Background: 5-Fluorouracil (5-FU) is the first-choice treatment for all grades of gastric carcinoma, one of the most common malignant digestive tract tumors worldwide. However, the resistance to 5-FU is a major problem affecting the treatment and prognosis of gastric cancer. As a monomer component of Chinese traditional herbs, tetrandrine has high efficiency, low toxicity, multitarget effects, and strong specificity, and can reverse multidrug resistance by several pathways. Organoid technology is a versatile tool for the generation and long-term maintenance of near-native three-dimensional epithelial tissues in vitro, and the generation of cancer organoids from primary patient material enables testing many therapeutic agents in the resulting organoid cultures. This article aims to build GCOs and explore the potential of tetrandrine to overcome drug resistance and the associated signaling pathways by organoid technology.Methods: The typical GC tumor fractions far away from necrotic areas were obtained by surgery. Genomic analysis, histology and imaging, and multiplex immunofluorescence were performed. Meanwhile, the GCOs were constructed and were cultured for six months. The GCOs retained histopathological features and drug reactivity of the primary tumor. To study the reversal and sensitization effect of tetrandrine on 5-FU resistance, 5-FU–resistant cell lines were constructed. Through whole-exon sequencing of two cell lines with different sensitivities, the related genes that may cause drug resistance were screened out. The protein levels in two cell lines were quantified using Western blot (WB) analysis.Findings: The patients’ resistance to 5-FU was reproduced at the organoid level, and tetrandrine improved the sensitivity of GCOs to 5-FU. In the MN-45 gastric cancer cell line, tetrandrine significantly improved the cell-killing effect of 5-FU. We found that the TGF-β signaling pathway and ABCB1 transporters were the main causes of drug resistance in gastric cancer. Tetrandrine can enhance the sensitivity of tumor cells to 5-FU by inhibiting the TGF-β signaling pathway and increasing the expression of ABCB1 transporter.Interpretation: Tetrandrine can enhance the sensitivity of tumor cells to 5-FU by inhibiting the TGF-β signaling pathway and increasing the expression of ABCB1 transporter.Funding: This work was not supported by any research project.Declaration of Interest: The authors declare no potential conflicts of interest.Ethical Approval: All experiments involving human tissue specimens were approved by the Ethics Committee of China-Japan Friendship Hospital (approved number is 2022-KY-228-1), and informed consent were obtained from all participating patients.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Background/aims To identify the risk factors for neuropathic corneal pain (NCP) following corneal refractive surgery and to report its clinical manifestations, imaging and proteomic characteristics. Methods This 1 year prospective cohort study included 100 eyes that underwent small incision lenticule extraction (SMILE) or laser-assisted in situ keratomileusis (LASIK). Ocular surface assessments, in-vivo confocal microscopy scans, tear neuromediators and proteomics analyses were performed. NCP was assessed using the ocular pain assessment survey. Univariate and multivariate analyses were conducted to identify the risk factors associated with postoperative NCP. Results The incidence of NCP was 13.3% and 10.5% after SMILE and LASIK, respectively (p=0.70). In SMILE, preoperative manifest refractive spherical equivalent (MRSE) and spherical power (both p=0.02) were significantly higher in the NCP compared with the non-NCP group. In LASIK, NCP eyes had a significantly lower corneal nerve fibre length (CNFL) (p=0.02), lower nerve fractal dimension (p=0.003), higher nerve fibre width (p=0.04) and larger neuroma area (p=0.04) than non-NCP eyes. In SMILE, higher preoperative MRSE was a significant risk factor for postoperative NCP (95% CI: 0.48—1.96, p=0.04). An MRSE greater than −8.0 diopter was 9.57 times more likely to develop postoperative NCP (OR=9.57, p=0.002). In LASIK, lower preoperative corneal nerve fibre density (95% CI:0.13—1.11, p=0.05) and CNFL (95% CI:0.09—1.25, p=0.05) were significant risk factors for postoperative NCP. Significant increases in tear nerve growth factor, calcitonin gene-related peptide, Frizzled class receptor 7 and nucleoside-diphosphate kinase three were observed in postoperative NCP. Conclusions The reported characteristics and risk factors would identify patients susceptible to NCP after corneal refractive surgery.
With non-professional based on-site detection mode and miniature, portable and intelligent techniques as the basis, the potential of point-of-care testing (POCT) to feedback the result timely and help to make right decisions to handle emergencies has drawn the attention from extensive fields, including clinical investigation, disease control and prevention, quality control, environmental protection, forensic investigation, import and export inspection and so on. In this review, the definition, history and challenge of POCT promotion from qualitative detection to quantitative one were discussed.（Chin J Lab Med，2014,37：801-803）
Key words:
Point-of-care systems; Quality assurance, health care; Quality control
Aims: To investigate whether Gou Qi Zi contains sufficient carotenoids and fatty acids to supply the special lipid requirements of the human retina. Materials and methods: Lipids were extracted from Gou Qi Zi by ethanol-hexane, then separated on a silica column and eluted by dioxane-hexane. The eluant was monitored by a photodiode array detector followed by a mass spectrometry detector. Results: Before hydrolysis, only one pigmented lipid was detected in the chromatogram. The molecular size was identical to that of dipalmityl zeaxanthin. The major non-pigmented lipids have the molecular size of triglycerides and diglycerides. After hydrolysis, a marked increase in oleic, linoleic acid, and long chain fatty acids with 22 and 24 carbons was observed. Conclusion: The lipid content in Gou Qi Zi matches the specific requirements of the human retina for long chain polyunsaturated fatty acids and zeaxanthin.
The tear proteomics and neuromediators are associated with clinical dry eye parameters following refractive surgery. To investigate and compare the tear proteomic and neuromediator profiles following small incision lenticule extraction (SMILE) versus laser-assisted in-situ keratomileusis (LASIK). In this randomized controlled trial with paired-eye design, 70 patients were randomized to receive SMILE in one eye and LASIK in the other eye. Tear samples were collected preoperatively, and 1 week, 1, 3, 6 and 12 months postoperatively, and were examined for protein concentration changes using sequential window acquisition of all theoretical fragment ion mass spectrometry (SWATH-MS). The data were analyzed with DAVID Bioinformatics Resources for enriched gene ontology terms and over-represented pathways. Tear neuromediators levels were correlated with clinical parameters. Post-SMILE eyes had significantly better Oxford staining scores and tear break-up time (TBUT) than post-LASIK eyes at 1 and 3 months, respectively. Tear substance P and nerve growth factor levels were significantly higher in the LASIK group for 3 months and 1 year, respectively. SMILE and LASIK shared some similar biological responses postoperatively, but there was significant up-regulation in leukocyte migration and wound healing at 1 week, humoral immune response and apoptosis at 1 month, negative regulation of endopeptidase activity at 3 to 6 months, and extracellular structure organization at 1 year in the post-LASIK eyes. Tear mucin-like protein 1 and substance P levels were significantly correlated with TBUT (r = -0.47, r = -0.49, respectively). Significant differences in the tear neuromediators and proteomics were observed between SMILE and LASIK, even though clinical dry eye signs have subsided and became comparable between 2 procedures.
This study aimed to investigate the correlation between serum laminin (LN) levels and clinical stages of heart failure in patients with chronic heart failure.A total of 277 patients with chronic heart failure were selected from September 2019 to June 2020 in the Department of Cardiology, Second Affiliated Hospital of Nantong University. Based on stages of heart failure, the patients were divided into four groups: stage A, stage B, stage C, and stage D, with 55, 54, 77, and 91 cases, respectively. At the same time, 70 healthy people in this period were selected as the control group. Baseline data were recorded and serum Laminin (LN) levels were measured. The research compared, the differences in baseline data among the four groups of HF and normal controls, and analyzed the correlation between N-terminal pro-brain natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF). The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of LN in the C-D stage of heart failure. Logistic multivariate ordered analysis was applied to screen the independent related factors of clinical stages of heart failure.Serum LN levels in patients with chronic heart failure were significantly higher than those in healthy people, which were 33.2 (21.38, 101.9) ng/ml and 20.45 (15.53, 23.04) ng/ml, respectively. With the progression of clinical stages of HF, serum LN and NT-proBNP levels increased, while LVEF gradually decreased (P < 0.05). Correlation analysis showed that LN was positively correlated with NT-proBNP (r = 0.744, P = 0.000) and negatively correlated with LVEF (r = -0.568, P = 0.000). The area under the ROC curve of LN for predicting C and D stages of heart failure was 0.913, 95% confidence interval was 0.882-0.945, P = 0.000, specificity 94.97%, and sensitivity 77.38%. Multivariate Logistic analysis showed that LN, Total bilirubin, NT-proBNP and HA were all independent correlates of heart failure staging.Serum LN levels in patients with chronic heart failure are significantly increased and are independently correlated with the clinical stages of heart failure. It could potentially be an early warning index of the progression and severity of heart failure.
Cell therapy (also known as cell transplantation) has been considered promising as a next-generation living-cell therapy strategy to surpass the effects of traditional drugs. However, their practical clinical uses and product conversion are hampered by the unsatisfied viability and efficacy of the transplanted cells. Herein, we propose a synergistic enhancement strategy to address these issues by constructing 3D stem cell spheroids integrated with urchin-like hydroxyapatite microparticles (uHA). Specifically, cell-sized uHA microparticles were synthesized
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