Establishing an evaluation index system of nursing quality for clinical drug trials: A Delphi study.

AIMS: To construct a quality evaluation index system for clinical drug trials nursing management and obtain the weight of all indicators. DESIGN: A mixed-method research design with a quantitative component was used, primarily qualitative. METHODS: Through a literature review and semi-structured interview, an expert consultation questionnaire on the quality of nursing evaluation indicators for clinical drug trials was developed in April 2021. Eighteen experts in clinical drug trial nursing, medical, and pharmacy conducted 2 rounds of consultation according to the Delphi method to determine the indicators for evaluating the quality of clinical drug trial nursing. The weights of each indicator were determined using analytic hierarchical analysis. RESULTS: The established quality evaluation system of clinical drug trial nursing mainly includes 3 first-level indicators, 12 second-level indicators, and 59 third-level indicators. The positive coefficients of the two rounds of expert consultation were 90%-100%, and the authority coefficients were 0.831 and 0.885, respectively; the coordination coefficients were 0.189 and 0.214, respectively. The consulting results and weight settings are reliable. The evaluation index system we constructed is in line with the characteristics of the clinical drug trial nursing profession, with clear index levels and strong clinical operability, which can provide a reference for the assessment, monitoring and improvement of nursing quality in clinical drug trials. It will also clarify how nurses contribute to subjects' safety.

ATP-binding cassette protein ABCC8 promotes anthocyanin accumulation in strawberry fruits.

Anthocyanins are important health-promoting flavonoid compounds that substantially contribute to fruit quality. Anthocyanin biosynthesis and most regulatory mechanisms are relatively well understood. However, the functions of anthocyanin transport genes in strawberry fruit remain unclear. In this study, a gene encoding an ATP-binding cassette (ABC) protein of type C, ABCC8, was isolated from strawberry fruits. qRT-PCR analysis demonstrated that the transcript levels of FvABCC8 were the highest and were strongly correlated with anthocyanin accumulation during strawberry fruit ripening. Transient overexpression and RNAi of FvABCC8 led to an increase and decrease in anthocyanin content in strawberry fruits, respectively. Moreover, the ABCC8 promoter was activated by MYB and bHLH transcription factors MYB10, bHLH33, and MYC1. Sucrose enhanced anthocyanin accumulation in FvABCC8-overexpressing Arabidopsis, particularly at higher concentrations. FvABCC8-overexpressing lines were less sensitive to ABA during seed germination and seedling development. These results suggest that strawberry vacuolar anthocyanin transport may be mediated by the ABCC transporter ABCC8, the expression of which may be regulated by transcription factors MYB10, bHLH33, and MYC1.

C1632 inhibits ovarian cancer cell growth and migration by inhibiting LIN28 B/let-7/FAK signaling pathway and FAK phosphorylation.

The highly conserved RNA-binding protein LIN28B and focal adhesion kinase (FAK) are significantly upregulated in ovarian cancer (OC), serving as markers for disease progression and prognosis. Nonetheless, the correlation between LIN28B and FAK, as well as the pharmacological effects of the LIN28 inhibitor C1632, in OC cells have not been elucidated. The present study demonstrates that C1632 significantly reduced the rate of DNA replication, arrested the cell cycle at the G0/G1 phase, consequently reducing cell viability, and impeding clone formation. Moreover, treatment with C1632 decreased cell-matrix adhesion, as well as inhibited cell migration and invasion. Further mechanistic studies revealed that C1632 inhibited the OC cell proliferation and migration by concurrently inhibiting LIN28 B/let-7/FAK signaling pathway and FAK phosphorylation. Furthermore, C1632 exhibited an obvious inhibitory effect on OC cell xenograft tumors in mice. Altogether, these findings identified that LIN28 B/let-7/FAK is a valuable target in OC and C1632 is a promising onco-therapeutic agent for OC treatment.

FAK inhibitor PF-562271 inhibits the migration and proliferation of high-grade serous ovarian cancer cells through FAK and FAK mediated cell cycle arrest.

Focal adhesion kinase (FAK) is a promising therapeutic target for various cancers and its inhibitor development is in full swing. PF-562271 is a classic FAK inhibitor that has shown promising preclinical data and has been found to exhibit an anti-migration effect on some cancer cells. However, its anticancer effect on high-grade serous ovarian cancer (HGSOC) has not been reported. In this study, we evaluated the anti-migration and anti-proliferation effects of PF-562271 against HGSOC SKOV3 and A2780 cells, as well as the underlying mechanism. The results demonstrated that FAK was overexpressed in clinical HGSOC tissues and was positively correlated with the pathological progression of HGSOC. Moreover, HGSOC patients with high FAK expression levels exhibited low survival rates. PF-562271 treatment significantly inhibited the cell adhesion and migration of SKOV3 and A2780 cells by inhibiting p-FAK expression and decreasing the FA surface area. Additionally, PF-562271 treatment inhibited colony formation and induced cell senescence through G1 phase cell cycle arrest mediated DNA replication inhibition. Taken together, the findings demonstrated that FAK inhibitor PF-562271 significantly inhibits HGSOC cell adhesion, migration, and proliferation process through FAK and/or FAK mediated cell cycle arrest, and suggested that PF-562271 could serve as a potential oncotherapeutic agent for HGSOC targeting treatment.

Ginkgetin suppresses ovarian cancer growth through inhibition of JAK2/STAT3 and MAPKs signaling pathways.

BACKGROUND: Ginkgo biloba L., a kind of traditional Chinese medicine, is always used to treat various diseases. Ginkgetin is an active biflavonoid isolated from leaves of Ginkgo biloba L., which exhibits diverse biological activities, including anti-tumor, anti-microbial, anti-cardiovascular and cerebrovascular diseases, and anti-inflammatory effects. However, there are few reports on the effects of ginkgetin on ovarian cancer (OC). HYPOTHESIS/PURPOSE: OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC. METHODS: The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo. RESULTS: We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo. CONCLUSION: Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.

Optical properties, bioimaging and theoretical calculation of a Zn(II) complex based on triphenylamine derivative.

A luminescent material with various optical properties based on a triphenylamine Zn(II) complex is described. The ultraviolet-visible absorption, one-photon excited fluorescence (OPEF) and two-photon excited fluorescence (TPEF) of the complex indicate that the material has good OPEF and TPEF properties. And the results of one- and two-photon HepG2 cells imaging experiments show the potential of the complex in fluorescence microscopy bioimaging. The experimental Stokes shift and the FWHM (full-width at half-maximum) in different solvents were correlated with the rMPI polarity of the solvent, and the perfect Boltzmann curves were obtained, where the Boltzmann correlation between Stokes shift and solvent polarity is reported for the second time. But the Boltzmann correlation between FWHM and solvent polarity is reported for the first time. In addition, the computational results indicate that, the covalent bond within the salt ZnBr2 is strengthened by the coordination, and the newly formed coordination bond Zn-N is stronger than the original covalent bond Zn-Br.

The R2R3-MYB transcription factor FaMYB63 participates in regulation of eugenol production in strawberry.

The biosynthetic pathway of volatile phenylpropanoids, including 4-allyl-2-methoxyphenol (eugenol), has been investigated in petunia (Petunia hybrida). However, the regulatory network for eugenol accumulation in strawberry (Fragaria × ananassa Duch.) fruit remains unclear. Here, an R2R3-type MYB transcription factor (TF; FaMYB63) was isolated from strawberry by yeast one-hybrid (Y1H) screening using the promoter of the FaEGS1 (eugenol synthase 1 [EGS 1]) gene, which encodes the enzyme responsible for the last step in eugenol biosynthesis. FaMYB63 is phylogenetically distinct from other R2R3-MYB TFs, including FaEOBІІ (EMISSION OF BENZENOID II [EOBII]), which also participates in regulating eugenol biosynthesis in strawberry receptacles. Reverse transcription quantitative PCR (RT-qPCR) assays showed that the expression of FaMYB63 was tissue-specific and consistent with eugenol content through strawberry fruit development, was repressed by abscisic acid, and was activated by auxins (indole-3-acetic acid). Overexpression and RNA interference-mediated silencing of FaMYB63 resulted in marked changes in the transcript levels of the biosynthetic genes FaEGS1, FaEGS2, and FaCAD1 (cinnamyl alcohol dehydrogenase 1 [CAD1]) and, thereby, the accumulation of eugenol. Electrophoretic mobility shift, Y1H, GUS activity, and dual-luciferase activity assays demonstrated that the transcript levels of FaEOBІІ and FaMYB10 were regulated by FaMYB63, but not the other way around. Together, these results demonstrate that FaMYB63 directly activates FaEGS1, FaEGS2, FaCAD1, FaEOBІІ, and FaMYB10 to induce eugenol biosynthesis during strawberry fruit development. These findings deepen the understanding of the regulatory network that influences eugenol metabolism in an edible fruit crop.

FvMYB24, a strawberry R2R3-MYB transcription factor, improved salt stress tolerance in transgenic Arabidopsis.

Salinity is one of the major environmental stresses that limit crop growth and productivity. In this study, the FvMYB24 gene that encodes an R2R3-type MYB transcription factor was cloned and characterized. An expression analysis showed that FvMYB24 had a tissue- and stage-specific profile and was induced by salt treatment. Arabidopsis plants that overexpressed transgenic FvMYB24 exhibited a higher germination rate, fresh weight, chlorophyll content, and longer root length than the wild type (WT) under salt stress. The transgenic plants had higher activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) and the accumulation of proline, while these plants accumulated lower amounts of malondialdehyde (MDA) compared with the WT. Furthermore, our results also revealed that the overexpression of FvMYB24 up-regulated the expression of several stress-related genes (AtSOS1, AtSOS2, AtSOS3, AtSOD, AtPOD, AtCAT1, AtNHX1, and AtLEA3) in response to salt stress, thus, enhancing the tolerance of transgenic Arabidopsis. An analysis of the cis-acting elements in the SOS1, SOS2, and SOS3 promoters revealed MYB-binding sites. However, FvMYB24 could only bind to the SOS1 promoter to mediate salt tolerance but not to the SOS2 and SOS3 promoters. These findings suggest that FvMYB24 could potentially be used as a positive regulator in transgenic plant breeding to improve the tolerance of strawberry plants to salt.

A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer.

PURPOSE: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen. PATIENTS AND METHODS: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin. RESULTS: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039). CONCLUSIONS: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.

Designing wearable computing devices for improved comfort and user acceptance.

This study identified acceptable range of physical attributes (form factors, weight, volume and contact area) of wearable computing devices (WCD) on different body areas in relation to human factors, through human performance tests with 41participants. Findings of this study discovered that there is a different level of threshold to discomfort on each part of the body; forearm has the smallest estimated mean of acceptable maximum weight of WCD followed by shirt pocket and collar area. On the other hand, front waist and back waist, when placed on one side, showed significantly higher estimated means of acceptable maximum weight of WCD than any other areas. Similar data trend was found in acceptable maximum volume and contact area of WCD. Body movement and posture influence the users' comfort, as the weight of WCD can cause unhealthy posture over time, and increased energy expenditure, which may cause orthopaedic problems and discomfort. Practitioner summary: This study discovered that in carrying wearable computing devices (WCD), there is a different level of threshold to discomfort on each part of the body, as evidenced by significantly different acceptable maximum weight, volume and contact area of WCD on different body part. Abbreviations: WCD: wearable computing devices.

[Investigation of pathogenic bacteria for pulmonary infections and their drug resistance in neurological intensive care unit].

OBJECTIVE: To investigate the pathogenic bacterial spectrum responsible for pulmonary infections and their drug resistance in patients admitted to neurological care unit. METHODS: Sputum specimens were obtained from patients who developed pulmonary infections in neurological intensive care unit between January, 2001 and June, 2002 for bacterial culture and isolation. K-B paper disc method was employed for determination of the drug sensitivity of the bacterial isolates. RESULTS: In the 207 strains obtained from the patients, the majority (68.51%) were Gram-negative and 30.91/ Gram-positive bacteria, with fungi detected in one case (0.48%). The major pathogenic bacteria for pulmonary infection were, in the order of frequency, Staphylococcus aureus(14.49%), Pseudomonas aeruginosa (14.49%), Klebsiella pneumoniae (8.7%), Enterobacter cloacae (6.76%), and Enterobacter aerogenes (6.28%). Drug sensitivity tests showed increased drug resistance of the bacteria, but Staphylococcus aureus still remained sensitive to vancomycin and most of the Gram-negative bacillus sensitive to imipenem. CONCLUSION: The major pathogenic bacteria causing pulmonary infections in neurological intensive care unit are Staphylococcus aureus and Pseudomonas aeruginosa, and their drug resistance is obviously increased, suggesting the necessity of strengthening bacterial surveillance and more adequate clinical use of antibiotics.