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1.
Ann N Y Acad Sci ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34761396

RESUMO

Individual recognition via communication signals is a critical component of social behavior, and provides the basis of conflict resolution, territorial behavior, and mate choice. However, the function of chemical signals in mammalian individual recognition and conflict resolution has largely been unexplored despite olfaction being a dominant sensory modality in many mammalian species. Here, we describe behavioral tests designed to evaluate the potential role of forehead gland secretions during conflict related to territorial defense in male Great Himalayan leaf-nosed bats. We used gas chromatography-mass spectrometry to quantify the chemical composition. Our results showed that forehead gland secretions contain 16 categories of compounds, including 84 volatile compounds. The concentrations of compounds and their categories differed significantly among individuals. Moreover, behavioral studies indicated that males can use chemical signals for individual recognition. Contests were staged between males with or without functioning forehead glands. Paired males without functioning forehead glands displayed more physical contact and longer contest duration compared with pairs with functioning glands. Moreover, males with a functioning gland were more likely to win in contests when paired with males without a functioning gland. These findings support a growing amount of evidence that chemical signals play a vital role in conflict resolution in mammals.

3.
Blood Adv ; 5(19): 3799-3806, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605871

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Benzoatos/efeitos adversos , Criança , Pré-Escolar , China , Humanos , Hidrazinas , Estudos Longitudinais , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis , Resultado do Tratamento
4.
Adv Mater ; : e2104427, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676913

RESUMO

Transition-metal sulfides are promising electrochemical energy storage materials due to their abundant active sites, large interlayer space, and high theoretical capacities, especially for sodium storage. However, the low conductivity and poor cycling stability at high current densities hamper their applications. Herein, a versatile dual-template method is reported to elaborate ordered mesoporous single-layered MoS2 /carbon composite with high specific area, uniform pore size, and large pore volume. The single-layered MoS2 is confined in the carbon matrix. The mesopores between the composite nanorods provide fast electrolyte diffusion. The obtained nanocomposite shows a high sodium-storage capability, excellent rate capacity, and very good cycling performance. A capacity of 310 mAh g-1 can remain at 5.0 A g-1 after 2500 cycles. Furthermore, a sodium-ion battery (SIB) full cell composed of the MoS2 /carbon composite anode and a Na3 V2 (PO4 )3 (NVP) cathode maintains a specific capacity of 330 mAh g-1 at 1.0 A g-1 during 100 cycles. The mechanism is investigated by in situ and ex situ characterizations as well as density functional theory (DFT) calculations.

5.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4300-4306, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467745

RESUMO

Currently available drugs for complex diseases have such limitations as unsatisfactory efficacy, drug resistance, and toxic side effects. Complexity of biological systems is a determinant of drug efficacy. It is not an effective approach to find disturbance strategies for the complicated biological network for complex diseases based on the static topological structures, as biological systems undergo dynamic changes all the time. Supported by profound theoretical basis and rich clinical experience, traditional Chinese medicine(TCM) emphasizes systematic and dynamic treatment depending on changes. Guided by TCM theory in practical treatment, Chinese medicine dynamically and comprehensively regulates the overall state. Therefore, if the dynamic factors are taken into consideration in design, the resultant drugs will be more effective. This study proposes state-regulating(SR) medicine from the perspective of system dynamics, elaborating the concept in terms of the connotations and principle and verifying the feasibility of SR medicine design with the attractor method. Thus, SR medicine is a new concept for drug discovery and design from the aspect of system dynamics, which integrates the TCM focusing on holistic dynamic regulation with biomedicine that features local microscopic research such as molecular mechanisms. The attractor method is a feasible techinical way for SR medicine design.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Descoberta de Drogas , Projetos de Pesquisa
6.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2794-2802, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472297

RESUMO

Estrogen receptor (esr) mediates the effects of estrogen on the expression of related genes, thereby regulating the growth and reproduction of mammals. To investigate the effect of retrotransposon insertion polymorphism (RIP) of the porcine esr gene on porcine growth performance, retrotransposon insertion polymorphism of the esr gene were predicted by comparative genomics and bioinformatics, and PCR was used to verify the insertion polymorphisms in different porcine breeds. Finally, the correlation analysis between the genotypes and performance of Large White pigs was conducted. The results showed that four retrotransposon polymorphic sites were identified in the esr1 and esr2 genes, which are esr1-SINE- RIP1 located in intron 2 of the esr1 gene, esr1-LINE-RIP2 and RIP3-esr1- SINE located in intron 5 of the gene, and esr2-LINE-RIP located in intron 1 of the esr2 gene, respectively. Among them, insertion of a 287 bp of SINE into intron 2 of the esr1 gene significantly affected (P<0.05) the live back fat thickness and 100 kg body weight back fat thickness of Large White pigs. Moreover, the live back fat thickness and back fat thickness at 100 kg body weight of homozygous with insertion (SINE+/+) was significantly greater than that of heterozygous with insertion (SINE+/-) and homozygous without insertion (SINE-/-). Therefore, esr1-SINE-RIP1 could be used as a molecular marker to assist the selection of deposition traits in Large White pigs.


Assuntos
Polimorfismo Genético , Retroelementos , Animais , Genótipo , Íntrons/genética , Fenótipo , Polimorfismo Genético/genética , Retroelementos/genética , Suínos/genética
7.
Cell Death Dis ; 12(9): 845, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518524

RESUMO

Tumor cells require high levels of cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize cholesterol. The molecular mechanism underlying cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the cholesterol synthesis enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.

8.
Histol Histopathol ; : 18377, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590705

RESUMO

Postpartum uterine diseases are associated with significant imbalance in the levels of biogenic amines (BAs) in rat uterus. Mast cells (MCs) are the main suppliers of BAs such as serotonin, catecholamines, and histamine in uterus. There is limited evidence of the BA-positive elements involved in the physiological regulation of uterus during postpartum involution. The aim of present study is to determine the concentration and distribution of biogenic amines (BAs) such as histamine, serotonin, and catecholamines in the uterine endometrium, myometrium, and peritoneal fluid (PF) during the postpartum uterine involution. A total of 110 nulliparous outbred female nonpregnant Wistar rats of mature age were divided into eleven groups (n=10 per group) according to days of postpartum involution. Tissue specimens of uterine segments, PF were prepared. Serotonin, catecholamines, and histamine concentrations were examined by fluorescence-histochemical techniques. The fluorescence of the BA-positive elements was detected and analyzed by microspectrofluorimetry. Results were analyzed using the Kruskal-Wallis chi-squared test and pairwise Mann-Whitney-Wilcoxon tests with "Benjamini-Hochberg correction" in R 3.6.3. Mast cells in uterine segments, PF exhibited characteristic yellowish-green fluorescence. The highest MCs number was reported in corpus uteri on the 15ᵗᵸ day of postpartum involution. Serotonin, catecholamines, and histamine levels were significantly higher in BA-positive elements in the initial days. BA content was dynamic and relies on the time elapsed after parturition. There was statistically significant difference in the levels of BAs in the cornu and cervix uteri. A single morphofunctional complex of BA supply was noticed in the reproductive system of the rats. The coupled interactions of intra- and extra-organic BA-positive elements was associated with anabolic/catabolic equilibrium in uterus through the metabolism of serotonin, catecholamines, and histamine during postpartum involution.

9.
Elife ; 102021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544549

RESUMO

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/imunologia , Vacinas Bacterianas/administração & dosagem , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Pneumonia Bacteriana/prevenção & controle , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/microbiologia , Administração Intranasal , Transferência Adotiva , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Imunidade Inata/efeitos dos fármacos , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/transplante , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Fatores de Tempo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Vacinação , Vacinas de Produtos Inativados/administração & dosagem
10.
Phlebology ; : 2683555211047286, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34541959

RESUMO

OBJECTIVES: Functional impairment is a common complaint in patients with venous malformations. Equinus can occur when the venous malformation involves the lower limb, a challenging condition with only a few studies to guide treatment choices. This study was aimed to investigate the operative management of equinus associated with lower limb venous malformations. METHOD: Between August 2015 and September 2017, a total of 12 patients presented with equinus associated with lower limb venous malformations and underwent surgical correction. Preoperative and postoperative clinical symptoms, physical examination and orthopaedic evaluation were retrospectively reviewed. 8 patients who experienced pain underwent percutaneous sclerotherapy prior to the operation. Surgical management included gastrocnemius intramuscular aponeurotic recession, Z-lengthening of the Achilles tendon, Hoke technique and Taylor Spatial Frame external fixation. RESULTS: There were eight female and four male patients with a mean age of 14.3 ± 5.9 years. The mean follow-up period was 34.8 ± 9 months. The range of motion of ankle dorsiflexion (with knee extended) improved for each patient (mean, 25.4 degrees; standard deviation, 8.5 degrees). No neurovascular complications were observed. CONCLUSION: Operative correction of equinus associated with lower limb venous malformations is safe and effective. Selective preoperative sclerotherapy is necessary for optimal outcomes.

11.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3722-3731, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402297

RESUMO

This study aims to explore the efficacy of Chinese medicine injections( CMIs) for promoting blood circulation and removing blood stasis for acute cerebral infarction from the perspectives of clinical medication and mechanism of action based on two complex network analysis methods. Firstly,the current 13 kinds of CMIs for acute cerebral infarction were obtained from 2019 List of medicines for national basic medical insurance,industrial injury insurance and maternity insurance with the method of network Meta-analysis. Secondly,with the use of network pharmacology,the mechanisms of top 2 CMIs with the highest therapeutic effect for acute cerebral infarction were explored from two levels including core target and network function enrichment. The result of network Meta-analysis showed Mailuoning Injection was superior to Danhong Injection in terms of total effectiveness rate for neurological deficit score and NIHSS score. The network pharmacology results showed that Mailuoning Injection had more core targets,interaction networks,enriched biological functions and more signaling pathways than Danhong Injection for cerebral infarction. Both two CMIs can play a role in treating cerebral infarction through core targets such as TP53 and NOS3,biological processes such as fibrinolysis,nitric oxide biosynthesis,nitric oxide-mediated signal transduction,negative regulation of apoptosis in endothelial cells and apoptosis process,as well as the signaling pathways such as PI3 K-Akt signaling pathway,HIF-1 signaling pathway and cell apoptosis signaling pathways. The results of pharmacological studies explained their differences in clinical efficacy to a certain extent. A research strategy based on curative effect should be advocated in efficacy evaluation of traditional Chinese medicine,where comparative research on clinical efficacy can be conducted firstly,and then mechanism research based on outstanding effective drugs to better provide references and basis for selection of similar competitive drugs for one disease in the clinical practice.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais , Feminino , Humanos , Injeções , Gravidez , Transdução de Sinais
12.
Hum Cell ; 34(6): 1812-1829, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34431063

RESUMO

Mesenchymal stem cell (MSCs)-derived exosomes have been frequently used as useful tools in disease control. This research aimed to study the function of MSC-derived exosomes (Exo) in the stemness of cancer stem cells (CSCs) of hepatocellular carcinoma (HCC) and the molecular mechanism. Exo from the procured human bone marrow-MSCs were extracted and identified. CSCs from HCC cell lines were collected. The CSCs were treated with Exo, and then the proliferation, migration, invasion, angiogenesis-stimulating and self-renewal abilities of the Hep3B-CSCs and HuH7-CSCs were significantly reduced. C5orf66-AS1 was found as the most upregulated long noncoding RNAs (lncRNAs) in CSCs after Exo treatment. The integrated bioinformatic analyses and luciferase assays suggested that C5orf66-AS1 upregulated DUSP1 expression through sequestering microRNA-127-3p (miR-127-3p). Either artificial overexpression of miR-127-3p or silencing of DUSP1 blocked the inhibitory functions of Exo in the CSCs. DUSP1 inhibition increased the phosphorylation of ERK. Similar results were reproduced in vivo where Exo reduced the growth of xenograft formed by CSCs in nude mice, and this reduction was blocked upon miR-127-3p overexpression or DUSP1 silencing. To conclude, this research reported that MSC-derived Exo block malignant behaviors of HCC-sourced CSCs through a C5orf66-AS1/miR-127-3p/DUSP1/ERK axis.

13.
Carbohydr Polym ; 269: 118294, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294320

RESUMO

Breast cancer stem cell (BCSC) properties are correlated with the malignancy of tumor cells. Sulforaphane (SFN), a natural isothiocyanate, has anti-cancer effects. However, SFN is an oil-like, hydrophobic and unstable substance. To enhance the inhibitory effect of SFN on BCSC-like properties, the mineralized hyaluronic acid-SS-tetradecyl nano-carriers (M-HA-SS-TA) were prepared. The nano-carriers possessed high SFN entrapment rate (92.36%) and drug-loading efficiency (33.64%). The carriers were responsive to the high reducing and mild acidic tumor micro-environment, leading to rapid SFN releasing from SFN-loaded nano-drug (SFN/M-HA-SS-TA). Through the specific recognition of breast cancer cells bearing CD44+ by HA, M-HA-SS-TA nano-carriers showed excellent tumor-targeting ability. Moreover, compared with free SFN, SFN/M-HA-SS-TA showed much stronger inhibition on the BCSC-like properties (invasiveness, self-renewal and tumor growth) both in vitro and in vivo. Together, these results suggested M-HA-SS-TA nano-carriers were promising platforms for tumor-targeted delivery of SFN, enhancing the therapeutic efficacy against BCSC-like properties by SFN.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Dissulfetos/química , Portadores de Fármacos/química , Ácido Hialurônico/análogos & derivados , Isotiocianatos/uso terapêutico , Nanopartículas/química , Sulfóxidos/uso terapêutico , Animais , Dissulfetos/síntese química , Dissulfetos/metabolismo , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Feminino , Glutationa/metabolismo , Humanos , Ácido Hialurônico/metabolismo , Concentração de Íons de Hidrogênio , Isotiocianatos/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/metabolismo , Sulfóxidos/química , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Adipocyte ; 10(1): 350-360, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34224297

RESUMO

Adipogenesis is regulated by genetic interactions, in which post-transcriptional regulation plays an important role. Staufen double-stranded RNA binding protein 1 (Staufen1 or STAU1) plays diverse roles in RNA processing and adipogenesis. Previously, we found that the downregulation of STAU1 affects the expression of fatty acid-binding protein 4 (FABP4) at the protein level but not at the mRNA level. This study aimed to determine the mechanism underlying the regulation of FABP4 expression by STAU1, explaining the inconsistency between FABP4 mRNA and protein levels. We used RNA interference, photoactivatable ribonucleoside enhanced cross-linking and immunoprecipitation, and an adeno-associated virus to examine the functions of STAU1 in adipogenesis. Our results indicate that STAU1 binds to the coding sequences of FABP4, thereby regulating the translation of FABP4 mRNA by unwinding the double-stranded structure. Furthermore, STAU1 mediates adipogenesis by regulating the secretion of free fatty acids. However, STAU1 knockdown decreases the fat weight/body weight ratio but does not affect the plasma triglyceride levels. These findings describe the mechanisms involved in STAU1-mediated regulation of FABP4 expression at the translational level during adipogenesis.

15.
Int J Immunopathol Pharmacol ; 35: 20587384211025934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34187243

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) usually presents in childhood with fever, nonmalignant splenomegaly, and lymphadenopathy along with cytopenia, which is caused by mutations in the FAS apoptotic pathway. The TCRαß + CD4/CD8 double-negative T cells (DNT), one of required criteria of ALPS, will rise markedly in ALPS. Human Protein kinase C delta (PRKCD) deficiency (OMIM # 615559) was recently identified to be causative for an ALPS-type III with significant B-cell proliferation particularly of immature B cells. We report a pedigree homozygous variation of PRKCD gene (c.36T>G, p. Y12X) which presented with refractory cytopenia, splenomegaly, and polarization of DNT/regulatory T cells (Treg) axis. After repeated recurrence, the patient was treated with mTOR inhibitor sirolimus, which had a safety mechanism and specifically rebalance the DNT/Treg axis. The patient's hemoglobin and clinical condition improved gradually by the application of sirolimus (1.5 mg/m2, actual blood concentration 4.27-10.3 ng/l). Homozygous variation in PRKCD may lead to typical ALPS clinical manifestations. Targeting DNT/Treg axis, use of sirolimus in such patients may help to achieve good clinical control.

16.
Front Med (Lausanne) ; 8: 654696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34164412

RESUMO

Early detection and treatment of visual impairment diseases are critical and integral to combating avoidable blindness. To enable this, artificial intelligence-based disease identification approaches are vital for visual impairment diseases, especially for people living in areas with a few ophthalmologists. In this study, we demonstrated the identification of a large variety of visual impairment diseases using a coarse-to-fine approach. We designed a hierarchical deep learning network, which is composed of a family of multi-task & multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy. A multi-level disease-guided loss function was proposed to learn the fine-grained variability of eye disease features. The proposed framework was trained for both ocular surface and retinal images, independently. The training dataset comprised 7,100 clinical images from 1,600 patients with 100 diseases. To show the feasibility of the proposed framework, we demonstrated eye disease identification on the first two levels of the eye disease taxonomy, namely 7 ocular diseases with 4 ocular surface diseases and 3 retinal fundus diseases in level 1 and 17 subclasses with 9 ocular surface diseases and 8 retinal fundus diseases in level 2. The proposed framework is flexible and extensible, which can be inherently trained on more levels with sufficient training data for each subtype diseases (e.g., the 17 classes of level 2 include 100 subtype diseases defined as level 3 diseases). The performance of the proposed framework was evaluated against 40 board-certified ophthalmologists on clinical cases with various visual impairment diseases and showed that the proposed framework had high sensitivity and specificity with the area under the receiver operating characteristic curve ranging from 0.743 to 0.989 in identifying all identified major causes of blindness. Further assessment of 4,670 cases in a tertiary eye center also demonstrated that the proposed framework achieved a high identification accuracy rate for different visual impairment diseases compared with that of human graders in a clinical setting. The proposed hierarchical deep learning framework would improve clinical practice in ophthalmology and broaden the scope of service available, especially for people living in areas with a few ophthalmologists.

17.
Des Monomers Polym ; 24(1): 162-172, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34104074

RESUMO

Electrospinning provides a versatile, efficient and low-cost method for the preparation of continuous nanofibres from various polymers. In this study, the polyhedral oligomeric silsesquioxanes (POSS) block copolymer was synthesized via atom transfer radical polymerization. The smooth fiber, porous fiber or hierarchically porous microspheres were prepared by electrospinning from POSS block copolymer, poly(vinylidene fluoride) (PVDF) and aluminium oxide (Al2O3). The influence of copolymer concentration, the ratio of the solvents, the diameter and concentration of the Al2O3 on the surface morphology were investigated. Porous fibers and porous microspheres were prepared by regulating the ratio of the solvents from the phase separation and breath figure methods. The dynamic behavior of the water droplet with the constant volume impacting on the electrospinning films were reported. The morphology evolution, restitution coefficient, the change of energy of the water droplets are examined. The droplet bounces several times on the superhydrophobic surface, while the droplet remains pinned and does not rebound when the contact angles was lower than 150°. On the other hand, the water droplets were splashed on the Al2O3 based electrospinning films. Finally, the mechanical properties of the electrospinning films were investigated.

18.
J Cell Mol Med ; 25(12): 5497-5510, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955151

RESUMO

Studies showed that the increase of myeloid-derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour-derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)-secreted exosomes (BCC-Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour-bearing mice and BCC-Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC-Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs-related functional proteins Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC-Ex significantly down-regulated the expressions of chemokine receptor CXCR4 and markedly up-regulated the levels of inflammatory cytokines IL-6 and IL-10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC-Ex, indicating that BCC-Ex-induced MDSCs might be dependent on the down-regulation of CXCR4. Western blot showed that BCC-Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.


Assuntos
Células da Medula Óssea/patologia , Neoplasias da Mama/patologia , Exossomos/metabolismo , Células Supressoras Mieloides/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores CXCR4/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Diferenciação Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Fator de Transcrição STAT3/genética , Transdução de Sinais , Linfócitos T/imunologia , Microambiente Tumoral
19.
J Magn Reson Imaging ; 54(4): 1108-1116, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33991357

RESUMO

BACKGROUND: Preoperative imaging assessment of venous malformations (VMs) and prediction of foam sclerotherapy efficacy might be achievable by DCE-MRI but elaborate quantitive analysis was absent. PURPOSE: To evaluate the value of DCE-MRI in predicting the effectiveness of foam sclerotherapy in VMs. STUDY TYPE: Retrospective. POPULATION: Fifty-five patients (M:F = 17:38; mean age ± SD, 15.4 ± 13.0 years) with VMs. FIELD STRENGTH/SEQUENCE: Three Tesla MRI with 3D T1 -weighted volume interpolated body examination. ASSESSMENT: Patients who underwent pretreatment DCE-MRI were divided into "effective" and "ineffective" groups according to the response to foam sclerotherapy. Clinical characteristics and morphologic features were assessed. The semiquantitative parameters, such as maximum intensity time ratio (MITR), enhancement ratio (ER), and Slope, were obtained from ROI and volume of interest (VOI). The quartile and mean values of these parameters were acquired from VOI, while mean values denoted as Mean# were acquired from ROI. Establishment of two predictive models was based on ROI and VOI respectively. Model 1 was based on morphologic parameters and ROI semiquantitative parameters, while model 2 was based on morphologic parameters and VOI semiquantitative parameters. STATISTICAL ANALYSIS: Mann-Whitney U-test, Cohen's kappa, multivariate logistic regression analysis (backward stepwise), and ROC analyses. RESULTS: The lesion classification, presence of phlebolith, semiquantitative parameters of VOI (quartile and mean of MITR), and semiquantitative parameters of ROI (Slopemean # , MITRmean # ) were significantly different between two groups. Lesion classification (P = 0.002) and MITRmean# (P = 0.027) were independent predictors for poor efficacy in model 1 as determined by multivariate binary logistic regression analysis. For model 2, lesion classification (P = 0.006) and MITR25 (P = 0.001) were independent predictors. The predictive model based on VOI (AUC = 0.961) performed better than that based on ROI (AUC = 0.909) in predicting therapeutic response. DATA CONCLUSION: DCE-MRI is promising in predicting the response to foam sclerotherapy for VMs. The whole lesion VOI-based model showed better performance and could instruct surgical approach in the future. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.


Assuntos
Escleroterapia , Malformações Vasculares , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/terapia
20.
Eur J Pediatr ; 180(11): 3411-3417, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34046719

RESUMO

Chronic immune thrombocytopenia (CITP) is an autoimmune disease with many immune dysfunctions, including T helper type 17 cell (Th17)/regulatory T cells (Tregs) imbalance. Low quality of life and side effects of drugs are severe, especially in pediatrics. This study aimed to determine Th17/Treg polarization in pediatric CITP when first diagnosing ITP and evaluate its use as a predictive marker for pediatric CITP. This was a pilot study from a multi-center. Setting the effective data size to 100 patients, data entry ended in the 142nd patient who had completed a 1-year follow-up. The percentages of Treg cells and Th17 cells were quantified by flow cytometry when new diagnosed ITP patients first arrived. The association between the Th17/Treg ratio and CITP was analyzed statistically. The percentages of Treg cells and Th17 cells were lower (P = 0.0008) and higher (P = 0.0001), respectively, in the CITP-outcome group compared with the remission group. The receiver operating characteristic analysis showed that the area under the curve (AUC) of Treg and Th17 cells was 0.811 and 0.834, respectively. The ratio of Th17/Treg exhibited the largest AUC of 0.897 (cutoff value 0.076).Conclusions: Thus, the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. It is a promising predictive marker for the development of CITP to some extent.Trial registration: ChiCTR1900022419 (10th April 2019) What is Known: • The percentage of Th17 /Treg ratio of pediatric CITP is elevated. What is New: • This study shows that the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. This work may provide a new point for pediatric CITP's prediction. The imbalanced ratio of Th17/Treg was obvious when first diagnose ITP in pediatric CITP patients, rendering them as potential predictive tools for discriminating CITP to facilitate with the management of pediatric patient care. In addition, the combination of them may serve as a predictive marker in pediatric CITP.


Assuntos
Pediatria , Púrpura Trombocitopênica Idiopática , Criança , Humanos , Projetos Piloto , Púrpura Trombocitopênica Idiopática/diagnóstico , Qualidade de Vida , Linfócitos T Reguladores , Células Th17
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