Exploring the problems and coping strategies of pharmacy internship in large general hospitals in China: from the perspective of preceptors.

OBJECTIVE: The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. METHODS: This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. RESULTS: Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs' perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. CONCLUSION: This study found that from the HPPs' perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.

Chemical profiling of Zilong Jin tablets using ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry.

Zilongjin tablets as a traditional Chinese medicine are widely used for primary lung cancer patients with deficiency of "qi " and "blood " syndrome undergoing chemotherapy. It is a compound preparation that consists of eight herbs. To clarify the chemical profiling of Zilong Jin tablets rapidly, a feasible and accurate strategy was developed by the ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry. According to the accurate mass and fragment ion information provided by high resolution mass spectrometry, the compounds were reasonably identified. In total, 74 compounds were characterized, including 20 flavonoids, 14 quinones, 15 organic acids, 6 phthalide compounds, and 19 other compounds. Among them, 34 major compounds were unambiguously confirmed by comparing with reference standards. This study could provide an important scientific basis for further research on quality control, pharmacokinetics and pharmacodynamics, and clinical application of Zilong Jin tablets.

Study on the mechanism of Shenkang injection in the treatment of chronic renal failure based on the strategy of "Network pharmacology-Molecular docking-Key target validation".

OBJECTIVE: To explore the potential mechanism of Shenkang injection (SKI) in the treatment of chronic renal failure based on network pharmacology and molecular docking technology, and to verify the core targets and key pathways by using the renal failure model. METHODS: The active components and targets of Shenkang injection were retrieved by TCMSP database, and the disease related targets were obtained by OMIM, GeneCards and other databases. Then, the intersection was obtained, and were imported into String database for PPI analysis. After further screening of core targets, GO and KEGG analysis were performed. Autodock software was used to predict the molecular docking and binding ability of the selected active ingredients and core targets. Chronic renal failure (CRF) model was established by adenine induction in rats, and the pathological observation of renal tissues was conducted. Meanwhile, the effects of Shenkang injection and its active components on core targets and pathways of renal tissues were verified. RESULTS: The results of network pharmacology showed that the main components of Shenkang injection might be hydroxysafflor yellow A (HSYA)、tanshinol、rheum emodin、Astragaloside IV. Through enrichment analysis of core targets, it was found that Shenkang injection may play an anti-chronic renal failure effect through PI3K-Akt signaling pathway. Molecular docking results showed that the above pharmacodynamic components had strong binding ability with the target proteins PI3K and Akt. The results of animal experiments showed that renal function indexes of Shenkang injection group and pharmacodynamic component group were significantly improved compared with model group. HE staining results showed that the pathological status of the kidney was significantly improved in SKI and pharmacodynamic component treatment groups. Immunohistochemical results showed that the renal fibrosis status was significantly reduced in SKI and pharmacodynamic component treatment groups. q-RTPCR and WB results showed that the expression levels of PI3K and Akt were significantly decreased in the treatment groups (P< 0.05). CONCLUSIONS: Shenkang injection may inhibit PI3K-Akt signaling pathway to play an anti-chronic renal failure role through the pharmacodynamic component hydroxysafflor yellow A (HSYA), tanshinol, rheum emodin, Astragaloside IV.

Self-assembled insulin-like growth factor 1 peptides induce adipose stem cell differentiation to repair cartilage injury.

BACKGROUND: Tissue engineering using adipose-derived mesenchymal stem cells (ADSCs) promotes the regeneration of articular cartilage. However, insulin-like growth factor 1 (IGF-1), which is used to induce the differentiation of ADSCs into chondrocytes during treatment, is prone to instability and short tissue retention. METHODS: Nap-FFG-GYGSSSRRAPQT was used as an IGF-1 mimicking molecule. MTT and CCK-8 assays were performed to evaluate the proliferation ability of ADSCs. QRT-PCR and Western blot assays were used to assess the expression of cartilage-related genes. International Cartilage Regeneration and Joint Preservation Society (ICRS) scoring was used for the evaluation of cartilage repair. Repaired tissues were analyzed by hematoxylin-eosin, Safranin-O and immunohistochemical staining. RESULTS: Nap-FFG-GYGSSRRAPQT stimulated the proliferation and migration of ADSCs through the activation of IGF-1 receptor. Gel Nap-FFG-GYGSSRRAPQT treatment upregulated the expression of cartilage-related genes in ADSCs. ADSCs/Gel Nap-FFG-GYGSSRRAPQT treatment significantly promoted the regeneration of cartilages. CONCLUSION: Self-assembled IGF-1 peptide, Nap-FFG-GYGSSRRAPQT, can induce ADSC differentiation and proliferation to repair cartilage injury.

Rapid determination of 30 bioactive constituents in XueBiJing injection using ultra high performance liquid chromatography-high resolution hybrid quadrupole-orbitrap mass spectrometry coupled with principal component analysis.

Xuebijing injection (XBJ) is a traditional Chinese herbal prescription widely used in the treatment of sepsis. Extensive chemical studies revealed that XBJ injection contains amino acids, phenolic acids, flavonoid glycosides, terpeneglycosides and phthalides. In this study, the applicability of ultra high performance liquid chromatography coupled with high resolution hybrid quadruple-orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) for the simultaneous quantitative analysis of 30 bioactive constituents in XueBiJing injection (XBJ) was investigated. The mass spectrometer was operated in full MS scan mode. The use of 70,000FWHM mass resolution and narrow mass windows (5ppm) could effectively improve the selectivity of the method. Separation was achieved on a Waters ACQUITY UPLC® HSS C18 column (2.1mm×100mm, 1.8µm) with a gradient mobile phase consisting of acetonitrile-water (containing 10mM ammonium acetate) at a flow rate of 0.2mL/min. Satisfactory linearity was achieved within wide linear range and all correlation coefficients (r) of analytes were more than 0.9996. The limits of detection (LODs) were in the range of 0.1180-27.82ng/mL for different analytes. The relative standard deviations (RSDs) of inter- and intra-day precisions were less than 3.0% and the recoveries of the assay were in the range of 98.5%-101.5%. The validated method was successfully applied for simultaneous determination of 30 bioactive compounds in XueBiJing injection from 10 batches samples by UHPLC-Q-Orbitrap MS within 10min. Moreover, the results were evaluated principal component analysis and two compounds might be the most important chemical markers for chemical quality control of XBJ injection. The novel Q-Orbitrap mass spectrometry has been proved to be a very promising and powerful tool for routine screening of bioactive compounds in traditional Chinese medicine injection, ensuring drug safety and public health.

pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer.

Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis.

The use of lipid-coated nanodiamond to improve bioavailability and efficacy of sorafenib in resisting metastasis of gastric cancer.

The metastasis is one of the greatest challenges for successful cancer therapy. Herein, we report a lipid-coated nanodiamond (ND) system loading water-insoluble sorafenib (SND) to improve the bioavailability and efficacy on suppression of cancer metastasis. SND was homogenous nanoassemblies with the mean diameter of 127.6 ± 12.9 nm. Compared with the drug suspension, the sorafenib concentration in gastrointestinal (GI) tract and major organs was significantly increased by SND. Moreover, the oral bioavailability of sorafenib was greatly improved 7.64-fold by SND. However, the ND in SND could not be absorbed into the mucus of GI tract or distributed into major organs after oral administration. Furthermore, the sorafenib concentration in tumor tissue was markedly improved 14.95 folds by SND, and SND demonstrated an efficient and impressive tumor growth inhibition effect in tumor xenograft models. In particular, the metastasis of gastric cancer to distant organs of liver and kidney was remarkably suppressed by SND, which was verified by the detection of macroscopic metastatic nodules, histological examination and immunofluorescence measurements. Thereby, the lipid-coated ND could be a promising drug delivery platform for improving the oral bioavailability of lipophilic drugs and treatment of cancer metastasis.