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BACKGOUND: Conbercept and ranibizumab have been used to treat retinopathy of prematurity (ROP). However, the clinical effectiveness of conbercept and ranibizumab remains controversial. AIM: This meta-analysis aimed to compare the effectiveness of conbercept and ranibizumab for treating ROP. METHOD: We systematically searched Pubmed, Web of Science, Embase, the Cochrane Library, Ovid, Scopus, China National Knowledge Infrastructure, Wanfang Database, CQVIP, Duxiu Database, SinoMed, and X-MOL to screen relevant studies up to November 2022. Retrospective cohort studies and randomized controlled trials (RCTs) evaluating the effectiveness of conbercept and ranibizumab in treating patients with ROP were selected. The outcomes assessed were the rates of primary cure, ROP recurrence, and retreatment. Statistical analysis was performed using Stata. RESULTS: Seven studies (n = 989) were selected in the meta-analysis. There were 303 cases (594 eyes) treated with conbercept and 686 patients (1,318 eyes) treated with ranibizumab. Three studies reported the primary cure rate. Compared to ranibizumab, conbercept had a significantly higher primary cure rate (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.05-3.49, P < 0.05). Five studies reported the rate of ROP recurrence, and there were no significant differences between conbercept and ranibizumab (OR 0.62, 95% CI 0.28-1.38, P > 0.05). Three studies reported the rate of retreatment, and the rates were not significantly different between conbercept and ranibizumab (OR 0.78, 95% CI 0.21-2.93, P > 0.05). CONCLUSION: Conbercept had a higher rate of primary cure in ROP patients. More RCTs are needed to compare the efficacy of conbercept and ranibizumab in treating ROP.
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Dams built on rivers can bring economic benefits to local production and are considered to be environmentally friendly. However, in recent years, many researchers found that the establishment of dams has created excellent conditions for the production of methane (CH4) in rivers, making it change from a "weak source" of rivers to a "strong source" of dams. In particular, reservoir dams have a great impact on CH4 emission in rivers within their regions in terms of time and space. Spatially, the sedimentary layer and water level fluctuation zone of reservoirs are the main direct and indirect causes of CH4 production. Temporally, the synergetic effect between water level adjustment of the reservoir dam and environmental factors leads to large changes in the substances of the water body, impacts on the production and transport of CH4. Finally, the generated CH4 is emitted into the atmosphere through several important emission modes: molecular diffusion, bubbling, and degassing. The contribution of CH4 emitted from reservoir dams to the global greenhouse effect cannot be ignored.
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Listeria monocytogenes (LM) is an important foodborne pathogen that is associated with a high mortality rate. Currently, there is an urgent need for an inexpensive and rapid assay for the large-scale diagnosis and monitoring of LM. To meet these requirements, we designed a one-step, low-cost platform for the simultaneous amplification and detection of LM based on the CRISPR/Cas12a system with a micro-amplification (named Cas12a-MA). This method utilizes a combination of CRISPR/Cas12a and recombinase polymerase amplification (RPA) in the same vessel to provide a contamination-free platform for rapid nucleic acid detection with high specificity and ultra-sensitivity. In this study, we screened for three specific genes and selected the hly gene in LM as the final target. Our data showed that the number of amplification products plays a crucial role in the function of the CRISPR/Cas12a system. Our method was then further optimized for the specific detection of target DNA on 4.4 CFU/g in 25min. These assays successfully detected LM in spiked pork samples and natural meat samples (pork, beef, and mutton). All results indicate that Cas12a-MA shows great promise for foodborne pathogen detection.
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Listeria monocytogenes , Ácidos Nucleicos , Bovinos , Animais , Sistemas CRISPR-Cas , Listeria monocytogenes/genética , Bioensaio , Contaminação de Medicamentos , Recombinases , Técnicas de Amplificação de Ácido NucleicoRESUMO
BACKGROUND: To assess the correlation between clinical and biochemical hyperandrogenism parameters in polycystic ovary syndrome (PCOS) according to age. METHODS: This prospective study included 256 PCOS patients diagnosed according to the Rotterdam criteria in a university-based hospital. Androgen levels were measured using liquid chromatography-tandem mass spectrometry. Hirsutism, acne, and alopecia were assessed using the modified Ferriman-Gallwey (mF-G) score, Comprehensive Acne Severity Scale (CASS), and the Ludwig scale, respectively. The correlation between biochemical and clinical hyperandrogenism parameters was assessed in younger and older women with PCOS. RESULTS: The 256 PCOS patients were classified by age into two groups: age 18-29 years (n = 151) and age 30-40 years (n = 84). In women with PCOS, mF-G was significantly positively correlated with the free androgen index (FAI), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S). CASS had a significant positive correlation with DHEA. mF-G was positively correlated with FAI in those aged 18-29 years, but the correlations were not significant in those aged 30-40 years. The positive correlation between specific body regions of clinical hyperandrogenism, especially mF-G of chin, lower abdomen, and thighs, and testosterone, as well as with FAI, was highest in those aged 18-29 years. In those aged 30-40 years clinical hyperandrogenism was mainly affected by DHEA, DHEA-S, and dihydrotestosterone. CONCLUSION: The correlation between biochemical and clinical hyperandrogenism parameters varied with age in our East Asian population. Clinical hyperandrogenism was positively correlated with FAI in younger women with PCOS. The correlation between biochemical and clinical hyperandrogenism was not significant in older women with PCOS.
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Acne Vulgar , Hiperandrogenismo , Síndrome do Ovário Policístico , Feminino , Humanos , Idoso , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Androgênios , Estudos Prospectivos , Hiperandrogenismo/complicações , Testosterona , Acne Vulgar/epidemiologia , DesidroepiandrosteronaRESUMO
BACKGROUND: This study aimed to evaluate the predictive value of the initial screening characteristics of women with anovulatory polycystic ovary syndrome (PCOS) who did or did not respond to 2.5 mg letrozole (LET). METHODS: The clinical and laboratory characteristics of women with PCOS who underwent LET treatment were evaluated. Women with PCOS were stratified according to their responses to LET (2.5 mg). The potential predictors of their responses to LET were estimated using logistic regression analysis. RESULTS: Our retrospective study included 214 eligible patients with a response to 2.5 mg LET (n = 131) or no response to 2.5 mg LET (n = 83). PCOS patients who responded to 2.5 mg LET showed better outcomes than those who did not (2.5 mg LET) for pregnancy rate, live birth rate, pregnancy rate per patient, and live birth rate per patient. Logistic regression analyses showed that late menarche (odds ratio [OR], 1.79 [95% confidence intervals (CI), 1.22-2.64], P = 0.003), and increased anti-müllerian hormone (AMH) (OR, 1.12 [95% CI, 1.02-1.23], P = 0.02), baseline luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (OR, 3.73 [95% CI, 2.12-6.64], P < 0.001), and free androgen index (FAI) (OR, 1.37 [95% CI, 1.16-1.64], P < 0.001) were associated with a higher possibility of no response to 2.5 mg LET. CONCLUSIONS: PCOS patients with an increased LH/FSH ratio, AMH, FAI, and late menarche may need an increased dosage of LET for a treatment response, which could be helpful in designing a personalized treatment strategy.
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Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Letrozol/uso terapêutico , Síndrome do Ovário Policístico/complicações , Estudos Retrospectivos , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Foliculoestimulante , Indução da Ovulação , Hormônio LuteinizanteRESUMO
Endometriosis is a common chronic inflammatory and estrogen-dependent disease that mostly affects people of childbearing age. The dietary inflammatory index (DII) is a novel instrument for assessing the overall inflammatory potential of diet. However, no studies have shown the relationship between DII and endometriosis to date. This study aimed to elucidate the relationship between DII and endometriosis. Data were acquired from the National Health and Nutrition Examination Survey (NHANES) 2001-2006. DII was calculated using an inbuilt function in the R package. Relevant patient information was obtained through a questionnaire containing their gynecological history. Based on an endometriosis questionnaire survey, those participants who answered yes were considered cases (with endometriosis), and participants who answered no were considered as controls (without endometriosis) group. Multivariate weighted logistic regression was applied to examine the correlation between DII and endometriosis. Subgroup analysis and smoothing curve between DII and endometriosis were conducted in a further investigation. Compared to the control group, patients were prone to having a higher DII (P = 0.014). Adjusted multivariate regression models showed that DII was positively correlated with the incidence of endometriosis (P < 0.05). Analysis of subgroups revealed no significant heterogeneity. In middle-aged and older women (age ≥ 35 years), the smoothing curve fitting analysis results demonstrated a non-linear relationship between DII and the prevalence of endometriosis. Therefore, using DII as an indicator of dietary-related inflammation may help to provide new insight into the role of diet in the prevention and management of endometriosis.
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Endometriose , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Adulto , Inquéritos Nutricionais , Endometriose/epidemiologia , Dieta/efeitos adversos , Inflamação/diagnóstico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Various methods exist to intervene with and control myopia, including bifocal lenses, multifocal lenses, pirenzepine, atropine, soft gas-permeable contact lenses and aberration control frame lenses, each with its own advantages and disadvantages. OBJECTIVE: To compare the clinical effectiveness of digital keratoplasty lenses and traditional orthokeratology (OK) lenses in correcting juvenile myopia. METHODS: Sixty-one patients (122 eyes) with an average age of 10.43 ± 1.71 years and with myopia were enrolled from January 2021 to January 2022 in the treatment centre of our hospital. The patients were randomly divided into two groups. Group I (the experimental group) consisted of 30 patients who were treated with digital corneal shaping (MCT) lenses, while group II (the control group) consisted of 31 patients who were treated with traditional OK lenses. Clinical indicators, such as visual acuity, ocular axis, intraocular pressure, degree of central positioning, naked visual acuity and first-order spotting, were statistically analysed before and after fitting. RESULTS: The naked eye vision of patients using MCT lenses was significantly improved compared with patients who used traditional OK lenses (0.95 ± 0.28 > 0.58 ± 0.25; p< 0.05). Moreover, the risk of primary spot staining was reduced (p< 0.05), intraocular pressure was lower (p< 0.05) and the centre position reached 100% in patients wearing MCT lenses, suggesting that wearing MCT lenses may be more beneficial than wearing traditional OK lenses. CONCLUSION: Compared with traditional OK lenses, MCT lenses reduce the degree of myopia, have significant effects and have the added advantages of safety and reliability.
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Ovarian cancer (OC) is the seventh most prevalent type of cancer in women and the second most common cause of cancer-related deaths in women worldwide. Because of the high rates of relapse, there is an immediate and pressing need for the discovery of innovative sensitive biomarkers for OC patients. Using TCGA and GSE26712 datasets, we were able to identify 17 survival-related DEGs in OC that had differential expression. CLDN4 was the gene that caught our attention the most out of the 17 important genes since its expression was much higher in OC samples than in nontumor samples. The findings of the ROC assays then confirmed the diagnostic utility of the test in screening OC specimens to differentiate them from nontumor specimens. Patients with high CLDN4 expression predicted a shorter overall survival (OS) and disease-specific survival (DSS) than those with low CLDN4 expression, according to clinical research. Patients with low CLDN4 expression predicted longer OS and DSS. Analysis using both univariate and multivariate techniques revealed that CLDN4 expression was an independent factor associated with a poor prognosis for OS and DSS. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram suggested an effective predictive performance for OC patients. After that, we investigated whether or not there was a link between the infiltration of immune cells and the expression of the CLDN4 gene. We found that the expression of CLDN4 was positively associated with Th17 cells, NK CD56bright cells, while negatively associated with Th2 cells, pDC, and T helper cells. In the end, we carried out RT-PCR on our cohort and confirmed that the level of CLDN4 expression was noticeably elevated in OC specimens in comparison to nontumor tissues. The diagnostic usefulness of CLDN4 expression for OC was also validated by the findings of ROC tests. Thus, our findings revealed that CLDN4 may serve as a predictive biomarker in OC to assess both the clinical outcome of OC patients and the level of immune infiltration.
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Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Neoplasias Ovarianas/diagnóstico , Células Matadoras Naturais , Análise Multivariada , Nomogramas , Claudina-4RESUMO
Follicular lymphoma (FL) is a highly prevalent indolent lymphoma, and the risk of histological transformation is approximately 2-3% per year. Transformation of FL generally occurs in the same lineage (B cell lineage). Another rare form of disease progression is the transformation of neoplastic B-cells to another cell lineage such as acute myeloid leukemia (AML). The low incidence of B-myeloid transformation associated with poor prognosis hinders the establishment of model systems to identify molecular mechanisms. A 64-year-old woman was diagnosed with FL and achieved a satisfactory response after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Approximately one month after treatment terminated, the disease progressed to AML with an increased white blood cell count and abnormal coagulation. Interestingly, nucleotide sequence analysis of the genomic region encoding the immunoglobulin heavy-chain variable domain showed the possibility of homologous transformation from lymphoma to leukemia cells. Although the patient experienced transient improvement after undergoing treatment with one cycle of idarubicin and cytarabine combined with etoposide, she relapsed and died 8 days after venetoclax salvage therapy. Patient with B-myeloid transformation was associated with an aggressive clinical course and poor prognosis. Conventional strategies for treating histologically transformed AML were ineffective. However, treatment with a Bcl-2 inhibitor could serve as an option. Here we review the literature relevant to this rare histological transformation of FL.
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Objective: Trauma is China's fifth leading cause of death and ranked first among youths. Trauma databases have been well-established in many countries to announce the current state of trauma rescue, treatment and care. Nevertheless, China hasn't yet established a comparable database. This paper included two national-level databases in China to describe the current situation of trauma treatment and the epidemiological characteristics of trauma incidence, which sought to provide data support for decision-making, resource allocation, trauma prevention, trauma management, and other aspects. Methods: This study used the diagnosis and treatment data from the Hospital Quality Monitoring System (HQMS) and the China Trauma Rescue and Treatment Association (CTRTA) in 2019. A descriptive analysis was conducted to explore the demographic characteristics, trauma causes, injury degrees of trauma patients, disease burden and mortality rates in the abstracted hospitalized cases. Results: A total of 4,532,029 trauma patients were included, of which 4,436,653 were from HQMS and 95,376 from CTRTA respectively. The age group with the highest proportion is 50-54 years old (493,320 [11.12%] in HQMS and 12,025 [12.61%] in CTRTA). Fall was the most frequent cause of trauma hospitalization, accounting for 40.51% of all cases, followed by traffic injuries, accounting for 25.22%. However, for trauma patients aged between 20 and 24 years old, the most common cause of injury was traffic accidents (28.20%). Hospital expenses for trauma patients in 2019 exceeded 100.30 billion yuan, which increases significantly with age, and fall costs the most. The mortality rate of trauma inpatients was 0.77%, which gradually increased with age after 30-year-old, and was the highest in the age group above 85 (1.86%). Conclusion: This paper summarizes the demographic characteristics, trauma causes distribution, disease burden, mortality rate, and other relative data of inpatients in 2019, which can now be used as an up-to-date clinical evidence base for national healthcare prevention and management in China.
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Acidentes de Trânsito , Hospitalização , Adolescente , Humanos , Adulto Jovem , Adulto , Estudos Retrospectivos , Incidência , China/epidemiologiaRESUMO
OBJECTIVE: To explore clinical outcomes and complications of modified Transvaginal mesh (M-TVM) for advanced anterior vaginal wall prolapse in 1 year follow-up. METHODS: 574 patients underwent TVM surgeries from 2019 to 2020 were collected and divided into TVM group and M-TVM group, all preoperative and postoperative data was obtained and compared between the two groups. RESULTS: 285 women were involved eventually, including 181 in TVM group and 104 in M-TVM group. No significant difference of general conditions was found between these two groups. After long-term follow-up, patients in TVM group were more likely to suffer from pelvic pain than M-TVM group (P = 0.046). Meshes seemed much wider in M-TVM group (4.5 ± 0.69 cm) than in TVM group (3.0 ± 0.91 cm). No matter TVM or M-TVM, surgeries can significantly change point Aa and Ba when compared to preoperative data. Compared to TVM group, point C and D were significant changed in patients in M-TVM group after surgery (P < 0.001) CONCLUSION: M-TVM is a commendable procedure that can significant correct anterior prolapse with mesh extended wider, and also supply stable apical support at the same time.
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Prolapso de Órgão Pélvico , Humanos , Feminino , Prolapso de Órgão Pélvico/cirurgia , Prolapso de Órgão Pélvico/complicações , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Vagina/cirurgia , Próteses e Implantes , Resultado do TratamentoRESUMO
Inflammatory bowel disease (IBD) is a specific immune-associated intestinal disease. At present, the conventional treatment for patients is not ideal. Probiotics are widely used in the treatment of IBD patients due to their ability to restore the function of the intestinal mucosal barrier effectively and safely. Lactiplantibacillus plantarum subsp. plantarum is a kind of probiotic that exists in the intestines of hosts and is considered to have good probiotic properties. In this study, we evaluated the therapeutic effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 (SC-5) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. We estimated the effect of SC-5 on the clinical symptoms of mice through a body weight change, colon length, and DAI score. The inhibitory effects of SC-5 on the levels of cytokine IL-1ß, IL-6, and TNF-α were determined by ELISA. The protein expression levels of NF-κB, MAPK signaling pathway, and the tight junction proteins occludin, claudin-3, and ZO-1 were verified using Western Blot and immunofluorescence. 16S rRNA was used to verify the modulatory effect of SC-5 on the structure of intestinal microbiota in DSS-induced colitis mice. The results showed that SC-5 could alleviate the clinical symptoms of DSS-induced colitis mice, and significantly reduce the expression of pro-inflammatory cytokines in the colon tissue. It also attenuated the inflammatory response by inhibiting the protein expression of NF-κB and MAPK signaling pathways. SC-5 improved the integrity of the intestinal mucosal barrier by strengthening tight junction proteins. In addition, 16S rRNA sequencing demonstrated that SC-5 was effective in restoring intestinal flora balance, as well as in increasing the relative abundance and diversity of beneficial microbiota. These results indicated that SC-5 has the potential to be developed as a new probiotic candidate that prevents or alleviates IBD.
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Avian Angara disease caused by fowl adenovirus serotype 4 (FAdV-4) has spread widely and brought economic losses to the poultry industry in some countries. Effective vaccines for Angara disease control are currently lacking. In this study, four capsid proteins (hexon, penton, fiber1 and fiber2) from FAdV-4 were selected, and their optimal efficient antigenic epitopes predicted by bioinformatics software were tandemly linked with the flexible linker GGGGS. Based on their amino acid sequences, the DNA sequences for the genes encoding the multiantigen epitope tandem proteins (MAETPs) FAdV4:F1, FAdV4:P, FAdV4:F2 and FAdV4:H were chemosynthesized and then ligated by T4 ligases at the cleavage sites of restriction endonucleases to construct DNAs encoding the multilinked fusion recombinant proteins (MLFRPs) used as protective antigens from avian Angara disease. These genes ligated into the expression vector pET-28a were successfully expressed using the Escherichia coli prokaryotic expression system to prepare five kinds of MLFRPs (FAdV4:F1-P-F2-H, FAdV4:F1-F2-P-H, FAdV4:F1-F2-H-P, FAdV4:F1-P-H-F2 and FAdV4:F1-H-F2-P) for use to immunize chicks. FAdV-4 was injected into MLFRP-immunized chickens, and the challenge protection rate was evaluated. FAdV4:F1-P-F2-H produced the best protection against FAdV-4, with a single immunization resulting in a 100 % protection rate, followed by FAdV4:F1-F2-P-H (83.33 %) and FAdV4:F1-F2-H-P (66.67 %). FAdV4:F1-P-H-F2 and FAdV4:F1-H-F2-P were not able to induce a good immune protection effect after one immunization. However, all of the MLFRPs were capable of protecting the host from FAdV-4 infection after two immunizations. In conclusion, these MLFRPs generated based on capsid proteins of FAdV-4 are promising candidate subunit vaccines against Angara disease.
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Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves , Doenças das Aves Domésticas , Animais , Galinhas , Proteínas do Capsídeo/genética , Epitopos/genética , Infecções por Adenoviridae/prevenção & controle , Infecções por Adenoviridae/veterinária , Capsídeo , Sorogrupo , Aviadenovirus/genética , Adenoviridae/genética , Proteínas RecombinantesRESUMO
Foam concrete possesses low density and excellent thermal insulation properties and has been widely used in construction industry. Considering the recycling and reusing of coal gasification slag (CGS), a solid waste product in the coal chemical industry, CGS was used as the supplementary cementations material to prepare foam concrete (CGS-FC) in this work. The influence of the CGS content and water-binder ratio on the pore structure, mechanical and thermal properties was investigated. The results show that the CGS content and water-binder ratio directly impact the fluidity of the slurry, which affects the internal pore structure of the specimens after molding. And a CGS-FC with a compressive strength of 6.89 MPa, thermal conductivity of 0.24 W/m K, and a bulk density of 867 kg/m3 was successfully produced when the CGS content was 30% and water-binder ratio was 0.5. In particular, the utilization of CGS to prepare foam concrete product has recycling efficiency and environmental benefit.
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Cinza de Carvão , Carvão Mineral , Resíduos Sólidos , Força Compressiva , ÁguaRESUMO
Coagulation/flocculation is one of the most widely used and cost-effective pretreatment methods for improving the dewaterability of sludge. In this study, a cationic modified starch-based flocculant (St-CTA) in conjunction with a popular clay, attapulgite (ATP), was used for the conditioning of waste-activated sludge. The dewatering properties, including the filter cake moisture content, filtration specific resistance, capillary suction time, filtration rate and compressibility coefficient, were measured and compared by varying the doses of St-CTA and ATP. By combination of the apparent dewatering performance and the changes in the contents and distributions of the extracellular polymeric substance (EPS) fractions and components, sludge flocs, and microstructures of sludge cakes, the dewatering mechanisms were discussed in detail. St-CTA in conjunction with ATP can exhibit an enhanced dewaterability of sludge and the water content in final sludge cake can be stably reduced below 80% owing to the synergistic effects of St-CTA and ATP. In addition to the efficient charge neutralization of St-CTA, ATP not only acts as a skeleton builder in the sludge dewatering process which makes the sludge flocs more compact and improves the filterability and permeability, but also tightly interacts with the proteins in EPS of the sludge which reduces the protein content and further enhances the dewatering effect. This study provides an economical, green, and effective way to further improve the dewaterability of sludge.
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Esgotos , Amido , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Matriz Extracelular de Substâncias Poliméricas , Proteínas/química , Água/química , Filtração , Trifosfato de AdenosinaRESUMO
Tyrosol is one of the main polyphenol compounds in white wine and extra virgin olive oil (EVOO), which plays an antioxidant and anti-inflammatory role in vitro. In the present study, we investigated the possible anti-inflammatory mechanism of tyrosol in Escherichia coli (ETEC)-induced diarrhea in mice. ICR mice were randomly divided into control group, ETEC group, and ETEC + Tyrosol group with 10 mice in each group. In addition to the control group, a bacterial diarrhea model was induced in mice by continuous administration of 0.2 ml × 109 CFU/ml ETEC. After 7 days, the ETEC + Tyrosol group was given tyrosol (20 mg/kg) once a day by gavage, during which the body weight of mice and the degree of diarrhea were measured daily. On the 15th day, all animals in this experiment were sacrificed, colon tissue was collected, and colon length was recorded. Our results indicate that tyrosol significantly attenuated the extent of ETEC-induced diarrhea, including inhibition of pro-inflammatory cytokine, repair of the intestinal epithelial mechanical barrier, and significant inhibition of NF-κB activation. This finding is helpful for the development and further application of tyrosol in the treatment of diarrhea.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Animais , Camundongos , NF-kappa B , Infecções por Escherichia coli/microbiologia , Camundongos Endogâmicos ICR , Diarreia/microbiologiaRESUMO
After cataract surgery, to prevent possible postoperative endophthalmitis (POE) caused by attached pathogenic bacteria onto the surface of implanted intraocular lens (IOL), various antibiotic-loaded IOLs have been proposed and widely studied to inhibit bacterial infection. However, most of these developed antibiotic-loaded IOLs still suffer from shortcomings such as insufficient drug loading, short release time, poor biocompatibility, and risk of secondary infection. Herein, we propose a zwitterionic and high-drug loading coating for surface modification of commercial hydrophobic IOL with both antifouling and antibacterial properties to effectively prevent POE. In this strategy, zwitterionic poly(carboxylbetaine-co-dopamine methacrylamide) copolymers (pCBDA) and dopamine (DA) were first robustly co-deposited onto IOL surface via facile mussel-inspired chemistry, resulting in a hydrophilic coating (defined as PCB) without sacrificing the high light transmittance of the native IOL. Subsequently, amikacin (AMK), an amine-rich antibiotic was reversibly conjugated onto the coating through the acid-sensitive Schiff base bonds formed by the reaction between amino and catechol groups, with high-drug payload over â¼35.5 µg per IOL and 30 days of sustained drug release under weak acid environment. Benefiting from the antifouling property of zwitterionic pCBDA copolymers, the intraocularly implanted PCB/AMK-coated IOL could effectively resist the adhesion and proliferation of residual LECs to inhibit the development of posterior capsule opacification (PCO) without affecting the normal ocular tissues, demonstrating excellent in vivo biocompatibility. Moreover, the synergy of zwitterionic pCBDA and conjugated AMK with acidic-dependent release behavior endowed this PCB/AMK-coated IOL strong antibacterial activity against both in vitro biofilm formation and in vivo postoperative Staphylococcus aureus infection, suggesting its promising application in preventing POE.
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Opacificação da Cápsula , Catarata , Endoftalmite , Lentes Intraoculares , Humanos , Catarata/patologia , Antibacterianos/farmacologia , Dopamina , Complicações Pós-Operatórias , Endoftalmite/prevenção & controle , Polímeros/químicaRESUMO
Objective: The objective of this study was to analyze the quantitative association between advanced glycation end products (AGEs) and adjusted FRAX by rheumatoid arthritis (FRAX-RA) in postmenopausal type 2 diabetic (T2D) patients. The optimal cutoff value of AGEs was also explored, which was aimed at demonstrating the potential value of AGEs on evaluating osteoporotic fracture risk in postmenopausal T2D patients. Methods: We conducted a cross-sectional study including 366 postmenopausal participants (180 T2D patients [DM group] and 186 non-T2D individuals [NDM group]). All the subjects in each group were divided into three subgroups according to BMD. Physical examination, dual-energy x-ray absorptiometry (DXA), and serum indicators (including serum AGEs, glycemic parameters, bone turnover markers and inflammation factors) were examined. The relationship between FRAX-RA, serum laboratory variables, and AGEs were explored. The optimal cutoff value of AGEs to predict the risk of osteoporotic fracture was also investigated. Results: Adjusting the FRAX values with rheumatoid arthritis (RA) of T2D patients reached a significantly increased MOF-RA and an increasing trend of HF-RA. AGEs level was higher in the DM group compared to the NDMs, and was positively correlated with MOF-RA (r=0.682, P<0.001) and HF-RA (r=0.677, P<0.001). The receiver operating characteristic curve analysis revealed that the area under the curve was 0.804 (P<0.001), and the optimal AGEs cut-off value was 4.156mmol/L. Subgroup analysis for T2D patients revealed an increase in TGF-ß, IL-6 and SCTX in the osteoporosis group, while a decreased PINP in the osteoporosis group compared to the other two subgroups. AGEs were positively associated with FBG, HbA1c, HOMA-IR, S-CTX, IL-6 and TGF-ß in T2D patients, and negatively associated with PINP. Conclusions: RA-adjusted FRAX is a relevant clinical tool in evaluating fracture risk of postmenopausal T2D patients. Our study analyzed the relationship between AGEs and FRAX-RA, and explored the threshold value of AGEs for predicting fracture risk in postmenopausal T2D patients. AGEs were also associated with serum bone turnover markers and inflammation factors, indicating that the increasing level of AGEs in postmenopausal T2D patients accelerated the expression of inflammatory factors, which led to bone metabolism disorders and a higher risk of osteoporotic fractures.
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Artrite Reumatoide , Diabetes Mellitus Tipo 2 , Osteoporose , Fraturas por Osteoporose , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Densidade Óssea , Estudos Transversais , Pós-Menopausa , Interleucina-6 , Medição de Risco , Osteoporose/diagnóstico , Artrite Reumatoide/complicações , Inflamação/complicações , Diabetes Mellitus Tipo 2/complicações , Produtos Finais de Glicação AvançadaRESUMO
BACKGROUND: Dengue virus type 2 (DENV-2) was used to infect primary human umbilical vein endothelial cells (HUVECs) to examine autophagy induced by activation of the adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway following tripartite motif-containing 22 (TRIM22)-mediated DENV-2 infection to further reveal the underlying pathogenic mechanism of DENV-2 infection. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen putative interference targets of TRIM22 and determine the knockdown efficiency. The effect of TRIM22 knockdown on HUVEC proliferation was determined using the CCK8 assay. Following TRIM22 knockdown, transmission electron microscopy (TEM) was used to determine the ultrastructure of HUVEC autophagosomes and expression of HUVEC autophagy and AMPK pathway-related genes were measured by qRT-PCR. Moreover, HUVEC autophagy and AMPK pathway-related protein expression levels were determined by western blot analysis. Cell cycle and apoptosis were assessed by flow cytometry (FCM) and the autophagosome structure of the HUVECs was observed by TEM. RESULTS: Western blot results indicated that TRIM22 protein expression levels increased significantly 36 h after DENV-2 infection, which was consistent with the proteomics prediction. The CCK8 assay revealed that HUVEC proliferation was reduced following TRIM22 knockdown (P < 0.001). The TEM results indicated that HUVEC autolysosomes increased and autophagy was inhibited after TRIM22 knockdown. The qRT-PCR results revealed that after TRIM22 knockdown, the expression levels of antithymocyte globulin 7 (ATG7), antithymocyte globulin 5 (ATG5), Beclin1, ERK, and mTOR genes decreased (P < 0.01); however, the expression of AMPK genes (P < 0.05) and P62 genes (P < 0.001) increased. FCM revealed that following TRIM22 knockdown, the percentage of HUVECs in the G2 phase increased (P < 0.001) along with cell apoptosis. The effect of TRIM22 overexpression on HUVEC autophagy induced by DENV-2 infection and AMPK pathways decreased after adding an autophagy inhibitor. CONCLUSIONS: In HUVECs, TRIM22 protein positively regulates autophagy and may affect autophagy through the AMPK/ERK/mTOR signaling pathway. Autophagy is induced by activation of the AMPK/ERK/mTOR signaling pathway following TRIM22-mediated DENV-2 infection of HUVECs.
Assuntos
Proteínas Quinases Ativadas por AMP , MAP Quinases Reguladas por Sinal Extracelular , Humanos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Células Endoteliais da Veia Umbilical Humana , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sirolimo/farmacologia , Soro Antilinfocitário/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , Autofagia , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/farmacologia , Proteínas Repressoras/metabolismo , Antígenos de Histocompatibilidade Menor/farmacologiaRESUMO
As the leading cause of death, heart attacks result in millions of deaths annually, with no end in sight. Early intervention is the only strategy for rescuing lives threatened by heart disease. However, the detection time of the fastest heart-attack detection system is >15 min, which is too long considering the rapid passage of life. In this study, a machine learning (ML)-driven system with a simple process, low-cost, short detection time (only 10 s), and high precision is developed. By utilizing a functionalized nanofinger structure, even a trace amount of biomarker leaked before a heart attack can be captured. Additionally, enhanced Raman profiles are constructed for predictive analytics. Five ML models are developed to harness the useful characteristics of each Raman spectrum and provide early warnings of heart attacks with >98% accuracy. Through the strategic combination of nanofingers and ML algorithms, the proposed warning system accurately provides alerts on silent heart-attack attempts seconds ahead of actual attacks.