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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 217-224, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38686718

RESUMO

Objective To gain an in-depth understanding of the motivations,patterns,and related factors in family decision-making regarding the referral of terminal patients in tertiary hospitals. Methods Using purposive sampling,terminal patients and their family members from three tertiary hospitals in Beijing were selected as subjects.Semi-structured interviews were conducted,and the interview data were subjected to thematic analysis. Results Following the saturation principle,a total of 11 patients and 15 family members were included.The interview data were organized and analyzed,yielding six major themes:decision premises,decision patterns,family support,support from the referring hospital's medical team,referral channel conditions,and involvement of volunteer teams and social support.Based on these findings,a flowchart illustrating the family decision-making process for the referral of terminal patients was constructed. Conclusions The study provides a comprehensive analysis of various factors influencing family decision-making in the referral of terminal patients in tertiary hospitals.The results underscore the significance of internal and external factors,emphasizing the integrated impact of decision patterns,family support,medical team support,referral channel conditions,and the involvement of volunteer teams and social support.The research offers profound insights into improving the referral process for terminal patients and enhancing the quality of family decision-making.It provides valuable recommendations for future improvements in medical services and decision support.


Assuntos
Tomada de Decisões , Família , Encaminhamento e Consulta , Centros de Atenção Terciária , Humanos , Família/psicologia , Feminino , Masculino , Assistência Terminal/psicologia , Pessoa de Meia-Idade , Apoio Social , Adulto
2.
Front Oncol ; 14: 1296328, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577329

RESUMO

Renal metastasis of breast angiosarcoma is rare. This article reports the medical records of a patient diagnosed with breast angiosarcoma who underwent radical mastectomy and was found to have multiple lung metastases 3 years after surgery and renal pelvic metastasis 4 years after surgery. The patient underwent robot-assisted laparoscopic radical nephroureterectomy and sleeve resection of the intramural segment of the ureter, and postoperative pathology and immunohistochemical staining confirmed the diagnosis of renal pelvic metastasis of breast angiosarcoma. The patient received anlotinib for lung metastases following surgery and was followed up for 4 months after surgery. Currently, the patient has symptoms of coughing and hemoptysis but no other discomfort. The diagnosis and treatment of this rare malignant tumor remain challenging.

3.
Viruses ; 16(4)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38675960

RESUMO

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.


Assuntos
Modelos Animais de Doenças , Exossomos , Células-Tronco Mesenquimais , Muromegalovirus , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Muromegalovirus/fisiologia , Camundongos Endogâmicos C57BL , Macrófagos/imunologia , Infecções por Citomegalovirus/terapia , Infecções por Citomegalovirus/virologia , Pulmão/virologia , Pulmão/patologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Infecções por Herpesviridae/terapia , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/imunologia , Pneumonia/terapia , Pneumonia/virologia
4.
Nat Commun ; 15(1): 2799, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555282

RESUMO

Creating microenvironments that mimic an enzyme's active site is a critical aspect of supramolecular confined catalysis. In this study, we employ the commonly used chiral 1,1'-bi-2-naphthol (BINOL) phosphates as subcomponents to construct supramolecular hollow nanotube in an aqueous medium through non-covalent intermolecular recognition and arrangement. The hexagonal nanotubular structure is characterized by various techniques, including X-ray, NMR, ESI-MS, AFM, and TEM, and is confirmed to exist in a homogeneous aqueous solution stably. The nanotube's length in solution depends on the concentration of chiral BINOL-phosphate as a monomer. Additionally, the assembled nanotube can accelerate the rate of the 3-aza-Cope rearrangement reaction by up to 85-fold due to the interior confinement effect. Based on the detailed kinetic and thermodynamic analyses, we propose that the chain-like substrates are constrained and pre-organized into a reactive chair-like conformation, which stabilizes the transition state of the reaction in the confined nanospace of the nanotube. Notably, due to the restricted conformer with less degrees of freedom, the entropic barrier is significantly reduced compared to the enthalpic barrier, resulting in a more pronounced acceleration effect.

5.
Neuropathology ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448392

RESUMO

Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 68-71, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433634

RESUMO

Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.


Assuntos
Cuidados Paliativos , Humanos
7.
Transl Res ; 269: 64-75, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38395391

RESUMO

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.


Assuntos
Estresse do Retículo Endoplasmático , Hipertensão Pulmonar , Janus Quinase 2 , Ratos Sprague-Dawley , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Fator de Transcrição STAT3/metabolismo , Janus Quinase 2/metabolismo , Ratos , Masculino , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fator 6 Ativador da Transcrição/metabolismo , Fator 6 Ativador da Transcrição/genética , Proliferação de Células , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Movimento Celular , Remodelação Vascular
8.
Oncogene ; 43(16): 1190-1202, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38409551

RESUMO

Protein ubiquitination is a common post-translational modification and a critical mechanism for regulating protein stability. This study aimed to explore the role and potential molecular mechanism of ubiquitin-specific peptidase 38 (USP38) in the progression of lung adenocarcinoma (LUAD). USP38 expression was significantly higher in patients with LUAD than in their counterparts, and higher USP38 expression was closely associated with a worse prognosis. USP38 silencing suppresses the proliferation of LUAD cells in vitro and impedes the tumorigenic activity of cells in xenograft mouse models in vivo. Further, we found that USP38 affected the protein stability of transcription factor Krüppel-like factors 5 (KLF5) by inhibiting its degradation. Subsequent mechanistic investigations showed that the N-terminal of USP38 (residues 1-400aa) interacted with residues 1-200aa of KLF5, thereby stabilizing the KLF5 protein by deubiquitination. Moreover, we found that PIAS1-mediated SUMOylation of USP38 was promoted, whereas SENP2-mediated de-SUMOylation of USP38 suppressed the deubiquitination effects of USP38 on KLF5. Additionally, our results demonstrated that KLF5 overexpression restored the suppression of the malignant properties of LUAD cells by USP38 knockdown. SUMOylation of USP38 enhances the deubiquitination and stability of KLF5, thereby augmenting the malignant progression of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Fatores de Transcrição , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Proliferação de Células/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Ubiquitinação
9.
Transl Lung Cancer Res ; 13(1): 95-111, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38404999

RESUMO

Background: At present, there is a lack of studies in invasive mucinous adenocarcinoma (IMA) that combine clinicopathological and imaging features to stratify risk and select optimal treatment regimen. We aimed to develop and validate a nomogram for predicting recurrence-free survival (RFS) and identifying adjuvant chemotherapy (ACT) beneficiaries for completely resected stage I primary IMA. Methods: This retrospective study included 750 patients from three hospitals. Patients from two hospitals were divided into training (n=424) and validating cohort (n=185), and patients from the remaining other one hospital constituted external test cohort (n=141) and preoperative computed tomography (CT) image features of each patient were consecutively evaluated. The nomogram was developed by integrating significant prognostic factors of RFS identified in the multivariate analysis. The risk score (RS) based on nomogram was calculated in the entire cohort and the optimal cut-off point for risk stratification was obtained by X-tile software. The Kaplan-Meier method, log-rank test and interaction were used to evaluate the difference in RFS and overall survival (OS) between different risk and treatment groups. Results: Visceral pleural invasion (VPI, P<0.001), lymph-vascular invasion (LVI, P<0.001), tumor size (P<0.001), smoking history (P<0.001), lobulation (P<0.001) were identified as independent prognostic factors for RFS. The concordance index (C-index) of the nomogram was higher than that of tumor-node-metastasis (TNM) staging system (validation cohort: 0.73±0.09 vs. 0.62±0.08, P<0.001; external test cohort: 0.74±0.10 vs. 0.70±0.09, P=0.035). The patients with higher RS were associated with worse RFS [hazard ratios (HRs) ≥4.76] and OS (HRs ≥2.55) in all included cohorts. Chemotherapy benefits in terms of RFS and OS were observed for patients in higher RS group in both stage IB (interaction P=0.012 for RFS and P=0.037 for OS) and stage I IMA (interaction P<0.001 for both RFS and OS). Conclusions: The nomogram based on CT image and clinicopathologic features showed superior performance in predicting RFS for stage I IMA and might identify ACT candidates for personalized patient treatment.

10.
Sensors (Basel) ; 24(4)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38400357

RESUMO

Parkinson's disease (PD) is the second most prevalent dementia in the world. Wearable technology has been useful in the computer-aided diagnosis and long-term monitoring of PD in recent years. The fundamental issue remains how to assess the severity of PD using wearable devices in an efficient and accurate manner. However, in the real-world free-living environment, there are two difficult issues, poor annotation and class imbalance, both of which could potentially impede the automatic assessment of PD. To address these challenges, we propose a novel framework for assessing the severity of PD patient's in a free-living environment. Specifically, we use clustering methods to learn latent categories from the same activities, while latent Dirichlet allocation (LDA) topic models are utilized to capture latent features from multiple activities. Then, to mitigate the impact of data imbalance, we augment bag-level data while retaining key instance prototypes. To comprehensively demonstrate the efficacy of our proposed framework, we collected a dataset containing wearable-sensor signals from 83 individuals in real-life free-living conditions. The experimental results show that our framework achieves an astounding 73.48% accuracy in the fine-grained (normal, mild, moderate, severe) classification of PD severity based on hand movements. Overall, this study contributes to more accurate PD self-diagnosis in the wild, allowing doctors to provide remote drug intervention guidance.


Assuntos
Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Humanos , Doença de Parkinson/diagnóstico , Movimento , Índice de Gravidade de Doença , Extremidade Superior
11.
Environ Sci Pollut Res Int ; 31(15): 22945-22961, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418783

RESUMO

Under the challenge of global environmental change and rapid development, tremendous risks brought about by natural disasters and human activities have increased environmental pressures for sustainable development. How to improve coastal resilience in the process of urban development has become an important topic in academia. In this study, a variable fuzzy recognition model was used to measure the level of coastal resilience in 17 cities in the Bohai Rim region, and then the kernel density, thiel index, and random forest model were used to explore the spatiotemporal characteristics and influencing factors of coastal resilience. The results show that (1) The overall resilience level of the Bohai Rim region is increasing over time, but at a relatively slow rate. (2) Coastal resilience has significant spatial unevenness, with high-level cities dominated by Tianjin, Qingdao, Yantai, etc. and low-level cities dominated by Cangzhou, Panjin, Yingkou, Binzhou, etc. (3) The influence of economic development, infrastructure, innovation ability, technology investment, and government regulation on coastal resilience decreases in order. Based on the research findings, the study can not only make suggestions for the actual regulation strategy but also provide empirical and theoretical experience for other coastal countries.


Assuntos
Resiliência Psicológica , Humanos , Cidades , Desenvolvimento Sustentável , China
12.
Cell Mol Life Sci ; 81(1): 88, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349408

RESUMO

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.


Assuntos
Fibrilação Atrial , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Camundongos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas de Transporte/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica , Espécies Reativas de Oxigênio , Tiorredoxinas/genética
13.
Patient Prefer Adherence ; 18: 29-37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38204758

RESUMO

Background: Terminally ill patients can benefit from hospice care, which specifically addresses the needs of patients and families affected by terminal illness. However, there is a lack of standardized evaluation criteria to assess the quality of hospice care for terminally ill patients in the ICU, and it is impossible to evaluate the service quality of hospice care. To use the Delphi method to construct a hospice care system for terminally ill patients in ICU that meets clinical needs, and to provide theoretical support for nursing decision-making of terminally ill patients in clinical ICU. Methods: Obtain relevant literatures by entering specific key words into the database, the hospice care nursing system for terminally ill patients in ICU was preliminarily drawn up by literature analysis, and 24 experts in this field were consulted for 3 rounds by Delphi method to discuss the development status of hospice care and finally establish the hospice care nursing system. Results: In the three rounds of letter inquiries, the positive coefficients of experts were all high, the expert authority coefficient (Cr) were 0.864, 0.849, 0.832, and the expert opinion coordination coefficient(W) were 0.186, 0.319, 0.224; The system includes 8 first-level indicators, 27 second-level indicators and 9 third-level indicators. Conclusion: In this study, three rounds of Delphi consultation methods were used to construct an evaluation index system for the nursing quality of hospice care for ICU patients. The evaluation indicators formulated closely focus on the physiological and psychological characteristics of ICU patients, which can provide a better reference for ICU patients with advanced life in the future.

14.
Cell Mol Biol Lett ; 29(1): 5, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172714

RESUMO

BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Linfoma Difuso de Grandes Células B , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Regiões Promotoras Genéticas , Linfoma Difuso de Grandes Células B/genética , Hematopoese , Linhagem Celular Tumoral , Proteínas Nucleares/metabolismo
15.
Int J Rheum Dis ; 27(1): e15031, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38287544

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of adalimumab (ADA) combined with Tripterygium wilfordii Hook F (TwHF) in the treatment of methotrexate (MTX)-inadequate response patients with rheumatoid arthritis (RA). METHODS: In this multicenter, open-label, randomized controlled clinical trial, 64 RA patients with inadequate response to MTX were 1:1 randomly assigned into treatment or control groups. The treatment group was treated with ADA in combination with TwHF, and the control group was treated with ADA in combination with MTX for 24 weeks. The primary endpoint was the percentage of patients having low disease activity (2.6 ≤ DAS28-ESR < 3.2) and remission rates (DAS28-ESR < 2.6) at week 24. RESULTS: In total, 53 of the 64 patients (82.8%) completed this 24-week clinical trial. By intent-to-treat (ITT) analysis, a comparable outcome was observed between the two groups. The percentage of patients achieving low disease activity in the treatment group and control group were 43.8% and 46.9% (95% CI, 21.28 to 27.48, p = .802). Percentage of patients achieving low disease activity rates were respectively 28.1% and 31.3% in the treatment group and control group (95% CI, 19.18 to 25.58, p = .784). In per-protocol (PP) analysis, the results were consistent with the ITT model. The incidence of adverse events was comparable between the two groups. CONCLUSIONS: There were no significant differences in efficacy and safety between ADA combined with TwHF versus ADA combined with MTX in the treatment of RA. TwHF might be an alternative treatment for RA patients who are intolerant to MTX.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Adalimumab/efeitos adversos , Antirreumáticos/efeitos adversos , Tripterygium , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Metotrexato/efeitos adversos , Quimioterapia Combinada , Resultado do Tratamento
16.
Birth Defects Res ; 116(1): e2303, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38277410

RESUMO

INTRODUCTION: In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague-Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21. METHODS: During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance. RESULTS: Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results. CONCLUSION: In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.


Assuntos
Reprodução , Motilidade dos Espermatozoides , Gravidez , Ratos , Masculino , Animais , Feminino , Ratos Sprague-Dawley , Parto , Peso Corporal
17.
Small ; 20(13): e2308165, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37968247

RESUMO

During the layer-by-layer (LBL) processing of polymer solar cells (PSCs), the swelling and molecule interdiffusion are essential for achieving precise, controllable vertical morphology, and thus efficient PSCs. However, the influencing mechanism of material properties on morphology and correlated device performance has not been paid much attention. Herein, a series of fluorinated/non-fluorinated polymer donors (PBDB-T and PBDB-TF) and non-fullerene acceptors (ITIC, IT-2F, and IT-4F) are employed to investigate the performance of LBL devices. The impacts of fluorine substitution on the repulsion and miscibility between the donor and acceptor, as well as the molecular arrangement of the donor/acceptor and the vertical distribution of the LBL devices are systematically explored by the measurement of donor/acceptor Flory-Huggins interaction parameters, spectroscopic ellipsometry, and neutron reflectivity, respectively. With efficient charge transfer due to the ideal vertical and horizon morphology properties, devices based on PBDB-TF/IT-4F exhibit the highest fill factors (FFs) as well as champion power conversion efficiencies (PCEs). With this guidance, high-performance LBL devices with PCE of 17.2%, 18.5%, and 19.1% are obtained by the fluorinated blend of PBDB-TF/Y6, PBDB-TF/L8-BO, and D18/L8-BO respectively.

19.
BMC Palliat Care ; 22(1): 196, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087244

RESUMO

BACKGROUND: Most Chinese patients chose to die at home, therefore there is a reliance on the family caregivers to be involved in their palliative care. The needs and coping strategies of family caregivers in home-based palliative care are rooted in culture. Little is known about the needs and coping strategies of family caregivers taking care of dying patients at home. METHODS: A field study using semi-structured interview, participant observation, documents and records collection was employed. The study was conducted in two palliative care outpatient departments in tertiary hospitals and four communities in Beijing, China from March 2021 to July 2022. Using purposive sampling, twenty-five family caregivers were recruited. All collected data were analyzed using content analysis approach. RESULTS: Five themes emerged, including three care needs and two coping strategies. Family caregivers need to learn care skills and acquire care resources, including (i) decision-making about home-based palliative care, (ii) improving patient's quality of life, and (iii) signs of final hours and funeral procedures. In facing the care burden, family caregivers coped by (iv) balancing the roles of caregivers and individuals: giving priority to patient care while maintaining their own normal life. In facing the death of a loved one, family caregivers responded by (v) making room for coming death by facing death indirectly and "rescuing" patients for consolation while preparing for the coming death. CONCLUSION: Family caregivers strive to balance the roles of being caregivers and being themselves. As caregivers, they actively prepare patients for good death with no regrets. As individuals, they preserve themselves from being hurt to maintain normal life. The needs of family caregivers focus on caregiver role and are manifested in care skills and resources. TRIAL REGISTRATION: Not registered.


Assuntos
Cuidadores , Serviços de Assistência Domiciliar , Humanos , Qualidade de Vida , Cuidados Paliativos/métodos
20.
Artigo em Inglês | MEDLINE | ID: mdl-38082694

RESUMO

Creating a digital twin has enormous potential in biomedical engineering. However, it is also technically challenging. No existing system can allow people who don't have the art-and-design background to create their own digital twin. To fill this gap, this study proposes a low-cost wearable system and a user-friendly framework for creating personalized digital twins with a fast speed and high fidelity. The personalized human digital twin can capture synchronized facial expressions, gaze direction, and whole-body movements for real-time rendering. The system simplifies the complex process of creating digital humans, and allows for the creation of data-driven characters without specialized skills.Clinical Relevance- This system can be used to help doctors keep track record of the patient's health status in a more visual and realistic way, supporting them in making more accurate clinical decisions, and facilitating a more detailed medical intervention.


Assuntos
Avatar , Expressão Facial , Humanos , Computadores
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