogenesis, and the phenotype is rescued by the overexpression of AMOT-CT, a C-terminal AMOT cleavage product. In either physiological or pathological angiogenesis, AMOT-CT is required for vascular expansion, whereas uncleavable AMOT represses this process. Thus, our work uncovers a signaling pathway that regulates angiogenesis by modulating a cleavage-dependent activation of AMOT.
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Angiomotinas , Pez Cebra , Animales , Ratones , Pez Cebra/metabolismo , Proteínas de Microfilamentos/metabolismo , Péptido Hidrolasas , Péptidos y Proteínas de Señalización Intercelular/genéticaRESUMEN
The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Vía de Señalización Hippo , Transducción de Señal , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Carcinoma Hepatocelular/genética , Proteínas Señalizadoras YAP , Neoplasias Hepáticas/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Carcinogénesis/genética , Transformación Celular Neoplásica , Fosfoproteínas/genética , Fosfoproteínas/metabolismoRESUMEN
Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.
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Masculino , Femenino , Humanos , Hemangiosarcoma/diagnóstico , Células Endoteliales/patología , Neoplasias Hepáticas/cirugía , Pronóstico , BiopsiaRESUMEN
The Hippo tumor-suppressor pathway is frequently dysregulated in human cancers and represents a therapeutic target. However, strategies targeting the mammalian Hippo pathway are limited because of the lack of a well-established cell-surface regulator. Here, we show that transmembrane protein KIRREL1, by interacting with both SAV1 and LATS1/2, promotes LATS1/2 activation by MST1/2 (Hippo kinases), and LATS1/2 activation, in turn, inhibits activity of YAP/TAZ oncoproteins. Conversely, YAP/TAZ directly induce the expression of KIRREL1 in a TEAD1-4-dependent manner. Indeed, KIRREL1 expression positively correlates with canonical YAP/TAZ target gene expression in clinical tumor specimens and predicts poor prognosis. Moreover, transgenic expression of KIRREL1 effectively blocks tumorigenesis in a mouse intrahepatic cholangiocarcinoma model, indicating a tumor-suppressor role of KIRREL1. Hence, KIRREL1 constitutes a negative feedback mechanism regulating the Hippo pathway and serves as a cell-surface marker and potential drug target in cancers with YAP/TAZ dependency.
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Proteínas Adaptadoras Transductoras de Señales , Carcinogénesis , Proteínas de Ciclo Celular , Vía de Señalización Hippo , Proteínas de la Membrana , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Carcinogénesis/genética , Carcinogénesis/metabolismo , Proteínas de Ciclo Celular/metabolismo , Colangiocarcinoma/metabolismo , Retroalimentación , Humanos , Mamíferos/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas , Factores de Transcripción/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Señalizadoras YAP/metabolismoRESUMEN
BACKGROUND: Pathological cardiac hypertrophy occurs in response to numerous stimuli and precedes heart failure (HF). Therapies that ameliorate pathological cardiac hypertrophy are highly needed. METHODS: The expression level of miR-30d was analyzed in hypertrophy models and serum of patients with chronic heart failure by qRT-PCR. Gain and loss-of-function experiments of miR-30d were performed in vitro. miR-30d gain of function were performed in vivo. Bioinformatics, western blot, luciferase assay, qRT-PCR, and immunofluorescence were performed to examine the molecular mechanisms of miR-30d. FINDINGS: miR-30d was decreased in both murine and neonatal rat cardiomyocytes (NRCMs) models of hypertrophy. miR-30d overexpression ameliorated phenylephrine (PE) and angiotensin II (Ang II) induced hypertrophy in NRCMs, whereas the opposite phenotype was observed when miR-30d was downregulated. Consistently, the miR-30d transgenic rat was found to protect against isoproterenol (ISO)-induced pathological hypertrophy. Mechanistically, methyltransferase EZH2 could promote H3K27me3 methylation in the promotor region of miR-30d and suppress its expression during the pathological cardiac hypertrophy. miR-30d prevented pathological cardiac hypertrophy via negatively regulating its target genes MAP4K4 and GRP78 and inhibiting pro-hypertrophic nuclear factor of activated T cells (NFAT). Adeno-associated virus (AAV) serotype 9 mediated-miR-30d overexpression exhibited beneficial effects in murine hypertrophic model. Notably, miR-30d was reduced in serum of patients with chronic heart failure and miR-30d overexpression could significantly ameliorate pathological hypertrophy in human embryonic stem cell-derived cardiomyocytes. INTERPRETATION: Overexpression of miR-30d may be a potential approach to treat pathological cardiac hypertrophy. FUNDING: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to J Xiao), National Natural Science Foundation of China (82020108002 to J Xiao, 81900359 to J Li), the grant from Science and Technology Commission of Shanghai Municipality (20DZ2255400 and 21XD1421300 to J Xiao, 22010500200 to J Li), Shanghai Sailing Program (19YF1416400 to J Li), the "Dawn" Program of Shanghai Education Commission (19SG34 to J Xiao), the "Chen Guang" project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (19CG45 to J Li).
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Insuficiencia Cardíaca , MicroARNs , Angiotensina II/farmacología , Animales , Cardiomegalia/genética , China , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinasas , RatasRESUMEN
The interface between structural electrodes and solid electrolytes plays a key role in the electrical-mechanical properties of energy storage structures. Herein, we present a surface functionalization method to improve the ion conduction efficiency at the interface between a structural electrode and a solid electrolyte that consists of a bi-continuous network of epoxy and ionic liquid (IL). Composite supercapacitors made with this electrolyte and carbon fiber (CF) electrodes coated with manganese dioxide (MnO2) demonstrate that treating the electrodes with the silane can increase the areal capacitance by 300% without degrading the tensile strength. The dual-phase electrolyte containing 40 wt % IL and 60 wt % epoxy exhibits the highest multifunctional performance, measured by the product of stiffness and ionic conductivity. The outstanding mechanical and energy storage properties demonstrate that the silane treatment of MnO2-coated CF fabric structural electrodes is a promising method for future high-performance structural composite supercapacitors.
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YAP and TAZ (YAP/TAZ), two major effectors of the Hippo signaling pathway, are frequently activated in human cancers. The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. However, it is unclear how LATS1/2 are precisely regulated by upstream factors such as Hippo kinases MST1/2. Here, we show that WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. Hence, WWC1/2/3 play an organizer role in a signaling module that mediates LATS1/2 activation by MST1/2. Moreover, we have defined a minimum protein interaction interface on WWC1/2/3 that is sufficient to activate LATS1/2 in a robust and specific manner. The corresponding minigene, dubbed as SuperHippo, can effectively suppress tumorigenesis in multiple tumor models. Our study has uncovered a molecular mechanism underlying LATS1/2 regulation and provides a strategy for treating diverse malignancies related to Hippo pathway dysregulation.
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Proteínas Serina-Treonina Quinasas , Transducción de Señal , Carcinogénesis , Vía de Señalización Hippo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/fisiología , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Objective@#To understand levels of various foods and nutrients in school lunch based on digital platform and to provide reference for food preparation and serving.@*Methods@#A total of 13 018 school lunch recipes in Binhai New Area of 96 schools in Tianjin from November 2020 to April 2021 were collected by using digital management platform for food safety and nutritional health.Food types including cereals and tubers, vegetables, fruits, livestock and poultry meat, fish and shrimp, eggs, milk and dairy products, legumes and their products/nuts and others energy, and nutrients including protein, fat, carbohydrate, calcium, iron, zinc, selenium, vitamin A, vitamin B 1, vitamin B 2, vitamin C and dietary fiber were evaluated.@*Results@#The qualified rate of all kinds of food for students lunch from high to low were 96.8% (116.4 g) of livestock and poultry meat, 92.3% (179.5 g) of cereal and potato, 65.0% (170.6 g) of vegetables, 47.7% (21.4 g) of soybeans and their products/nuts, 33.4% (18.0 g) of eggs, 14.4% (8.5 g) of fish and shrimp, 14.1% (19.6 g) of fruits, 0.3% (35.4 g) of milk and dairy products. There were significant differences in the qualified rate of various food intake among different grades( P <0.05). The qualified rate of students lunch energy was 76.9%(932.6 kcal). The qualified rates of various nutrients from high to low were iron 96.9%(9.7 mg), zinc 96.8%(5.9 mg), protein 96.4%(43.8 g), carbohydrate 87.6%(130.8 g) and selenium 82.9%(23.5 μg), vitamin C 78.5%(48.8 mg), vitamin B 1 75.9%(0.5 mg), fat 74.3%(28.5 g), vitamin A 74.1%(327.1 μ g) vitamin B 2 49.9%(0.5 mg), dietary fiber 19.5%(5.9 g) and calcium 13.4%(246.1 mg). There were significant differences in the qualified rates of energy and nutrients among different grades( P <0.05).@*Conclusion@#The digital platform basically meets school lunch requirments on food types and nutrients, but still with problems regarding insufficient fish and shrimp, fruits, milk and dairy products, vitamin B 2, dietary fiber and calcium. It is suggested to optimize school lunch recipes or increase corresponding nutrients content in other meals.
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The activation of the renin-angiotensin system (RAS) induced by increased angiotensin II (AngII) levels has been implicated in muscle atrophy, which is involved in the pathogenesis of congestive heart failure. Although peroxisome proliferator-activated receptor gamma (PPARγ) activation can suppress RAS, the exact role of PPARγ in AngII-induced muscle atrophy is unclear. Here we identified PPARγ as a negative regulator of miR-29b, a microRNA that is able to promote multiple types of muscle atrophy. Suppression of miR-29b could prevent AngII-induced muscle atrophy both in vitro and in vivo. IGF1, PI3K(p85α), and Yin Yang 1 (YY1) were identified as target genes of miR-29b, and overexpression of these targets could rescue AngII-induced muscle atrophy. Importantly, inhibition of PPARγ was sufficient to induce muscle atrophy, while PPARγ overexpression could attenuate that. These data indicate that the PPARγ/miR-29b axis mediates AngII-induced muscle atrophy, and increasing PPARγ or inhibiting miR-29b represents a promising approach to counteract AngII-induced muscle atrophy.
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Muscle atrophy is associated with negative outcomes in a variety of diseases. Identification of a common therapeutic target would address a significant unmet clinical need. Here, we identify a long non-coding RNA (lncRNA) (muscle-atrophy-associated transcript, lncMAAT) as a common regulator of skeletal muscle atrophy. lncMAAT is downregulated in multiple types of muscle-atrophy models both in vivo (denervation, Angiotensin II [AngII], fasting, immobilization, and aging-induced muscle atrophy) and in vitro (AngII, H2O2, and tumor necrosis factor alpha [TNF-α]-induced muscle atrophy). Gain- and loss-of-function analysis both in vitro and in vivo reveals that downregulation of lncMAAT is sufficient to induce muscle atrophy, while overexpression of lncMAAT can ameliorate multiple types of muscle atrophy. Mechanistically, lncMAAT negatively regulates the transcription of miR-29b through SOX6 by a trans-regulatory module and increases the expression of the neighboring gene Mbnl1 by a cis-regulatory module. Therefore, overexpression of lncMAAT may represent a promising therapy for muscle atrophy induced by different stimuli.
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MicroARNs/genética , Atrofia Muscular/terapia , ARN Largo no Codificante/antagonistas & inhibidores , Secuencias Reguladoras de Ácidos Nucleicos , Factores de Transcripción SOXD/metabolismo , Animales , Diferenciación Celular , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/genética , Mioblastos/metabolismo , Mioblastos/patología , ARN Largo no Codificante/genética , Factores de Transcripción SOXD/genéticaRESUMEN
Objective:To compare the clinical, pathological features and prognosis of patients who underwent pancreaticoduodenectomy with standard or extended lymph node dissection for pancreatic ductal adenocarcinoma.Methods:A retrospective study was performed on 158 pancreatic head cancer patients who underwent radical resection at the First Affiliated Hospital of Nanjing Medical University from Jul 2017 to Feb 2019. The clinicopathological characteristics and prognosis between the standard dissection group and the extended dissection group were compared. The relationship between the number of examined lymph nodes, positive lymph nodes, and the lymph node ratio, together with their relationship with survival were analyzed.Results:Survival analysis showed no statistical difference in survival between the standard resection group and the extended resection group ( P=0.99). There were statistical differences in gender and age composition between the two group, but no significant differences in operation time, blood loss, or postoperative complications were found. Patients with less examined lymph nodes tended to be of stage N0. examined lymph nodes is positively correlated with positive lymph nodes but is not significantly correlated with lymph node ratio. Positive lymph nodes is strongly correlated with lymph node ratio. The location of lymph node metastasis was not survival-related. Conclusions:There is no prognostic difference between standard lymph node dissection and extended lymph node dissection in pancreatic cancinoma patients after Whipple procedure.
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Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.
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Objective:To compare anti-mullerian hormone (AMH) , sex hormone and inhibitor B (Inhibin B, INH-B) levels in children with different karyotypes, ages, and gender disorders of sex developmemt (DSD).Methods:A total of 101 patients with suspected gonadal dysplasia in children who underwent serological examination at the Children′s Hospital of Hunan Province from January 2019 to June 2019 were finally diagnosed by pathological biopsy. With reference to previous studies of the same type, the 101 patients included in this study were divided into 4 levels (<1 year old, 1-2 years old, 2-4 years old, >4 years old), and the social gender was divided into two levels: male and female. At the same time, 89 cases of normal gonadal development children without endocrine abnormality were selected as control. Serum levels of AMH, INH-B, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and testosterone (T) were measured by chemiluminescence method.Results:Among the 101 cases, 62 were male and 39 were female; aged 23 days to 12 years, with a median age of 3.3 years; karyotype: 52 cases were 46, XX; 21 cases were 46, XY; 12 cases were 45, X; 7 cases were 46X, del (Xq); 5 cases were 46X, i (Xq); 2 cases were 45X, inv9; 2 cases were 45X / 46XX. There were 65 cases of partial gonadal dysplasia, 25 cases of disappearing testicular syndrome, and 11 cases of mixed gonadal dysplasia. One patient had a family history of infertility. Among the causes of children′s consultation, the most common were abnormal appearance of the external genitalia (54 cases, 53.47%), followed by small penile development and / or scrotal emptiness (25 cases, 24.75%). Other reasons included primary amenorrhea, double lateral groin mass, hypertension, clitoral hypertrophy, and labia minora adhesions. The levels of serum AMH, INH-B, and T in the gonadal dysplasia group were significantly higher than those in the normal gonadal development group, while the levels of LH, FSH, E2, and PRL were significantly lower than those in the normal gonadal development group ( P<0.05). The INH-B level of children with gonadal dysplasia in different age groups was statistically significant ( P<0.05), in which the INH-B level was the highest in <1-year-old children with gonadal dysplasia, and the lowest in 2-4-year-old children with gonadal dysplasia; the LH, FSH, E2, PRL, T levels of 46, XX and other karyotypes were statistically significant ( P<0.05); Compared with other age groups, the levels of LH, FSH, E2, and PRL were relatively higher in >4 year-old children with gonadal dysplasia, while the level of T was relatively lower; There were significant differences in E2, PRL and T levels in children with gonadal dysplasia in different age groups of 46, XY karyotype ( P<0.05). Compared with other age groups, E2, PRL and T levels of children with gonadal dysplasia >4 year-old old were relatively higher and T levels were relatively lower. The levels of AMH, LH, FSH, E2 and PRL in boys with glandular dysplasia were lower than those in girls ( P<0.05), while the levels of INH-B and T were higher in boys than those in girls ( P<0.05). Conclusions:The levels of anti-mullerian hormones, inhibin B, and sex hormones in children with gonadal dysplasia are different from the normal population, and may be related to the age, chromosome karyotype, and gender distribution of the child, but there are some confounding factors (such as etiology, treatment Scheme), so more samples are needed to verify it.
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OBJECTIVE@#To explore the clinical pathological features of the patients with diffuse large B cell lymphoma (DLBCL) and their prognostic factors.@*METHODS@#The prognosis of the clinical pathological features and their influence on prognosis of 177 patients diagnosed as DLBCL at the first visit from January 2013 to May 2017 in our hospital were analyzed retrospectively.@*RESULTS@#The univariate analysis showed that overall survival (OS) and progression-free survival (PFS) were associated with later Ann Arbor stage (Ⅲ-Ⅳ) ( P<0.01, P<0.05), high performance status (ECOG score 2-4) (P<0.01, P<0.05), extranodal involvement >1 (P<0.01, P<0.05), elevated LDH level (P<0.01, P<0.05). B symptom (P<0.05) and elevated β2-MG level (P<0.05) also influenced OS. COX multivariate analysis showed that the elevated β2-MG level (P<0.05) and later stage (Ⅲ-Ⅳ) (P<0.05) have an independent influence on OS, later stage (Ⅲ-Ⅳ) (P<0.05) also independently influenced PFS. The patients with high aaIPI score (2-3) and bone marrow involvement before treatment had poor OS (P<0.01, P<0.01) and PFS (P<0.05, P<0.01).@*CONCLUSION@#Elevated β2-MG level can independently influence OS, and later stage (Ⅲ-Ⅳ) can independently influence both OS and PFS. High aaIPI score (2-3) and bone marrow involvement before treatment have an inferior influence on OS and PFS.
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Humanos , Linfoma de Células B Grandes Difuso , Análisis Multivariante , Pronóstico , Estudios RetrospectivosRESUMEN
Mycoplasma infection is the most prevalent contamination in cell culture. Analysis of cell culture in laboratories from different countries shows that mycoplasma contamination ranges from 15% to 80% and, in some cases, even reaches 100% (Chernov et al., 2014). Whilst mycoplasma infection is not visible to the naked eye in cell culture, the consequences of mycoplasma contamination have been shown to induce a number of cellular changes, for example, increased resistance to chemotherapeutic drugs. Therefore, any results obtained from tissue culture studies, in the presence of mycoplasma contamination, potentially render the data invalid (Kim et al., 2015; Gedye et al., 2016). As such, mycoplasmas are not harmless bystanders and cannot be ignored in in vitro studies.
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Humanos , Arginina/farmacología , Células HEK293 , Mycoplasma/aislamiento & purificación , Plásmidos , TransfecciónRESUMEN
Objective@#To explore the international development trends and research hotspots of outdoor activities affecting the progression of children’s myopia, and to provide a reference for researching on effective ways to prevent children’s myopia.@*Methods@#Totally 291 relevant documents included in the "Web of Science" core set database were used as research objects, and CiteSpace software was used for visual analysis.@*Results@#At present, the publications in this field were mainly in the United States(81), China(80), Australia(76), and Singapore(33); the top three research institutions were "Natl Univ Singapore"(29), "Australian Natl Univ"(27), "Capital Med Univ"(25); the main authors were "Saw SM", "Morgan IG", "Mitchell P". The field has been developed on the basis of "Ophthalmology", "Public, Environmental and Occupational Health", and has been integrated into 32 disciplines. The research content included "exploration of high risk factors for the progression of children’s myopia" and "outdoor activities", "intervention in children’s progression of myopia" and "longitudinal tracking of children’s vision development". Randomized clinical trials that longitudinally track the correlation between changes in eyeballs and the progression of myopia and the effects of outdoor activities on the biological characteristics of children’s eyeballs have become a hot topic in this field.@*Conclusion@#Research on the effects of outdoor activities on the progression of myopia in children has increased dramatically. The study of increasing outdoor activities to interfere with the progression of myopia in children and the vertical tracking of key factors affecting the biological characteristics of children’s eyeballs have become the current international trends.
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In recent years,the application of immune checkpoint blockades has brought dramatical revolution to the treatment of malignant tumors,which not only significantly increase the clinical benefits of partial advanced lung cancer,but also gradually change the landscape of available treatment options for patients with local advanced and early-staged lung cancer.But problems of immunotherapy about efficacy and safety follows.It is urgent to find dynamic biomarkers to identify the patients who are most likely to benefit from immunotherapy and to monitor tumor-specific immune responses.Several dynamic biomarkers have been identified,we will review some of lung cancer-related biomarkers,such as PD-L1 、TMB 、ctDNA 、TILs and peripheral blood biomarkers.