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Objective: This study aimed to develop an individual WeChat Mini Program to provide pharmaceutical care to better manage cancer pain patients and to evaluate its feasibility and the differences in analgesic efficacy, medication adherence and safety versus conventional pharmacy interventions. Methods: In this parallel randomized clinical trial, 42 cancer pain patients were equally allocated into the experimental group and the control group. The experimental group received individualized pharmaceutical care based on the "Yao Nin You Wo" WeChat Mini Program, while the control group received conventional care during the 4-week period. Main outcomes contained pain scores, medication adherence, incidences and relief rates of breakthrough pain, and incidences of adverse events. Relief rates of pain were also calculated according to pain scores. Results: At the beginning of intervention, none of the pain scores and medication adherence showed relevant differences between the two groups (all P > .05). After intervention, the experimental group had significantly lower pain scores compared to the control group (P = .003). Breakthrough pain of both groups was alleviate; not only the incidence of breakthrough pain considerably was lower at 4 weeks than at baseline, but the relief rate of breakthrough in the experimental group was higher than that in the control group. Compared with the control group, the medication adherence rate of the experimental group was significantly improved (P = .02). Types of adverse events that happened in experimental and groups were similar, but the total incidence of adverse events in the experimental group was lower than that in the control group. Conclusions: WeChat Mini Program is a useful and facilitative tool with the potential to improve cancer pain self-management ability in discharged patients. In addition, pharmacists could play a key role through the Mini Program to connect with patients successfully by providing personalized pharmaceutical services.
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Disintegrins, a family of snake venom protein, which are capable of modulating the activity of integrins that play a fundamental role in the regulation of many physiological and pathological processes. The main purpose of this study is to obtain the recombinant disintegrin (r-DI) and evaluate its biological activity. In this study, we explored a high-level expression prokaryotic system and purification strategy for r-DI. Then, r-DI was treated to assay effects on cell growth, migration, and invasion. The affinity for the interactions of r-DI with integrin was determined using Surface plasmon resonance (SPR) analyses. The r-DI can be expressed in Escherichia coli and purified by one-step chromatography. The r-DI can inhibit B16F10 cells proliferation, migration, and invasion. Also, we found that r-DI could interact with the integrin αIIbß3 (GPIIb/IIIa). The r-DI can be expressed, purified, characterized through functional assays, and can also maintain strong biological activities. Thus, this study showed potential therapeutic effects of r-DI for further functional and structural studies.
Assuntos
Desintegrinas , Escherichia coli , Proteínas Recombinantes , Escherichia coli/genética , Escherichia coli/metabolismo , Animais , Desintegrinas/química , Desintegrinas/genética , Desintegrinas/isolamento & purificação , Desintegrinas/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Camundongos , Viperidae/genética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/química , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Linhagem Celular Tumoral , Expressão Gênica , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Venenos de Crotalídeos/química , Venenos de Crotalídeos/genética , Crotalinae , Serpentes PeçonhentasRESUMO
BACKGROUND: Rituximab resistance is one of the great challenges in the treatment of diffuse large B-cell lymphoma (DLBCL), but relevant biomarkers and signalling pathways remain to be identified. Coptis chinensis and its active ingredients have antitumour effects; thus, the potential bioactive compounds and mechanisms through which Coptis chinensis acts against rituximab-resistant DLBCL are worth exploring. OBJECTIVE: To elucidate the core genes involved in rituximab-resistant DLBCL and the potential therapeutic targets of candidate monomers of Coptis chinensis. METHODS: Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Similarity Ensemble Approach and Swiss Target Prediction, the main ingredients and pharmacological targets of Coptis chinensis were identified through database searches. Through the overlap between the pharmacological targets of Coptis chinensis and the core targets of rituximab-resistant DLBCL, we identified the targets of Coptis chinensis against rituximab-resistant DLBCL and constructed an active compound-target interaction network. The targets and their corresponding active ingredients of Coptis chinensis against rituximab-resistant DLBCL were molecularly docked. RESULTS: Berberine, quercetin, epiberberine and palmatine, the active components of Coptis chinensis, have great potential for improving rituximab-resistant DLBCL via PIK3CG. CONCLUSION: This study revealed biomarkers and Coptis chinensis-associated molecular functions for rituximab-resistant DLBCL.
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Biologia Computacional , Coptis , Resistencia a Medicamentos Antineoplásicos , Linfoma Difuso de Grandes Células B , Simulação de Acoplamento Molecular , Farmacologia em Rede , Rituximab , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Humanos , Rituximab/farmacologia , Rituximab/uso terapêutico , Farmacologia em Rede/métodos , Coptis/química , Biologia Computacional/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa/métodosRESUMO
Anti-PD-1 immunotherapy has been widely applied in patients with some types of lymphoma. Classical Hodgkin's lymphoma (cHL) is highly sensitive to immunotherapy, but non-Hodgkin's lymphoma (NHL) does not show a good response. Studies have indicated that haematopoietic progenitor kinase 1 (HPK1) suppresses T cells and reduces antitumour immunity. Therefore, HPK1 inhibitors may restore and elicit antitumour immune responses and are promising candidate drug targets for cancer immunotherapy. We first explored the Gene Expression Profile Interactive Analysis (GEPIA) database and predicted that HPK1 expression was increased in diffuse large B-cell lymphoma (DLBCL) and associated with Nod-like receptor protein 3 (NLRP3) expression. We investigated whether an HPK1 inhibitor could enhance the tumour response to anti-PD-1 immunotherapy in NHL and the association between HPK1 and NLRP3 expression. Employing shHPK1 and an inhibitor, we demonstrated that the HPK1 inhibitor increased anti-PD-1-mediated T-cell cytotoxicity in BJAB and WSU-DLCL2 cells cocultured with peripheral blood mononuclear cells (PBMCs). HPK1 inhibitor treatment increased PD-1, PD-L1, Bax, p53 and NK-kB expression but decreased NLRP3 expression, indicating that the HPK1 inhibitor promoted apoptosis and blocked the NLRP3 inflammasome pathway to affect anti-PD-1-mediated T-cell cytotoxicity. Moreover, the HPK1 inhibitor enhanced the efficiency of anti-PD-1 immunotherapy in vivo in a zebrafish xenograft model of NHL. In summary, this study provides evidence that an HPK1 inhibitor enhanced the tumour response to anti-PD-1 immunotherapy in NHL by promoting apoptosis and blocking the NLRP3 pathway. These findings provide a potential therapeutic option for NHL combining HPK1 inhibitor treatment and anti-PD-1 immunotherapy.
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Doença de Hodgkin , Inibidores de Checkpoint Imunológico , Linfoma não Hodgkin , Animais , Humanos , Imunoterapia , Leucócitos Mononucleares/metabolismo , Linfoma não Hodgkin/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Peixe-Zebra , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
BACKGROUND: Durvalumab plus gemcitabine and cisplatin has a significant clinical benefit for advanced biliary tract cancer (BTC). However, the high price of durvalumab warrants an exploration of the economics. OBJECTIVE: To investigate the cost-effectiveness of adding durvalumab to gemcitabine and cisplatin compared with gemcitabine and cisplatin in first-line therapy of advanced BTC from the perspective of the Chinese healthcare system. METHODS: According to the TOPAZ-1 trial, a three-state Markov model was built by the TreeAge Pro 2022 software. The total costs and quality-adjusted life years (QALYs) were estimated, and the incremental cost-effectiveness ratio (ICER) was used as the evaluation index. The triple 2021 Chinese per capita gross domestic product (GDP) of $37,663.26/QALY was used as the willingness-to-pay (WTP) threshold. Outputs were analyzed for two scenarios with and without a durvalumab drug charity assistance policy. In the scenario analysis, the base-case model was run multiple times with different prices of durvalumab to determine the effect on the ICER. Moreover, the robustness of the model was tested through sensitivity analyses. RESULTS: Compared with chemotherapy alone, durvalumab plus chemotherapy resulted in an additional 0.12 QALY and an incremental cost of $18,555.19, the ICER was $159,644.70/QALY under the situation of charity assistance, and the ICER was $696,571.11/QALY without charity assistance, both exceeding the WTP threshold in China. The scenario analysis demonstrated that when the price of durvalumab fell by more than 94.2% to less than $0.33/mg, durvalumab plus chemotherapy will be more economical compared with chemotherapy alone under the situation of no charity assistance. One-way sensitivity analyses suggested that the cost of durvalumab had the greatest influence on the ICERs, and the probabilistic sensitivity analyses demonstrated that durvalumab plus chemotherapy was impossible to be cost-effective at the WTP threshold whether the charity assistance was available or not. CONCLUSIONS: Adding durvalumab to gemcitabine and cisplatin was not cost-effective for advanced BTC regardless of receiving and not receiving charitable assistance.
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Background: Ibrutinib, one Food and Drug Administration-approved, orally available, small-molecule Bruton tyrosine kinase (BTK) inhibitor, is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). YouTube is increasingly used for health purposes. However, videos for ibrutinib on YouTube have not been previously evaluated. This study assessed the accuracy and quality of YouTube videos on ibrutinib, to better understand the information shown on a dominant media platform. Methods: The first 150 video results returned by the YouTube search engine in response to the keyword "ibrutinib" were included (up to June 27, 2022). Typically used predefined inclusion and exclusion criteria were applied to screen the videos based on our needs. A 5-point Global Quality Scale (GQS) determined whether the videos would be useful to patients or not, and the quality of content was analyzed by five content-specific items. The quality of the included videos was classified as "low", "moderate", or "excellent" according to GQS and content score. The median and interquartile range were used to describe the values and Kruskal-Wallis test were used in the analysis. Results: A total of 99 videos with a median of 237 views met the inclusion criteria. The videos were categorized into educational videos (n=6, 6.07%), personal experience and blog (n=3, 3.03%) and interviews videos (n=90, 90.9%). Almost half of the videos were classified as moderate (n=51, 51.51%), followed by excellent (n=25, 25.26%) and low (n=23, 23.23%). Between the groups, no statistically significant differences were observed in the numbers of dislikes, comments, posted days, percentage positivity and viewing rate (P>0.05). There were marked differences in the length, likes, views, viewers' interaction and likeability (P<0.05). Conclusions: YouTube could be an effective source for different groups of people to obtain helpful information about ibrutinib. The physicians, pharmacists, nurses and healthcare organizations should prepare and upload more comprehensible and reliable videos with evidence-based information.