Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.183
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38629676

RESUMO

Background: Due to the limited role of chronic pain medication in military personnel and the distress caused to the military population, mindfulness-based therapy has been considered for the follow-up treatment of military personnel with chronic pain. The purpose of this review is to explore the effect and the implementation of mindfulness-based therapy for the military population with chronic pain. Methods: The keywords for the search included "mindfulness" AND ("pain" OR "chronic pain") AND ("military" OR "veteran"). The PubMed, Embase, and Cochrane Library databases were searched. The Cochrane Collaboration tool was used to independently assess the risk of bias of the included randomized controlled trials, and the Newcastle-Ottawa Scale was used to independently assess the risk of bias of the included case-control studies. Results: A total of 175 papers were identified; 65 duplicates were excluded, and 59 papers that did not meet the inclusion criteria were excluded after reading the titles and abstracts. The remaining 51 papers were read in full, 42 of which did not meet the inclusion criteria. Nine papers met the inclusion criteria and were included in the study. The nine studies included 507 veterans and 56 active-duty female military personnel. All pain interventions were mindfulness-based therapy, and all of them were integrated into or adapted from standard mindfulness courses. The results all showed that after mindfulness-based therapy, the relevant indicators improved. Conclusions: Mindfulness-based therapy is an effective treatment method for the military population with chronic pain. The review indicates that future research should focus on the best setting for mindfulness-based therapy, including the course content and time.

2.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1327-1334, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621980

RESUMO

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Flavonoides , Neoplasias Hepáticas , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/genética , Espécies Reativas de Oxigênio , Células Hep G2 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Transdução de Sinais
3.
J Gastroenterol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613690

RESUMO

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

4.
Front Oncol ; 14: 1390438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595816

RESUMO

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

5.
J Mol Biol ; : 168571, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604528

RESUMO

Extracellular vesicles and particles (EVPs) play a crucial role in mediating cell-to-cell communication by transporting various molecular cargos, with small non-coding RNAs (ncRNAs) holding particular significance. A thorough investigation into the abundance and sorting mechanisms of ncRNA within EVPs is imperative for advancing their clinical applications. We have developed EVPsort, which not only provides an extensive overview of ncRNA profiling in 3,162 samples across various biofluids, cell lines, and disease contexts but also seamlessly integrates 19 external databases and tools. This integration encompasses information on associations between ncRNAs and RNA-binding proteins (RBPs), motifs, targets, pathways, diseases, and drugs. With its rich resources and powerful analysis tools, EVPsort extends its profiling capabilities to investigate ncRNA sorting, identify relevant RBPs and motifs, and assess functional implications. EVPsort stands as a pioneering database dedicated to comprehensively addressing both the abundance and sorting of ncRNA within EVPs. It is freely accessible at https://bioinfo.vanderbilt.edu/evpsort/.

6.
Talanta ; 274: 126010, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38569372

RESUMO

Intracellular glucose detection is crucial due to its pivotal role in metabolism and various physiological processes. Precise glucose monitoring holds significance in diabetes management, metabolic studies, and biotechnological applications. In this study, we developed an innovative and expedient cell-permeable nanoreactor for intracellular glucose based on surface-enhanced Raman scattering (SERS). The nanoreactor was designed with gold nanoparticles (AuNPs), which were engineered with glucose oxide (GOx) and a H2O2-responsive Raman reporter 2-mercaptohydroquinone (2-MHQ). The interaction between 2-MHQ and H2O2 generated by glucose and GOx could simultaneously induce the appearance in the peak at 985 cm-1. Our results showed excellent performance in detecting glucose within the concentration range from 0.1 µM to 10 mM, with a low detection limitation of 14.72 nM. In addition, the glucose distribution in single HeLa cells was evaluated by real time SERS mapping. By combining noble metal particles and natural oxidases, the nanoreactor possesses both Raman activity and enzymatic functionality, thus enables sensitive glucose detection and facilitates imaging at a single cell level, which offers an insightful monitoring of cellular processes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38565964

RESUMO

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

8.
iScience ; 27(4): 109328, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500837

RESUMO

We theoretically propose a multiple-mode-coupling hybrid quantum system comprising two-mode-coupling nanomechanical carbon nanotube (CNT) resonators realized by a phase-dependent phonon-exchange interaction interacting with the same nitrogen-vacancy (NV) center in diamond. We investigate the coherent optical responses of the NV center under the condition of resonance and detuning. In particular, two-color electromagnetically induced transparency (EIT) can be achieved by controlling the system parameters and coupling regimes. Combining the spin-phonon interactions and phonon-phonon coupling with the modulation phase, the switching of one and two EIT windows has been demonstrated, which generates a light delay or advance. The slow-to-fast and fast-to-slow light transitions have been studied in different coupling regimes, and the switch between slow and fast light can be controlled periodically by tuning the modulation phase. The study can be applied to phonon-mediated optical information storage or information processing with spin qubits based on multiple-mode hybrid quantum systems.

9.
BMC Musculoskelet Disord ; 25(1): 188, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431562

RESUMO

BACKGROUND: Implant choice for the fixation of femoral neck fracture is one of the most important management controversies. This study aims to evaluate and compare the short-term outcomes associated with the use of the Femoral Neck System (FNS), Multiple Cancellous Screws (MCS), and Dynamic Hip Screws (DHS) in treating femoral neck fractures in a young patient population. METHODS: From June 2018 to June 2021, a total of 120 surgeries for a primary femoral neck fracture were retrospectively analyzed. This review encompassed demographic details of the patients and the mechanisms behind the injuries. Key surgical parameters such as operation duration, intraoperative blood loss, fluoroscopy duration, and hospital stay were meticulously documented. The employed surgical technique was described. All patients were followed up at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Avascular necrosis of the femoral head (AVN), nonunion, malreduction, implant failure or other complications were noted. The functional status at the last follow-up was assessed using the Harris functional scoring criteria. RESULTS: There were 90 males and 30 females, with a mean age of 40.4 years. As to patient characteristics, there were no significant differences between the three groups. DHS group showed longer operation time(52.15 ± 4.80 min), more blood loss(59.05 ± 5.87 ml) and longer time of hospitalization(7.6 ± 0.90 d) than FNS group (39.65 ± 2.84 min, 45.33 ± 9.63 ml and 4.87 ± 0.48 d) and MCS group (39.45 ± 3.10 min, 48.15 ± 7.88 ml and 5.04 ± 0.49 d) (p < 0.05). In addition, the time of fluoroscopy in FNS group (15.45 ± 3.67) was less than that in MCS group (26.3 ± 4.76) and DHS group (27.1 ± 5.67) (p < 0.05). The cost of FNS group(44.51 ± 2.99 thousand RMB) was significantly higher than the MCS and DHS groups. The FNS, MCS and DHS groups showed a similar mean length of femoral neck shortening (LFNS) and Harris score. The FNS, MCS and DHS groups showed a similar mean rate of AVN and internal fixation failure. CONCLUSIONS: Following successful fracture reduction, FNS, MCS, and DHS are effective for in the young femoral neck fractures. No difference was found in complications between the three groups. However, the reduced fluoroscopy time associated with FNS contributes to shorter operation durations. The adoption of minimally invasive techniques correlates with decreased blood loss and shorter hospital stays. Nevertheless, these advantages may be offset by the potential economic burden they impose.


Assuntos
Fraturas do Colo Femoral , Colo do Fêmur , Masculino , Feminino , Humanos , Adulto , Estudos Retrospectivos , Parafusos Ósseos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Resultado do Tratamento
10.
Respir Res ; 25(1): 139, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521900

RESUMO

BACKGROUND: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology. METHODS: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. RESULTS: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. CONCLUSION: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.


Assuntos
Asma , Diabetes Mellitus Tipo 2 , Dietilexilftalato , Dietilexilftalato/análogos & derivados , Hipertensão , Ácidos Ftálicos , Adulto , Animais , Humanos , Dietilexilftalato/toxicidade , Dietilexilftalato/urina , Exposição Ambiental , Estudos de Casos e Controles , Asma/induzido quimicamente , Asma/diagnóstico , Asma/epidemiologia , Citocinas
11.
Appl Environ Microbiol ; 90(4): e0000724, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38501861

RESUMO

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.


Assuntos
Equol , Isoflavonas , Animais , Humanos , Camundongos , Ratos , Suínos , Equol/genética , Equol/metabolismo , Racemases e Epimerases , Galinhas/metabolismo , Isoflavonas/metabolismo , Oxirredutases/metabolismo
12.
J Stroke Cerebrovasc Dis ; 33(5): 107670, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438086

RESUMO

BACKGROUND AND PURPOSE: The pathophysiological mechanisms underlying brain injury resulting from intracerebral hemorrhage (ICH) remain incompletely elucidated, and efficacious therapeutic interventions to enhance the prognosis of ICH patients are currently lacking. Previous research indicates that MicroRNA-7 (miR-7) can suppress the expression of Nod-like receptor protein 3 (NLRP3), thereby modulating neuroinflammation in Parkinson's disease pathogenesis. However, the potential regulatory effects miR-7 on NLRP3 inflammasome after ICH are yet to be established. This study aims to ascertain whether miR-7 mitigates secondary brain injury following experimental ICH by inhibiting NLRP3 and to investigate the underlying mechanisms. METHODS: An ICH model was established by stereotaxically injecting 100 µL of autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. Subsequently, these rats were allocated into three groups: sham, ICH + Vehicle, and ICH + miR-7, each comprising 18 animals. Twelve hours post-modeling, rats received intraventricular injections of 10 µL physiological saline, 10 µL phosphate, and 10 µL phosphate-buffered saline solution containing 0.5 nmol of miR-7 mimics, respectively. Neurological function was assessed on day three post-modeling, followed by euthanasia for brain tissue collection. Brain water content was determined using the dry-wet weight method. The expression of inflammatory cytokines in cerebral tissues surrounding the hematoma was analyzed through immunohistochemistry and Western blot assays. These cytokines were re-evaluated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Moreover, bioinformatics tools were employed to predict miR-7's binding to NLRP3. A wild-type luciferase reporter gene vector and a corresponding mutant vector were constructed, followed by transfection of miR-7 mimics into HEK293T cells to assess luciferase activity. RESULTS: Our study demonstrates that the administration of miR-7 mimics markedly reduced neurological function scores and attenuated brain edema in rats following ICH. A significant upregulation of NLRP3 expression in microglia/macrophage adjacent to the hematoma was observed, substantially reduced after the treatment with miR-7 mimics. Furthermore, this intervention ameliorated neurodegenerative changes and effectively decreased the protein and mRNA levels of pro-inflammatory cytokines, namely TNF-α, IL-1ß, IL-6, and Caspase1, in the cerebral tissues proximate to the hematomas. In addition, miR-7 mimics distinctly inhibited the luciferase activity associated with the wild-type reporter gene, an effect not mirrored in its mutant variant. CONCLUSIONS: The miR-7 suppressed NLRP3 expression in microglia/macrophage to reduce the production of inflammatory cytokines, leading to conducting certain neuroprotection post-ICH in rats.


Assuntos
Lesões Encefálicas , MicroRNAs , Humanos , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Proteínas NLR , Células HEK293 , Hemorragia Cerebral/complicações , MicroRNAs/genética , Lesões Encefálicas/etiologia , Citocinas/genética , Citocinas/metabolismo , Hematoma/complicações , Luciferases/uso terapêutico , Fosfatos
14.
Nat Commun ; 15(1): 2107, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453911

RESUMO

Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45+ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1Bhi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1Bhi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1Bhi monocytes. Exhausted CD8+ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1Bhi myeloid cells communicated with CD8+ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1Bhi macrophages as a possible therapeutic target in PD-1-IA.


Assuntos
Artrite Reumatoide , Inibidores de Checkpoint Imunológico , Humanos , Linfócitos T CD8-Positivos/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Líquido Sinovial , Interleucina-1beta/genética , Interleucina-1beta/metabolismo
15.
BMJ Open ; 14(3): e079208, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521533

RESUMO

INTRODUCTION: Progestin can inhibit the pituitary luteinising hormone (LH) surge during ovarian stimulation for in vitro fertilisation (IVF) and studies show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH surge in IVF. More and more centres are using PPOS because this regimen appears simpler and cheaper. This study aims to compare the euploidy rate of blastocysts following the PPOS protocol and the gonadotropin-releasing hormone antagonist protocol in women undergoing preimplantation genetic testing for aneuploidy (PGT-A). METHODS/ANALYSIS: This is a randomised trial. A total of 400 women undergoing PGT-A will be enrolled and randomised according to a computer-generated randomisation list to either (1) the antagonist group: an antagonist given once daily from day 6 of ovarian stimulation till the day of the ovulation trigger; or (2) the PPOS group: dydrogesterone from the first day of ovarian stimulation till the day of ovulation trigger. The primary outcome is the euploidy rate of blastocysts. ETHICS/DISSEMINATION: An ethical approval was granted from the ethics committee of assisted reproductive medicine in Shanghai JiAi Genetics and IVF institute (JIAIE2020-03). A written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this randomised trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04414748.


Assuntos
Transferência Embrionária , Progestinas , Feminino , Humanos , Gravidez , Aneuploidia , Blastocisto , China , Transferência Embrionária/métodos , Fertilização In Vitro/métodos , Testes Genéticos , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios , Hormônio Luteinizante , Indução da Ovulação/métodos , Taxa de Gravidez , Progestinas/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Artigo em Inglês | MEDLINE | ID: mdl-38547026

RESUMO

OBJECTIVE: To evaluate the muscle thickness and walking test in people with haemophilia A (PWH) and their correlation to joint health and functional impairments. DESIGN: Cross-sectional study. RESULTS: 29 severe/moderate PWH were enrolled. Muscle thickness of quadriceps and medial gastrocnemius were measured using ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), 6-Minute Walking test (6MWT), Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), and Haemophilia Activities List (HAL). Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was inversely associated with the HJHS ankle. 6MWT was found to significantly correlate with HJHS total, HEAD-US total, Haem-A-QoL, and HAL. CONCLUSION: Muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PWH. Ultrasound measurement of muscle thickness and walking test appear to be useful tools for the assessment of joint health and functional status in PWH.

17.
Invest Ophthalmol Vis Sci ; 65(3): 15, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38466286

RESUMO

Purpose: To explore the role of substrate stiffness and the mechanism beneath corneal endothelial cells' (CECs') stemness maintenance and differentiation. Methods: CECs were divided into central zone (8 mm trephined boundary) and peripheral zone (8 mm trephined edge with attached limbal). Two zones were analyzed by hematoxylin-eosin staining and scanning electron microscopy for anatomic structure. The elastic modulus of Descemet's membrane (DM) was analyzed by atomic force microscopy. Compressed type I collagen gels with different stiffness were constructed as an in vitro model system to test the role of stiffness on phenotype using cultured rabbit CECs. Cell morphology, expression and intracellular distribution of Yes-associated protein (YAP), differentiation (ZO-1, Na+/K+-ATPase), stemness (FOXD3, CD34, Sox2, Oct3/4), and endothelial-mesenchymal transition (EnMT) markers were analyzed by immunofluorescence, quantitative RT-PCR, and Western blot. Results: The results showed that the peripheral area of rabbit and human DM is softer than the central area ex vivo. Using the biomimetic extracellular matrix collagen gels in vitro model, we then demonstrated that soft substrate weakens the differentiation and EnMT in the culture of CECs. It was further proved by the inhibitor experiment that soft substrate enhances stemness maintenance via inhibition of paxillin-YAP signaling, which was activated on a stiff substrate. Conclusions: Our findings confirm that substrate stiffness modulates the stemness maintenance and differentiation of CECs and suggest a potential strategy for CEC-based corneal tissue engineering.


Assuntos
Células Endoteliais , Endotélio Corneano , Humanos , Animais , Coelhos , Paxilina , Córnea , ATPase Trocadora de Sódio-Potássio , Géis
18.
Hepatology ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537134

RESUMO

BACKGROUND AIMS: Hepatitis B virus (HBV) infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in pyroptotic liver, and HMGB1 derived from pyroptotic liver constituted an important factor triggering generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of MPO-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring liver function of HBV-related ACLF patients.

20.
Chin J Traumatol ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38548574

RESUMO

PURPOSE: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. METHODS: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher's exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. RESULTS: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p < 0.001), less blood loss (p < 0.001), better hematoma evacuation (p = 0.003), and a shorter stay in the intensive care unit (p = 0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group (p = 0.014). CONCLUSIONS: Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...