RESUMO
OBJECTIVE: To screen differentially expressed long non-coding RNAs (lncRNAs) in the liver of mice infected with Schistosoma japonicum during the chronic pathogenic stage and identify their functions, so as to provide insights into unravelling the role of lncRNAs in S. japonicum infection-induced liver disorders. METHODS: Twenty 6-week-old C57BL/6 mice were randomly divided into two groups, of 10 animals each group. Each mouse in the experimental group was infected with (15 ± 2) S. japonicum cercariae via the abdomen for modeling chronic S. japonicum infection in mice, and distilled water served as controls. All mice were sacrificed 70 days post-infection, and mouse liver specimens were sampled for RNA extraction and library construction. All libraries were sequenced on the Illumina NovaSeq 6000 sequencing platform. Data cleaning was performed using the fastp software, and reference genome alignment and gene expression (FPKM) calculation were performed using the HISAT2 software. Potential lncRNA sequences were predicted using the software CNIC, CPC, Pfam, and PLEK, and potential lncRNAs were screened. Differentially expressed lncRNAs were screened with the DESeq2 software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify biological processes and metabolic pathways involved in target genes of differentially expressed lncRNAs. RESULTS: A total of 333 potential lncRNAs were screened, and 67 were identified as differentially expressed lncRNAs, including 49 up-regulated and 18 down-regulated lncRNAs. A total of 53 target genes were predicted for differentially expressed lncRNAs. GO enrichment analysis showed that these target genes were mainly enriched in biological process and molecular function, among which Sema7a, Arrb1, and Ccl21b genes may be hub target genes for positive regulation of extracellular regulated protein kinase 1 (ERK1) and ERK2 cascades and may participate in the regulation of collagen expression. KEGG enrichment analysis showed that the target genes of differentially expressed lncRNAs were mainly enriched in cytokine-cytokine receptor interaction, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear factor kappa-B (NF-κB) signaling pathway. CONCLUSIONS: This study identifies differentially expressed lncRNAs and functional enrichment of their target genes in the liver of mice during the chronic pathogenic stage of S. japonicum infection. Up-regulated lncRNAs may affect biological processes of ERK1/2 cascades and chemokine signaling pathways via target genes Sema7a, Arrb1, and Ccl21b, thereby affecting collagen expression and inflammatory signal pathways, ultimately affecting the development of liver disorders.
Assuntos
Fígado , Camundongos Endogâmicos C57BL , RNA Longo não Codificante , Schistosoma japonicum , Esquistossomose Japônica , Animais , Esquistossomose Japônica/parasitologia , RNA Longo não Codificante/genética , Camundongos , Schistosoma japonicum/fisiologia , Schistosoma japonicum/genética , Fígado/parasitologia , Fígado/metabolismo , Perfilação da Expressão Gênica , Doença Crônica , FemininoRESUMO
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium-silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.
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Proliferação de Células , Ferro , Neoplasias Bucais , Nanocompostos , Microambiente Tumoral , Nanocompostos/química , Animais , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Camundongos , Humanos , Proliferação de Células/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Ferrocianetos/uso terapêutico , Silicatos/uso terapêutico , Silicatos/farmacologia , Concentração de Íons de Hidrogênio , Movimento Celular/efeitos dos fármacos , Nanopartículas , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Camundongos Nus , Ferroptose/efeitos dos fármacos , Peróxido de Hidrogênio , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. METHODS: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. RESULTS: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon y and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36y expression and neutrophilic inflammation in CRSwNP. CONCLUSION: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36y production and neutrophilic inflammation in CRSwNP.
Assuntos
Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Sinusite/metabolismo , Pólipos Nasais/complicações , Pólipos Nasais/metabolismo , Rinite/metabolismo , Calcifediol/metabolismo , Calcifediol/farmacologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/farmacologia , Inflamação , Células Epiteliais/metabolismo , Doença CrônicaRESUMO
Objective: To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis. Methods: The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result: Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III-IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ2=6.293,P=0.043). The proportions of TNM Stage III-IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ2=13.994,P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ2=10.457,P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ2=5.086,P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ2=19.791,P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ2=4.601,P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ2=11.996,P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ2=7.643, P=0.006), had a higher proportion of TNM Stage III-IV disease (60.2% [100/166] vs. 24.2% [8/33], χ2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively (P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS (P=0.026). Conclusions: Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.
Assuntos
Adenocarcinoma Mucinoso , Neoplasias Colorretais , Neoplasias Primárias Múltiplas , Humanos , Masculino , Feminino , Neoplasias Colorretais/patologia , Metástase Linfática , Estudos Retrospectivos , Prognóstico , Instabilidade de Microssatélites , Neoplasias Primárias Múltiplas/genéticaRESUMO
Objective: To explore the toxic effect of carbon black nanoparticles on human bronchial epithelial cells, and identify the differentially expressed circular RNA based on the full transcriptome high-throughput sequencing, so as to provide evidence for the development of biomarkers exposed to carbon black nanoparticles and their application on epigenetic toxicology. Methods: In June 2020, 16 HBE cells were treated with carbon black nanoparticles at concentrations of 20, 40 and 80 µg/ml, and 16 HBE cells without any intervention were used as the control group. The cytotoxicity of carbon black nanoparticles was detected by CCK8 and LDH experiments. Real-time quantitative fluorescent PCR (qRT-PCR) and ELISA were used to detect the changes of interleukin-6 (IL-6) and interleukin-8 (IL-6, IL-8) mRNA and protein levels of carbon black nanoparticles with concentration gradient after 72 h exposure. Western blot analysis was conducted to detect the expression levels of toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (P-NF-κB), apoptosis-related speckled protein (ASC) and Caspase-1 associated with nuclear factor-κB. According to high-throughput sequencing results, differentially expressed Circrnas were screened and identified by qRT-PCR, and those with stable differentially expressed circrnas and the strongest association with the NF-κB pathway were selected for ring performance identification. Results: After being exposed to carbon black nanoparticles for 72 h, the activity of 16HBE cells decreased significantly (P<0.05), and the release of lactate dehydrogenase increased significantly (P<0.05). Compared with control group, mRNA expression levels of IL-6 and IL-8, protein levels of IL-6 and IL-8 were increased, and protein levels of TLR4, p-NF-κB, ASC and Caspase-1 were significantly up-regulated in 16 HBE cells of different concentrations, with statistical significance (P<0.05). Compared with the control group, a total of 492 differentially expressed circular Rnas (|log2 FC|>1) were detected. Among the 5 differentially expressed (P<0.05) circular Rnas, circ_002642 was selected as the object of subsequent research on circular Rnas, affter 72 hours of exposure to 80 µg/ml CBNPs, 16HBE cells showed signlficantly higher expression of circ_002642 (P<0.05) . Conclusion: Carbon black nanoparticles can induce differentially expressed circular RNAs associated with inflammatory response in human bronchial epithelial cells.
Assuntos
NF-kappa B , RNA Circular , Humanos , Interleucina-8 , Fuligem/toxicidade , Receptor 4 Toll-Like , Interleucina-6 , Células Epiteliais , Caspase 1RESUMO
Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.
Assuntos
Heparina , Trombocitopenia , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Heparina/efeitos adversos , Anticoagulantes , Estudos Prospectivos , Solução Salina/efeitos adversos , Trombocitopenia/induzido quimicamente , Fibrinolíticos/efeitos adversosRESUMO
We provide an overview of the latest evidence on computer-aided detection (CAD) software for automated interpretation of chest radiographs (CXRs) for TB detection. CAD is a useful tool that can assist in rapid and consistent CXR interpretation for TB. CAD can achieve high sensitivity TB detection among people seeking care with symptoms of TB and in population-based screening, has accuracy on-par with human readers. However, implementation challenges remain. Due to diagnostic heterogeneity between settings and sub-populations, users need to select threshold scores rather than use pre-specified ones, but some sites may lack the resources and data to do so. Efficient standardisation is further complicated by frequent updates and new CAD versions, which also challenges implementation and comparison. CAD has not been validated for TB diagnosis in children and its accuracy for identifying non-TB abnormalities remains to be evaluated. A number of economic and political issues also remain to be addressed through regulation for CAD to avoid furthering health inequities. Although CAD-based CXR analysis has proven remarkably accurate for TB detection in adults, the above issues need to be addressed to ensure that the technology meets the needs of high-burden settings and vulnerable sub-populations.
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Inteligência Artificial , Tuberculose , Adulto , Criança , Humanos , Tuberculose/diagnóstico por imagem , Leitura , Raios X , Radiografia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To assess the therapeutic effect and adverse effect of intravesical instillation of bacillus Calmette-Guerin (BCG) for treatment of non-muscle invasive bladder cancer (NMIBC) and analyze the independent predictors of patient survival. METHODS: We retrospectively collected the clinical data from 421 patients (mean age 61.79±11.51 years) with NMIBC, who received intravesical instillation of BCG after surgery in Sun Yat-sen University Cancer Center from September, 2015 to September, 2021. Recurrence-free survival (RFS), progression-free survival (PFS), and disease specific survival (DSS) of the patients were analyzed, and the adverse effects were assessed using Common Terminology Criteria for Adverse Events 5.0. Kaplan-Meier analysis, univariate and multivariate COX regression analyses were used to identify the independent predictors of the patients' survival outcomes. RESULTS: The median follow-up of the patients was 17 months, during which 88 (20.9%) patients experienced recurrence (median time to recurrence of 10 months, range 3-58 months); 40 (9.5%) patients showed tumor progression (median time to progression of 18 months, range 3-50 months); and 14 (3.3%) patients died (median survival time of 30 months, range 8-52 months). Adverse events of grade 1, 2, and 3 occurred in 69, 110, and 23 of the patients, respectively. Survival analysis indicated that an age below 67.5 years (P=0.013), first tumor onset (P < 0.001), solitary tumor (P= 0.010), time to recurrence over one year (P=0.042), low levels of neutrophils (P=0.005), monocytes (P=0.005) and neutrophil/lymphocyte ratio (NLR; P=0.014), and cytokeratin 19 fragment 21-1 (CyFra21-1; P=0.002) were all associated with a higher PFS rate. Multivariate COX analysis suggested that the time of tumor recurrence (P=0.007, HR=2.669, 95% CI: 1.316-5.414), monocyte counts (P=0.015, HR=0.376, 95% CI: 0.171-0.829), and serum CyFra21-1 level (P=0.002, HR=0.312, 95% CI: 0.151-0.647) were independent predictors of RFS; primary tumor or tumor relapse (P=0.003, HR=0.301, 95% CI: 0.138-0.660), neutrophil counts (P=0.028, HR=0.302, 95% CI: 0.103-0.882), and CyFra21-1 level (P=0.029, HR=0.358, 95% CI: 0.142-0.903) were independent predictors of PFS following BCG instillation. CONCLUSION: Intravesical instillation of BCG is effective for treatment of intermediate or high-risk NMIBC, and the adverse effects are tolerable in most cases. The time of tumor recurrence, monocyte counts, and serum CyFra21-1 level are independent predictors of RFS, and primary tumor or tumor relapse, neutrophil counts, and CyFra21-1 level are independent predictors of PFS.
Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Idoso , Administração Intravesical , Vacina BCG/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Invasividade NeoplásicaRESUMO
OBJECTIVE: To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability. METHODS: A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1ßwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry. RESULTS: The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1ß (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01). CONCLUSION: SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.
Assuntos
Isquemia Encefálica , Ferroptose , Isoflavonas , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Metaloproteinase 9 da Matriz/metabolismo , Glycine max/metabolismo , Ocludina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/ultraestrutura , Isquemia Encefálica/metabolismo , Infarto Cerebral , Traumatismo por Reperfusão/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Infarto da Artéria Cerebral MédiaRESUMO
Rapid, sensitive and specific detection tools are critical for the prevention and control of infectious diseases. The in vitro nucleic acid amplification assays, including polymerase chain reaction and isothermal amplification technology, have been widely used for the detection of pathogens. Recently, nucleic acid detection-based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) have been developed, which are rapid, highly sensitive, highly specific, and portable. This review describes the classification and principle of CRISPR/Cas systems and their applications in pathogen detection, and discusses the prospects of CRISPR/Cas systems.
Assuntos
Doenças Transmissíveis , Ácidos Nucleicos , Humanos , Sistemas CRISPR-Cas/genética , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da PolimeraseRESUMO
Objective: To investigate the diagnosis and treatment of Chiari malformation patients with hoarseness and other otorhinolaryngological symptoms. Methods: The clinical data of 18 patients of Chiari malformation with hoarseness were retrospectively collected, which was composed of 5 men and 13 women, aged 3-71 with median age of 52. All the patients were admitted to the Affiliated Hospital of Qingdao University from January 1989 to January 2020. All patients underwent brain MRI and laryngoscopy. The patient's symptoms and first diagnosis department, diagnosis time, total course of disease, hoarseness course, diagnosis and treatment, and postoperative recovery time were summarized. Follow-up time was 3-16 years, with median follow-up time of 6.5 years. Descriptive methods were used for analysis. Results: The first visit departments of 18 patients included neurology (9 cases), otorhinolaryngology head and neck surgery (5 cases), pediatrics (2 cases), orthopedics (1 case) and respiratory department (1 case). Except for the 7 cases in neurology department, the other 11 patients were not diagnosed in time. The disease duration of 18 patients with Chiari malformation ranged from 2 months to 5 years, and hoarseness was present from 20 days to 5 years. After diagnosis, 9 patients underwent posterior fossa decompression surgery, and 1 of them underwent syrinx drainage at the same time. The symptoms of 8 cases improved significantly after operation, with the improvement time from 1 to 30 days. In addition, 9 patients chose conservative treatment, among whom 8 had no improvement in symptoms and 6 progressed. Conclusions: Posterior fossa decompression is an effective treatment for Chiari malformation, and the prognosis is good. Timely diagnosis and treatment can improve the prognosis of patients.
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Tratamento Conservador , Rouquidão , Masculino , Humanos , Feminino , Criança , Rouquidão/diagnóstico , Rouquidão/etiologia , Estudos Retrospectivos , Drenagem , LaringoscopiaRESUMO
Currently, the national schistosomiasis control program of China is moving from transmission interruption to elimination, and there are multiple challenges during the stage moving towards the progression of schistosomiasis elimination, including a high difficulty in shrinking snail-infested areas, unstable achievements for infectious source control, imperfect surveillance system and a reduction in schistosomiasis control and administration. Based on the core suggestions proposed in the 2022 WHO guideline on control and elimination of human schistosomiasis, recommendations on schistosomiasis surveillance system building, development of novel diagnostics, adjustment of the schistosomiasis control strategy and maintaining and improvements of the schistosomiasis control capability are proposed for the national schistosomiasis control program of China in the new era according to the actual status of schistosomiasis control in China. Formulation of the national schistosomiasis control strategy and goal from One Health perspective, verification of transmission interruption and elimination of schistosomiasis, precision implementation of schistosomiasis control interventions with adaptations to local circumstances, development and application of highly sensitive and specific diagnostics are recommended for elimination of schistosomiasis in China. In addition, the implementation of the 2022 WHO guideline on control and elimination of human schistosomiasis may guide the elimination of schistosomiasis in China.
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Objetivos , Esquistossomose , Animais , China/epidemiologia , Humanos , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Caramujos , Organização Mundial da SaúdeRESUMO
To summarize the clinical experience of sandwich-shaped resection and cheiloplasty in the treatment of macrocheilia secondary to arteriovenous malformation, and to observe its clinical efficacy and complications. The clinical data of 27 patients with macrocheilia secondary to arteriovenous malformation who received surgical treatment from January 2018 to October 2020 in Linyi Cancer Hospital were retrospectively analyzed. There were 14 males and 13 females. The median age was 4.5 years (ranged from 2 to 57 years). There were 18 cases of upper lip and 9 cases of lower lip. All patients had received interventional embolization sclerotherapy for 5 to 10 times before surgery with unsatisfied effect. There was no obvious improvement in the appearance,whereas 3 cases progressed presenting as abnormal enlargement. Sandwich-shaped resection and cheiloplasty was performed in all the patients. Histopathological examinations confirmed arteriovenous malformations in all 27 cases. Twenty-six patients received one course of operation and one received two courses. Partial mucosal necrosis occurred in 1 case and healed after dressing change, while the rest healed by first intention. Local recurrence occurred in 2 cases within 6 months after operation. A four-level standard was used for long-term evaluation, and 24 cases got grade â ¢ (good), three cases got grade â ¡ (moderate) after 1 to 3 years of follow-up. Sandwich-shaped resection and cheiloplasty can achieve good long-term efficacy with excellent appearance and function. Due to its advantages of hidden incision and three-dimensional resection and reservation, it is worthy of further clinical promotion.
Assuntos
Malformações Arteriovenosas , Embolização Terapêutica , Adolescente , Adulto , Malformações Arteriovenosas/terapia , Criança , Pré-Escolar , Embolização Terapêutica/métodos , Feminino , Humanos , Lábio , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: This study aimed to investigate the association between depressive symptoms and diet- and lifestyle-related behaviors among adolescents. STUDY DESIGN: Cross-sectional study. METHODS: Our study used stratified random cluster sampling method to recruit 6,251 adolescents aged 11-19 years as samples for research and analysis. The Center for Epidemiological Studies Depression Scale was used to assess depressive symptoms. Chi-squared test, t test, and logistic regression were used to explore the diet and lifestyle factors of depressive symptoms. Backpropagation (BP) neural network model was used to investigate the ranking of diet and lifestyle behaviors factors of depressive symptoms. RESULTS: The prevalence of depressive symptoms among adolescents was 32.1%. Multivariable logistic regression was used to determine 10 important variables of depressive symptoms. After ranking the importance by BP neural network, the top three important variables were found, which were sleep duration (100%), screen time (49.1%), and breakfast (23.6%). CONCLUSION: Sleep duration, screen time, and breakfast were associated factors with the most significant impacts on depressive symptoms.
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Depressão , Estilo de Vida , Adolescente , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Humanos , Redes Neurais de Computação , Tempo de TelaRESUMO
Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.
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Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Reto/patologia , Resultado do TratamentoRESUMO
To realize the resource utilization of waste mask fibers (MF), a layer of ZnS nanoparticles was grown on MF by a one-step hydrothermal method, and a MF/ZnS sensor was successfully prepared. This is the first time that resource utilization of MF has been combined with the development of a high-performance gas sensor. The MF/ZnS sensor showed high sensitivity and recoverability to target vapors at room temperature. Compared with ZnS powder loaded on a ceramic substrate, the MF/ZnS composite responses to four analytes have been improved by 8.4~35.2 times. In addition, the time for the MF/ZnS sensor to complete one response-recovery cycle for all four analytes was less than 30 s. This should be attributed to the high gas permeability of the MF substrate, which made the ZnS particles loaded on the MF more fully exposed to contact with the target vapors. This work not only provides a simple and low-cost method to optimize the sensing performance of gas sensors but also provides a new way for the resource utilization of MF. Supplementary Information: The online version contains supplementary material available at 10.1007/s11664-022-09644-1.
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AIM: To evaluate the risk stratification of hepatocellular carcinoma (HCC) and overall malignancies in different contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) categories, and to explore the diagnostic performance of LR-5 for HCC and LR-M for non-HCC malignancies. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Central databases were searched from 2016 to February 2021 for studies on CEUS LI-RADS v2016 and v2017. The proportion of HCC and overall malignancy in each LI-RADS category and the sensitivity, specificity, accuracy, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LR-5 and LR-M categories were determined using a random effects model. RESULTS: A total of 113 studies were retrieved and 10 studies were included. A total of 5,543 patients with 6,124 lesions were included, including 4,492 HCC. There was no HCC in LR-1, and the proportion of HCC in LR-2-5 increased with the increase of category. The proportion of HCC in LR-5 was 97%, and that in LR-M was 44%. The sensitivity, specificity, and accuracy of CEUS LR-5 for HCC were 0.76, 0.95, and 0.82, respectively, and the area under the SROC curve was 0.83. The sensitivity, specificity, and accuracy of CEUS LR-M for non-HCC malignancies were 0.81, 0.92, and 0.91, and the area under the SROC curve was 0.89. CONCLUSION: The risk of HCC increases gradually from LR-1 to LR-5, in which there was no HCC lesion in LR-1 and the proportion of HCC in LR-3 was 22%, lower than that reported in earlier studies. The proportion of HCC in LR-5 was 97% and that in LR-M was 44%. LR-5 has a high specificity of 95% for the diagnosis of HCC.