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1.
Food Chem ; 431: 137066, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37572484

RESUMO

This study investigated the non-volatile metabolites and antioxidant activity of Douchi, an edible mushroom by-product. A total of 695 non-volatile metabolites were detected using UPLC-MS/MS-based metabolomics analysis, and the greatest impact on metabolite composition was observed during Koji-making and the first 5 days of post-fermentation. Throughout the fermentation process, 366 differential metabolites were identified, with flavonoids being the most prominent followed by amino acids and their derivatives, which were found to be important for the quality of edible mushroom by-product Douchi (EMD). The antioxidant capacity of EMD significantly increased with the longer fermentation time, which might be associated with the conversion of isoflavone glycosides to aglycones, amino acids and their derivatives, free fatty acids, group A saponins, and phenolic acids. These findings suggested that different fermentation phases of EMD significantly affected the non-volatile metabolite profile and antioxidant capacity.


Assuntos
Agaricales , Antioxidantes , Antioxidantes/metabolismo , Agaricales/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Fermentação , Aminoácidos/metabolismo , Metabolômica
2.
Huan Jing Ke Xue ; 44(8): 4448-4457, 2023 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-37694639

RESUMO

Northwest Guizhou is a karst area with a high geological background. Affected by historical soil zinc smelting, the heavy metal content of atmospheric dust in the region is high, and soil pollution is severe. In order to explore the accumulation pathway of heavy metals in leafy vegetables, Chinese cabbage was used as the test crop, and the geological high background soil and zinc smelting-contaminated soil with the same contents of Cd, Pb, and Zn were selected. A pot experiment was carried out in the polluted area of zinc smelting and the non-polluting control area. The heavy metal content, enrichment coefficient (BCF), and transport coefficient (TF) of Chinese cabbage were studied under open-air, plastic mulching film, and greenhouse cultivation conditions. The results showed that the contents of Cd, Pb, and Zn in Chinese cabbage in the polluted area and the control area were 0.10-1.01 and 0.10-0.91 mg·kg-1, 0.31-0.62 and 0.23-0.37 mg·kg-1, and 7.50-32.74 and 4.88-21.79 mg·kg-1, respectively. Overall, the contents of heavy metals in the polluted area were relatively high. The contents of Cd and Pb in Chinese cabbage planted in soil with a high geological background met the requirements of the national food safety standard limits. Affected by atmospheric deposition, the contents of Pb and Zn in Chinese cabbage in the polluted area were significantly higher than that in the control area, and the difference in Cd was insignificant. The proportions of weak acid-soluble Cd, Pb, and Zn in the contaminated soil were 48%, 3.0%, and 16%, respectively, which were 3.15, 1.01, and 1.57 times higher than those in the control soil with a high geological background. Affected by the activity of heavy metals, the contents of Cd and Zn in Chinese cabbage planted in the contaminated soil exceeded the national standard and were significantly higher than those in the control soil. The root-soil BCF of Cd, Pb, and Zn in polluted soil was significantly higher than that in the control soil, and the BCF of Cd and Zn was higher than that of Pb. The TF aboveground root Cd and Zn in Chinese cabbage was significantly higher than in the control soil, whereas the TF aboveground root Pb in the polluted area was significantly higher than that in the control area. The Pb content of Chinese cabbage in the two study areas showed open field>plastic mulching film>greenhouse cultivation. In conclusion, the content of Cd and Zn in Chinese cabbage was greatly affected by the activity of heavy metals in soil, and the main accumulation pathway was root absorption and transportation. In addition to root absorption, atmospheric deposition was an important accumulation pathway of Pb. Therefore, in areas with high geological backgrounds, attention should be paid to controlling the exposure risk of Cd and Zn in leafy vegetables planted on exogenously polluted soils. Additionally, greenhouse cultivation could effectively reduce the accumulation of Pb.


Assuntos
Brassica , Cádmio , Chumbo , Verduras , Zinco , Poluição Ambiental , Plásticos
3.
Medicine (Baltimore) ; 102(36): e35063, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37682194

RESUMO

Maintenance hemodialysis (MHD) patients are the high-risk population of infection and death of novel coronavirus disease 2019 (COVID-19), our study aimed to investigate the infection status and clinical characteristics of COVID-19 in MHD patients at a single-center in Wuhan during the Omicron pandemic. In this retrospective, single-center study, we analyzed the clinical data of all MHD patients in Hemodialysis Center of Wuhan No. 1 Hospital from December 2, 2022 to January 6, 2023 during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron pandemic outbreak. We analyzed the epidemiological and clinical characteristics of deaths and survivors of MHD patients. The infection rate of SARS-CoV-2 in MHD patients was 93.32% (573/614), mortality rate was 8.14% (50/614), hospitalization rate was 23.29% (143/614), and the vaccination rate of COVID-19 was 4.89% (30/614). The median survival time of dead patients was 11 days, the mortality rate of male MHD patients was significantly higher than female. Elderly MHD patients had a higher mortality rate, with a average age of death higher than 70 years old. Additionally, the mortality rate of MHD patients infected with SARS-CoV-2 was higher if the primary disease was hypertensive renal damage or diabetic nephropathy. Laboratory results showed that the lower the albumin level and the higher the C-reactive protein level of MHD patients who died of SARS-CoV-2 infection and severe and critical survival patients. In surviving MHD patients infected with SARS-CoV-2, the most common symptoms were hypodynamia (84.70%), decreased appetite (81.26%) and cough (80.69%). The symptoms of fever, chest tightness and panting, cough, pharyngalgia, hypodynamia, decreased appetite in surviving MHD patients with severe and critical type were significantly higher than those in patients with mild and moderate type. MHD patients are a highly vulnerable population at increased risk of mortality during the Omicron pandemic. Elderly, male, primary disease was hypertensive renal damage or diabetic nephropathy, hypoproteinemia and high C-reactive protein level, all of which will lead to increased mortality in MHD patients.


Assuntos
COVID-19 , Nefropatias Diabéticas , Idoso , Humanos , Feminino , Masculino , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Proteína C-Reativa , Tosse , Hipocinesia , Pandemias , Estudos Retrospectivos , Diálise Renal
4.
Nutrients ; 15(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37686836

RESUMO

BACKGROUND: Previous cross-sectional studies have failed to definitively establish a causal relationship between serum 25-hydroxyvitamin D (25OHD) concentrations and the onset of rosacea. OBJECTIVE: To investigate the potential association between serum 25OHD levels, vitamin D receptor (VDR) polymorphisms, and the risk of developing incident rosacea. METHODS: This cross-sectional population-based cohort study utilizing 370,209 individuals from the UK Biobank. Cox proportional hazard regression models and two-sample Mendelian randomization (MR) analyses were applied to explore the causative relationship between 25OHD and incident rosacea. RESULTS: Our findings revealed that elevated levels of serum 25OHD were inversely correlated with the risk of incident rosacea. Specifically, compared to participants with 25OHD levels below 25 nmol/L, the multivariate-adjusted HR for incident rosacea was 0.81 (95% CI: 0.70, 0.94) in those with 25OHD levels exceeding 50 nmol/L. Further, in comparison to individuals with serum 25OHD less than 25 nmol/L and the rs731236 (TaqI) AA allele, those with serum 25OHD higher than 75 nmol/L and the TaqI GG allele had a multivariate-adjusted HR of 0.51 (95% CI 0.32 to 0.81) for developing rosacea. Results from the MR study supported a significant association, with each standard deviation increase in serum 25OHD concentrations correlating to a 23% reduced risk of rosacea (HR = 0.77, 95% CI: 0.63, 0.93). CONCLUSIONS: The findings of this cohort study indicate an inverse association between increased concentrations of serum 25OHD and the risk of developing incident rosacea. While our results highlight the potential protective role of vitamin D, the definitive efficacy of vitamin D supplementation as a preventive strategy against rosacea requires further investigation.


Assuntos
Receptores de Calcitriol , Rosácea , Humanos , Receptores de Calcitriol/genética , Estudos de Coortes , Bancos de Espécimes Biológicos , Estudos Transversais , Análise da Randomização Mendeliana , Vitamina D , Vitaminas , Rosácea/epidemiologia , Rosácea/genética , Reino Unido/epidemiologia
5.
Molecules ; 28(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37687125

RESUMO

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.


Assuntos
Gastrite Atrófica , Proteínas Hedgehog , Camundongos , Ratos , Animais , Gastrite Atrófica/induzido quimicamente , Gastrite Atrófica/tratamento farmacológico , Metilnitronitrosoguanidina , Quinazolinas , Nitrosoguanidinas , Transdução de Sinais
6.
Int J Biol Macromol ; : 126801, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37689288

RESUMO

Histone lysine-specific demethylase 1 (LSD1) expression has been evaluated in multiple tumors, including gastric cancer (GC). However, the mechanisms underlying LSD1 dysregulation in GC remain largely unclear. In this study, neural precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) was identified to be conjugated to LSD1 at K63 by ubiquitin-conjugating enzyme E2 M (UBE2M), and this neddylated LSD1 could promote LSD1 ubiquitination and degradation, leading to a decrease of GC cell stemness and chemoresistance. Herein, our findings revealed a novel mechanism of LSD1 neddylation and its contribution to decreasing GC cell stemness and chemoresistance. Taken together, our findings may whistle about the future application of neddylation inhibitors.

7.
China CDC Wkly ; 5(33): 737-741, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37663900

RESUMO

Introduction: Bacillus cereus (B. cereus) is a common gram-positive bacterium that contaminates starch-rich food and can cause outbreaks of foodborne diseases. This study describes the characteristics of outbreaks caused by B. cereus in China during 2010-2020 and explore the possible reasons for changes in the number of outbreaks over time. Results of this analysis can efficiently help guide and allocate public resources to prevent B. cereus-caused foodborne diseases. Methods: Descriptive statistical methods were used to analyze the data on B. cereus outbreaks in China during this period. The data were identified and reported at all levels in China through National Foodborne Disease Outbreak Surveillance System. Results: From 2010 to 2020, a total of 419 foodborne outbreaks prompted by B. cereus were reported in China, leading to 7,892 cases, 2,786 hospital admissions, and 5 fatalities. The bulk of the outbreaks were recorded in the summer, primarily between May and September. The most recurrent food vehicle was linked with rice or flour-based products, notably those made with rice or fried rice. School canteens bore the brunt of the B. cereus outbreaks. In multifactor outbreaks, food contamination was identified as the most common culprit; while in instances where only one factor contributed, improper storage was most frequently implicated. Conclusion: The prevalence of B. cereus outbreaks remained relatively consistent throughout the studied period. Understanding the types of foods, causative factors, and contributing elements leading to B. cereus outbreaks can help inform prevention strategies for foodborne illnesses. The majority of outbreaks were associated with rice- or flour-based foods in school canteens, suggesting contamination and improper storage during food preparation. Consequently, it is essential to prioritize continuous education for canteen staff on food safety, efficacious management, and proper practices. The implementation of comprehensive guidelines, encompassing multiple critical aspects, can potentially reduce the occurrence of B. cereus outbreaks.

8.
bioRxiv ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37662192

RESUMO

Aspergillus fumigatus , an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores or conidia for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of A. fumigatus , two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis , and the cryptic pathogen Aspergillus lentulus . After identifying 62 proteins uniquely expressed on the A. fumigatus conidial surface, we deleted 42 genes encoding conidial proteins. We found deletion of 33 of these genes altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. Notably, a gene that encodes glycosylasparaginase, which modulates levels of the host pro-inflammatory cytokine IL-1ß, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins and effectors are important for evasion and modulation of the immune response at the onset of fungal infection.

9.
J Microbiol ; 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37665552

RESUMO

Accumulating studies have raised concerns about gut dysbiosis associating autism spectrum disorder (ASD) and its related symptoms. However, the effect of gut microbiota modification on the Chinese ASD population and its underlying mechanism were still elusive. Herein, we enrolled 24 ASD children to perform the first course of fresh washed microbiota transplantation (WMT), 18 patients decided to participate the second course, 13 of which stayed to participate the third course, and there were 8 patients at the fourth course. Then we evaluated the effects of fresh WMT on these patients and their related symptoms. Our results found that the sleeping disorder symptom was positively interrelated to ASD, fresh WMT significantly alleviated ASD and its sleeping disorder and constipation symptoms. In addition, WMT stably and continuously downregulated Bacteroides/Flavonifractor/Parasutterella while upregulated Prevotella_9 to decrease toxic metabolic production and improve detoxification by regulating glycolysis/myo-inositol/D-glucuronide/D-glucarate degradation, L-1,2-propanediol degradation, fatty acid ß-oxidation. Thus, our results suggested that fresh WMT moderated gut microbiome to improve the behavioral and sleeping disorder symptoms of ASD via decrease toxic metabolic production and improve detoxification. Which thus provides a promising gut ecological strategy for ASD children and its related symptoms treatments.

10.
Biochim Biophys Acta Rev Cancer ; 1878(6): 188970, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37657682

RESUMO

Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of monosaccharide found in human body fluids and tissues, primarily functions in protein glycosylation rather than carbohydrate metabolism. Recent research has demonstrated direct anticancer effects of mannose in vitro and in vivo. Simply supplementing cell culture medium or drinking water with mannose achieved these effects. Moreover, mannose enhances the effectiveness of current cancer treatments including chemotherapy, radiotherapy, targeted therapy, and immune therapy. Besides the advancements in basic research on the anticancer effects of mannose, recent studies have reported its application as a biomarker for cancer or in the delivery of anticancer drugs using mannose-modified drug delivery systems. This review discusses the progress made in understanding the regulatory roles of mannose in cancer progression, the mechanisms underlying its anticancer effects, and its current application in cancer diagnosis and treatment.

11.
Turk J Phys Med Rehabil ; 69(2): 161-170, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37671384

RESUMO

Objectives: This study aimed to evaluate the effect of manual lymphatic drainage (MLD) combined with targeted rehabilitation therapies on the recovery of upper limb function in patients with breast cancer after modified radical mastectomy. Patients and methods: In the randomized controlled study conducted between October 2019 and June 2020, 104 eligible breast cancer patients who underwent modified radical mastectomy were randomly divided into two groups. The routine functional exercise group (Group RF) received regular functional exercise guidance. In addition, the MLD combined with targeted rehabilitation therapies group (Group MLDT) received MLD, targeted rehabilitation therapies, and regular functional exercise guidance. The primary endpoints were shoulder range of motion, arm circumference and the incidence of axillary web syndrome (AWS). The secondary endpoints included the duration of axillary drainage, the duration of chest wall drainage, and complications. Results: One hundred participants (mean age: 51.9±8.0 years; range, 28 to 72 years) were included in the final analysis as four patients could not complete the study. A significant improvement in shoulder range of motion was observed in Group MLDT compared to Group RF (p<0.05). Additionally, in Group MLDT, the duration of chest wall drainage was reduced (p=0.037). The frequency of AWS in Group RF was twice that in Group MLDT (p=0.061), but there was no significant difference in arm circumference (p>0.05) or the duration of axillary drainage (p=0.519). Regarding complications, there was one case of necrosis in the MLDT group and four cases in the RF group, including wound infection and seroma. Conclusion: Manual lymphatic drainage combined with targeted rehabilitation therapies is an effective strategy to improve shoulder function, shorten the duration of chest wall drainage, reduce complications, and partly lower the incidence of AWS.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37672020

RESUMO

OBJECTIVE: Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank(UKB). METHODS: To avoid immortal-time-biases in pharmacoepidemiologic studies, Mendelian randomisation was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with HbA1c, serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 407 159 participants were analyzed, including 9,126 EOP and 3,324 LOP. The AMPK-genetic-risk-score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022-1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062-1.395) in male psoriasis patients. CONCLUSIONS: AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed.

13.
Front Immunol ; 14: 1232981, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37691954

RESUMO

Background: The evidence from observational studies on the association between the use of aspirin and the risk of hayfever or allergic rhinitis is conflicting, with a dearth of high-quality randomized controlled trials. Objective: This study aims to investigate the causal relationship between aspirin use and the risk of hayfever or allergic rhinitis. Methods: We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We utilized publicly available summary statistics datasets from genome-wide association studies (GWAS) meta-analyses on aspirin use in individuals of European descent (n = 337,159) as the exposure variable, and a GWAS on doctor-diagnosed hayfever or allergic rhinitis in individuals from the UK Biobank (n = 83,529) as the outcome variable. Results: We identified 7 single nucleotide polymorphisms (SNPs) at genome-wide significance from the GWASs associated with aspirin use as instrumental variables (P<5×10-8; linkage disequilibrium r2 <0.1). The IVW method provided evidence supporting a causal association between aspirin use and reduced risk of hayfever or allergic rhinitis (ß = -0.349, SE = 0.1356, P = 0.01008). MR-Egger regression indicated no causal association between aspirin use and hayfever or allergic rhinitis (ß = -0.3742, SE = 0.3809, P = 0.371), but the weighted median approach yielded evidence of a causal association (ß = -0.4155, SE = 0.1657, P = 0.01216). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. Conclusion: The findings of the MR analysis support a potential causal relationship between aspirin use and the reduced risk of hayfever or allergic rhinitis.


Assuntos
Rinite Alérgica Sazonal , Rinite Alérgica , Humanos , Aspirina , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Rinite Alérgica/genética
14.
Clin Exp Dermatol ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37710038

RESUMO

Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity, mostly presenting as acneiform eruptions, paronychia and xerosis. Erosive pustular dermatosis of the scalp (EPDS) is a rare cutaneous adverse reaction that develops during treatment with EGFRIs. The pathogenesis of EGFRI-induced EPDS is poorly understood. Here we present three cases of EPDS induced by EGFRIs. The proteins LTA4H (leukotriene A-4 hydrolase), METAP1 (methionine aminopeptidase 1), BID (BH3-interacting domain death agonist), SMAD1 (mothers against decapentaplegic homologue), PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A), YES1 (tyrosine-protein kinase Yes) and EGFL7 (epidermal growth factor-like protein 7) were significantly upregulated in EGFRI-stimulated peripheral blood mononuclear cell cultures, and validated in the lesions. All of the proteins colocalized with CD4+ and CD8+ T-cell expression. Next-generation-based human leucocyte antigen (HLA) typing showed all patients carried HLA-C*15:02, and modelling studies showed that afatinib and erlotinib bound well within the E/F binding pockets of HLA-C*15:02. Moreover, T cells were preferentially activated by EGFRIs in individuals carrying HLA-C*15:02. The case series revealed that EGFRI-induced EPDS may be mediated by drug-specific T cells.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37713048

RESUMO

Association of distinct inflammatory profiles with short-term mortality is little known in type A aortic dissection (TAAD). Latent class analysis was used to identify distinct inflammatory profiles based on leukocyte, neutrophils, monocyte, lymphocytes, platelet, fibrinogen, D-dimer, neutrophils-lymphocyte ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio. We identified 193 patients with median age of 56 (IQR 47-63) years and 146 males. Patients were divided as hyper-inflammatory profiles (84 [43.5%]) and hypo-inflammatory profiles (109 [56.5%]). Although baseline characteristics were not different, hyper-inflammatory patients had higher 6-month mortality (20 [23.8%] vs. 11 [10.1%]; P = 0.014) and 30-day mortality (18 [21.4%] vs. 9 [8.3%], P = 0.009) than hypo-inflammatory patients. After adjustment for potential confounders, hyper-inflammatory profiles remain associated with higher risk of 6-month mortality than hypo-inflammatory profiles (adjusted OR 2.427 [95%CI 1.154, 5.105], P = 0.019). Assessment of preoperative inflammatory profiles adds clarity regarding the extent of inflammatory response to TAAD aetiopathologies, highlighting individual anti-inflammatory pharmacotherapy for TAAD. ClinicalTrials.gov Identifier: NCT04398992.

16.
J Biomed Res ; : 1-4, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37705088

RESUMO

Scapular surgery has mainly been studied in the setting of fractures; regional anesthesia can be utilized as part of a multimodal analgesia regimen for postoperative pain relief. Previous studies are limited to scapular fracture pain. The available literature supports the use of various types of nerve blocks and even combinations of different blocks, of which the paravertebral nerve block is one such block that has been effective. We present a case of a patient undergoing excision of a scapular osteochondroma who received a single-shot paravertebral nerve block after surgery with an effective analgesia.

17.
Appl Opt ; 62(23): 6169-6170, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707085

RESUMO

This erratum reports corrections for the original publication, Appl. Opt.61, 2834 (2022)APOPAI0003-693510.1364/AO.450805.

18.
J Transl Med ; 21(1): 611, 2023 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689699

RESUMO

BACKGROUND: Recurrent or metastatic cervical cancer (r/m CC) often has poor prognosis owing to its limited treatment options. The development of novel therapeutic strategies has been hindered by the lack of preclinical models that accurately reflect the biological and genomic heterogeneity of cervical cancer (CC). Herein, we aimed to establish a large patient-derived xenograft (PDX) biobank for CC, evaluate the consistency of the biologic indicators between PDX and primary tumor tissues of patients, and explore its utility for assessing patient's response to conventional and novel therapies. METHODS: Sixty-nine fresh CC tumor tissues were implanted directly into immunodeficient mice to establish PDX models. The concordance of the PDX models with their corresponding primary tumors (PTs) was compared based on the clinical pathological features, protein biomarker levels, and genomic features through hematoxylin & eosin staining, immunohistochemistry, and whole exome sequencing, respectively. Moreover, the clinical information of CC patients, RNA transcriptome and immune phenotyping of primary tumors were integrated to identify the potential parameters that could affect the success of xenograft engraftment. Subsequently, PDX model was evaluated for its capacity to mirror patient's response to chemotherapy. Finally, PDX model and PDX-derived organoid (PDXO) were utilized to evaluate the therapeutic efficacy of neratinib and adoptive cell therapy (ACT) combination strategy for CC patients with human epidermal growth factor receptor 2 (HER2) mutation. RESULTS: We established a PDX biobank for CC with a success rate of 63.8% (44/69). The primary features of established PDX tumors, including clinicopathological features, the expression levels of protein biomarkers including Ki67, α-smooth muscle actin, and p16, and genomics, were highly consistent with their PTs. Furthermore, xenograft engraftment was likely influenced by the primary tumor size, the presence of follicular helper T cells and the expression of cell adhesion-related genes in primary tumor tissue. The CC derived PDX models were capable of recapitulating the patient's response to chemotherapy. In a PDX model, a novel therapeutic strategy, the combination of ACT and neratinib, was shown to effectively inhibit the growth of PDX tumors derived from CC patients with HER2-mutation. CONCLUSIONS: We established by far the largest PDX biobank with a high engraftment rate for CC that preserves the histopathological and genetic characteristics of patient's biopsy samples, recapitulates patient's response to conventional therapy, and is capable of evaluating the efficacy of novel therapeutic modalities for CC.


Assuntos
Neoplasias do Colo do Útero , Humanos , Animais , Camundongos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Xenoenxertos , Recidiva Local de Neoplasia , Adesão Celular , Modelos Animais de Doenças
19.
ACS Omega ; 8(36): 32555-32564, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37720737

RESUMO

A fast, easy-to-implement, highly sensitive, and point-of-care (POC) detection system for frog virus 3 (FV3) is proposed. Combining recombinase polymerase amplification (RPA) and CRISPR/Cas12a, a limit of detection (LoD) of 100 aM (60.2 copies/µL) is achieved by optimizing RPA primers and CRISPR RNAs (crRNAs). For POC detection, smartphone microscopy is implemented, and an LoD of 10 aM is achieved in 40 min. The proposed system detects four positive animal-derived samples with a quantitation cycle (Cq) value of quantitative PCR (qPCR) in the range of 13 to 32. In addition, deep learning models are deployed for binary classification (positive or negative samples) and multiclass classification (different concentrations of FV3 and negative samples), achieving 100 and 98.75% accuracy, respectively. Without temperature regulation and expensive equipment, the proposed RPA-CRISPR/Cas12a combined with smartphone readouts and artificial-intelligence-assisted classification showcases the great potential for FV3 detection, specifically POC detection of DNA virus.

20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(7): 1026-1032, 2023 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37724405

RESUMO

OBJECTIVES: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases involving multiple systems, and kidney is one of the most commonly involved target organs. Some patients may rapidly progress to end-stage renal disease in a short time. Whereas some patients have poor remission and renal prognosis after standard induction therapy. As a selective blood purification therapy, protein a immunoadsorption (PAIA) has shown great advantages on treating of severe autoimmune diseases. This study aims to evaluate the short-term efficacy of PAIA therapy combined with glucocorticoids and immunosuppressants on treating of severe AAV renal injury. METHODS: A total of 10 AAV cases with severe kidney involvement in the Second Xiangya Hospital of Central South University from 2019 to 2020 were selected for this retrospective study. During the induction remission stage, each patient was treated with PAIA on the basis of standard therapy of glucocorticoids and immunosuppressive treatment. Before and after the initial treatment, 1 month and 3 months after treatment, clinical data including demographic characteristics, immunological indicators, and Birmingham Vasculitis Activity Score (BVAS) were compared. The related adverse reactions during treatment were recorded to evaluate the short-term efficacy. RESULTS: In this study, all 10 patients were MPO positive, and 2 patients were PR3 positive (≥2.3 U/mL). There are 6 males and 4 females at (61.5±11.4) years old, with the median time from onset to admission to hospital at (2.8±1.8) months. Multisystem damage, especially kidney damage, can be seen with eGFR lower than 30 mL/(min·1.73 m2). During the 3-month follow-up, BVAS, erythrocyte sedimentation rate, and hemoglobin of 10 patients showed continuous improvement compared with the initial admission levels (all P<0.05). ANCA titer, serum creatinine and urine red blood cell were all decreased and eGFR levels were increased in 3 months after treatment (all P<0.05). Serum albumin, urinary protein, C-reactive protein and complement levels showed no significant changes after treatment (all P>0.05). One patient who had received renal replacement therapy was still dialysis dependent after PAIA treatment. One patient who had transient hypotension was corrected by routine treatment. The rest of the patients were all tolerant with PAIA during their treatments. CONCLUSIONS: Treatment with PAIA combined with glucocorticoids and cyclophosphamide can rapidly lower serum ANCA level and improve disease activity in patients with AAV complicated with severe kidney damage, suggesting a good short-term renal prognosis and good overall safety.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Rim , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia
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