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1.
Bioact Mater ; 19: 88-102, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35441114

RESUMO

Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice. Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface, graft necrosis and sclerosis. However, poor gap integration is a serious concern, which eventually leads to deterioration of joint function. To deal with such complications, this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl (GelMA) hydrogel (BSN-GelMA). A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty, as early as six weeks. Moreover, the International Cartilage Repair Society score, histology score, glycosaminoglycan content, subchondral bone volume, and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group. This improved outcome was due to bio-interactive materials, which acted as tissue fillers to bridge the gap, prevent cartilage degeneration, and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel. This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty. It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.

2.
Cancer Med ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36082949

RESUMO

BACKGROUND: To evaluate the diagnostic performance of radiologists on breast cancer with or without artificial intelligence (AI) support. METHODS: A retrospective study was performed. In total, 643 mammograms (average age: 54 years; female: 100%; cancer: 62.05%) were randomly allocated into two groups. Seventy-five percent of mammograms in each group were randomly selected for assessment by two independent radiologists, and the rest were read once. Half of the 71 radiologists could read mammograms with AI support, and the other half could not. Sensitivity, specificity, Youden's index, agreement rate, Kappa value, the area under the receiver operating characteristic curve (AUC) and the reading time of radiologists in each group were analyzed. RESULTS: The average AUC was higher if the AI support system was used (unaided: 0.84; with AI support: 0.91; p < 0.01). The average sensitivity increased from 84.77% to 95.07% with AI support (p < 0.01), but the average specificity decreased (p = 0.07). Youden's index, agreement rate and Kappa value were larger in the group with AI support, and the average reading time was shorter (p < 0.01). CONCLUSIONS: The AI support system might contribute to enhancing the diagnostic performance (e.g., higher sensitivity and AUC) of radiologists. In the future, the AI algorithm should be improved, and prospective studies should be conducted.

3.
Hepatol Int ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083440

RESUMO

BACKGROUND: The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized. METHODS: MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and abstracts of major international hepatology meetings were searched for publications from Jan 1, 1995 to Nov 30, 2021. Randomized control trials and observational studies reporting the efficacy of NAs in ACLD patients were eligible. Pooled risk ratios (RRs) for outcomes of interest were calculated with a random-effect or fixed-effect model, as appropriate. RESULTS: Thirty-nine studies including 14,212 ACLD patients were included. NA treatment was associated with reduced risks of overall hepatic decompensation events (RR, 0.51; 95% confidence interval [CI]: 0.37-0.71), such as variceal bleeding (RR, 0.44; 95% CI: 0.26-0.74) and ascites (RR, 0.10; 95% CI: 0.01-1.59), on a trend-wise level. Moreover, the risks of hepatocellular carcinoma (HCC) (RR, 0.48; 95% CI: 0.30-0.75) and liver transplantation/death (RR, 0.36; 95% CI: 0.25-0.53) were also reduced by NA treatment and the first-line NAs were superior to non-first-line NAs in improving these outcomes (RR, 0.85; 95% CI: 0.75-0.97 and RR, 0.85; 95% CI: 0.73-0.99, respectively). CONCLUSION: NA therapy lowers the risk of portal hypertension-related complications, including variceal bleeding, HCC, and liver transplantation/death.

4.
Nat Commun ; 13(1): 5211, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064711

RESUMO

Critical-sized bone defects often lead to non-union and full-thickness defects of the calvarium specifically still present reconstructive challenges. In this study, we show that neurotrophic supplements induce robust in vitro expansion of mesenchymal stromal cells, and in situ transplantation of neurotrophic supplements-incorporated 3D-printed hydrogel grafts promote full-thickness regeneration of critical-sized bone defects. Single-cell RNA sequencing analysis reveals that a unique atlas of in situ stem/progenitor cells is generated during the calvarial bone healing in vivo. Notably, we find a local expansion of resident Msx1+ skeletal stem cells after transplantation of the in situ cell culture system. Moreover, the enhanced calvarial bone regeneration is accompanied by an increased endochondral ossification that closely correlates to the Msx1+ skeletal stem cells. Our findings illustrate the time-saving and regenerative efficacy of in situ cell culture systems targeting major cell subpopulations in vivo for rapid bone tissue regeneration.


Assuntos
Células-Tronco Mesenquimais , Engenharia Tecidual , Regeneração Óssea , Osteogênese , Crânio , Células-Tronco , Tecidos Suporte
5.
Reprod Biol Endocrinol ; 20(1): 136, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068569

RESUMO

Pre-eclampsia (PE), associated with placental malperfusion, is the primary reason for maternal and perinatal mortality and morbidity that can cause vascular endothelial injury and multi-organ injury. Despite considerable research efforts, no pharmaceutical has been shown to stop disease progression. If women precisely diagnosed with PE can achieve treatment at early gestation, the maternal and fetal outcomes can be maximally optimized by expectant management. Current diagnostic approaches applying maternal characteristics or biophysical markers, including blood test, urine analysis and biophysical profile, possess limitations in the precise diagnosis of PE. Biochemical factor research associated with PE development has generated ambitious diagnostic targets based on PE pathogenesis and dissecting molecular phenotypes. This review focuses on current developments in biochemical prediction of PE and the corresponding interventions to ameliorate disease progression, aiming to provide references for clinical diagnoses and treatments.


Assuntos
Pré-Eclâmpsia , Biomarcadores , Progressão da Doença , Feminino , Feto , Humanos , Placenta/patologia , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/terapia , Gravidez
6.
Front Cell Neurosci ; 16: 971100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072565

RESUMO

This study aimed to explore the mechanism underlying cognitive dysfunction mediated by the lateral hypothalamic area (LHA) in a hypothalamic-hippocampal circuit in rats with lesion-induced hypothalamic obesity (HO). The HO model was established by electrically lesioning the hypothalamic nuclei. The open field (OP) test, Morris water maze (MWM), novel object recognition (NOR), and novel object location memory (NLM) tests were used to evaluate changes in cognition due to alterations in the hypothalamic-hippocampal circuit. Western blotting, immunohistochemical staining, and cholera toxin subunit B conjugated with Alexa Fluor 488 (CTB488) reverse tracer technology were used to determine synaptophysin (SYN), postsynaptic density protein 95 (PSD95), ionized calcium binding adaptor molecule 1 (Iba1), neuronal nuclear protein (NeuN), and Caspase3 expression levels and the hypothalamic-hippocampal circuit. In HO rats, severe obesity was associated with cognitive dysfunction after the lesion of the hypothalamus. Furthermore, neuronal apoptosis and activated microglia in the downstream of the lesion area (the LHA) induced microglial infiltration into the intact hippocampus via the LHA-hippocampal circuit, and the synapses engulfment in the hippocampus may be the underlying mechanism by which the remodeled microglial mediates memory impairments in HO rats. The HO rats exhibited microglial infiltration and synapse loss into the hippocampus from the lesioned LHA via the hypothalamic-hippocampal circuit. The underlying mechanisms of memory function may be related to the circuit.

7.
Hortic Res ; 9: uhac141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072841

RESUMO

Pear (Pyrus spp.) is one of the most common fruit crops grown in temperate regions worldwide. Genetic enhancement of fruit quality is a fundamental goal of pear breeding programs. The genetic control of pear fruit quality traits is highly quantitative, and development of high-density genetic maps can facilitate fine-mapping of quantitative trait loci (QTLs) and gene identification. Bin-mapping is a powerful method of constructing high-resolution genetic maps from large-scale genotyping datasets. We performed whole-genome sequencing of pear cultivars 'Niitaka' and 'Hongxiangsu' and their 176 F 1 progeny to identify genome-wide single-nucleotide polymorphism (SNP) markers for constructing a high-density bin-map of pear. This analysis yielded a total of 1.93 million SNPs and a genetic bin-map of 3190 markers spanning 1358.5 cM, with an average adjacent interval of 0.43 cM. This bin-map, along with other high-density genetic maps in pear, improved the reference genome assembly from 75.5 to 83.7% by re-anchoring the scaffolds. A quantitative genetic analysis identified 148 QTLs for 18 fruit-related traits; among them, QTLs for stone cell content, several key monosaccharides, and fruit pulp acids were identified for the first time in pear. A gene expression analysis of six pear cultivars identified 399 candidates in the identified QTL regions, which showed expression specific to fruit developmental stages in pear. Finally, we confirmed the function of PbrtMT1, a tonoplast monosaccharide transporter-related gene responsible for the enhancement of fructose accumulation in pear fruit on linkage group 16, in a transient transformation experiment. This study provides genomic and genetic resources as well as potential candidate genes for fruit quality improvement in pear.

8.
Comput Math Methods Med ; 2022: 4261329, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060650

RESUMO

Skin cutaneous melanoma (SKCM) is a common malignant skin cancer. Early diagnosis could effectively reduce SKCM patient's mortality to a large extent. We managed to construct a model to examine the prognosis of SKCM patients. The methylation-related data and clinical data of The Cancer Gene Atlas- (TCGA-) SKCM were downloaded from TCGA database. After preprocessing the methylation data, 21,861 prognosis-related methylated sites potentially associated with prognosis were obtained using the univariate Cox regression analysis and multivariate Cox regression analysis. Afterward, unsupervised clustering was used to divide the patients into 4 clusters, and weighted correlation network analysis (WGCNA) was applied to construct coexpression modules. By overlapping the CpG sites between the clusters and turquoise model, a prognostic model was established by LASSO Cox regression and multivariate Cox regression. It was found that 9 methylated sites included cg01447831, cg14845689, cg20895058, cg06506470, cg09558315, cg06373660, cg17737409, cg21577036, and cg22337438. After constructing the prognostic model, the performance of the model was validated by survival analysis and receiver operating characteristic (ROC) curve, and the independence of the model was verified by univariate and multivariate regression. It was represented that the prognostic model was reliable, and riskscore could be used as an independent prognostic factor in SKCM patients. At last, we combined clinical data and patient's riskscore to establish and testify the nomogram that could determine patient's prognosis. The results found that the reliability of the nomogram was relatively good. All in all, we constructed a prognostic model that could determine the prognosis of SKCM patients and screened 9 key methylated sites through analyzing data in TCGA-SKCM dataset. Finally, a prognostic nomogram was established combined with clinical diagnosed information and riskscore. The results are significant for improving the prognosis of SKCM patients in the future.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Metilação , Prognóstico , Reprodutibilidade dos Testes , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
9.
J Immunol Res ; 2022: 2280973, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061305

RESUMO

Rheumatoid arthritis (RA) is a chronic, persistent autoimmune disease that causes severe joint tissue damage and irreversible disability. Cumulative evidence suggests that patients suffering from RA for long durations are at risk of functional damage to cardiovascular, kidney, lung, and other tissues. This seriously affects the quality of work and life of patients. To date, no clear etiology of RA has been found. Recent studies have revealed that the massive proliferation of synoviocytes and immune cells requires a large amount of energy supply. Rapid energy supply depends on the anaerobic glucose metabolic pathway in both RA animal models and clinical patients. Anaerobic glycolysis can increase intracellular lactic acid (LA) content. LA induces the overexpression of monocarboxylate transporters (MCTs) in cell membranes. MCTs rapidly transport LA from the intracellular to the intercellular or articular cavity. Hence, a relatively high accumulation of LA could be formed in the intercellular and articular cavities of inflammatory joints. Moreover, LA contributes to the migration and activation of immune cells. Immune cells proliferate and secrete interleukins (IL) including IL-1, IL-2, IL-13, IL-17, and other inflammatory factors. These inflammatory factors enhance the immune inflammatory response of the body and aggravate the condition of RA patients. In this paper, the effects of LA on RA pathogenesis will be summarized from the perspective of the production, transport, and metabolism of synoviocytes and immune cells. Additionally, the drugs involved in the production, transport, and metabolism of LA are highlighted.


Assuntos
Artrite Reumatoide , Sinoviócitos , Animais , Interleucinas/metabolismo , Articulações/patologia , Ácido Láctico , Sinoviócitos/patologia
10.
World J Gastroenterol ; 28(26): 3201-3217, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-36051342

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.


Assuntos
Estresse do Retículo Endoplasmático , Hepatopatias , Animais , Apoptose , Hepatócitos/patologia , Humanos , Hepatopatias/patologia , Camundongos , Necroptose , alfa-Fetoproteínas/metabolismo
11.
World J Gastrointest Oncol ; 14(7): 1239-1251, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36051093

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. A total of 45 kinesin superfamily proteins (KIFs) have been identified in humans, among which several family members have demonstrated varied functions in tumor pathobiology via different mechanisms, including regulation of cell cycle progression and metastasis. KIFC3 has microtubule motor activity and is involved in cancer cell invasion and migration, as well as survival. However, the role of KIFC3 in ESCC is still unknown. AIM: To evaluate the role of KIFC3 in ESCC and the underlying mechanisms. METHODS: Expression of KIFC3 was evaluated in ESCC tissues and adjacent normal esophageal tissues. The prognostic value of KIFC3 was analyzed using Kaplan-Meier Plotter. Colony formation, EdU assays, cell cycle analysis, Transwell assay, immunofluorescence, and western blotting were performed in ESCC cell lines after transfection with pLVX-Puro-KIFC3-shRNA- and pLVX-Puro-KIFC3-expressing lentiviruses. A xenograft tumor model in nude mice was used to evaluate the role of KIFC3 in tumorigenesis. Inhibitor of ß-catenin, XAV-939, was used to clarify the mechanism of KIFC3 in ESCC. To analyze the differences between groups, t test and nonparametric tests were used. P < 0.05 was considered statistically significant. RESULTS: Immunohistochemical staining indicated that KIFC3 was upregulated in ESCC tissues compared with adjacent normal tissues. Kaplan-Meier Plotter revealed that overexpressed KIFC3 was associated with poor prognosis in ESCC patients. Colony formation and EdU assay showed that KIFC3 overexpression promoted cell proliferation, while KIFC3 knockdown inhibited cell proliferation in ESCC cell lines. In addition, cell cycle analysis showed that KIFC3 overexpression promoted cell cycle progression. KIFC3 knockdown suppressed ESCC tumorigenesis in vivo. Transwell assay and western blotting revealed that KIFC3 overexpression promoted cell migration and invasion, as well as epithelial-mesenchymal transition (EMT), while KIFC3 knockdown showed the opposite results. Mechanistically, KIFC3 overexpression promoted ß-catenin signaling in KYSE450 cells; however, the role of KIFC3 was abolished by XAV-939, the inhibitor of ß-catenin signaling. CONCLUSION: KIFC3 was overexpressed in ESCC and was associated with poor prognosis. Furthermore, KIFC3 promoted proliferation, migration and invasion of ESCC via ß-catenin signaling and EMT.

12.
Front Neurosci ; 16: 917721, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051643

RESUMO

Background: The study aimed to investigate how acupuncture modulates brain activities across multiple frequency bands to achieve therapeutic effects in PDM. Methods: A total of 47 patients with PDM were randomly assigned to the verum acupuncture group and sham acupuncture group with three menstrual cycles of the acupuncture course. The fMRI scans, visual analog scale (VAS) scores, and other clinical evaluations were assessed at baseline and after three menstrual-cycles treatments. The global functional connectivity density (gFCD) analyses were performed between the pre-and post-acupuncture course of two groups at full-low frequency band, Slow-3 band, Slow-4 band, and Slow-5 band. Results: After the acupuncture treatments, the patients with PDM in the verum acupuncture group showed significantly decreased VAS scores (p < 0.05). The frequency-dependent gFCD alternations were found in the verum acupuncture group, altered regions including DLPFC, somatosensory cortex, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), precuneus, hippocampus, and insula. The sham acupuncture modulated regions including angular gyrus, inferior frontal gyrus, and hippocampus. The gFCD alternation in DLPFC at the Slow-5 band was negatively in the patients with PDM following verum acupuncture, and S2 at the Slow-4 band was positively correlated with VAS scores. Conclusion: These findings supported that verum acupuncture could effectively modulate frequency-dependent gFCD in PDM by influencing abnormal DLPFC at Slow-5 band and hippocampus at the Slow-3 band. The outcome of this study may shed light on enhancing the potency of acupuncture in clinical practice.

13.
Front Neurosci ; 16: 925398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051648

RESUMO

Background: Currently, only a few studies have examined the link between dental health, cognitive impairment, and physical activity. The current study examined the relationship between denture use and physical activity in elderly patients with different cognitive abilities. Methods: The study data was sourced from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database, which included information on denture use and amount of daily physical activity undertaken by older persons. Physical activity was categorized into three levels using the International Physical Activity General Questionnaire and the International Physical Activity Scale (IPAQ) rubric. The relationship between denture use and physical activity in middle-aged and older persons with varying degrees of cognitive functioning was studied using logistic regression models. Results: A total of 5,892 older people with varying cognitive abilities were included. Denture use was linked to physical activity in the cognitively healthy 60 + age group (p = 0.004). Denture use was positively related with moderate physical activity in the population (odds ratio, OR: 1.336, 95% confidence interval: 1.173-1.520, p < 0.001), according to a multivariate logistic regression analysis, a finding that was supported by the calibration curve. Furthermore, the moderate physical activity group was more likely to wear dentures than the mild physical activity group among age-adjusted cognitively unimpaired middle-aged and older persons (OR: 1.213, 95% CI: 1.053-1.397, p < 0.01). In a fully adjusted logistic regression model, moderate physical activity population had increased ORs of 1.163 (95% CI: 1.008-1.341, p < 0.05) of dentures and vigorous physical activity population had not increased ORs of 1.016 (95% CI: 0.853-1.210, p > 0.05), compared with mild physical activity population. Conclusion: This findings revealed that wearing dentures affects physical activity differently in older persons with different cognitive conditions. In cognitively unimpaired older adults, wearing dentures was associated with an active and appropriate physical activity status.

14.
Front Pharmacol ; 13: 855964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052143

RESUMO

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.

15.
Front Mol Neurosci ; 15: 971361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046710

RESUMO

Lysosomal-associated transmembrane protein 5 (LAPTM5) has been demonstrated to be involved in regulating immunity, inflammation, cell death, and autophagy in the pathophysiological processes of many diseases. However, the function of LAPTM5 in cerebral ischemia-reperfusion (I/R) injury has not yet been reported. In this study, we found that LAPTM5 expression was dramatically decreased during cerebral I/R injury both in vivo and in vitro. LAPTM5 knockout (KO) mice were compared with a control, and they showed a larger infarct size and more serious neurological dysfunction after transient middle cerebral artery occlusion (tMCAO) treatment. In addition, inflammatory response and apoptosis were exacerbated in these processes. Furthermore, gain- and loss-of-function investigations in an in vitro model revealed that neuronal inflammation and apoptosis were aggravated by LAPTM5 knockdown but mitigated by its overexpression. Mechanistically, combined RNA sequencing and experimental verification showed that the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway was mainly involved in the detrimental effects of LAPTM5 deficiency following I/R injury. Specifically, LAPTM5 directly interacts with ASK1, leading to decreased ASK1 N-terminal dimerization and the subsequent reduced activation of downstream JNK/p38 signaling. In conclusion, LAPTM5 was demonstrated to be a novel modulator in the pathophysiology of brain I/R injury, and targeting LAPTM5 may be feasible as a stroke treatment.

16.
Breast Cancer ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36063308

RESUMO

BACKGROUND: Early breast cancer (EBC) is a potentially curable disease. Some patients with EBC require chemotherapy, exposing patients to undesirable side effects. Loss of muscle mass, or sarcopenia, has been associated with worse outcomes in patients with EBC and worse treatment-related toxicity in patients with advanced breast cancer. CT scans can identify sarcopenia; however, most patients with EBC do not require routine CT scans. Bioelectrical impedance spectrometry (BIS) is another method to detect sarcopenia and can be performed quickly in the office without radiation exposure. We sought to investigate whether sarcopenia measurements by CT scan versus BIS correlated with each other and whether sarcopenia identified by each method is associated with chemotherapy toxicity and adherence in patients with EBC. METHODS: This is a retrospective study; eligible patients received chemotherapy treatment for EBC and had undergone BIS. A subset of patients had also had a CT abdomen with a Lumbar L3 level. Measures of sarcopenia were obtained from the BIS and CT data. In addition, patient characteristics, treatment, and toxicity-related outcomes were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status with toxicity endpoints, adjusted for other patient characteristics. RESULTS: There was a moderate correlation between sarcopenia detected by CT scan and BIS (r = 0.64 p < 0.0001). Patients with sarcopenia detected by BIS had more chemotherapy toxicity (OR = 2.56; CI 1.72-3.84), dose reductions or dose delays (OR = 1.58; CI 1.06-2.38), and hospitalizations (OR = 2.38; CI 1.33-4.16) due to side effects than patients without sarcopenia. CONCLUSION: The presence of sarcopenia in patients with EBC is associated with worse chemotherapy tolerance. BIS represents a high-value alternative to CT scans for sarcopenia assessment.

17.
Nanoscale ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047737

RESUMO

The fabrication of van der Waals (vdWs) heterostructures mainly extends to two-dimensional (2D) materials. Nevertheless, the current processes for obtaining high-quality 2D films are mainly exfoliated from their bulk counterparts or by high-temperature chemical vapor deposition (CVD), which limits industrial production and is often accompanied by defects. Herein, we first fabricated the type-II p-PdSe2/n-InSe vdWs heterostructure using the ultra-high vacuum laser molecular beam epitaxy (LMBE) technique combined with the vertical 2D stacking strategy, which is reproducible and suitable for high-volume manufacturing. This work found that the introduction of 365 nm UV light illumination can significantly improve the electrical transport properties and NO2 sensing performance of the PdSe2/InSe heterojunction-based device at room temperature (RT). The detailed studies confirm that the sensor based on the PdSe2/InSe heterojunction delivers the comparable sensitivity (Ra/Rg = ∼2.6 at 10 ppm), a low limit of detection of 52 ppb, and excellent selectivity for NO2 gas under UV light illumination, indicating great potential for NO2 detection. Notably, the sensor possesses fast response and full recovery properties (275/1078 s) compared to the results in the dark. Furthermore, the mechanism of enhanced gas sensitivity was proposed based on the energy band alignment of the PdSe2/InSe heterojunction with the assistance of investigating the surface potential variations. This work may pave the way for the development of high-performance, room-temperature gas sensors based on 2D vdWs heterostructures through the LMBE technique.

18.
ACS Nano ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047811

RESUMO

The use of functional DNA nanostructures as carriers to ship proteins through solid-state nanopores has recently seen substantial growth in single-protein-molecule detection (SPMD), driven by the potential of this methodology and implementations that it may enable. Ultrasmall nanopores have exhibited obvious advantages in spatiotemporal biological detection due to the appropriate nanoconfined spaces and unique properties. Herein, a 6.8 nm DNA tetrahedron (TDN) with a target-specific DNA aptamer (TDN-apt) was engineered to carry the representative target of acetylcholinesterase (AChE) through an ultrasmall nanopipet with a 30 nm orifice, underpinning the advanced SPMD of AChE with good performance in terms of high selectivity, low detection limit (0.1 fM), and especially superior signal-to-noise ratio (SNR). The kinetic interaction between TDN-apt and AChE was studied and the practical applicability of the as-developed SPMD toward real samples was validated using serum samples from patients with Alzheimer's disease. This work not only presented a feasible SPMD solution toward low-abundance proteins in complex samples and but also was envisioned to inspire more interest in the design and implementation of synergized DNA nanostructure-ultrasmall nanopore systems for future SPMD development.

19.
Zhongguo Zhen Jiu ; 42(9): 999-1003, 2022 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-36075595

RESUMO

OBJECTIVE: To observe the clinical effect of chicken-claw needling at Xiaguan (ST 7) combined with intradermal needling on negative emotion in primary trigeminal neuralgia (PTN) of phlegm obstruction and blood stasis. METHODS: Sixty cases of patients with PTN of phlegm obstruction and blood stasis were randomly divided into an observation group and a control group, 30 cases in each group. The observation group was treated with chicken-claw needling at Xiaguan (ST 7) combined with intradermal needling (acupoints Sibai [ST 2], Yuyao [EX-HN 4], Hegu [LI 4], Taichong [LR 3] and auricular points Xin [CO15], Shenmen [TF4], Pizhixia [AT4], etc.), once a day, 6 d as a course of treatment, rest 1 d between courses, a total of 2 courses of treatment; and the control group was given oral carbamazepine tablets for 13 days. Before and after treatment, the pain visual analogue scale (VAS), TCM syndromes, self-rating anxiety scale (SAS) scores and the contents of serum neurotransmitter (ß-endorphin [ß-EP], substance P [SP] and 5-hydroxytryptamine [5-HT]) were compared, and the clinical efficacy was evaluated. RESULTS: After treatment, the VAS, SAS, TCM syndrome scores and the contents of serum SP in the two groups were lower than those before treatment (P<0.05), and the above indexes in the observation group was lower than those in the control group (P<0.05). The contents of serum ß-EP and 5-HT in the two groups were higher than those before treatment (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was higher than 83.3% (25/30) in the control group (P<0.05). CONCLUSION: Chicken-claw needling at Xiaguan (ST 7) combined with intradermal needling can relieve pain symptoms and negative emotions in patients with primary trigeminal neuralgia of phlegm obstruction and blood stasis, which may be related to the regulation of serum neurotransmitter levels.


Assuntos
Terapia por Acupuntura , Neuralgia do Trigêmeo , Pontos de Acupuntura , Emoções , Humanos , Dor , Serotonina , Síndrome , Resultado do Tratamento , Neuralgia do Trigêmeo/terapia
20.
Biomed Pharmacother ; 153: 113558, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076621

RESUMO

OBJECTIVE: To study whether organic anion transporter 3 (OAT3) is involved in the development of methotrexate (MTX) resistance in the treatment of rheumatoid arthritis. METHODS: The experimental components of the animals were the normal group, collagen-induced arthritis (CIA) model group, and MTX treatment group. MTX-treated rats were divided into the MTX effective group (MTX-E) and the MTX ineffective group (MTX-N). MTX-N receives additional treatment with OAT3 lentivirus injected into the joint cavity. Transient transfection was used to alter the expression of OAT3 in rat fibroblast-like synovial (rat-FLS). RESULTS: The rate of effectiveness of MTX in treating CIA rats was 48.98%. Compared with CIA rats, MTX-E can greatly improve ankle joint synovial hyperplasia and joint damage, but MTX-N has no significant changes. The expression of OAT3 in the synovium of MTX-E was significantly higher than that of MTX-N. The MTX content in the MTX-E synovium was also higher than that in the MTX-N synovium. After injection of OAT3 overexpression lentivirus into the joint cavity of MTX-N, the effective rate of MTX reached 80%. The ankle synovial hyperplasia and joint damage were significantly improved in the overexpression group, and the MTX content was also significantly increased in the synovium. After rat FLS overexpressed OAT3, the inhibitory effect of MTX on rat FLS proliferation activity was significantly enhanced, and the absorption of MTX was also significantly increased, while silencing the expression of rat FLS OAT3 reversed the outcomes. CONCLUSION: OAT3 mediates the formation of MTX resistance and is a potential target for improving MTX resistance.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Hiperplasia/patologia , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Ratos , Membrana Sinovial/patologia
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