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OBJECTIVE: To investigate the correlation between glucose and lipid metabolism, renal function, and retinopathy in patients with diabetic retinopathy (DR) based on optical coherence tomography angiography (OCTA). METHODS: A total of 584 diabetic patients who underwent treatment at The Second Affiliated Hospital of Dalian Medical University from March 2022 to June 2023 were retrospectively selected as research participants. They were categorized into a NDR group (n=366) and a DR group (n=218) based on the presence or absence of DR. Relevant indexes of glucose and lipid metabolism, renal function, and OCTA findings were collected. Logistic regression analysis was applied to identify the influencing factors of diabetes mellitus complicated with DR. ROC curves were drawn to examine the diagnostic value of the screened influencing factors for diabetes mellitus complicated with DR. Finally, Spearman correlation coefficients were calculated to examine the relevance between influencing factors and the severity of DR Lesions. RESULTS: Logistic regression showed that high levels of angiography 3 × 3 inner vascular density (IVD_33) and angiography 3 × 3 inner perfusion density (IPD_33) were protective factors for diabetes mellitus complicated with DR, and diabetic peridiabetic vascular disease (DPVD), elevated blood urea nitrogen (BUN), and urea levels were risk factors for diabetes mellitus complicated with DR (all P<0.05). ROC curve displayed that the areas under the curve (AUC) of IVD_33, DPVD, BUN, IPD_33, and Urea in predicting diabetes mellitus with DR were 0.779, 0.705, 0.621, 0.723, and 0.632, respectively. The AUC of combined prediction with OCTA index was higher than that of combined prediction without OCTA index (0.781 VS 0.84, P<0.05). Spearman correlation coefficient displayed that IVD_33 and IPD_33 were negatively correlated with the severity of DR, whereas DPVD and Urea showed a positive correlation (P<0.05). CONCLUSION: Our findings provide valuable insights for the initial clinical assessment of diabetic patients with DR and aid in the early determination of DR severity. Corresponding intervention measures should be formulated as early as possible to remedy patients' outcomes.
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Reactive oxygen species (ROS)-induced oxidative DNA damages have been considered the main cause of mutations in genes, which are highly related to carcinogenesis and tumour progression. Extracellular vesicles play an important role in cancer metastasis. However, the precise role of DNA oxidative damage in extracellular vesicles (EVs)-mediated cancer cell migration and invasion remains unclear. Here, we reveal that ROS-mediated DNA oxidative damage signalling promotes tumour metastasis through increasing EVs release. Mechanistically, 8-oxoguanine DNA glycosylase (OGG1) recognises and binds to its substrate 8-oxo-7,8-dihydroguanine (8-oxoG), recruiting NF-κB to the synaptotagmin 7 (SYT7) promoter and thereby triggering SYT7 transcription. The upregulation of SYT7 expression leads to increased release of E-cadherin-loaded EVs, which depletes intracellular E-cadherin, thereby inducing epithelial-mesenchymal transition (EMT). Notably, Th5487, the inhibitor of DNA binding activity of OGG1, blocks the recognition and transmission of oxidative signals, alleviates SYT7 expression and suppresses EVs release, thereby preventing tumour progression in vitro and in vivo. Collectively, our study illuminates the significance of 8-oxoG/OGG1/SYT7 axis-driven EVs release in oxidative stress-induced tumour metastasis. These findings provide a deeper understanding of the molecular basis of cancer progression and offer potential avenues for therapeutic intervention.
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DNA Glicosilases , Vesículas Extracelulares , Metástase Neoplásica , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Dano ao DNA , DNA Glicosilases/metabolismo , Transição Epitelial-Mesenquimal , Vesículas Extracelulares/metabolismo , Guanina/análogos & derivados , Guanina/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
The adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA), are strongly correlated with water-soluble vitamins, but how to predict RSA occurrence using them remains unsatisfactory. This study aims to investigate the possibility of predicting RSA based on the baseline levels of water-soluble vitamins tested by ultra-liquid chromatography-tandem mass spectrometry. A total of 918 pregnant women was consecutively enrolled in this cross-sectional study. According to the miscarriage numbers, they were divided into normal first pregnancy (NFP, n = 608), once spontaneous abortion (OSA, n = 167), and continuous spontaneous abortion (CSA, n = 143) groups. The Cox proportional-hazards regression model was employed to establish a risk model for predicting RSA. The RSA occurrence was 6.54% in overall pregnant women, with a prevalence of 12.57% in the OSA group and 27.27% in the CSA group. Significant differences were observed in baseline deficiencies of vitamin B3, B5, B6, and B9 among NFP, OSA, and CSA groups (χ2 = 12.191 ~ 37.561, all P < 0.001). Among these vitamins, B9 (HR = 0.89 and 0.88, all P < 0.001) and B6 (HR = 0.83 and 0.78, all P < 0.05) were identified as independent factors in both the OSA and CSA groups; whereas B5 was identified as an additional independent factor only in the CSA group (HR = 0.93, P = 0.005). The Cox proportional-hazards model established using these three vitamins exhibited poor or satisfactory predictive performance in the OSA (Sen = 95.2%, Spe = 39.0%) and CSA (Sen = 92.3%, Spe = 60.6%) groups, respectively. However, B5, B6, and B9 compensatory levels were not associated with RSA occurrence (all P > 0.05). Our study presents a highly sensitive model based on mass spectrometry assay of baseline levels in B vitamins to predict the RSA occurrence as possible.
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Aborto Habitual , Vitaminas , Feminino , Humanos , Adulto , Aborto Habitual/etiologia , Gravidez , Estudos Transversais , Modelos de Riscos Proporcionais , Espectrometria de Massas em Tandem/métodos , Solubilidade , Fatores de Risco , Água/químicaRESUMO
Protease-activated receptor-2 (PAR2) is a class-A G protein-coupled receptor (GPCR) activated by serine proteases and is expressed by multiple tissues, including the skin. PAR2 is involved in the skin inflammatory response, promoting Th2 inflammation, delaying skin barrier repair, and affecting the differentiation of keratinocytes. It also participates in the transmission of itch and pain sensations in the skin. Increasing evidence indicates that PAR2 plays an important role in the pathogenesis of inflammatory skin diseases such as acne vulgaris, rosacea, psoriasis, and atopic dermatitis. Additional focus will be placed on potential targeted therapies based on PAR2. The Goal of this review is to outline the emerging effects of PAR2 activation in inflammatory skin disease and highlight the promise of PAR2 modulators.
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Receptor PAR-2 , Humanos , Receptor PAR-2/metabolismo , Animais , Pele/metabolismo , Pele/imunologia , Pele/patologia , Dermatopatias/imunologia , Dermatopatias/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Transdução de Sinais , Queratinócitos/metabolismo , Queratinócitos/imunologia , Inflamação/imunologia , Inflamação/metabolismoRESUMO
BACKGROUND: To explore the pathogenesis of different subtypes of gallstones in high-altitude populations from a molecular perspective. METHODS: We collected bile samples from 20 cholesterol gallstone disease (CGD) patients and 20 pigment gallstone disease (PGD) patients. Proteomics analysis was performed by LC/MS DIA, while metabolomics analysis was performed by UPLC- Q-TOF/MS. RESULTS: We identified 154 up-regulated and 196 down-regulated differentially expressed proteins, which were significantly enriched in neurodegenerative diseases, energy metabolism, amino acid metabolism etc. In metabolomics analysis, 20 up-regulated and 63 down-regulated differentially expressed metabolites were identified, and they were significantly enriched in vitamin B6 metabolism. Three pathways of integrated proteomics and metabolomics were significantly enriched: porphyrin and chlorophyll metabolism, riboflavin metabolism and aminoacyl-tRNA biosynthesis. Remarkably, 7 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. CONCLUSION: The findings of our metabolomics and proteomics analyses help to elucidate the underlying mechanisms of gallstone formation in high-altitude populations.
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Altitude , Bile , Biomarcadores , Cálculos Biliares , Metabolômica , Proteômica , Humanos , Bile/metabolismo , Bile/química , Feminino , Cálculos Biliares/metabolismo , Masculino , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Adulto , Regulação para Cima , Colesterol/metabolismo , Regulação para Baixo , IdosoRESUMO
RATIONALE: Glucagon-like peptide-1 is an endogenous incretin that plays an active role in weight loss and hypoglycemia. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which has been approved for the treatment of patients with type 2 diabetes (T2D). GLP-1RAs can increase insulin secretion and inhibit glucagon release, thereby leading to a decrease in blood glucose levels within the body. Specifically, GLP-1RAs control postprandial blood glucose levels by inhibiting hepatic glucose production and delaying gastric emptying. However, attention should be given to gastrointestinal adverse reactions. There are currently a few cases of GLP-1RA causing diabetic ketoacidosis (DKA). PATIENT CONCERNS: The following report details the case of a 50-year-old Chinese female who has been living with diabetes for 12 years. Initially diagnosed with T2D, she was subsequently identified as a patient with latent autoimmune diabetes in adults (LADA) following treatment. The patient presented severe nausea, vomiting, and fatigue 1 day after injecting dulaglutide 1 time and discontinuing insulin therapy. She was diagnosed with severe DKA in the emergency department. DIAGNOSES: LADA and DKA. INTERVENTIONS: Changed from dulaglutide to insulin therapy. OUTCOMES: After discontinuing dulaglutide and switching to insulin for blood glucose reduction, the patient's DKA was corrected, and blood glucose levels returned to normal. LESSONS: This case suggests that clinicians should be alert to patients with severe DKA in cases of severe gastrointestinal adverse reactions after the use of GLP-1RAs. In addition, in most countries, GLP-1RAs are administered to patients with T2D, but we should consider the use of GLP-1RAs in patients with type 1 diabetes and LADA.
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Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Fragmentos Fc das Imunoglobulinas , Proteínas Recombinantes de Fusão , Humanos , Feminino , Pessoa de Meia-Idade , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Autoimune Latente em Adultos/tratamento farmacológico , Insulina/efeitos adversosRESUMO
BACKGROUND: Meige's syndrome severely impacts quality of life. Current treatments struggle to balance cost, risk, and effectiveness. METHODS: Patients with blepharospasm were treated with facial nerves partial radiofrequency ablation guided by CT. Treatment efficacy, complications, and recurrences were evaluated during follow-up. RESULTS: 116 facial nerves in 58 patients with Meige's syndrome were treated using CT guidance. The average temperature at the end of radiofrequency treatment was 77.93 ± 9.8 °C, and the procedure lasted an average of 30.79 ± 7.69 min. Spasms stopped after treatment, but mild facial paralysis remained. Follow-ups ranging from 12 to 57 months showed that facial paralysis improved in an average of 3.12 ± 0.94 months. Nine patients had unilateral recurrence within 6-13 months, and three had bilateral recurrence at 14, 18, and 22 months. CONCLUSIONS: Partial radiofrequency ablation of the facial nerve through percutaneous access to the bilateral stylomastoid foramen using CT navigation is an effective, safe, promising treatment for blepharospasm in Meige's syndrome patients.
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Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule, which has been shown to play an important role in plant growth and development by coupling with various phytohormones. However, the relationship between H2S and cytokinin (CTK) and the mechanisms by which H2S and CTK affect root growth remain poorly understood. Endogenous CTK was analyzed by UHPLC-ESI-MS/MS. Persulfidation of cytokinin oxidase/dehydrogenases (CKXs) was analyzed by mass spectrometry (MS). ckx2/CKX2wild-type (WT), OE CKX2 and ckx2/CKX2Cys(C)62alanine(A) transgenic lines were isolated with the ckx2 background. H2S is linked to CTK content by CKX2, which regulates root system architecture (RSA). Persulfidation at cysteine (Cys)62 residue of CKX2 enhances CKX2 activity, resulting in reduced CTK content. We utilized 35S-LCD/oasa1 transgenic lines to investigate the effect of endogenous H2S on RSA, indicating that H2S reduces the gravitropic set-point angle (GSA), shortens root hairs, and increases the number of lateral roots (LRs). The persulfidation of CKX2Cys62 changes the elongation of cells on the upper and lower flanks of LR elongation zone, confirming that Cys62 of CKX2 is the specificity target of H2S to regulate RSA in vivo. In conclusion, this study demonstrated that H2S negatively regulates CTK content and affects RSA by persulfidation of CKX2Cys62 in Arabidopsis thaliana.
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The hydrazone functional group, when coupled with a pyridyl substituent, offers a unique class of widely tunable photoswitches, whose E-to-Z photoisomerization equilibria can be controlled through intramolecular hydrogen bonding between the N-H hydrazone donor and the pyridyl acceptor. However, little is known about the photoisomerization mechanism in this class of compounds. To address this issue, we report a pyridine-appended iminoguanidinium photoswitch that is functionally related to acylhydrazones and provides insight into the photoisomerization processes between the E and Z configurations. The E-to-Z photoisomerization of the E-2-pyridyl-iminoguanidinium cation (2PyMIG) in DMSO, prepared as the bromide salt, was quantified by 1H NMR, and probed in real time with ultrafast laser spectroscopy. The photoisomerization process occurs on a picosecond timescale, resulting in low fluorescence yields. The multiconfigurational reaction path found with the growing string method features a small barrier (4.3 or 6.5 kcal mol-1) that the E isomer in the π-π* state must overcome to reach the minimum energy conical intersection (MECI) connecting the E and Z isomers of 2PyMIG. While two possible pathways exist depending on the orientation of the pyridine ring, both exhibit the same qualitative features along the path and at their MECIs, involving simultaneous changes in the CCNN and CNNC dihedral angles. Furthermore, the ground state barrier for pyridine ring rotation is readily accessible, thus a low barrier pathway to the experimentally observed Z isomer exists for both MECIs leading to a transition from the E isomer to photoproduct. Combining multiconfigurational reaction path calculations using growing string method with time-resolved fluorescence spectroscopy provided crucial insights into the photoisomerization process of 2PyMIG, resulting in both the computational and experimental results pointing to rapid photoisomerization via a surface crossing between the singlet π-π* and the ground states.
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This paper explores the significant role of epigenetics in women's reproductive health, focusing on the impact of environmental factors. It highlights the crucial link between epigenetic modifications-such as DNA methylation and histones post-translational modifications-and reproductive health issues, including infertility and pregnancy complications. The paper reviews the influence of pollutants like PM2.5, heavy metals, and endocrine disruptors on gene expression through epigenetic mechanisms, emphasizing the need for understanding how dietary, lifestyle choices, and exposure to chemicals affect gene expression and reproductive health. Future research directions include deeper investigation into epigenetics in female reproductive health and leveraging gene editing to mitigate epigenetic changes for improving IVF success rates and managing reproductive disorders.
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Epigênese Genética , Saúde Reprodutiva , Saúde da Mulher , Humanos , Feminino , Gravidez , Metilação de DNA , Exposição Ambiental/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Poluentes Ambientais/toxicidadeRESUMO
Bacterial infection and free radical oxidative stress at the wound site could easily cause cascade inflammation and hinder the healing process of the wound. In this study, chitosan-cysteine-gallic acid (CCG) hydrogel with antibacterial and antioxidant properties was synthesized by chitosan (CS), cysteine (Cys), and gallic acid (GA) for a preliminary evaluation of its therapeutic efficacy in a mouse model of full-layer skin defect. In vitro analysis showed that the CCG hydrogel had good antibacterial activity and blood compatibility. In vivo, the CCG hydrogel wound dressings accelerated wound healing, stimulate angiogenesis, increase collagen deposition and anti-inflammatory factor expression. The CCG hydrogel wound dressing is designed to promote the regeneration of damaged skin tissue and is expected to become a potential candidate for clinical treatment.
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Synaptotagmin 7 (SYT7), a member of the synaptotagmin family, exhibits high expression in various tumors and is closely associated with patient prognosis. The tight regulation of SYT7 expression assumes paramount significance in the progression of tumorigenesis. In this study, we detected a high GC content in the first 1000 bp of the promoter region of SYT7, suggesting a potential role of the G-quadruplex in its transcriptional regulation. Circular dichroism spectroscopy results showed that -187 to -172 bp sequence can form a typical parallel G-quadruplex structure, and site mutation revealed the critical role of the ninth guanine in its formation. Then, treatment of two ligands of G-quadruplex (TMPyP4 and Pyridostatin) reduced both the expression of SYT7 and subsequent tumor proliferation, demonstrating the potential of the G-quadruplex as a targeted therapy for tumors. By shedding light on the pivotal role of the G-quadruplex in regulating SYT7 transcription, our study not only advances our comprehension of this intricate regulatory mechanism but also emphasizes the significance of SYT7 in tumor proliferation. These findings collectively contribute to a more comprehensive understanding of the interplay between G-quadruplex regulation and SYT7 function in tumor development.
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BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) as a novel clinical conception was modified on the basis of idiopathic non-cirrhotic portal hypertension (INCPH). This study aimed to compare the clinical, biochemical histological features and prognosis between the diagnostic criteria for PSVD and that of INCPH. METHODS: A total of 65 patients who underwent liver biopsies were analyzed retrospectively. The clinical, pathological and prognosis date were reviewed and screened according to the latest diagnostic criteria of PSVD and INCPH. RESULTS: A total of 65 patients were diagnosed with PSVD, of which 31 (47.69%) also fulfilled INCPH criteria. Specific histological and specific clinical portal hypertension (PH) signs were found in 34 (52.31%) and 30 (46.15%) of the patients, respectively. PSVD patients showed higher LSM levels (11.45 (6.38, 18.08) vs. 7.90 (6.70, 13.00), p = 0.039) than the INCPH patients. INCPH patients had a higher cumulative incidence of liver-related complications than the PSVD patients (86.95% vs. 35.71%, log-rank p < 0.001). CONCLUSION: Novel PSVD criteria facilitate early diagnosis. PSVD patients with other liver diseases may have higher LSM values. Disease progression and survival outcomes are correlated with PH in PSVD patients.
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BACKGROUND: To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. METHODS: We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. RESULTS: 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: - 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. CONCLUSION: Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.
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Vacinas contra COVID-19 , COVID-19 , Hospitalização , SARS-CoV-2 , Eficácia de Vacinas , Vacinas de Produtos Inativados , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Adulto , Idoso , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , SARS-CoV-2/imunologia , Pequim/epidemiologia , Adulto Jovem , Estudos de Coortes , Adolescente , Vacinação/estatística & dados numéricos , Estudos Prospectivos , China/epidemiologia , Criança , Idoso de 80 Anos ou maisRESUMO
Mast cell tryptases, a family of serine proteases involved in inflammatory responses and cancer development, present challenges in structural characterization and inhibitor development. We employed state-of-the-art protein structure prediction algorithms to model the three-dimensional structures of tryptases α, ß, δ, γ, and ε with high accuracy. Computational docking identified potential substrates and inhibitors, suggesting overlapping yet distinct activities. Tryptases ß, δ, and ε were predicted to act on phenolic compounds, with ß and ε additionally hydrolyzing cyanides. Tryptase δ may possess unique formyl-CoA dehydrogenase activity. Virtual screening revealed 63 compounds exhibiting strong binding to tryptase ß (TPSB2), 12 exceeding the affinity of the known inhibitor. Notably, the top hit (3-chloro-4-methylbenzimidamide) displayed over 10-fold selectivity for tryptase ß over other isoforms. Our integrative approach combining protein modeling, functional annotation, and molecular docking provides a framework for characterizing tryptase isoforms and developing selective inhibitors of therapeutic potential in inflammatory and cancer conditions.
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Objective : To explore the roles of Neural precursor cell expressed developmentally down-regulated 1(NEDD1) in lung cancer tumorigenesis and the relationship between NEDD1 expression and clinicopathology of patients with lung adenocarcinoma (LUAD). Methods: Expression of NEDD1 or other proteins in tissues and cell lines were determined with immunohistochemistry or western blot, the data of patients with LUAD in The Cancer Genome Atlas (TCGA) datasets and LUAD tissue array were collected and analyzed, the effects of NEDD1 on proliferation, migration, cell cycle progression and apoptosis of cancer cells were detected with colony formation assay, transwell assay and Flow cytometry (FCM) analysis respectively. the impact of NEDD1 knockdown on DNA damage was analyzed using Immunofluorescence staining of H2AX and comet assay. Furthermore, the effect of NEDD1 on cancer cell proliferation in vivo was investigated in nude mice. Results : NEDD1 was upregulated in lung tissues and the NEDD1 immune score was an independent prognostic factor. Overexpression of NEDD1 promoted epithelial-mesenchymal transition, accelerated cell cycle progression, and enhanced the proliferation and migration of A549 and H1299 cells, while knockdown of NEDD1 resulted in the opposite phenotype and leaded to DNA damage. In addition, NEDD1 improved cell tumorigenicity in vivo. Conclusion : These findings suggest that NEDD1 plays important roles in lung cancer development and may therefore be a potential prognostic marker and promising therapeutic target for lung cancer therapy.
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Objective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels >34 g/L, APACHE II scores <13, and treatment duration >10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.
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BACKGROUND: Hearing loss (HL) is the most common sensory birth deficit worldwide, with causative variants in more than 150 genes. However, the etiological contribution and clinical manifestations of X-linked inheritance in HL remain unclear within the Chinese HL population. In this study, we focused on X-linked hereditary HL and aimed to assess its contribution to hereditary HL and identify the genotype-phenotype relationship. METHODS: We performed a molecular epidemiological investigation of X-linked hereditary HL based on next-generation sequencing and third-generation sequencing in 3646 unrelated patients with HL. We also discussed the clinical features associated with X-linked non-syndromic HL-related genes based on a review of the literature. RESULTS: We obtained a diagnostic rate of 52.72% (1922/3646) among our patients; the aggregate contribution of HL caused by genes on the X chromosome in this cohort was ~ 1.14% (22/1922), and POU3F4 variants caused ~ 59% (13/22) of these cases. We found that X-linked HL was congenital or began during childhood in all cases, with representative audiological profiles or typical cochlear malformations in certain genes. Genotypic and phenotypic analyses showed that causative variants in PRPS1 and AIFM1 were mainly of the missense type, suggesting that phenotypic variability was correlated with the different effects that the replaced residues exert on structure and function. Variations in SMPX causing truncation of the protein product were associated with DFNX4, which resulted in typical audiological profiles before and after the age of 10 years, whereas nontruncated proteins typically led to distal myopathy. No phenotypic differences were identified in patients carrying POU3F4 or COL4A6 variants. CONCLUSIONS: Our work constitutes a preliminary evaluation of the molecular contribution of X-linked genes in heritable HL (~ 1.14%). The 15 novel variants reported here expand the mutational spectrum of these genes. Analysis of the genotype-phenotype relationship is valuable for X-linked HL precise diagnostics and genetic counseling. Elucidation of the pathogenic mechanisms and audiological profiles of HL can also guide choices regarding treatment modalities.
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Doenças Genéticas Ligadas ao Cromossomo X , Perda Auditiva , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China , População do Leste Asiático/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Genômica , Genótipo , Perda Auditiva/genética , Mutação/genética , Fenótipo , Fatores do Domínio POU/genéticaRESUMO
Organic crystal-based superimposed heterostructures with inherent multichannel characteristics demonstrate superior potential for manipulating excitons/photons at the micro/nanoscale for integrated optoelectronics. However, the precise construction of organic superimposed heterostructures with fixed superimposed sites remains challenging because of the random molecular nucleation process. Here, organic vertically superimposed heterostructures (OSHs) with fixed superimposed positions are constructed via semi-wrapped core/shell heterostructures with partially exposed cores, which provide preferential nucleation sites for further molecular epitaxial growth processes. Furthermore, the relative length ratio from 21.7% to 95.3% between interlayers is accurately adjusted by regulating the exposed area of the semi-wrapped core/shell heterostructures. Significantly, these OSHs with anisotropic optical characteristics demonstrate well regulation of excitation position-dependent waveguide behaviors and can function as photonic barcodes for information encryption. This strategy provides a facile approach for controlling the nucleation sites for the controllable preparation of organic heterostructures and advanced applications for integrated optoelectronics.