FOSL1 promotes stem cell­like characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.

Metastasis is the leading cause of cancer­related death in osteosarcoma (OS). OS stem cells (OSCs) and anoikis resistance are considered to be essential for tumor metastasis formation. However, the underlying mechanisms involved in the maintenance of a stem­cell phenotype and anoikis resistance in OS are mostly unknown. Fos­like antigen 1 (FOSL1) is important in maintaining a stem­like phenotype in various cancers; however, its role in OSCs and anoikis resistance remains unclear. In the present study, the dynamic expression patterns of FOSL1 were investigated during the acquisition of cancer stem­like properties using RNA sequencing, PCR, western blotting and immunofluorescence. Flow cytometry, tumor­sphere formation, clone formation assays, anoikis assays, western blotting and in vivo xenograft and metastasis models were used to further investigate the responses of the stem­cell phenotype and anoikis resistance to FOSL1 overexpression or silencing in OS cell lines. The underlying molecular mechanisms were evaluated, focusing on whether SOX2 is crucially involved in FOSL1­mediated stemness and anoikis in OS. FOSL1 expression was observed to be upregulated in OSCs and promoted tumor­sphere formation, clone formation and tumorigenesis in OS cells. FOSL1 expression correlated positively with the expression of stemness­related factors (SOX2, NANOG, CD117 and Stro1). Moreover, FOSL1 facilitated OS cell anoikis resistance and promoted metastases by regulating the expression of apoptosis related proteins BCL2 and BAX. Mechanistically, FOSL1 upregulated SOX2 expression by interacting with the SOX2 promoter and activating its transcription. The results also showed that SOX2 is critical for FOSL1­mediated stem­like properties and anoikis resistance. The current findings indicated that FOSL1 is an important regulator that promotes a stem cell­like phenotype and anoikis resistance to facilitate tumorigenesis and metastasis in OS by regulating the transcription of SOX2. Thus, FOSL1 might represent an attractive target for therapeutic interventions in OS.

Targeted anti-angiogenesis therapy for advanced osteosarcoma.

To date, despite extensive research, the prognosis of advanced osteosarcoma has not improved significantly. Thus, patients experience a reduced survival rate, suggesting that a reevaluation of current treatment strategies is required. Recently, in addition to routine surgery, chemotherapy and radiotherapy, researchers have explored more effective and safer treatments, including targeted therapy, immunotherapy, anti-angiogenesis therapy, metabolic targets therapy, and nanomedicine therapy. The tumorigenesis and development of osteosarcoma is closely related to angiogenesis. Thus, anti-angiogenesis therapy is crucial to treat osteosarcoma; however, recent clinical trials found that it has insufficient efficacy. To solve this problem, the causes of treatment failure and improve treatment strategies should be investigated. This review focuses on summarizing the pathophysiological mechanisms of angiogenesis in osteosarcoma and recent advances in anti-angiogenesis treatment of osteosarcoma. We also discuss some clinical studies, with the aim of providing new ideas to improve treatment strategies for osteosarcoma and the prognosis of patients.

Impact of ginsenoside Rb1 on gut microbiome and associated changes in pharmacokinetics in rats.

Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

1/2 order subharmonic waves of two cavitation bubbles.

In the work, the 1/2 order subharmonic wave of two coupling cavitation bubbles is investigated numerically via Fourier spectrum analysis. By analyzing the dynamics of bubble, we find that the mutual interaction between bubbles can affect the appearance of 1/2 order subharmonic. The results of parameter dependence show that the intensity of 1/2 order subharmonic would be promoted or inhibited with the increase of mutual interaction. The higher the driving amplitude or the smaller the distance between bubbles, the stronger the mutual interaction is, and also the greater the promotion or suppression of the 1/2 order subharmonic is. Moreover, while the 1/2 order subharmonic occurs, the energy of bubble would alternate between two different peaks, and the temperature inside bubble has a similar fluctuation while the bubble collapses. This qualitative analysis suggests that the bubble's dynamics for multi-bubble case is complex. Understanding the generation of subharmonic of bubble's dynamics is of great significance for helpful applying of cavitation bubble.

[Rapid determination of chlorate and perchlorate in tea by ion exchange chromatography-tandem mass spectrometry].

Ion exchange chromatography-tandem mass spectrometry (IEC-MS/MS) has recently become the preferred method for detecting ionic substances in tea. In this study, an IEC-MS/MS method was developed for the rapid determination of chlorate and perchlorate residues in tea samples. The optimal sample extraction process, pretreatment column, and chromatographic and mass spectrometric conditions were systematically investigated. In the optimal process, the tea samples were ultrasonically extracted with methanol-water (13∶7, v/v), and a PRiME HLB SPE column was used to purify the sample extract. An AceChrom Hybri-A IEC column (150 mm×2.1 mm, 5.0 µm) was used for separation, and 100 mmol/L ammonium acetate-acetonitrile (40∶60, v/v) was used as the mobile phase for isocratic elution. The flow rate was 0.3 mL/min, the column temperature was 40 ℃, and the injection volume was 5.0 µL. The mass spectrometric data were collected in negative electrospray ionization mode combined with multiple reaction monitoring (MRM) mode to achieve the rapid and accurate separation and qualitative analysis of the desired chemical components. Quantification was performed using the internal standard (IS) method. The measurement results showed a good linear relationship when the mass concentrations of chlorate and perchlorate were between 2.00-200 and 1.00-100 µg/L, respectively, with correlation coefficients (r2) greater than 0.9990. The average recoveries of chlorate and perchlorate at three spiked levels of low, medium, and high ranged from 88.54% to 97.25% with relative standard deviations (RSDs, n=7) of 3.2%-5.2%. The limits of detection for chlorate and perchlorate were 12.0 and 8.0 µg/kg, respectively, while the limits of quantification were 40.0 and 26.6 µg/kg, respectively. The results of tests conducted to assess the linearity, specificity, accuracy, precision, and applicability of the method to the analysis of chlorate and perchlorate in 15 tea samples collected from a local market demonstrated its validity for the routine analysis of tea samples. The proposed method is simple, rapid, sensitive, and accurate, and can meet requirements for the rapid screening and quantitative analysis of residual trace chlorate and perchlorate in large quantities of tea samples.

Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review of the last decade.

IMPORTANCE: Recurrent/metastatic adenoid cystic carcinoma (R/M AdCC) presents a clinical challenge with limited treatment options, particularly in the face of unsatisfactory efficacy from current therapeutic approaches. This review underscores the unmet clinical needs in managing R/M AdCC, emphasising the imperative for novel therapeutic strategies to address this critical gap. OBJECTIVE: The primary objective of this review is to comprehensively analyse and assess trials investigating therapeutic approaches for R/M AdCC. Emphasis is placed on endpoints such as tumour response rates and progression-free survival. The specific interventions, populations, and outcomes examined in these trials will be detailed to provide a focused and informative systematic review. EVIDENCE REVIEW: The systematic search spanned databases, including PubMed, EMBASE, and the Cochrane database of systematic reviews. Employing terms like "Carcinoma, Adenoid Cystic" and "trial," the search focused on English full-text articles from April 1, 2010, to August 9, 2023. Inclusion criteria encompassed studies with patients having R/M AdCC, involving drug interventions. Study quality was assessed using the Newcastle-Ottawa Scale for retrospective studies, Cochrane ROBINS-I tool for non-randomised trials, and the ROB-2 tool for randomised controlled trials. FINDINGS: A total of 46 trials involving 1244 patients are included in this review, encompassing a variety of therapeutic approaches for R/M AdCC. Targeted therapies, particularly Apatinib at 500 mg, exhibit efficacy with a 47.1% objective response rate (ORR). Conversely, immunotherapeutic agents demonstrate suboptimal performance, with an overall ORR ranging from 0 to 18%. While Apatinib shows promise, the review underscores the imperative for a thorough exploration of drugs targeting unique mechanisms in the immunologically cold nature of R/M AdCC. CONCLUSIONS AND RELEVANCE: Substantial progress in systemic therapy for R/M AdCC is evident, driven by early-phase clinical trials, particularly with promising outcomes in VEGF-2 inhibitors. However, challenges persist, notably in immunotherapy due to the cancer's immunologically cold nature. Ongoing research, prioritising early-stage trials, is crucial, emphasising exploration of emerging therapies like cell therapy and antibody-drug conjugates. Transitioning to Phase III trials is essential for more precise therapeutic insights. Collaborative efforts and a focus on personalised precision medicine are vital for overcoming challenges and advancing our understanding of treatment efficacy in this rare cancer.

(+)-Catechin attenuates CCI-induced neuropathic pain in male rats by promoting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome.

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1ß. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.

An additional proofreader contributes to DNA replication fidelity in mycobacteria.

The removal of mis-incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the ε-exonuclease DnaQ is a well-established proofreader in the model organism Escherichia coli, it has been shown that proofreading in a majority of bacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase, despite the presence of a DnaQ homolog that is structurally and functionally distinct from E. coli DnaQ. However, the biological functions of this type of noncanonical DnaQ remain unclear. Here, we provide independent evidence that noncanonical DnaQ functions as an additional proofreader for mycobacteria. Using the mutation accumulation assay in combination with whole-genome sequencing, we showed that depletion of DnaQ in Mycolicibacterium smegmatis leads to an increased mutation rate, resulting in AT-biased mutagenesis and increased insertions/deletions in the homopolymer tract. Our results showed that mycobacterial DnaQ binds to the ß clamp and functions synergistically with the PHP domain proofreader to correct replication errors. Furthermore, the loss of dnaQ results in replication fork dysfunction, leading to attenuated growth and increased mutagenesis on subinhibitory fluoroquinolones potentially due to increased vulnerability to fork collapse. By analyzing the sequence polymorphism of dnaQ in clinical isolates of Mycobacterium tuberculosis (Mtb), we demonstrated that a naturally evolved DnaQ variant prevalent in Mtb lineage 4.3 may enable hypermutability and is associated with drug resistance. These results establish a coproofreading model and suggest a division of labor between DnaQ and PHP domain proofreader. This study also provides real-world evidence that a mutator-driven evolutionary pathway may exist during the adaptation of Mtb.

Gut Lactococcus garvieae promotes protective immunity to foodborne Clostridium perfringens infection.

The gut microbiota, a pivotal component of the intestinal mucosal barrier, is critical for host resistance to enteric pathogen infection. Here, we report a novel function of the potentially probiotic Lactococcus garvieae strain LG1 (L. garvieae strain LG1) in maintaining intestinal mucosal barrier integrity and protecting against foodborne Clostridium perfringens (C. perfringens) infection. L. garvieae was isolated from the intestinal contents of Chinese Mongolian sheep (MS) and exhibited potential probiotic properties. In a C. perfringens enterocolitis model, L. garvieae-pretreated mice were less susceptible to C. perfringens infection compared with Phosphate buffered solution (PBS)-pretreated mice, which manifested as higher survival rates, lower pathogen loads, less weight loss, mild clinical symptoms and intestinal damage, and minor inflammation. Further mechanistic analysis showed that L. garvieae could ameliorate the disruption of intestinal permeability and maintain the integrity of the intestinal mucosal barrier by promoting the expression of tight junction proteins and mucoproteins. Moreover, L. garvieae was also able to facilitate antimicrobial peptide expression and ameliorate dysbiosis of the gut microbiota caused by C. perfringens. Together, these findings highlight the prospect of immunomodulatory potentially probiotic L. garvieae and might offer valuable strategies for prophylaxis and/or treatment of pathogenic C. perfringens mucosal infection. IMPORTANCE: C. perfringens necrotic enteritis leads to losses of about US $2 billion to the poultry industry worldwide every year. Worse, US Centers for Disease Control and Prevention (CDC) has estimated that C. perfringens causes nearly 1 million foodborne illnesses in the United States annually. Nowadays, the treatment recommendation is a combination of a broad-spectrum synergistic penicillin with clindamycin or a carbapenem, despite growing scientific concern over antibiotic resistance. The global understanding of the gut microbiome for C. perfringens infection may provide important insights into the intervention. L. garvieae originated from Mongolian sheep intestine, exhibited potentially probiotic properties, and was able to limit C. perfringens enterocolitis and pathogenic colonization. Importantly, we found that L. garvieae limits C. perfringens invasion via improving intestinal mucosal barrier function. Also, L. garvieae alleviates C. perfringens-induced gut microbiota dysbiosis. It allowed us to convince that utilization of probiotics to promote protective immunity against pathogens infection is of pivotal importance.

Mechanism underlying the effects of exercise against type 2 diabetes: A review on research progress.

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes (T2D) in certain nations. The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D. The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D, in addition to identify the limitations of the existing literature, thereby provide direction for future research in this field.

[Mechanism of salidroside in inhibiting proliferation, migration and promoting phenotypic switching of arterial smooth muscle cells].

This study aims to examine the effect of salidroside(SAL) on the phenotypic switching of human aortic smooth muscle cells(HASMC) induced by the platelet-derived growth factor-BB(PDGF-BB) and investigate the pharmacological mechanism. Firstly, the safe concentration of SAL was screened by the lactate dehydrogenase release assay. HASMC were divided into control, model, and SAL groups, and the cells in other groups except the control group were treated with PDGF-BB for the modeling of phenotypic switching. Cell proliferation and migration were detected by the cell-counting kit(CCK-8) assay and Transwell assay, respectively. The cytoskeletal structure was observed by F-actin staining with fluorescently labeled phalloidine. The protein levels of proliferating cell nuclear antigen(PCNA), migration-related protein matrix metalloprotein 9(MMP-9), fibronectin, α-smooth muscle actin(α-SMA), and osteopontin(OPN) were determined by Western blot. To further investigate the pharmacological mechanism of SAL, this study determined the expression of protein kinase B(Akt) and mammalian target of rapamycin(mTOR), as well as the upstream proteins phosphatase and tensin homologue(PTEN) and platelet-derived growth factor receptor ß(PDGFR-ß) and the downstream protein hypoxia-inducible factor-1α(HIF-1α) of the Akt/mTOR signaling pathway. The results showed that the HASMCs in the model group presented significantly increased proliferation and migration, the switching from a contractile phenotype to a secretory phenotype, and cytoskeletal disarrangement. Compared with the model group, SAL weakened the proliferation and migration of HASMC, promoted the expression of α-SMA(a contractile phenotype marker), inhibited the expression of OPN(a secretory phenotype marker), and repaired the cytoskeletal disarrangement. Furthermore, compared with the control group, the modeling up-regulated the levels of phosphorylated Akt and mTOR and the relative expression of PTEN, HIF-1α, and PDGFR-ß. Compared with the model group, SAL down-regulated the protein levels of phosphorylated Akt and mTOR, PTEN, PDGFR-ß, and HIF-1α. In conclusion, SAL exerts a protective effect on the HASMCs exposed to PDGF-BB by regulating the PDGFR-ß/Akt/mTOR/HIF-1α signaling pathway.

Phase-Field Model of Electronic Antidoping.

Charge carrier doping usually reduces the resistance of a semiconductor or insulator, but was recently found to dramatically enhance the resistance in certain series of materials. This remarkable antidoping effect has been leveraged to realize synaptic memory trees in nanoscale hydrogenated perovskite nickelates, opening a new direction for neuromorphic computing. To understand these phenomena, we formulate a physical phase-field model of the antidoping effect based on its microscopic mechanism and simulate the voltage-driven resistance change in the prototypical system of hydrogenated perovskite nickelates. Remarkably, the simulations using this model, containing only one adjustable parameter whose magnitude is justified by first-principles calculations, quantitatively reproduce the experimentally observed treelike resistance states, which are shown unambiguously to arise from proton redistribution-induced local band gap enhancement and carrier blockage. Our work lays the foundation for modeling the antidoping phenomenon in strongly correlated materials at the mesoscale, which can provide guidance to the design of novel antidoping-physics-based devices.

LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.

An ultra-efficient pretreatment method adopted LPUV/CoFe2O4/PMS-based photolysis for accurate detection of Cd(II) and Pb(II) in water via SWASV.

Dissolved organic matter (DOM) is a widely occurring substance in rivers that can strongly complex with heavy metal ions (HMIs), severely interfering with the electrochemical signal of anodic stripping voltammetry (ASV) and reducing the detection accuracy of HMIs in water. In this study, we investigated a novel advanced oxidation process (AOP) that involves the activation of peroxymonosulfate (PMS) using low-pressure ultraviolet (LPUV) radiation and CoFe2O4 photocatalysis. This novel AOP was used for the first time as an effective pretreatment method to break or weaken the complexation between HMIs and DOM, thereby restoring the electrochemical signals of HMIs. The key parameters, including the PMS concentration, CoFe2O4 concentration, and photolysis time, were optimized to be 6 mg/L, 12 mg/L, and 30 s for eliminating DOM interference during the electrochemical analysis of HMIs via LPUV/CoFe2O4-based photolysis. Investigations of the microstructure, surface morphology, specific surface area, and pore volume of CoFe2O4 were conducted to reveal the exceptional signal recovery capability of LPUV/CoFe2O4/PMS-based photolysis in mitigating interference from DOM during HMIs analysis. The PMS activation mechanism, which is critical to the signal recovery process, was elucidated by analyzing the reactive oxygen species (ROS) and the surface elemental composition of CoFe2O4. Additionally, the degradation and transformation behavior of humus-HMIs complexes were analyzed to study the mechanism of ASV signal recovery further. Notably, the detection results of HMIs in actual water samples obtained using the proposed pretreatment method were compared with those obtained from ICP-MS, yielding an RMSE less than 0.04 µg/L, which indicated the satisfactory performance of the proposed pretreatment method for the ASV detection of HMIs in complex actual samples.

Combined use of dexmedetomidine and nalbuphine in laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Radical laparoscopic gastrectomy is an important treatment modality for gastric cancer. Surgery requires general anesthesia, and patients are susceptible to the effects of anesthetic drugs and carbon dioxide insufflation during the procedure, leading to inflammation or severe pain, which can affect patient outcome. AIM: To explore the efficacy of combining dexmedetomidine (DEX) with nalbuphine in patients underwent laparoscopic radical gastrectomy for gastric cancer. METHODS: Patients scheduled to undergo laparoscopic radical gastrectomy were selected and randomly assigned to A or B group. In A group, patients received an intravenous injection of nalbuphine 0.2 mg/kg + DEX 0.4 µg/kg 10 min before the end of surgery; in B group, patients received only an intravenous injection of nalbuphine. The trends in hemodynamic parameter fluctuations, awakening quality during the recovery period, serum inflammatory markers, agitation scores, cough severity, incidence, and duration of postoperative delirium (POD) were compared. RESULTS: The mean arterial pressure and heart rate in the A group were more stable (P < 0.05). The A group had a lower average awakening time, extubation time, and agitation scores during recovery than the B group. Agitation control in the A group was more effective at different time points (P < 0.05). Patients in the A group had lower serum interleukin (IL)-6, tumour necrosis factor alpha, and IL-10 levels at 1 h after surgery than the B group. The incidence of coughing and duration of POD were lower and shorter in the A group than in the B group. Adverse reactions caused by the two anesthesia methods were less frequent in the A group than in the B group (P < 0.05). CONCLUSION: The use of DEX and nalbuphine in patients undergoing laparoscopic radical gastrectomy for gastric cancer help reducing the inflammatory response, cough severity, and agitation and helps maintain hemodynamic stability.

Toward a comprehensive solution for treating solid tumors using T-cell receptor therapy: A review.

T-cell receptor therapy (TCR-T) has demonstrated efficacy, durability, and safety advantages in certain solid tumors (such as human papillomavirus-related tumors, synovial sarcoma, and melanoma). This study aimed to provide careful considerations for developing TCR-T for solid tumors. Therefore, in this review, we have summarized the current clinical application, advantage of TCR-T modalities and explored efficacy/safety-related parameters, particularly avidity, pharmacokinetics/pharmacodynamics, and indications, for solid tumors. Furthermore, we have investigated critical factors related to avidity, including antigen selection, T-cell receptor acquisition, optimization, and co-receptor engagement. Moreover, we have re-examined the expression of tumor antigens for a potentially higher coverage rate of solid tumors based on the current RNA-seq datasets. Finally, we have discussed the current limitations and future directions of TCR-Ts.

Development and validation of a drug clinical trial participation feelings questionnaire for cancer patients.

Objective: The study was designed to develop and validate a new drug clinical trial participation feelings questionnaire (DCTPFQ) for cancer patients. Methods: Data collection and analysis involved a combination of qualitative and quantitative methods. There were two phases to this study. Phase Ⅰ involved developing a questionnaire to establish a list of items to be included in the pool: A theoretical framework was constructed based on the transitions theory and the Roper-Logan-Tierney theory. After incorporating a theoretical framework, interviewing participants, and reviewing the literature, 44 items were generated. After a Delphi consultation and a pilot test, 36 items proceeded to item analysis and exploratory factor analysis (EFA), and a four-factor structure with 21 items was formed. Confirmatory factor analysis (CFA), test-retest reliability, criteria-related validity, and internal consistency tests were conducted in phase II to examine the psychometric properties. Results: There were 21 items on the DCTPFQ, ranging from 1 (fully disagree) through 5 (fully agree). As a result of EFA and CFA, the four factors of DCTPFQ could be verified, including cognitive engagement, subjective experience, medical resources, and relatives and friends' support. Test-retest reliability of the DCTPFQ was 0.840, and Cronbach's alpha was 0.934. DCTPFQ is significantly correlated with the Fear of Progression Questionnaire-short form (r = 0.731, p < 0.05) and the Mishel's Uncertainty in Illness Scale (r = 0.714, p < 0.05). Conclusion: The DCTPFQ is a useful tool for measuring the drug clinical trial participation feelings among cancer patients.