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1.
Indian J Ophthalmol ; 71(2): 541-546, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36727357

RESUMO

Purpose: To evaluate a method using measured values of total corneal refractive power (TCRP) for a manufacturer's online calculator by comparing it with the Barrett toric calculator (BTC) and Kane toric calculator (KTC) combined with simulated keratometry values (SimK). Methods: This was a retrospective case series. Patient records were reviewed to identify the patients who had biometry with the IOL Master 700 and Pentacam recorded before toric IOL implantation and refractive follow-up data after implantation. The predicted error in residual astigmatism was calculated by vector analysis according to the calculation methods and the measurements used. Results: A total of 70 eyes of 56 patients were included. The mean absolute astigmatism prediction errors were 0.6 ± 0.32, 0.59 ± 0.35, and 0.61 ± 0.35 D for the ATCTCRP, BTCSimK, and KTCSimK calculators, respectively (P = 0.934), and the centroid of the prediction errors were 0.3 D @ 178°, 0.11 D @ 102°, and 0.09 D @ 147°, respectively (P = 0.23). In the with-the-rule subgroup, the centroid of the prediction error was 0.34 D @ 176° for ATCTCRP and was the highest among the three calculation methods (P = 0.046). Conclusion: The ATCTCRP, BTCSimK, and KTCSimK calculators had similar performance with regards to their astigmatism prediction accuracy. The ATCTCRP calculator combined with 4.0-mm apex/ring readings of TCRP was slightly intended to result in against-the-rule residual astigmatism.


Assuntos
Astigmatismo , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular/métodos , Astigmatismo/diagnóstico , Astigmatismo/cirurgia , Acuidade Visual , Estudos Retrospectivos , Topografia da Córnea , Córnea , Refração Ocular
2.
Cardiorenal Med ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724747

RESUMO

INTRODUCTION: Heart valvular calcification (HVC) is an important predictor of cardiovascular events (CEs) and all-cause mortality in dialysis patients. Patients in the early stage of dialysis or those with central venous catheters (CVCs) are also at high risk of cardiovascular and all-cause mortality. It could be a confounding factor for the prognosis of HVC on CE. METHODS: From March 2017 to April 2022, the prognosis of HVC on CE and all-cause mortality was studied retrospectively in 158 hemodialysis (HD) patients who used arteriovenous fistulas (AVFs) or arteriovenous grafts (AVGs) as vascular access and entered HD for more than 12 months. RESULTS: Out of 158 patients, 70 (44.3%) were diagnosed with HVC via echocardiography. A total of 180 CEs occurred during follow-up. Among them, acute heart failure (AHF) accounted for 62.66%, and its prevalence was significantly higher in the HVC group than that in the non-HVC group (p <0.0001). The cumulative incidence of CE-free survival in the HVC group was significantly lower than that in the non-HVC group (p = 0.030). Only 11 patients died and there was no significant difference in all-cause mortality between the two groups (p = 0.560). Multivariate COX regression analyses showed that HD vintage, mitral valve calcification (MVC), and aortic valve regurgitation (AR)/aortic valve stenosis (AS) but not aortic valve calcification (AVC) were risk factors for CE (p <0.05). CONCLUSION: After excluding the factors of the early stage of HD and CVC, HVC remained a predictor of adverse CE in HD patients.

4.
Nano Lett ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651872

RESUMO

Heterostructures comprising lanthanide-doped upconversion nanoparticles (DUCNPs) and metal-organic frameworks (MOFs) are emerging as promising nanosystems for integrating medical diagnosis and treatment. Here, the DUCNP@Mn-MOF nanocarrier was developed, which showed good efficiency for loading and delivering a cytotoxic antitumor agent (3-F-10-OH-evodiamine, FOE). The combined advantages of the pH-responsive and peroxidase-like properties of Mn-MOF and the unique optical features of DUCNPs granted the DUCNP@Mn-MOF/FOE system synergistic chemodynamic and chemotherapeutic effects. The DUCNP@Mn-MOF nanocarrier effectively overcame the intrinsic limitations of FOE, such as its unfavorable physicochemical properties and limited in vivo potency. This complexed nanosystem was responsive to the tumor microenvironment and showed excellent tumor targeting capability. Thus, DUCNP@Mn-MOF/FOE exhibited highly selective and bioavailable drug delivery properties and is promising for cancer therapy. In a mouse breast cancer model, DUCNP@Mn-MOF/FOE inhibited tumor growth without significant toxicity. Therefore, the proposed nanosystem represents a promising theragnostic platform for multimodal combination diagnosis and therapy of tumors.

5.
Molecules ; 28(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36677694

RESUMO

OBJECTIVE: To study the extraction process of agarwood active ingredients (AA) and investigate the safety and effectiveness of AA in the treatment of insomnia rats by nasal administration. METHOD: A ß-cyclodextrin (ß-CD) inclusion compound (a-ß-CD) was prepared from agarwood essential oil (AEO), and the preparation process was optimized and characterized. The safety of AA in nasal mucosa was evaluated through Bufo gargarizans maxillary mucosa and rat nasal mucosa models. Insomnia animal models were replicated by injecting p-chlorophenylalanine (PCPA), conducting behavioral tests, and detecting the expression levels of monoamine neurotransmitters (NE and 5-HT) and amino acids (GABA/Glu) in the rat hypothalamus. RESULTS: The optimum inclusion process conditions of ß-CD were as follows: the feeding ratio was 0.35:1.40 (g:g), the inclusion temperature was 45 °C, the inclusion time was 2 h, and the ICY% and IEO% were 53.78 ± 2.33% and 62.51 ± 3.21%, respectively. The inclusion ratio, temperature, and time are the three factors that have significant effects on the ICY% and IEO% of a-ß-CD. AA presented little damage to the nasal mucosa. AA increased the sleep rate, shortened the sleep latency, and prolonged the sleep time of the rats. The behavioral test results showed that AA could ameliorate depression in insomnia rats to a certain extent. The effect on the expression of monoamine neurotransmitters and amino acids in the hypothalamus of rats showed that AA could significantly reduce NE levels and increase the 5-HT level and GABA/Glu ratio in the hypothalamus of insomnia rats. CONCLUSION: The preparation of a-ß-CD from AEO can reduce its irritation, improve its stability, increase its curative effect, and facilitate its storage and transport. AA have certain therapeutic effects on insomnia. The mechanism of their effect on rat sleep may involve regulating the expression levels of monoamine neurotransmitters and amino acids in the hypothalamus.


Assuntos
Ciclodextrinas , Óleos Voláteis , Distúrbios do Início e da Manutenção do Sono , Animais , Ratos , Fenclonina/farmacologia , Ácido gama-Aminobutírico/metabolismo , Neurotransmissores , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Serotonina , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico
6.
Nat Commun ; 14(1): 117, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627270

RESUMO

Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40-60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.


Assuntos
Estado de Consciência , Epilepsia Tipo Ausência , Feminino , Ratos , Humanos , Animais , Estado de Consciência/fisiologia , Roedores , Convulsões , Tálamo , Eletroencefalografia/métodos , Neurônios/fisiologia , Córtex Cerebral
7.
J Exp Clin Cancer Res ; 42(1): 6, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36604718

RESUMO

BACKGROUND: Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. METHODS: Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. RESULTS: Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. CONCLUSION: Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Sorafenibe , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ácido Graxo Sintases/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Orlistate/farmacologia , Orlistate/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico
8.
J Med Virol ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719034

RESUMO

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.75 and BA.2.76 subvariants contained 35 and 29 additional mutations in its spike (S) protein compared to the reference SARS-CoV-2 genome, respectively. Here, we measured the evasion degree of the BA.1, BA.2, BA.4, BA.5, BA.2.75, and BA.2.76 subvariants from neutralizing immunity in people previously infected with the Omicron BA.1 and BA.2, determined the effect of vaccination on immune evasion, and compared the titers of neutralizing antibodies in serums between acute infection and convalescence. Results showed that the neutralization effect of serums from patients with different vaccination statuses and BA.1/BA.2 breakthrough infection decreased with the Omicron evolution from BA.1 to BA.2, BA.4, BA.5, BA.2.75, and BA.2.76. This study also indicated that the existing vaccines could no longer provide effective protection, especially for the emerging BA.2.75 and BA.2.76 subvariants. Therefore, vaccines against emerging epidemic strains should be designed specifically. In the future, we can not only focus on the current strains, but also predict and design new vaccines against potential mutant strains. At the same time, we can combine the virus strains' infection characteristics to develop protective measures for virus colonization areas, such as nasal protection spray. Besides, further studies on the Y248N mutation of BA.2.76 subvariant were also necessary to explore its contribution to the enhanced immune evasion ability. This article is protected by copyright. All rights reserved.

9.
Sci China Life Sci ; 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36607495

RESUMO

Genome sequencing has revealed that actinomycetes possess the potential to produce many more secondary metabolites than previously thought. The existing challenge is to devise efficient methods to activate these silent biosynthetic gene clusters (BGCs). In Streptomyces ansochromogenes, disruption of wblA, a pleiotropic regulatory gene, activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously. Overexpressing pathway-specific regulatory genes tylR1 and tylR2 can also trigger the biosynthesis of silent tylosin analogues, in which TylR1 exerted its function via enhancing tylR2 expression. Bacterial one-hybrid system experiments unveiled that WblA directly inhibits the transcription of tylR1 and tylR2 to result in the silence of tylosin analogues BGC. Furthermore, WblA can activate the nikkomycin production through up-regulating the transcription of pleiotropic regulatory gene adpA. More interestingly, AdpA can activate sanG (an activator gene in nikkomycin BGC) but repress wblA. Our studies provide a valuable insight into the complex functions of pleiotropic regulators.

10.
Sci Rep ; 13(1): 335, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611046

RESUMO

The TBC1 domain family member 10B (EPI64B/TBC1D10B), a member of the RabGAP EPI64 subfamily, contains a TBC domain that confers GTPase-activating protein activity. Even though overexpression of TBC1D10B has been reported to promote tumor invasion and metastasis in gastric adenocarcinoma, the prognostic value of TBC1D10B and its correlation with DNA methylation and immune infiltration in hepatocellular carcinoma are still not known. Transcriptional expression profiles of TBC1D10B between hepatocellular carcinoma tissues and normal tissues were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. The Clinical Proteomic Tumor Analysis Consortium and the Human Protein Atlas were used to assess the TBC1D10B protein expression. The biological functions of TBC1D10B were evaluated by the Metascape database and by Gene Set Enrichment Analysis (GSEA). Receiver operating characteristic (ROC) curve analysis was used to distinguish hepatocellular carcinoma from adjacent normal tissues. The effect of TBC1D10B on survival was estimated using the Kaplan-Meier method. DNA methylation in the TBC1D10B gene was assessed using the online MEXPRESS and MethSurv tools. The association between TBC1D10B mRNA expression and immune cell infiltration was investigated by the TIMER2 web server, tumor immune estimation resource and single-sample GSEA. This study found that TBC1D10B is highly expressed in hepatocellular carcinoma and that increased TBC1D10B mRNA expression is associated with female sex, lower Body Mass Index, high level of alpha fetal protein, and worse clinical stages. The mRNA and protein levels of TBC1D10B were verified in cells. Functional annotation indicated enrichment with negative regulation of the cell cycle, extracellular matrix, and corresponding pathways in the high-TBC1D10B phenotype. The ROC curve analysis showed that, with a cutoff level of 2.912, the accuracy, sensitive, and specificity in differentiate TBC1D10B hepatocellular carcinoma from adjacent controls were 0.931, 0.920, and 0.802, respectively. Kaplan-Meier survival analysis showed that hepatocellular carcinoma patients with high TBC1D10B had a worse prognosis than those with low TBC1D10B, especially in patients with a weight below 70 kg, height above 170 cm, and histological G2 and G3. We also found that the methylation of TBC1D10B was associated with the prognosis in patients with hepatocellular carcinoma. Moreover, correlation analysis indicated that TBC1D10B mRNA expression was positively correlated with infiltration levels of most immune cells, but negatively correlated with Th17 and cytotoxic cells infiltration. Our study indicates that increased TBC1D10B expression in hepatocellular carcinoma may play a role in tumorigenesis by regulating the cell cycle and extracellular matrix. TBC1D10B may be a novel prognostic and predictive marker and immune therapeutic target in hepatocellular carcinoma patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Feminino , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Prognóstico , Proteômica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Biomarcadores , Imunoterapia , Biomarcadores Tumorais/genética , Proteínas Adaptadoras de Transdução de Sinal
11.
Biol Pharm Bull ; 46(1): 1-11, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36596517

RESUMO

Inspired by the well-known phenomenon of stretch-induced airway dilation in normal lungs and the emerging stretch-responsive Piezo1 channels that can be chemically activated by specific agonists such as Yoda1, we attempted to investigate whether chemical activation of Piezo1 by Yoda1 can modulate the biomechanical behaviors of airway smooth muscle cells (ASMCs) so that it may be exploited as a novel approach for bronchodilation. Thus, we treated in vitro cultured rat ASMCs with Yoda1, and examined the cells for calcium signaling, cell stiffness, traction force, cell migration, and the mRNA expression and distribution of molecules relevant to cell biomechanics. The data show that ASMCs expressed abundant mRNA of Piezo1. ASMCs exposed to 1 µM Yoda1 exhibited a potent but transient Ca2+ signaling, and treatment with 1 µM Yoda1 for 24 h led to decreased cell stiffness and traction force, all of which were partially reversed by Piezo1 inhibitor GsMTx4 and Piezo1 knockdown, respectively. In addition, ASMCs treated with 1 µM Yoda1 for 24 h exhibited impaired horizontal but enhanced vertical cell migration, as well as significant changes in key components of cells' contractile machinery including the structure and distribution of stress fibers and alpha-smooth muscle actin (α-SMA) fibrils, the mRNA expression of molecules associated with cell biomechanics. These results provide the first evidence that chemical activation of Piezo1 by Yoda1 resulted in marked pro-relaxation alterations of biomechanical behaviors and contractile machinery of the ASMCs. These findings suggest that Piezo1-specific agonists may indeed have great potential as alternative drug agents for relaxing ASMCs.


Assuntos
Sinalização do Cálcio , Miócitos de Músculo Liso , Ratos , Animais , Células Cultivadas , Miócitos de Músculo Liso/metabolismo , RNA Mensageiro/metabolismo
12.
ACS Sens ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696535

RESUMO

Quantification of microRNA (miRNA) has attracted intense interest owing to its importance as a biomarker for the early diagnosis of multiple diseases. However, the inefficient capture of microRNAs from complex biological samples due to the passive diffusion of detection probes essentially restricts their accurate quantification. Herein, we report near-infrared (NIR)-powered Janus nanomotors composed of Au nanorods and periodic mesoporous organo-silica microspheres (AuNR/PMO JNMs) as "swimming probes" to assist a lateral flow test strip (LFTS) for direct, amplification-free, and quantitative miRNA-21 detection in serum and cell medium. The AuNR/PMO JNMs were conjugated with designed hDNA as a recognition probe for miRNA-21. Under NIR irradiation, the exposed AuNRs can generate asymmetric thermal gradients around the JNMs to achieve vigorous self-propelled thermophoretic motion. The active movement significantly accelerated the recognition of miRNA-21 targets, which greatly improved the capture efficiency from 59.39 to 86.12% in the reaction buffer. The enhanced miRNA-21 capture enabled direct quantitative miRNA-21 detection on the LFTS assay with both visual and thermal signals. Under the assistance of AuNR/PMO JNMs, a limit-of-detection of 18 fmol/L for miRNA-21 was achieved, which was 12.22-fold compared to that of LFTS assay with static probes. The constructed LFTS assay was further successfully deployed to directly sense the miRNA-21 in spiked serum samples and MDA-MB-231 medium. Overall, the AuNR/PMO JNM-assisted LFTS system unveils a concrete point-of-care testing strategy for precise miRNA detection in real biological samples, which holds great potential for early diagnosis and treatment of miRNA-related diseases.

13.
Anal Chim Acta ; 1242: 340782, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36657887

RESUMO

Ochratoxin A (OTA) is the most toxic class of ochratoxins and has become a major threat to the environment, humans and animals. Therefore, research on the methods for its detection is also more urgent. Herein, we propose a low-background electrochemical biosensor based on a DNA tetrahedron-besieged primer and a DNAzyme-activated programmatic rolling circle amplification (RCA) that can be ultimately utilized for OTA detection in wine samples. Low-background detection can be achieved using the besieged primer via sequenced assembly of DNA tetrahedral nanostructures so that non-specific extensions of primer can be avoided. The target OTA-mediated DNAzyme activation initiates the programmatic RCA. Additionally, the catalytic property of silver nanoclusters (AgNCs) is integrated with the electrochemical assay to achieve high sensitivity for OTA detection. Benefiting from the aforementioned processes, a low-background, and highly sensitive electrochemical biosensor has been successfully constructed. This design is capable of detecting OTA at concentrations from 1 pg/mL to 10 ng/mL, and its lowest concentration limit is 0.773 pg/mL. Simultaneously, its validation in the detection of actual samples reveals that the proposed electrochemical biosensor has a lot of potential in food safety and environmental detection.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA Catalítico , Ocratoxinas , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA/química , Primers do DNA , DNA Catalítico/química , Técnicas Eletroquímicas/métodos , Limite de Detecção , Ocratoxinas/análise
14.
ACS Appl Mater Interfaces ; 15(4): 5010-5018, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36681942

RESUMO

Ultrasensitive quantification of protein biomarkers has significant implications in disease diagnosis. Herein, we report a fluorescent bacteria counting immunoassay (FBCIA) strategy for protein biomarker detection based on a cascade signal conversion and amplification strategy including the copper metal-organic framework (Cu-MOF)-mediated Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) for fluorescent bacteria immobilization that converted the concentration of target protein to countable bacterial number and the further self-proliferation of bacteria to amplify the detectable bacterial number. The developed low-background and enzyme-free cascade methodology achieved highly sensitive detection of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) with detection limits down to 0.8 pg/mL and 64.5 fg/mL, respectively. On top of that, we also developed a smartphone device for visualizing individual bacteria and point-of-care counting of the resulting bacteria for the detection of clinical samples. The good consistency between FBCIA and clinical enzyme-linked immunosorbent assay (ELISA) validated the high reliability and promising potential of our developed platform in clinical applications.


Assuntos
Estruturas Metalorgânicas , Humanos , Masculino , Reprodutibilidade dos Testes , Antígeno Prostático Específico/análise , Cobre , Ensaio de Imunoadsorção Enzimática , Bactérias , Imunoensaio
15.
Medicine (Baltimore) ; 102(1): e32645, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607882

RESUMO

OBJECTIVE: To explore the curative effect of "Jiaotai Pill" combined with head rhythmic massage consistent with 5-tone rhythm on insomnia of heart-kidney disharmony type. METHODS: Sixty patients with insomnia in massage clinic and ward were randomly divided into treatment group A (30 cases) and treatment group B (30 cases). Patients in group A were treated with traditional head massage combined with oral estazolam tablets. Group B was treated with "Jiaotai Pill" combined with head rhythmic massage therapy consistent with 5-tone rhythm. After 2 weeks of treatment, the scores of Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index and Traditional Chinese Medicine Symptom Scale, as well as the expression changes of interleukin (IL)-6 and IL-8 in serum were compared between the 2 groups before and after treatment. RESULTS: After 2 weeks of treatment, the total effective rate of group B was 93. 33%, which was significantly higher than that of group A (66. 67%) (P < .05). After treatment, the scores of Hamilton Anxiety Scale, PQSI, insomnia severity index and traditional Chinese medicine symptom scores were significantly decreased in both groups, and the decrease in group B was more significant than that in group A (P < .05). After treatment, the serum levels of IL-6 and IL-8 were significantly decreased in both groups, and the decrease in group B was greater than that in group A, the difference was statistically significant (P < .05). CONCLUSION: The overall efficacy of Jiaotai Pill combined with head massage therapy consistent with 5-tone rhythm is significantly better than that of traditional massage combined with 5-element music therapy for insomnia patients with heart-kidney disharmony.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Humanos , Cafeína , Interleucina-8 , Rim , Massagem , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
16.
Medicine (Baltimore) ; 102(1): e32653, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607875

RESUMO

Diabetic peripheral neuropathy (DPN) is the most common neuropathy in the world, mainly manifested as bilateral symmetry numbness, pain or paresthesia, with a high rate of disability and mortality. Schwann cells (SCs), derived from neural ridge cells, are the largest number of glial cells in the peripheral nervous system, and play an important role in DPN. Studies have found that SCs are closely related to the pathogenesis of DPN, such as oxidative stress, endoplasmic reticulum stress, inflammation, impaired neurotrophic support and dyslipidemia. This article reviews the mechanism of SCs in DPN.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Estresse Oxidativo , Células de Schwann/patologia , Neuroglia/patologia , Diabetes Mellitus/patologia
17.
Breast Cancer ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656510

RESUMO

PURPOSE: With the release of promising data from clinical trials of novel anti-HER2 antibody-drug conjugates, there is a new therapeutic direction in HER2-low expression breast cancer (BC). This study aims to evaluate the differences in clinicopathological characteristics of HER2-low-positive and HER2-zero BC, including response to neoadjuvant chemotherapy (NACT) and prognosis. METHODS: Records of HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients who received NACT at our cancer center between January 2017 and December 2017 were retrospectively collected. HER2-low-positive was defined as immunohistochemistry (IHC) 1 + or IHC2 + /in-situ hybridization negative and HER2-zero was defined as IHC0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) and overall survival (OS) between the two groups. Univariate and multivariable logistic regression models and Cox-proportional hazards models were performed for analysis of the endpoints pCR, RFS, and OS. RESULTS: A total of 239 [84.5%] of 283 tumors were HER2-low-positive (including 132 [55.2%] HER2-1 + and 107 [44.8%] HER2-2 + /ISH non-amplified) and 44 [15.5%] were HER2-zero. Patients in the HER2-low-positive group had more commonly hormone receptor positivity than HER2-zero patients (188 [78.7%] vs. 19 [43.2%], P = 0.000), but there was no difference between HER2-1 + and HER2-2 + / ISH non-amplified (99 [75.0%] vs. 89 [83.2%], P = 0.125). HER2-zero tumors had a significantly higher pCR rate than HER2-low-positive tumors (15 [34.1%] of 44 vs. 22 [9.2%] of 239, P = 0.000). Pathological complete response was also significantly higher in HER2-zero tumors versus HER2-low-positive tumors in the hormone receptor-negative subgroup (13 [52.0%] of 25 vs. 14 [27.5%] of 51, P = 0.036), but not in the hormone receptor-positive subgroup (2 [10.5%] of 19 vs 8 [4.3%] of 188, P = 0.231). No significant difference was observed in 5-year RFS between the two groups (HR 0.577, 95% CI 0.298-1.118, P = 0.103). However, HER2-low-positive tumors showed significantly better OS than HER2-zero tumors (HR 0.280, 95% CI 0.122-0.697, P = 0.006). CONCLUSIONS: These results suggest that HER2-low-positive tumors have specific biological characteristics according to the hormone receptor status and exhibit different responses to NACT and prognosis.

18.
Phys Chem Chem Phys ; 25(3): 2294-2303, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36597910

RESUMO

DFT calculations have been performed to find the mechanism of the alkyloxycarbonylation of an internal alkene with HCOOH catalyzed by a palladium complex with P,N hemilabile ligands. Four different cycles have been explored in detail, and a plausible catalytic cycle involves the decomposition of HCOOH/HCOOMe to CO, internal alkene isomerization, terminal alkene insertion, CO migratory insertion and methanolysis. It is shown that decomposition and isomerization processes involve a cooperative P,N hemilabile ligand and Pd(0) (NH-Pd) rather than the Pd(II) hydride (Pd-H) mechanism. Intriguingly, the simultaneous presence of PTSA acts as a hydrogen shuttle (H-shuttle), assisting CO generation and methanolysis. With such a mechanism, the rate-determining transition state corresponds to internal alkene isomerization, which is consistent with the experimental observation that isomerization was the slow step in this process. The back-bonding between palladium and olefin and rapid hydrogen transfer in the presence of a PTSA H-shuttle are responsible for the moderate barriers. In addition, a careful study of the solvent effect indicates that polar solvents, which are capable of hydrogen bonding, can promote the catalytic reactions. Mechanistic insights gained by this theoretical study have not only rationalized the experimental observations well but also have implications for new reaction development.

19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(1): 1-6, 2023 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-36584991

RESUMO

OBJECTIVE: To explore the clinical and genetic characteristics of three children with KBG syndrome. METHODS: Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out. RESULTS: All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype. CONCLUSION: The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Anormalidades Dentárias , Feminino , Criança , Humanos , Anormalidades Múltiplas/genética , Deficiência Intelectual/genética , Doenças do Desenvolvimento Ósseo/genética , Anormalidades Dentárias/genética , Facies , Proteínas Repressoras/genética , Mães , Mutação
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(1): 47-52, 2023 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-36585000

RESUMO

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION: The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/genética , Testes Genéticos , Fenótipo , Heterozigoto , Mutação , Proteínas Cromossômicas não Histona/genética , Fosfoproteínas/genética
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