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1.
Chem Commun (Camb) ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39318167

RESUMO

Exploring the different spin states of central metals in the complex to regulate the anti-tumor activity of cancer cells is of great significance in drug design and clinical use. However, it is a challenge to build a strong coupling between spin states and anti-tumor activities in one system. Herein, we present two complexes {FeII2L2[PdII(CN)4]2}·2H2O (L = Bztpen (1), Bztppn (2); Bztpen = N-benzyl-N,N',N'-tris(2-pyridylmethyl)ethylenediamine, Bztppn = N-benzyl-N,N',N'-tris(2-pyridylmethyl)propylenediamine) showing different cytotoxic activities actuated by fine-tuning the structure with different spin states of Fe(II). Magnetic susceptibility measurements and X-ray diffraction revealed that the Fe(II) ion in complexes 1 and 2 remains in the LS and HS state, respectively, at room temperature. Cytotoxicity tests indicate that complex 1 is more biologically effective than complex 2. In complex 2, however, the high-spin Fe(II) played a key role in regulating its in vitro antitumor effects and seems to be associated with ROS-mediated apoptosis. These findings offer a new avenue for developing anti-cancer drugs by designing complexes with different spin states.

2.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1661-1670, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39235025

RESUMO

Water ecological restoration zoning, which involves articulating goals for restoring water ecosystems upwards and guiding the spatial layout of restoration projects downwards, is key to achieving systematic restoration of water resource elements. There are many challenges in water ecological restoration zoning, including disparate hierarchical systems, incomplete indicators, and vague boundaries. With Guangxi Hechi, a karst ecologically fragile region, as a case, we developed a multidimensional zoning system framework based on "watershed natural unit-dominant ecological function-ecological stress risk". The first-level zoning employed river systems and geomorphic types as indicators and delineated the sub-watershed unit as the boundary. The second-level zoning adopted a "top-down" division method to clarify the goal of water ecological restoration based on watershed natural geography and select three indicators (water conservation, biodiversity, and landscape cultural services) for evaluation. We used the K-means clustering method to identify dominant ecological functions in spatial units, with the sub-watershed unit demarcating second-level zoning boundaries. The third-level zoning was the specific implementation unit for ecological restoration projects. We used three indicators (soil erosion, flooding risk, and human interference) to characterize water ecosystem risk from external coercion, and defined the third-level zoning. We delineated 11 primary water ecological zones, four secondary zones, and three tertiary zones. Synthesizing tertiary zoning results accounted for spatial differentiation characteristics of watershed natural geography, dominant ecological functions, and ecological coercion risks, and combining sub-watershed and township administrative units determined zoning boundaries, water ecological restoration zoning was comprehensively classified into five categories and 32 sub-ecological zones. Corresponding ecological restoration strategies were proposed based on zoning and classification.


Assuntos
Conservação dos Recursos Hídricos , Ecossistema , Rios , China , Conservação dos Recursos Hídricos/métodos , Conservação dos Recursos Naturais/métodos , Recuperação e Remediação Ambiental/métodos , Ecologia , Monitoramento Ambiental/métodos
3.
Dalton Trans ; 53(35): 14692-14700, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39157994

RESUMO

Spin crossover (SCO) has long been a hot topic in the field of molecular magnetism owing to its unique bistability character. Rational control of thermal hysteresis and transition temperature (T1/2) is crucial for their practical applications, which rely on precise manipulation of the substituents of SCO coordinating ligands and molecular packing interactions. In this study, we designed two different bridging ligands (2-FDPB: 4,4'-(2-fluoro-1,4-phenylene)dipyridine; 2,3-FDPB: 4,4'-(2,3-difluoro-1,4-phenylene)dipyridine) featuring one and two fluoro substitution on the central benzene ring and applied a Schiff base-like equatorial tetradentate ligand {diethyl(E,E)-2,2'-[4,5-difluoro-1,2-phenyl-bis(iminomethylidyne)]bis(3-oxobutanoate)-(2-)-N,N',O3,O3'} (H2L) to coordinate with the FeII ion. Two FeII-coordination chain polymers [FeII(L)(2,3-FDPB)]·0.25CH2Cl2 (1) and [FeII(L)(2-FDPB)]·0.5CH3OH (2) were obtained. 1 crystallizes in the monoclinic P21/n space group with only one FeII center, while 2 crystallizes in the triclinic P1̄ space group with two independent FeII centers. Unlike the identical 2D layer stacking in 1, 2 exhibited alternating stacking of the extending 2D layers and meshed chains. Magnetic measurements revealed the typical thermally induced spin crossover behavior (SCO): 1 exhibited a 41 K-wide thermal hysteresis with transition temperatures of T1/2↑ = 245 K and T1/2↓ = 204 K, while 2 showed a higher transition temperature (T1/2 = 330 K) with no thermal hysteresis. Magneto-structural correlation studies suggest that the electron-withdrawing effect present in the fluoro substituents does not have a significant impact on the SCO behaviors. Despite the fluoro substituents having a similar atomic radius of hydrogen atoms, variations in the number of these substituents can alter the crystallization behavior of these complexes, which in turn affects the solvents, molecular stacking patterns, and intermolecular interactions, ultimately influencing the SCO behaviors.

4.
Nat Nanotechnol ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164412

RESUMO

Heteromeric pore-forming proteins often contain recognition patterns or stereospecific selection filters. However, the construction of heteromeric pore-forming proteins for single-molecule sensing is challenging due to the uncontrollability of producing position isomers and difficulties in purification of regio-defined products. To overcome these preparation obstacles, we present an in situ strategy involving single-molecule chemical modification of a heptameric pore-forming protein to build a stereo- and regio-specific heteromeric nanopore (hetero-nanopore) with a subunit stoichiometric ratio of 3:4. The steric hindrance inherent in the homo-nanopore of K238C aerolysin directs the stereo- and regio-selective modification of maleimide derivatives. Our method utilizes real-time ionic current recording to facilitate controlled voltage manipulation for stoichiometric modification and position-based side-isomer removal. Single-molecule experiments and all-atom molecular dynamics simulations revealed that the hetero-nanopore features an asymmetric stereo- and regio-defined residue structure. The hetero-nanopore produced was characterized by mass spectrometry and single-particle cryogenic electron microscopy. In a proof-of-concept single-molecule sensing experiment, the hetero-nanopore exhibited 95% accuracy for label-free discrimination of four peptide stereoisomers with single-amino-acid structural and chiral differences in the mixtures. The customized hetero-nanopores could advance single-molecule sensing.

5.
BMC Musculoskelet Disord ; 25(1): 551, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014378

RESUMO

BACKGROUND: The high prevalence of diabetic kidney disease (DKD) in the United States necessitates further investigation into its impact on complications associated with total hip arthroplasty (THA). This study utilizes a large nationwide database to explore risk factors in DKD cases undergoing THA. METHODS: This research utilized a case-control design, leveraging data from the national inpatient sample for the years 2016 to 2019. Employing propensity score matching (PSM), patients diagnosed with DKD were paired on a 1:1 basis with individuals free of DKD, ensuring equivalent age, sex, race, Elixhauser Comorbidity Index (ECI), and insurance coverage. Subsequently, comparisons were drawn between these PSM-matched cohorts, examining their characteristics and the incidence of post-THA complications. Multivariate logistic regression analysis was then employed to evaluate the risk of early complications after surgery. RESULTS: DKD's prevalence in the THA cohort was 2.38%. A 7-year age gap separated DKD and non-DKD patients (74 vs. 67 years, P < 0.0001). Additionally, individuals aged above 75 exhibited a substantial 22.58% increase in DKD risk (49.16% vs. 26.58%, P < 0.0001). Notably, linear regression analysis yielded a significant association between DKD and postoperative acute kidney injury (AKI), with DKD patients demonstrating 2.274-fold greater odds of AKI in contrast with non-DKD individuals (95% CI: 2.091-2.473). CONCLUSIONS: This study demonstrates that DKD is a significant risk factor for AKI in patients undergoing total hip arthroplasty. Optimizing preoperative kidney function through appropriate interventions might decrease the risk of poor prognosis in this population. More prospective research is warranted to investigate the potential of targeted kidney function improvement strategies in reducing AKI rates after THA. The findings of this study hold promise for enhancing preoperative counseling by surgeons, enabling them to provide DKD patients undergoing THA with more precise information regarding the risks associated with their condition.


Assuntos
Artroplastia de Quadril , Bases de Dados Factuais , Nefropatias Diabéticas , Complicações Pós-Operatórias , Humanos , Artroplastia de Quadril/efeitos adversos , Masculino , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Pessoa de Meia-Idade , Nefropatias Diabéticas/epidemiologia , Estudos de Casos e Controles , Estados Unidos/epidemiologia , Fatores de Risco , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/tendências , Prevalência , Idoso de 80 Anos ou mais , Incidência
6.
Rapid Commun Mass Spectrom ; 38(19): e9872, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39044122

RESUMO

RATIONALE: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology. RESULTS: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. CONCLUSIONS: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.


Assuntos
Lignanas , Farmacologia em Rede , Osteoporose , Ratos Sprague-Dawley , Animais , Lignanas/farmacologia , Lignanas/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/química , Metabolômica/métodos , Glucosídeos/farmacologia , Metaboloma/efeitos dos fármacos , Espectrometria de Massas/métodos
7.
Int J Mol Sci ; 25(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39000351

RESUMO

This study assessed the biocompatibility of two types of nanogold composites: fibronectin-gold (FN-Au) and collagen-gold (Col-Au). It consisted of three main parts: surface characterization, in vitro biocompatibility assessments, and animal models. To determine the structural and functional differences between the materials used in this study, atomic force microscopy, Fourier-transform infrared spectroscopy, and ultraviolet-visible spectrophotometry were used to investigate their surface topography and functional groups. The F-actin staining, proliferation, migration, reactive oxygen species generation, platelet activation, and monocyte activation of mesenchymal stem cells (MSCs) cultured on the FN-Au and Col-Au nanocomposites were investigated to determine their biological and cellular behaviors. Additionally, animal biocompatibility experiments measured capsule formation and collagen deposition in female Sprague-Dawley rats. The results showed that MSCs responded better on the FN-Au and Col-AU nanocomposites than on the control (tissue culture polystyrene) or pure substances, attributed to their incorporation of an optimal Au concentration (12.2 ppm), which induced significant surface morphological changes, nano topography cues, and better biocompatibility. Moreover, neuronal, endothelial, bone, and adipose tissues demonstrated better differentiation ability on the FN-Au and Col-Au nanocomposites. Nanocomposites have a crucial role in tissue engineering and even vascular grafts. Finally, MSCs were demonstrated to effectively enhance the stability of the endothelial structure, indicating that they can be applied as promising alternatives to clinics in the future.


Assuntos
Materiais Biocompatíveis , Diferenciação Celular , Ouro , Células-Tronco Mesenquimais , Nanocompostos , Ratos Sprague-Dawley , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ouro/química , Animais , Nanocompostos/química , Diferenciação Celular/efeitos dos fármacos , Ratos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Feminino , Proliferação de Células/efeitos dos fármacos , Colágeno/química , Biopolímeros/química , Fibronectinas/metabolismo , Células Cultivadas , Nanopartículas Metálicas/química , Teste de Materiais , Engenharia Tecidual/métodos , Espécies Reativas de Oxigênio/metabolismo , Movimento Celular/efeitos dos fármacos
8.
Iran J Public Health ; 53(5): 1087-1095, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38912154

RESUMO

Background: We aimed to investigate the clinical application effect of people-oriented nursing model on the negative emotions and psychological conditions of patients with bladder cancer. Methods: Eighty patients with bladder cancer were enrolled from January 2020 to January 2022 in the Second Affiliated Hospital of Qiqihar Medical University Heilongjiang, Province, China. The patients were randomly divided into the control group, each group consisted of 40 patients (conventional nursing mode) and the experimental group (people-oriented nursing mode) according to the admission time. The differences of the anxiety, depression and quality of life scores at the time of admission and discharge were compared between the two groups. Results: There was statistically significant differences in the Self-Rating Anxiety Scale (SAS) and Self-rating depression scale (SDS) score within each group of patients and between the two groups at the time of admission and discharge, respectively (P=0.001). In addition, there was a statistically significant difference in the scores at discharge, and the scores of the patients in the experimental group were better than those in the control group. There was a statistically significant difference in the scores at discharge, and the scores of the experimental group were lower than those of the control group P<0.001). After comparing the overall scores of admission and discharge of the two groups of patients, the differences were statistically significant, and the scores at discharge were better improved than those at admission were. Conclusion: The people-oriented nursing model could relieve the negative emotions, relieve pain and improve the life quality of patients with bladder cancer.

9.
Cornea ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38780430

RESUMO

PURPOSE: To compare the degree of myopic regression after myopia correction with either femtosecond laser-assisted in situ keratomileusis (FS-LASIK) or small-incision lenticule extraction (SMILE) over 18 months. METHODS: Patients undergoing FS-LASIK or SMILE surgery for myopia correction were retrospectively recruited. The propensity scores were used to match patients by age and preoperative manifest spherical equivalent (SEQ) from these 2 groups. Myopic regression was analyzed using the Cox proportional hazard model. RESULTS: A total of 416 eyes of 416 patients undergoing FS-LASIK and 416 eyes of 416 patients undergoing SMILE were matched. Using 1-month SEQ as baseline, the SEQ regression values after FS-LASIK were 0D, -0.17 ± 0.69D, -0.24 ± 0.65D, -0.31 ± 0.65D, -0.32 ± 0.63D, and -0.33 ± 0.62D and the SEQ regression values after SMILE were 0D, -0.07 ± 0.75D, -0.18 ± 0.77D, -0.23 ± 0.82 D, -0.21 ± 0.77D, and -0.24 ± 0.68D at 1, 3, 6, 9, 12, and 18 months, respectively. The Cox proportional hazard model showed that preoperative manifest SEQ (P = 0.021) and designed optical zone (P = 0.048) are significant predictors. The selected surgical procedure had no significant effect on predicting myopic regression (P = 0.470). The cumulative survival rates of myopic regression were 54.74% and 42.10% in the FS-LASIK group and 58.66% and 43.83% in the SMILE group, at 12 and 18 months, respectively (log-rank test, P = 0.11). CONCLUSIONS: After matching based on age and preoperative manifest SEQ, we found that higher myopia and a smaller optical zone contribute significantly to the development of myopic regression after undergoing FS-LASIK or SMILE surgery at 18 months. The selected surgical procedure, however, does not affect the likelihood of myopic regression.

10.
J Exp Med ; 221(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38607370

RESUMO

Cytokine release syndrome (CRS) is a frequently observed side effect of chimeric antigen receptor (CAR)-T cell therapy. Here, we report self-regulating T cells that reduce CRS severity by secreting inhibitors of cytokines associated with CRS. With a humanized NSG-SGM3 mouse model, we show reduced CRS-related toxicity in mice treated with CAR-T cells secreting tocilizumab-derived single-chain variable fragment (Toci), yielding a safety profile superior to that of single-dose systemic tocilizumab administration. Unexpectedly, Toci-secreting CD19 CAR-T cells exhibit superior in vivo antitumor efficacy compared with conventional CD19 CAR-T cells. scRNA-seq analysis of immune cells recovered from tumor-bearing humanized mice revealed treatment with Toci-secreting CD19 CAR-T cells enriches for cytotoxic T cells while retaining memory T-cell phenotype, suggesting Toci secretion not only reduces toxicity but also significantly alters the overall T-cell composition. This approach of engineering T cells to self-regulate inflammatory cytokine production is a clinically compatible strategy with the potential to simultaneously enhance safety and efficacy of CAR-T cell therapy for cancer.


Assuntos
Síndrome da Liberação de Citocina , Citocinas , Animais , Camundongos , Síndrome da Liberação de Citocina/etiologia , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos
11.
Dalton Trans ; 53(18): 7669-7676, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38646797

RESUMO

A dinuclear Fe(II) spin crossover (SCO) complex with the formula [Fe2L5(NCS)4]·2DMF·2H2O (1) was synthesised from 1-naphthylimino-1,2,4-triazole (L). Complex 1 exhibits an incomplete thermally induced spin transition with a transition temperature T1/2 of 95 K and a thermally trapped metastable high-spin state at low temperatures. Furthermore, it undergoes a reversible light-induced spin crossover by alternate irradiation with 532 and 808 nm lasers.

12.
Clin Exp Optom ; : 1-7, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616052

RESUMO

CLINICAL RELEVANCE: Acute anterior uveitis (AAU) can lead to the thickening of the peripapillary retinal nerve fibre layer (pRNFL) and induce refractive changes during its active phase. BACKGROUND: AAU is a common form of uveitis characterised by inflammation in the anterior chamber. A notable prevalence of optical coherence tomography - defined pRNFL thickening was observed among patients with AAU. The alterations in pRNFL thickness and their associations with other relevant ocular parameters in patients with AAU were investigated. METHODS: A retrospective, consecutive case series was conducted at a specialised uveitis referral clinic in Taiwan. This study gathered data on various demographic characteristics and various ocular parameters, namely anterior chamber cell grading, refractive error, best-corrected visual acuity, intraocular pressure, and optical coherence tomography measurements. A comparative analysis of baseline and subsequent follow-up data was conducted. Additionally, this study examined the correlations between alterations in pRNFL thickness and various ocular parameters. Twenty-one patients with AAU (21 affected eyes/21 unaffected eyes) were examined. RESULTS: Initial measurements revealed pRNFL thickening in 20 patients. Treatment led to significant improvements in best-corrected visual acuity, intraocular pressure recovery, and pRNFL thickening (p < 0.01). The correlation between changes in pRNFL thickness and best-corrected visual acuity was weak (r = 0.20, p = 0.41). By contrast, a significant negative correlation was identified between changes in pRNFL thickness and refractive error alterations (r = -0.71, p = 0.01). CONCLUSION: This study demonstrated that AAU is associated with pRNFL thickening, which in turn is inversely correlated with changes in refractive error alterations throughout the disease course. Monitoring changes in pRNFL thickness can be effective in assessing ocular inflammation status.

13.
Diagn Interv Radiol ; 30(4): 228-235, 2024 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-38528760

RESUMO

PURPOSE: Non-invasive methods for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) can provide distinct leverage in the management of patients with locally advanced rectal cancer (LARC). This study aimed to investigate whether including the golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion parameter (Ktrans), in addition to tumor regression grading (TRG) and apparent diffusion coefficient (ADC) values, can improve the predictive ability for pCR. METHODS: Patients with LARC who underwent nCRT and subsequent surgery were included. The imaging parameters were compared between patients with and without pCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of these parameters for pCR. RESULTS: A total of 111 patients were included in the study. A pCR was obtained in 32 patients (28.8%). MRI-based TRG (mrTRG) showed a negative correlation with pCR (r = -0.61, P < 0.001), and the average ADC value showed a positive correlation with pCR (r = 0.62, P < 0.001). Before nCRT, Ktrans in the pCR group was significantly higher than in the non-pCR group (1.30 ± 0.24 vs. 0.88 ± 0.34, P < 0.001), but no difference was identified after nCRT. Following ROC curve analysis, the area under the curve (AUC) of mrTRG (level 1-2), average ADC value, and Ktrans value for predicting pCR were 0.738 [95% confidence interval (CI): 0.65-0.82], 0.78 (95% CI: 0.69-0.86), and 0.84 (95% CI: 0.77-0.92), respectively. The model combining the three parameters had significantly higher predictive ability for pCR (AUC: 0.94, 95% CI: 0.88-0.98). CONCLUSION: The use of a combination of the GRASP DCE-MRI Ktrans with mrTRG and ADC can lead to a better pCR predictive performance.


Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Resultado do Tratamento , Quimiorradioterapia/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Curva ROC
14.
iScience ; 27(4): 109399, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38523794

RESUMO

The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.

15.
Front Med (Lausanne) ; 11: 1305579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482530

RESUMO

Dry eye disease (DED) is a common multifactorial disease affecting a substantial proportion of the population worldwide. Objective tests and subjective symptoms evaluation are necessary to assess DED. Although various treatments have been introduced, accurately evaluating the efficacy of those treatments is difficult because of the disparity between diagnostic tests and patient-reported symptoms. We reviewed the questionnaires used to evaluate DED and the improvements of quality of life with various treatments. In addition, we highlighted the importance of patient-reported outcomes (PRO) assessments for evaluating the effect of DED treatments. Given that the assessment of DED treatment effectiveness substantially relies on individual ocular experiences, acquiring qualitative PRO data is essential for comprehensive evaluation and optimal treatment management. Clinicians should not only focus on improving objective symptoms but also prioritize the well-being of patients in clinical management.

16.
Cancer Gene Ther ; 31(6): 894-903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38418842

RESUMO

This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.


Assuntos
Glioblastoma , Mutação , Humanos , Glioblastoma/genética , Glioblastoma/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Taiwan/epidemiologia , Idoso , Estudos Retrospectivos , Adulto Jovem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Sequenciamento de Nucleotídeos em Larga Escala , Prognóstico
17.
Int J Ophthalmol ; 17(1): 157-163, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38239943

RESUMO

AIM: To explore the factors influencing individuals' willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents' willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was "Uncertain efficacy". In terms of motivations, the willing group ranked "Better therapeutic benefits" (35.0%), "Professional monitoring" (34.3%), and "Trust in healthcare professionals" (33.1%) as their top three reasons, whereas the unwilling participants indicated "Full comprehension of the protocol" (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016427

RESUMO

Objective To understand the epidemiological characteristics and incidence trend of syphilis in Shiyan City, and to provide a scientific basis for formulating syphilis control strategies. Methods Descriptive epidemiological statistical analysis on the data of syphilis cases from 2008 to 2020 in Shiyan City was performed. Results A total of 9 578 syphilis cases were reported in Shiyan City from 2008 to 2020, with the reported incidence rate ranging from 16.80/100 000 to 27.48/100 000. The reported incidence rate of syphilis showed a downward trend from 2008 to 2014 (χ2 trend=44.869, P=0.000), and an upward trend from 2015 to 2020 (χ2 trend=69.642, P=0.000). The composition ratio of syphilis in each stage had changed, with a decreasing trend in stage I and II syphilis. The composition ratio of recessive syphilis cases increased from 58.90% in 2008 to 93.10% in 2020, and gradually became the main epidemic type. No cases of fetal syphilis were reported in the past three years. The incidence rate of syphilis reported from 2008 to 2020 was generally higher in women than that in men, with a male to female ratio of 0.67:1. Occupations were mainly farmer, housework, and unemployment. The high incidence areas of syphilis in Shiyan City included mainly Maojian District, Zhangwan District, and Fangxian County, with the annual reported incidence rates being 38.40/100 000, 37.97/100 000, and 29.37/100 000, respectively. Conclusion The syphilis epidemic in Shiyan City from 2008 to 2020 has showed a trend of first decline and then rise. The prevention and treatment of syphilis in key populations and key areas should be strengthened according to the epidemiological characteristics of syphilis to control the spread of syphilis and reduce the harm to the public.

19.
J Comput Assist Tomogr ; 48(3): 361-369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38110307

RESUMO

OBJECTIVE: The aim of the study is to explore the clinical value of the apparent diffusion coefficient (ADC) derived from the readout segmentation of long variable echo trains (RESOLVE) technique for identifying clinicopathologic features of distal rectal cancer and correlations between ADC and Ki-67 expression. METHODS: The data of 112 patients with a proven pathology of distal rectal cancer who underwent preoperative magnetic resonance imaging were retrospectively analyzed. The mean ADC value was measured using the "full-layer and center" method. Differences in ADC values and Ki-67 expression in different clinical stages, pathological types, and tumor differentiation were compared using analysis of variance. Correlations between ADC value and clinicopathologic features were assessed using Spearman correlation analysis. RESULTS: Interobserver agreement of confidence levels from 2 radiologists was excellent for ADC measurement ( k =  0.85). Patients with a lower clinical stage, well-differentiated adenocarcinomas, and a higher possibility of mucinous adenocarcinoma exhibited a positive correlation with higher ADC values, but these factors were negatively correlated with Ki-67 expression (all P < 0.05). We found that ADC value was negatively correlated with Ki-67 expression ( r = -0.62, P < 0.001). CONCLUSIONS: The ADC value generated by RESOLVE sequences was significantly associated with clinicopathologic features and Ki-67 expression in patients with distal rectal cancer in this study. Thus, the ADC value could be considered a new noninvasive imaging biomarker that could be helpful in predicting the biological properties of distal rectal cancer.


Assuntos
Imagem de Difusão por Ressonância Magnética , Antígeno Ki-67 , Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Antígeno Ki-67/metabolismo , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Interpretação de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Biomarcadores Tumorais/metabolismo
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