Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia.

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

[Deep Learning-Based Key Frame Recognition Algorithm for Adrenal Vascular in X-Ray Imaging].

Adrenal vein sampling is required for the staging diagnosis of primary aldosteronism, and the frames in which the adrenal veins are presented are called key frames. Currently, the selection of key frames relies on the doctor's visual judgement which is time-consuming and laborious. This study proposes a key frame recognition algorithm based on deep learning. Firstly, wavelet denoising and multi-scale vessel-enhanced filtering are used to preserve the morphological features of the adrenal veins. Furthermore, by incorporating the self-attention mechanism, an improved recognition model called ResNet50-SA is obtained. Compared with commonly used transfer learning, the new model achieves 97.11% in accuracy, precision, recall, F1, and AUC, which is superior to other models and can help clinicians quickly identify key frames in adrenal veins.

Alnustone promotes megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway.

OBJECTIVES: Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. METHODS: Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. RESULTS: Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. CONCLUSIONS: Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia.

A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments.

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

Efficacy and safety of music therapy for the treatment of anxiety and delirium in ICU patients: a meta-analysis and systematic review of randomized controlled trials.

INTRODUCTION: The medical application of music therapy (MT) has received widespread attention in recent years and some researchers have attempted to apply MT to the treatment of patients with anxiety and delirium in ICU. EVIDENCE ACQUISITION: Relevant randomized controlled trials (randomized controlled trials s) were searched in databases, such as Web of Science, PubMed, Embase, Cochrane Library, Medline, Scopus, and CINAHL. Researchers performed literature screening, data extraction, literature quality assessment, and heterogeneity analysis among RCTs. EVIDENCE SYNTHESIS: Fourteen studies met the inclusion criteria. In general, we included RCTs with low risk of bias, and the primary outcome indicators, including the Chinese version of the State-Trait Anxiety Inventory (C-STAI), Visual Analogue Scale for Anxiety Measurement (VAS-A), and Facial Anxiety Scale (FAS), with a recommended level of evidence of "strong". The pooled results indicated that MT was effective in alleviating the anxiety state of ICU patients (95% CI, SMD=-1.09 [-1.52, -0.67], P<0.05) and could reduce mental and physical fatigue in patients with anxious delirium in ICU (95% CI, WMD=-2.35 [-3.37, -1.33], P <0.05). There were significant differences in the therapeutic effects of MT with different intervention durations. Both 15-minute and 30-minute MT were effective in reducing anxiety levels in patients with anxiety disorders in the ICU (15min: 95%CI, SMD=-1.70[-2.15, -1.24], P<0.05; 30min: 95%CI, SMD=-0.73[-1.16, - 0.29], P<0.05). However, when the duration of MT exceeded 45 min, the overtreatment of MT instead interfered with patient rest and failed to produce a positive therapeutic effect (95% CI, SMD=-1.04 [-3.06, 0.97], P=0.31). In addition, a meta-analysis of physiological outcomes found that MT was effective in maintaining the stabilization of heart rate (HR), respiratory rate (RR), and systolic blood pressure (SBP) in ICU patients with anxiety (P<0.05), but did not affect patients' oxygen saturation, mean arterial pressure and diastolic blood pressure (P>0.05). No adverse events occurred during MT treatment in the reports of included 14 studies. CONCLUSIONS: MT can safely and effectively reduce the anxiety level of patients with anxiety and delirium in ICU and relieve their psychological and physical fatigue. And MT was able to maintain the stability of HR, RR, and SBP in ICU patients.

Beneficial implications of adjuvant chemotherapy for stage IB lung adenocarcinoma exhibiting elevated SUVmax in FDG-PET/CT: a retrospective study from a single center.

Background: Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods: We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion: The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.

Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Multisystem inflammatory syndrome in children with Kawasaki disease-like manifestations in MMA.

Not required for Clinical Vignette.

The moderating effect of environmental gamification on the relationship between social media marketing and consumer-brand engagement: A case study of Ant Forest Gen Z users.

Social media marketing plays a relevant role in the brand promotion of enterprises owing to its advantages of rapid and diversified communication with consumers. The Chinese Internet enterprise Alipay launched Ant Forest as a mobile application with gamified social functions, bringing consumer-brand engagement. Ant Forest provides a variety of gamification functions (e.g. point, leaderboard, badge, task and teamwork) to encourage users to participate in environmental protection and public welfare activities. These gamification mechanisms, combined with the spread of social media, have realised the co-creation of user brand value. In the current study, 305 Gen Z users of Ant Forest were surveyed through an online questionnaire, and the data analysis was conducted using the partial least squares structural equation modelling (PLS-SEM) method. This study indicates that the four elements of entertainment, trendiness, customisation and word-of-mouth in social media marketing have statistically significant direct effects on the consumer-brand engagement in Ant Forest. In addition, gamification shows a significant positive moderating effect on the relationship between customisation and consumer-brand engagement and a significant negative moderating effect on the relationship between trendiness and consumer-brand engagement in Ant Forest. This study adds gamification to the conceptual system of social media marketing and provides suggestions for the development of gamified social media marketing applications.

Glucose management in critically ill adults: A qualitative study from the experiences of health care providers.

Aims and objective: To explain the components and elements of glucose management in critically ill adult patients from the healthcare providers' experiences. Background: Critically ill adults are highly susceptible to stress-induced hyperglycaemia due to glucose metabolic disorders. Healthcare workers play a key role in the glycaemic management of critically ill patients. However, there is a lack of qualitative studies on the content and elements of glycaemic management and healthcare workers' perceptions about glycaemic management in China. Design: Qualitative study that followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. Methods: Individual semi-structured interviews were conducted from January to April 2022. Fifteen physicians and nurses were recruited from ten hospitals in mainland China. Data were analysed using inductive thematic analysis. Results: Glucose management in critically ill adult patients from their experiences included two parts: the inner ring (practice behaviours) and the external space (methods and drivers). The practice behaviours of glucose management include five elements, while the methods and drivers of glucose management focus on three elements. The content covered under each element was identified. Conclusion: This study developed a glycaemic management model for critically ill adult patients, clarified its elements based on the perceptions of healthcare providers and elaborated on the methods and drivers covered under each element to provide a reference for physicians and nurses to develop a comprehensive glycaemic management guideline for critically ill adult patients. Relevance to clinical practice: Our study proposed a glucose management practice model for critically ill adult patients, and the elements and components included in this model can provide a reference for physicians and nurses when performing glucose management in critically ill patients.

Carbon-reinforced Ni3S2/Ti3C2Tx MXene composite as an anode for superior-performance lithium-ion capacitors.

Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials. In this paper, to obtain a superior-rate and high-capacity Ni3S2-based anode, highly conductive Ti3C2Tx MXene sheets were introduced to sever as the carrier of Ni3S2 nanoparticles and simultaneously an amorphous carbon layer which coats onto the surface of Ni3S2 nanoparticles was in-situ generated by the carbonization of dopamine reactant. The as-synthesized Ni3S2/Ti3C2Tx/C composite exhibits a high specific surface area (112.6 m2/g) because of the addition of Ti3C2Tx that can reduce the aggregation of Ni3S2 nanoparticles and the in-situ generated amorphous carbon layer that can suppress the growth of Ni3S2 nanoparticles. The Ni3S2/Ti3C2Tx/C anode possesses a remarkable reversible discharge specific capacity (626.0 mAh/g under 0.2 A/g current density), which increases to 1150.8 mAh/g after 400-cycle charge/discharge measurement at the same measurement condition indicating eminent cyclability, along with superior rate capability. To construct a superior-performance LIC device, a sterculiae lychnophorae derived porous carbon (SLPC) cathode with an average discharge specific capacity of 73.4 mAh/g@0.1A/g was prepared. The Ni3S2/Ti3C2Tx/C//SLPC LIC device with optimal cathode/anode mass ratio has a satisfactory energy density ranging from 32.8 to 119.1 Wh kg-1 at the corresponding power density of 8799.4 to 157.5 W kg-1, together with a prominent capacity retention (95.5 %@1 A/g after 10,000 cycles).

Development and validation of nurse's assessment ability questionnaire in delirium subtypes: Based on Delphi expert consensus.

BACKGROUND: Delirium, a common occurrence in clinical work, can be divided into three subtypes according to Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition (DSM-5). Each subtype has its special significance and focus. As the primary caregivers and observer of delirious patients, nurses should be able to quickly and accurately indentify each subtype. Therefore, it is necessary to clarify nurses' assessment ability of delirium subtypes. However, there is currently no suitable questionnaire available for investigating nurses' assessment ability of delirium subtypes. OBJECTIVE: To develop a scientifically validated questionnaire for assessing nursing assessment ability of delirium subtypes based on Knowledge-Attitude-Practice(KAP) Model. METHODS: The questionnaire was conducted from October 2021 to February 2022 to assess the KAP status of nurses the regarding delirium subtype. A two-round Delphi Method was employed to revise the draft questionnaire, ensuring the importance and rationality of each item. Ten experts specializing in critically ill patients, clinical nursing, and nursing management were invited from seven provinces in China for the Delphi process. Additionally, we validated the reliability and validity of the questionnaire. RESULTS: The return rate in the first and second rounds were 83% and 100%, respectively. The individual authority coefficients for the two rounds of correspondence ranged from 0.787 to 0.987, while the overall authority coefficient of experts was 0.866. Kendall's coefficient of coordination for the importance scores were found to be 0.192 and 0.156, respectively, whereas those for rationality scores were calculated as 0.149 and 0.141, respectively. Notably, all mean values of importance and rationality scores in the two rounds were exceeded a threshold of 4.10 across both rounds of assessment with coefficient variations (CV) ranging from 0.00 to 0.19 for importance ratings and 0.00 to 0.16 for rationality ratings, both of which were <0.25. Experts proposed modifications to eleven items while introducing four new ones into consideration during this process; thus ensuring that reliability and validity standards were met by the final questionnaire design which consists of a total of thirty-seven items distributed across four dimensions: delirium subtype-related knowledge, assessment attitude, assessment practice, and knowledge source-thereby establishing its clinical relevance as a reliable scientific instrument. CONCLUSION: The development process is both scientific and theoretical, encompassing reliable expert correspondence results and a diverse range of question formats. As thus, effectively captures the current landscape of delirium subtypes assessment among clinical nurses from multiple perspectives, including knowledge level and source, attitude, assessment behavior, and assessment barriers. It offers comprehensive and detailed insights.

Interleukins in Platelet Biology: Unraveling the Complex Regulatory Network.

Interleukins, a diverse family of cytokines produced by various cells, play crucial roles in immune responses, immunoregulation, and a wide range of physiological and pathological processes. In the context of megakaryopoiesis, thrombopoiesis, and platelet function, interleukins have emerged as key regulators, exerting significant influence on the development, maturation, and activity of megakaryocytes (MKs) and platelets. While the therapeutic potential of interleukins in platelet-related diseases has been recognized for decades, their clinical application has been hindered by limitations in basic research and challenges in drug development. Recent advancements in understanding the molecular mechanisms of interleukins and their interactions with MKs and platelets, coupled with breakthroughs in cytokine engineering, have revitalized the field of interleukin-based therapeutics. These breakthroughs have paved the way for the development of more effective and specific interleukin-based therapies for the treatment of platelet disorders. This review provides a comprehensive overview of the effects of interleukins on megakaryopoiesis, thrombopoiesis, and platelet function. It highlights the potential clinical applications of interleukins in regulating megakaryopoiesis and platelet function and discusses the latest bioengineering technologies that could improve the pharmacokinetic properties of interleukins. By synthesizing the current knowledge in this field, this review aims to provide valuable insights for future research into the clinical application of interleukins in platelet-related diseases.

Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial.

BACKGROUND: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. METHODS/DESIGN: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model. DISCUSSION: This statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203 .

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Insulin Infusion Protocols for Blood Glucose Management in Critically Ill Patients: A Scoping Review.

BACKGROUND: Continuous insulin infusion is a method for maintaining blood glucose stability in critically ill patients with hyperglycemia. Many insulin infusion protocols have been applied in intensive care units. Understanding the content of these protocols can help clinical staff choose the most appropriate and convenient protocol and promote best practices in managing glucose levels in critically ill adult patients. OBJECTIVE: To examine the types of insulin infusion therapies performed for blood glucose management in critically ill patients. METHODS: For this scoping review, 3 Chinese-language and 8 English-language databases were searched for articles published from May 25, 2016, to October 25, 2022. RESULTS: Twenty-one articles met the inclusion criteria. Twenty-one insulin infusion protocols were examined. Most of the insulin infusion protocols were paper protocols. Fourteen glucose management indicators were included in the 21 protocols. The glucose target range for all 21 protocols ranged from 70 to 180 mg/dL (3.9-10.0 mmol/L). Nurses were primarily responsible for protocol implementation in most protocol development processes. The roles of nurses differed in nurse-led insulin infusion protocols and non-nurse-led insulin infusion protocols. DISCUSSION: This scoping review indicates an urgent need for more comprehensive glycemic control guidelines for patients receiving critical care. Because insulin infusion protocols are core aspects of blood glucose management guidelines, different population subgroups should also be considered. CONCLUSIONS: Nurse-led guidelines must be based on the best available evidence and should include other variables related to glucose management (eg, patient disease type, medication, and nutrition) in addition to insulin infusion.

A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.

The limitations of traditional two-dimensional (2D) cultures and animal testing, when it comes to precisely foreseeing the toxicity and clinical effectiveness of potential drug candidates, have resulted in a notable increase in the rate of failure during the process of drug discovery and development. Three-dimensional (3D) in-vitro models have arisen as substitute platforms with the capacity to accurately depict in-vivo conditions and increasing the predictivity of clinical effects and toxicity of drug candidates. It has been found that 3D models can accurately represent complex tissue structure of human body and can be used for a wide range of disease modeling purposes. Recently, substantial progress in biomedicine, materials and engineering have been made to fabricate various 3D in-vitro models, which have been exhibited better disease progression predictivity and drug effects than convention models, suggesting a promising direction in pharmaceutics. This comprehensive review highlights the recent developments in 3D in-vitro tissue models for preclinical applications including drug screening and disease modeling targeting multiple organs and tissues, like liver, bone, gastrointestinal tract, kidney, heart, brain, and cartilage. We discuss current strategies for fabricating 3D models for specific organs with their strengths and pitfalls. We expand future considerations for establishing a physiologically-relevant microenvironment for growing 3D models and also provide readers with a perspective on intellectual property, industry, and regulatory landscape.

Hypertension doctors' awareness and practice of medication adherence in hypertensive patients: a questionnaire-based survey.

Background: Poor adherence to antihypertensive drugs is a major cause of unsatisfactory blood pressure control. Hypertension doctors play an integral role in improving medication adherence in hypertensive patients. Although most existing studies have recognized the status quo and influencing factors of medication adherence, little attention has been paid to hypertension doctors' awareness and practice in hypertension management. Therefore, in this study, we aimed to investigate hypertension doctors' awareness and practice of medication adherence in hypertensive patients. Methods: This is a cross-sectional survey. A self-reported questionnaire was developed and sent to hypertension doctors in Hunan province, China, between May 1, 2022 and July 1, 2022. Univariate and generalized linear models were used to identify the factors influencing hypertension doctors' awareness and practice. The correlation between awareness and practice was determined using Spearman's correlation coefficient. Results: In total, 236 valid questionnaires were collected (valid response rate, 73.5%). Of the respondents, 44.1% were chief physicians and 64.4% were females. Approximately half of the respondents were ≥40 years old and had over 14 years of working experience. Most respondents (87.7%) did not have hypertension, but 54.2% had a family history of hypertension. The average awareness and practice scores were 29.8 ± 8.8 and 39.4 ± 7.1, respectively, out of 50, with higher scores indicating higher levels of awareness or practice. More hypertension consultations and more antihypertensive prescriptions issued were associated with better awareness and practice among respondents (ps < 0.05). Respondents with higher education and professional titles had higher awareness (ps < 0.05). Moreover, respondents with 6-13 years of work experience had better practice than those with <5 years of work experience (p = 0.017). There was a significant correlation between hypertension doctors' awareness and practice of medication adherence in hypertensive patients (R = 0.682, p < 0.001). These findings indicate that misconceptions persist in hypertension doctors' awareness and practice of patient medication adherence. Conclusion: Hypertension doctors lack sufficient and correct awareness and practice of medication adherence in hypertensive patients.

Retracted: Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Mei Mei Guan, Qun Xian Rao, Miao Ling Huang, Li Juan Wang, Shao Dan Lin, Qing Chen, Chang Hao Liu. Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines. Med Sci Monit, 2019; 25: 8131-8141. DOI: 10.12659/MSM.916292.

Characterization and In Vitro Fungicide Sensitivity of Two Fusarium spp. Associated with Stem Rot of Dragon Fruit in Guizhou, China.

Dragon fruit (Hylocereus polyrhizus) constitutes an important economic industry in Guizhou Province, China, and the occurrence of stem rot has become increasingly severe. In this study, we aimed to determine the causative pathogens of stem rot in this region and analyze their sensitivity to fungicides. Twenty-four fungal isolates were obtained from diseased tissues, from which H-4 and H-5 were confirmed as pathogens based on Koch's postulates. Based on the morphological characteristics of macroconidia, microconidia, and colony morphology, the polygenic phylogenetic tree constructed using internal transcribed spacer, elongation factor 1-alpha, and retinol-binding protein-2 gene fragments, and carbon source metabolism analysis using FF microplates, the two pathogens were identified as F. oxysporum and a newly discovered pathogen, F. concentricum. In addition, the in vitro toxicity of eight fungicides against both pathogens was measured based on the mycelial growth rate. The results showed that trifloxystrobin 25%·tebuconazole 50% (75 WG) exhibited the strongest inhibitory effect against both isolates, with EC50 values of 0.13 µg/mL and 0.14 µg/mL, respectively. These findings hold significant potential for guiding the effective treatment of stem rot in dragon fruit in Guizhou, China.