Background: Nowadays, mental health problems have become a major concern affecting economic and social development, with severe mental health disorders being the top priority. In 2013, Beijing began to implement the Community Free-Medication Service policy (CFMS). This article aims to evaluate the effect of the policy on medication adherence. Methods: In this study, multi-stage sampling was used to select representative patients as samples. Some of the baseline data were obtained by consulting the archives, and information about patient medication adherence measured by Brooks Medication Adherence Scale was obtained through face-to-face interviews. Logistic regression was used to examine the impact of the policy. Results: Policy participation had a significant positive impact on medication adherence (OR = 1.557). The effect of policy participation on medication adherence in the Medication-only mode and Subsidy-only mode were highly significant, but it was not significant in the Mixed mode. Conclusion: This study found that the CFMS in Beijing as an intervention is effective in improving the medication adherence of community patients. However, the impact of the policy is not consistent among service modes. Reinforcement magnitude and frequency should be considered when designing reinforcement interventions.
Protein dimerization, as the most common form of protein–protein interaction, can manifest more significant roles in cellular signaling than individual monomers. For example, excessive formation of EGFR–HER2 dimer has been implicated in cancer development and therapeutic resistance in addition to the overexpression of EGFR and HER2 proteins. Thus, quantitative evaluation of these heterodimers in living cells and revelation of their ratiometric relationship with protein monomers in dimerization may provide insights into clinical cancer management. To achieve this goal, the prerequisite is protein heterodimer quantification. Given the current lack of quantitative methods, we constructed a mass-tagged oligo nanoprobe set for quantification of EGFR–HER2 dimer in living cells. The mass-tagged oligo nanoprobe set contained two targeting probes (nucleic acid aptamers), a connector probe, a hairpin probe, and a photocleavable mass-tagged probe. Two distinct aptamers can recognize target protein monomers and initiate the subsequent hybridization cascade involving binding to the connector probe, formation of an initiator strand, opening of a hairpin probe, and ensuing hybridization with a photocleavable mass-tagged probe. Ultimately, the mass tag was released under ultraviolet light and then subjected to mass spectrometric analysis. In this way, the information regarding the interaction between two protein monomers was successfully converted to the quantitative signal of the mass tag. Using the assay, the expression level of EGFR–HER2 dimer and its relationship with individual protein monomers were determined in four breast cancer cell lines. We are among the first to obtain the absolute level of protein heterodimer, and this quantitative information may be vital in understanding the molecular basis of cancer.
Objective To investigate the pharmacokinetics of tramadol hydro-chloride-paracetamol tablets after oral administration in Chinese healthy volunteers. Methods Twenty heathy volunteers (6 men and 6 women) were given 1 or 2 tablets, 8 heathy male volunteers were given 1 tablets in fasted and fed treatment. The plasma concentrations of tramadol were determined by HPLC-MS and paracetamol by HPLC-UV. Results Pharmacokinetic profiles were fitted to a one compartment model calculated by BAPP2. 0 software. Pharmacokinetic parameters for 1 and 2 tablets were as followings:tramadol Cmax was (155.22 ±35.32) and (299.99 ± 56. 97) ng·mL-1, tmax was (2.5 ±0.8) and (2.5 ±1.0) h,t1/2 was (5.77 ±1.66) and (5.15 ± 1.24) h; in fasted and fed treatment, Cmax was (151.62 ±22.37) and (144. 86±25.49) ng·mL-1,tmax was (1.4±0.5) and (3.3 ±1.4) h,t1/2 was (5. 56 ±1. 51) and (5. 40 ± 1. 67) h. For 1 and 2 tablets, paracetamol Cmax was (4. 63 ± 1.46) and (10.01 ± 3. 08)μg·mL-1,tmax was (1.0 ± 0.5) and (1.0 ±0.5) h,t1/2 was (3.00±0.41) and (2.72 ±0.51) h; in fasted and fed treatment, Cmax was (3. 56 ±0. 81) and (3.16 ±0. 70) μg· mL-1,tmax was (0. 8 ±0.5) and (1. 8 ±0. 9) h,t1/2 was (3. 25 ±0.43) and (2. 89 ±0. 33) h. Conclusion It is a first order processes of tramadol hydrochloride - paracetamol tablets in vivo. Fed treatment may decrease the absorption rate of tramadol hydrochloride - paracetamol tablets but not reduces their absorption extent in vivo.
Despite a good and overall prognosis, papillary thyroid cancer (PTC) can still affect the quality of life of many patients, and can even be life-threatening due to its invasiveness and metastasis. Emerging studies demonstrate that circular RNAs (circRNAs) participate in the regulation of various cancers. However, the circRNA profile in invasive PTC is still not well understood. Competing endogenous RNA (ceRNA) microarrays were performed to determine circRNAs contributed to the tumorigenesis and invasiveness of PTC. Bioinformatics methods were used to narrow down the candidate circRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) assays revealed a significant upregulation of hsa_circ_0058124 in PTC tissue and a close correlation with a poor prognosis for PTC patients. RNA fluorescence in situ hybridization and Cell fractionation assay were used to investigate the subcellular location of hsa_circ_0058124. Then, we examined the functions of hsa_circ_0058124 in PTC by cell proliferation, cell cycle, apoptosis, migration and invasion assay. Mechanistically, RNA sequencing and GSEA analysis were applied to predict the downstream pathway of hsa_circ_0058124. Dual-luciferase report assays were used to explore the potential miRNA sponge role of hsa_circ_0058124. Western blotting, cell proliferation, cell cycle, cell apoptosis, migration and invasion, and mouse xenograft assay were used to validate the effects of hsa_circ_0058124/NOTCH3/GATAD2A axis on PTC progression. In the current study, a novel hsa_circ_0058124 on 2q35 was identified and explored in PTC. Hsa_circ_0058124 is associated with the malignant features and poor outcomes of PTC patients. Hsa_circ_0058124 acts as an oncogenic driver that promotes PTC cell proliferation, tumorigenicity, tumor invasion, and metastasis, which functions as a competing endogenous RNA to modulate miRNA-218-5p and its target gene NUMB expression, and consequently with repression of the NOTCH3/GATAD2A signaling axis in vitro and in vivo. This study unveils a novel biomarker panel consisting of the hsa_circ_0058124/NOTCH3/GATAD2A axis which is critical for PTC tumorigenesis and invasiveness and may represent a novel therapeutic target for intervening in PTC progression.
Histone post-translational modification (PTM) is a marker for gene transcription and is involved in a range of cancers, such as breast cancer. Most importantly, different modifications of a specific site (e.g., mono-, di- and tri-methylations and acetylation at a lysine residue) are individually enriched in particular regions of the genome, indicating that they may serve distinct functions. How these patterns are built and whether downstream events are dependent on the precise site-specific modification status are still poorly understood. One of the prerequisites is to obtain quantitative information on individual modification forms. Currently, the low abundance of these forms creates a great challenge. In this study, a targeted proteomics assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with single template oriented molecularly imprinted polymers (MIPs) was developed to attempt to simultaneously quantify site-specific histone mono-, di- and tri-methylated and acetylated forms. Surrogate peptides, including an unmodified one, were selected as targets in both MIP enrichment and subsequent LC-MS/MS detection. As a consequence, a limit of quantification (LOQ) of ∼0.5 nM was achieved, which was 10-fold more sensitive than without MIPs and much more sensitive than mass spectrometry involving a scanning mode. Finally, the assay was employed to quantitatively analyze the H3K79, H3K122 and H4K31 modification status in human breast cell lines.
Through protein-protein BLAST of homologous sequences in different species in NCBI database and preliminary simulating molecular docking and molecular dynamics by computer software discovery studio 3.1, three amino acids R25K26K27 of natural human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological activity of the mutant peptide was evaluated. Result showed that: root mean superposition deviation RMSD value between PTH (1-34)-(RKK-QEL) and PTH (1-34) peptide main chain was 2.509 3, indicating that the differences between the two main chain structural conformation was relatively small; the interaction energy between PTH (1-34)-(RKK-QEL) and its receptor protein PTH1R had been enhanced by 7.5% compared to nature PTH (1-34), from -554.083 kcal x mol(-1) to -599.253 kcal x mol(-1); the number of hydrogen bonds was increased from 32 to 38; PTH (1-34)-(RKK-QEL) can significantly stimulate the RANKL gene expression (P < 0.01) while inhibiting the OPG gene expression (P < 0.01) in UAMS-32P cells; in the co-culture system of UAMS-32P cells and mouse primary femur bone marrow cells, PTH (1-34)-(RKK-QEL) stimulated the formation of osteoclasts (P < 0.01) and had a higher biological activity than PTH (1-34) standard reagents.
MicroRNAs (miRNAs) play a vital role in regulating gene expression and are associated with a variety of cancers, including breast cancer. Their distorted and unique expression is a potential marker in clinical diagnoses and prognoses. Thus, accurate determination of miRNA expression levels is a prerequisite for their applications. However, the assays currently available for miRNA detection typically require pre-enrichment, amplification and labeling steps, and most of the assays are only semi-quantitative. Therefore, we developed a quasi-direct liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics approach to quantify target miRNA by innovatively converting the miRNA signal into the mass response of a reporter peptide via a covalently immobilized DNA-peptide probe. Specifically, the probe containing the targeted proteomics-selected substrate/reporter peptide, GDRAVQLGVDPFR/AVQLGVDPFR, and the DNA sequence complementary to the target miRNA (i.e., miR-21) was first immobilized on APMTS modified silica nanoparticles using PDITC. After the immobilized probe was recognized and hybridized with the target miRNA, the excess probe was degraded using MBN and followed by a trypsin digestion of the hybrids. The reporter peptide was released and quantified using LC-MS/MS. The obtained LOQ was 5 pM. Finally, the developed assay was used for the quantitative analysis of miR-21 in breast cells and tissue samples.
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