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BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.
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Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Idoso , Prognóstico , Variações do Número de Cópias de DNA/genética , Mutação/genética , Instabilidade de MicrossatélitesRESUMO
To investigate the relationship between acetyl cholinesterase associated collagen gene (COLQ) mutation in patients with acetyl cholinesterase deficiency and its clinical characteristics. Serum and red blood cell acetyl cholinesterase from patients with acetyl cholinesterase deficiency (n=6) and normal controls (n=20) were measured by butyryl thiocholine substrate. COLQ gene variations were detected by sequencing. And the cholinesterase (ChE) genotypes were measured by dibucaine inhibition in vitro. The distributions of ChE surrounded the blood vessels and nerve fibers in lung or pancreas tissues were detected by immunohistochemical staining and indirect immunofluorescence. Serum lactic acid, ammonia and other clinical data were analyzed. Serum ChE in patients with acetyl cholinesterase deficiency were only 1/50 to 1/1000 fold of normal controls. Comparing to controls, dibucaine inhibition values of patients were significantly lower, while there were no differences in red blood cells acetyl cholinesterase. Serum lactic acid and ammonia in patients were significantly higher than controls. Inser 1281-1282 GC of COLQ gene was found in 2 patients, while IVS 6 + 21 T > A, IVS 6 + 30 G > T, IVS 6 + 34 T > C and IVS66 + 12 inser T mutations were found in the other 4 patients, respectively. In addition, the patients with COLQ gene mutation were resistant to regular doses of anesthetics. COLQ gene mutation may be an important reason for the lack of serum ChE in patients with acetyl cholinesterase deficiency.
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Acetilcolinesterase/deficiência , Colágeno/genética , Erros Inatos do Metabolismo/genética , Proteínas Musculares/genética , Mutação , Acetilcolinesterase/sangue , Acetilcolinesterase/genética , Humanos , Pulmão/enzimologia , Pulmão/patologia , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/patologia , Pâncreas/enzimologia , Pâncreas/patologiaRESUMO
A novel glucoside bletilloside A (1) was isolated from the tubers of Bletilla striata, together with seven known compounds (2-8). Their structures were determined on the basis of extensive spectroscopic analyses. All compounds were evaluated for the inhibition on NO production effects in RAW 264.7 macrophage cells, while militarine (4) and dactylorhin A (5) exhibited moderate inhibitory effects.
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Bibenzilas/isolamento & purificação , Bibenzilas/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Orchidaceae/química , Animais , Bibenzilas/química , Glucosídeos/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Tubérculos/químicaRESUMO
PURPOSE: To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury. METHODS: Sixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1ß, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation. RESULTS: (1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1ß and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups. CONCLUSION: Level of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.
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Lesões por Radiação/imunologia , Cicatrização , Hormônio Adrenocorticotrópico/sangue , Animais , Citocinas/sangue , Feminino , Glucocorticoides/sangue , Humanos , Ratos , Ratos Wistar , Células Th1/imunologia , Células Th2/imunologiaRESUMO
An Affi-Prep Polymyxin column was combined with a Phenyl Sepharose column and a Sephacryl S-300 column, respectively, to remove the lipopolysaccharides(LPS) in the anti-complementary crude polysaccharides of Houttuynia Herba. The contents of LPS in the polysaccharides were determined by chromogenic tachypleus amebocyte lysate(TAL)method during the procedure of purifying. The anti-complementary activities of the polysaccharides were also compared before and after the removal of LPS. Less remanent LPS was detected after purified using Penyl Sepharose combined with polymyxin column, with the clearance rate of 42.85%. All the columns had no effect on the anti-complementary activity of the polysaccharides. Penyl Sepharose combined with polymyxin column would be sound for LPS removal of the anti-complementary polysaccharides without reducing their bioactivity.
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Houttuynia/química , Lipopolissacarídeos/isolamento & purificação , Polissacarídeos/química , Cromatografia , SefaroseRESUMO
OBJECTIVE: To explore some related problems in surgical treatment of ruptured anterior circulation intracranial aneurysms in elders. METHODS: The clinical data of 38 elderly patients with ruptured anterior circulation intracranial aneurysms were analyzed retrospectively.Such related problems as indication, timing and complications of operation were discussed through their Modified Rankin scales at discharge and half a year later. RESULTS: Their Hunt-Hess grades were I (n = 6), II (n = 17), III (n = 5), IV (n = 6) and V (n = 4) respectively. Among them, 33 cases were complicated preoperatively with other vital diseases while another 5 previously healthy (III, n = 3; II, n = 1; IV, n = 1). And their modified Rankin scales of discharge and half-a-year follow-up were 0 (n = 12 vs 12), 1 (n = 10 vs 10), 2 (n = 4 vs 4), 3 (n = 3 vs 1), 4 (n = 3 vs 3), 5 (n = 4 vs 3) and 6 (n = 2 vs 3) respectively. All scales of 5 cases of previously healthy patients were 0-2. CONCLUSION: Operation is vital for rescuing patient life and achieving excellent outcomes. Age is not a risk factor for intracranial aneurysms of elders.Early and aggressive operation is recommended for those without contraindications. Physical status is more important than age in decision-making.
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Aneurisma Roto/cirurgia , Aneurisma Intracraniano/cirurgia , Microcirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the value of high-resolution ultrasound the diagnosis and prognosis of cubital tunnel syndrome. METHODS: From January 2018 to June 2019, 47 patients with cubital tunnel syndrome were treated with ulnar nerve release and anterior subcutaneous transposition. There were 41 males and 6 females, aged from 27 to 73 years old. There were 31 cases on the right, 15 cases on the left, and 1 case on both sides. The diameter of ulnar nerve was measured by high-resolution ultrasound pre-and post-operatively, and measured directly during the operation. The recovery status of the patients was evaluated by the trial standard of ulnar nerve function assessment, and the satisfaction of the patients was assessed. RESULTS: All the 47 cases were followed up for an average of 12 months and the incisions healed well. The diameter of ulnar nerve at the compression level was (0.16±0.04) cm pre-operatively, and the diameter of ulnar nerve was (0.23±0.04) cm post-operatively. The evaluation of ulnar nerve function:excellent in 16 cases, good in 18 cases and fair in 13 cases. Twelve months post-operatively, 28 patients were satisfied, 10 patients were general and 9 patients were dissatisfied. CONCLUSION: The preoperative examination of ulnar nerve by high-resolution ultrasound is consistent with the intuitive measurement during operation, and the result of postoperative examination of ulnar nerve by high-resolution ultrasound is consistent with follow-up results. High-resolution ultrasound is an effective auxiliary method for the diagnosis and treatment of cubital tunnel syndrome.
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Síndrome do Túnel Ulnar , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Síndrome do Túnel Ulnar/diagnóstico por imagem , Síndrome do Túnel Ulnar/cirurgia , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/cirurgia , Procedimentos Neurocirúrgicos/métodos , Descompressão Cirúrgica/métodos , PrognósticoRESUMO
PURPOSE: To study thickness of RPE-BM complex in adult Chinese subjects and its correlation with systemic and ocular biometric parameters. DESIGN: Population-based longitudinal study. Cross-sectional study. PARTICIPANTS: The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years (range: 50-93 years). METHODS: A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD OCT) for measurement of the thickness of RPE-BM complex. Use Heidelberg software "Heidelberg Eye Explorer" for segmentation and measurements. MAIN OUTCOME MEASURE: Thickness of RPE-BM complex. RESULTS: In total, 3276 people (6530 eyes) were included in the study. In total, 1844 (56.3%) subjects were female. The mean age was 64.3 ± 9.6 years (range: 50-93 years). The mean refractive error (spherical equivalent) was -0.18 ± 2.04 diopters (range: -22.0 to +7.50 diopters). Mean thickness of the RPE-BM complex at the foveal center was 25.09 ± 3.98 µm (range: 17-37 µm). In multiple regression analysis, subfoveal thickness of the RPE-BM complex was associated with age (p = 0.039; beta: 0.22; B: 0.10 (95% CI: 0.01, 0.20)) and hypertension history (p = 0.038; beta: 0.23; B: 1.96 (95% CI: 0.12, 3.81)). CONCLUSION: Mean subfoveal thickness of the RPE-BM complex was 25.09 ± 3.98 µm in elderly subjects with a mean age of 64.3 years increased with age and hypertension history. The increase in the thickness of RPE-BM complex may play a role in the pathophysiologic features of various age-related ocular conditions.
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Lâmina Basilar da Corioide , Epitélio Pigmentado da Retina , Humanos , Adulto , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Epitélio Pigmentado da Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Estudos Transversais , População do Leste Asiático , Estudos LongitudinaisRESUMO
A polysaccharide, isolated and purified from the aqueous extract of nettle plant Urtica fissa, was found to consist of D-glucose and D-arabinose. Molecular weight was determined to be Mn 4140. The NMR experiments (¹H, ¹³C, ¹H--¹H COSY, TOCSY, HSQC, NOESY, and HMBC) revealed the structure as the following repeating unit: -->6)-α-D-Glcp-(1-->6)-α-D-Glcp-(1-->6)-ß-D-Glcp--(1-->5)-ß-D-Araf-(1-->3)-ß-D-Glcp-(1-->
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Medicamentos de Ervas Chinesas/isolamento & purificação , Ressonância Magnética Nuclear Biomolecular/métodos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Urticaceae/química , Sequência de Carboidratos , Medicamentos de Ervas Chinesas/química , Raízes de Plantas/químicaRESUMO
OBJECTIVE: To explore the correlation between surgical timing and clinical prognosis for ruptured intracranial aneurysms. METHODS: A series of 187 patients with intracranial aneurysm treated surgically at our department were analyzed retrospectively. Among them, 101 patients received an average follow-up period of 9 months (range: 6 - 14). Timings of operation that might affect the clinical efficacies of microsurgery were analyzed. The modified Rankin scale (mRS) of discharge and the corresponding follow-up mRS were all analyzed. RESULTS: Timing of operation was negatively correlated with mRS of hospital discharge (P < 0.05), but it had no correlation with follow-up mRS (P > 0.05); patients whose discharge mRS were 1, 2, 3 or 4 had better long-term efficacies (P < 0.05) while those with a discharge mRS of 5 fare worse (P > 0.05). CONCLUSION: The short-term efficacy of early microsurgery for intracranial aneurysms is worse than those of medium and late microsurgery. But no obvious differences exist between the long-term efficacies of early, medium and late microsurgery. The patients whose discharge mRS were 1, 2, 3 or 4 have better long-term efficacies.
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Aneurisma Roto/cirurgia , Aneurisma Intracraniano/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To summarize our own experiences of managing chronic expanding intracerebral hematoma (CEICH) and discuss its diagnosis and treatment. METHODS: The courses of CEICH, clinical and imaging features, intraoperative findings, pathological examinations and follow-up outcomes were reviewed retrospectively. The relevant literatures were reviewed simultaneously. RESULTS: The course of CEICHs ranged from 22 days to 10 years. Twenty-three cases (54.8%) were misdiagnosed as cystic gliomas, cystic gliomas, brain cysticercoses, brain abscesses and tumor strokes, etc. The misdiagnostic rate had decreased to 19.0% since June 1997. Thirty-eight patients underwent surgical operations and 4 had puncture drainage of hematoma. There was no operative death. Thirty-three cases achieved an excellent recovery and 9 cases had varying degrees of nervous dysfunctions. The follow-up period was 1-21 years. One patient had recurrence after 10 years. Among the cases of multiple CEICH, two lesions underwent no surgical treatment. One increased obviously after 7 years and another disappeared. CONCLUSION: The following five points may be used as the diagnostic criteria of CEICH: (1) intracerebral cystic space-occupying lesions on brain images; (2) circular or circle-like enhancement around lesions; (3) a mixed signal of concentric circular lamellar structures on MRI T1WI; (4) abnormal vascular lesions on CTA, MRA or DSA; (5) clinical signs and symptoms of slow progress of intracranial pressure. CEICHs with clinical symptoms of local mass effect shall be obliterated surgically. The abnormal tissues in cyst wall of hematoma should be resected. Small hematomas (< 2 cm) may be followed up.
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Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/cirurgia , Adolescente , Adulto , Criança , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To summarize the clinical efficacies and experiences of using rapid pore cranial drilling and external ventricular drainage (EVD) in the treatment of ventricular hemorrhage caused by thalamic hemorrhage. METHODS: Retrospective analysis was conducted for 401 patients at 5 hospitals from May 1983 to December 2010. They underwent EVD with an infusion of urokinase for intraventricular hemorrhage caused by thalamic hemorrhage. There were 212 males and 189 females with an age range of 19 - 78 years. RESULTS: After a 1-month therapy, the outcomes were cure 147/401 (36.7%), improvement 192/401 (47.9%) and others (death and against-advice discharge) 62/401 (15.4%). After 1-3-month treatment, their prognoses were evaluated by activity of daily living (ADL): ADLI 147/401, ADLII 82/401, ADLIII 76/401, ADLIV 19/401, ADLV 15/401, death 43/401 and against-advice discharge 19/401. During a follow-up period of 1 - 3 years, 274 patients showed the following outcomes: ADLI 122/243, ADLII 63/243, ADLIII 58/243 while 31 patients died from pulmonary infection. CONCLUSION: The procedure of EVD (including an infusion of urokinase) with rapid pore cranial drilling is preferred treatment for ventricular hemorrhage caused by thalamic hemorrhage.
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Hemorragia Cerebral/cirurgia , Drenagem/métodos , Adulto , Idoso , Hemorragia Cerebral/patologia , Ventrículos Cerebrais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tálamo/patologia , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: To summarize the clinical experiences of normal saline pressed injection via lumbar puncture in the treatment of acute tonsillar hernia induced apnea. This procedure was routinely carried out after external ventricular drainage and/or lesion removal via open craniotomy. METHODS: During the period of 1969 to 2005, a total of 43 patients failed to regain respiratory after external ventricular drainage using rapid small hole cranio-puncture apparatus or lesion removal via open craniotomy. They underwent lumbar puncture and normal saline was pressed injected via a lumbar puncture needle. The patient data were retrospectively analyzed. RESULTS: Eleven of 43 patients had spontaneous respiration and fully recovered (25.6%), 16 patients regained respiration but died eventually (37.2%) and 16 patients failed to regain respiration (37.2%). The effective rate was 62.8%. CONCLUSION: For the patients failing to regain respiration after external ventricular drainage or supratentorial lesion removal via open craniotomy, the conservative treatment should not be the first choice. The pressed injection of normal saline via lumbar puncture may rescue some patients.
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Apneia/terapia , Encefalocele/terapia , Punção Espinal , Adolescente , Adulto , Apneia/etiologia , Criança , Craniotomia , Drenagem/métodos , Encefalocele/complicações , Feminino , Forame Magno , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
This meta-analysis aimed to analyze retinal microvasculature features in eyes with Behçet's disease (BD) using optical coherence tomography angiography (OCTA). Electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched for published studies comparing retinal microvasculature characteristics between eyes with BD and controls. Continuous variables were calculated using the mean difference (MD) with 95% confidence interval (CI). Review Manager software (version 5.30) was used to conduct statistical analysis. A total of 13 eligible studies involving 599 eyes with BD and 622 control eyes were included in the meta-analysis. The pooled results showed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in eyes with BD than in control eyes (superficial VD: MD = - 3.05, P < 0.00001; deep VD: MD = - 4.05, P = 0.0004). The foveal superficial and deep VD values were also significantly lower in the BD group than in the control group (superficial VD: MD = - 1.50, P = 0.009; deep VD: MD = - 4.25, - = 0.03). Similarly, the analysis revealed a significant reduction in the parafoveal superficial and deep VD in eyes with BD than in control eyes (superficial VD: MD = - 3.68, P < 0.00001; deep VD: MD = - 4.95, P = 0.0007). In addition, the superficial and deep foveal avascular zones (FAZs) were significantly larger in patients with BD than in controls (superficial FAZ: MD = 0.06, P = 0.02; deep FAZ: MD = 0.12, P = 0.03). The present meta-analysis found that macular whole enface VD, foveal VD, and parafoveal VD were lower in eyes with BD, and the FAZ was larger in patients with BD. The findings suggest that OCTA can assist clinicians in diagnosing and monitoring the status of patients with BD.
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Síndrome de Behçet/patologia , Microvasos/patologia , Vasos Retinianos/patologia , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico por imagem , Feminino , Fóvea Central/irrigação sanguínea , Humanos , Macula Lutea/irrigação sanguínea , Edema Macular/diagnóstico por imagem , Edema Macular/etiologia , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Vasculite Retiniana/diagnóstico por imagem , Vasculite Retiniana/etiologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência ÓpticaRESUMO
Although negative life events are a risk factor for developing depression, cognitive control can help maintain one's mental health. However, whether thought-control ability (TCA) can alleviate the adverse effects of negative life events on depression is unclear. Therefore, two studies were conducted to test if it does, by having participant's complete measures of negative life events, TCA, and depression. Study 1, which included 140 healthy young adults, showed TCA mediated the relationship between negative life events and depressive symptoms, and that TCA also moderated the relationship between negative life events and depressive symptoms. Study 2 recruited patients with major depressive disorder (MDD) to test whether the findings could be generalized to individuals with MDD. Study 2 found TCA also mediated the relationship between negative life events and symptoms of MDD. Suggesting that improving the ability to control negative thoughts in daily life help maintain mental health and prevent depressive symptoms.
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BACKGROUND: Abnormal lipid metabolism is closely associated with the invasiveness and metastasis of cancer. Fatty acid-binding proteins (FABPs) play essential roles in lipid metabolism, and miRNAs can affect lipid metabolism by targeting FABPs. However, the exact mechanism is unknown. METHODS: FABP1 expression in HCC tissues was analyzed by immunochemistry with tissue microarrays. The lipid content was detected by Oil Red O staining, and the interaction between FABP1 and free fatty acid (FFA) was studied by a labeling and tracking method. miRNA arrays were used to detect the expression of miRNAs in IL-6-stimulated HCC cells. miR-603 expression was verified by qPCR. The proteins were checked by Western blot analysis. Gain and loss function evaluation was assessed by lentivirus and miRNA mimic transfection in Huh-7 cells, while reactive oxygen species (ROS) were detected by fluorescence. RESULTS: FABP1 expression was significantly decreased in approximately 90% (81/90) of HCC patients. FABP1 expression in adjacent tissues was closely associated with overall survival. Meanwhile, lipid was abundant in the adjacent tissues, yet significantly reduced in HCC tissues. FABP1 and FFA can promote each other for being uptaken by Huh-7 cells. FABP1 overexpression induced apoptosis and inhibited the proliferation, migration, invasion, and metastasis of Huh-7 cells. IL-6 treatment affected the expression of miRNAs, and miR-603 was overexpressed in HCC tissues. Also, miR-603 overexpression promoted the proliferation, migration, invasion, and metastasis of Huh-7 cells. Bioinformatic analysis predicted that miR-603 targets the 3'-UTR region of FABP1. However, miR-603 overexpression inhibited the expression of the FABP1 but increased the CPT1A, PPAR-α, and SREBP1 expressions. FABP1 overexpression reduced ROS in HCC cells, while miR-603 can reverse these effects. CONCLUSION: Our results indicate that in the pathogenesis of HCC, IL-6 induces miR-603 expression, which subsequently inhibits FABP1 expression, promotes the lipid metabolism- and synthesis-related proteins, and finally increases the cellular oxidative stress level and leads to the metastasis of HCC.
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Carcinoma Hepatocelular/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Interleucina-6/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Regiões 3' não Traduzidas , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a Ácido Graxo/genética , Ácidos Graxos/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologiaRESUMO
Purpose: This study aimed to quantitative assess the fundus tessellated density (FTD) and associated factors on the basis of fundus photographs using artificial intelligence. Methods: A detailed examination of 3468 individuals was performed. The proposed method for FTD measurements consists of image preprocessing, sample labeling, deep learning segmentation model, and FTD calculation. Fundus tessellation was extracted as region of interest and then the FTD could be obtained by calculating the average exposed choroid area of per unit area of fundus. Besides, univariate and multivariate linear regression analysis have been conducted for the statistical analysis. Results: The mean FTD was 0.14 ± 0.08 (median, 0.13; range, 0-0.39). In multivariate analysis, FTD was significantly (P < 0.001) associated with thinner subfoveal choroidal thickness, longer axial length, larger parapapillary atrophy, older age, male sex and lower body mass index. Correlation analysis suggested that the FTD increased by 33.1% (r = 0.33, P < .001) for each decade of life. Besides, correlation analysis indicated the negative correlation between FTD and spherical equivalent (SE) in the myopia participants (r = -0.25, P < 0.001), and no correlations between FTD and SE in the hypermetropia and emmetropic participants. Conclusions: It is feasible and efficient to extract FTD information from fundus images by artificial intelligence-based imaging processing. FTD can be widely used in population screening as a new quantitative biomarker for the thickness of the subfoveal choroid. The association between FTD with pathological myopia and lower visual acuity warrants further investigation. Translational Relevance: Artificial intelligence can extract valuable clinical biomarkers from fundus images and assist in population screening.
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Inteligência Artificial , Miopia Degenerativa , Idoso , Estudos Transversais , Fundo de Olho , Humanos , Masculino , Tomografia de Coerência ÓpticaRESUMO
Purpose: To predict the prognosis of craniopharyngioma in children by optical coherence tomography angiography (OCTA). Methods: We evaluated if the relationship between preoperative OCTA of the choroidal capillary density (CCD) and visual outcome continued over long-term visual recovery in 38 patients undergoing craniopharyngioma resection. Patients were evaluated 3 times: 1 week before surgery (Visit1), followed-up at 6-10 weeks (Visit2), and 9-15 months (Visit3) after surgery. Results: In total 38 patients (70 eyes) with craniopharyngiomas, which included 20 (52.6%) boys and 18 (47.4%)girls, the mean age was 11.8 ± 2.7 years (range: 6-18 years). The age (p = 0.71), gender (p = 1.00), mean refractive error (p = 0.55), and axial length (p = 0.23) of 38 normal volunteers (76 eyes) were matched. After surgery, the cross-compression of patients was relieved. The average visual acuity change in the normal CCD group was 0.07 ± 0.02; the average visual acuity change in the low CCD group was 0.01 ± 0.01, p < 0.001. Preoperative CCD value is related to the preoperative BCVA (p < 0.001), and the visual function after the long-term follow-up (9-15 months) (p < 0.001). The prognosis of CCD has the same trend as the BCVA. Further correlation analysis shows that CCD and BCVA are significantly correlated (r = 0.878; p < 0.001). CCD has a weak but significant correlation both with MD (r = 0.19; p < 0.001) and PSD (r = -0.21; p <0.001). A natural cutoff of CCD is approximately 38%. With the normal CCD group the maximum improvement of BCVA exceeds 0.3 post-operatively, compared to eyes in the low CCD group that improve by <0.03, and worse after surgery. Conclusions: Long-term vision recovery after surgical decompression of craniopharyngiomas in children can be predicted by preoperative by OCTA. Patients with normal CCD before surgery showed a tendency to improve vision; this trend of improvement persisted in subsequent follow-ups. The CCD baseline natural cutoff value for predicting visual prognosis before and after surgery is about 38%.
RESUMO
Surgery of the superior sagittal sinus (SSS) is a challenging areas for neurosurgeons. To better understand the anatomy of the SSS, we examined the chordae and arachnoid granulations in the lumen of the SSS and torcular herophili with the aid of an endoscope and a microscope, and re-evaluated the role of the chordae Willisii in preventing blood backflow. We prepared 10 SSS from fresh human cadavers during autopsies. After the cranial vaults were removed, an endoscope was inserted into the lumen of the sinus to examine the structures and morphological features of the chordae Willisii, and the topographic distribution of the arachnoid granulations. The sinuses were subsequently opened using standard anatomical methods and the intraluminal structures of the dural sinus were subjected to microanatomic analysis. In another five formalin-embalmed cadaver heads, blue latex was injected from the posterior end of the SSSs to observe filling of the SSS tributaries. We identified three types of chordae in the lumen of the SSS: valve-like chordae (48.3% of all chordae), followed by trabecular (31.5%) and laminar (20.2%) chordae. The laminar chordae at the posterior end of the SSS divide the sinus into two separate channels of different sizes. Similar structures were also seen in the lumen of the torcular herophili. The majority of arachnoid granulations were found as digitations in the lumen at the lateral wall or lateral recess of the middle segment of the SSS. Microscopic examination of the intraluminal structures of the SSS confirmed endoscopic findings. In the injection test we found that the SSS tributaries could be filled retrogradely with artificial dye, suggesting that the function of valve-like chordae in preventing the backflow of blood is restricted only to physiological conditions. Thus, we could visualize and examine endoscopically the intact intraluminal structures of the SSS, which may have therapeutic or diagnostic significance.
Assuntos
Cavidades Cranianas/anatomia & histologia , Endoscopia/métodos , Microscopia/métodos , Seio Sagital Superior/anatomia & histologia , Cadáver , Cavidades Cranianas/fisiologia , Humanos , Seio Sagital Superior/fisiologia , Seios Transversos/anatomia & histologia , Seios Transversos/fisiologiaRESUMO
Three polysaccharides were isolated from the roots of Urtica fissa by extraction, ultrafiltration, anion-exchange, and gel-filtration chromatography. The structures were characterized using acetylation, methylation, and spectral methods (GCMS, NMR). All three polysaccharides are mainly composed of D-arabinofuranosyl, D-galactopyranosyl, D-glucopyranosyl residues with different structural characteristics. Polysaccharide A of MW 5.2 x 10(3) contained a linear chain of 1-linked beta-D-glucopyranosyl, 1,6-linked beta-D-glucopyranosyl, 1,6-linked alpha-galactopyranosyl, and 1,5-linked beta-arabinofuranosyl moieties. Polysaccharide B of MW 7.7 x 10(4) possessed a chain consisting of 1,5-linked alpha-D-arabinofuranosyl, 1,3-linked beta-D-mannopyranosyl, 1,6-linked beta-D-glucopyranosyl, and 1,6-linked alpha-D-galactopyranosyl residues, but 4-O of alpha-D-galactopyranosyl residues were branched by terminal beta-D-glucopyranosyl residues. Polysaccharide C of MW 5.3 x 10(4) composed of a chain of 1,5-linked alpha-D-arabinofuranosyl, 1,4-linked beta-D-galactopyranosyl, 1,5-linked beta-D-xylopyranosyl, 1,4-linked beta-D-mannopyranosyl, 1-linked beta-D-glucopyranosyl residues, and the terminal beta-D-glucopyranosyl residues are attached to 3-O positions of 1,6-linked alpha-D-glucopyranosyl residues.