Fructose-bisphosphatase1 (FBP1) alleviates experimental osteoarthritis by regulating Protein crumbs homolog 3 (CRB3).

PURPOSE: To identify the role of gluconeogenesis in chondrocytes in osteoarthritis (OA). MATERIALS AND METHODS: Cartilage samples were collected from OA patients and C57 mice and were stained with Safranin O-Fast Green to determine the severity of OA. Periodic acid Schiff staining was used to characterize the contents of polysaccharides and SA-ßGal staining was used to characterize the aging of chondrocytes. Immunohistochemistry and western blotting were used to detect fructose-bisphosphatase1 (FBP1), SOX9, MMP13, P21, and P16 in cartilage or chondrocyte. The mRNA levels of fbp1, mmp13, sox9, colX, and acan were analyzed by qPCR to evaluate the role of FBP1 in chondrocytes. RESULTS: The level of polysaccharides in cartilage was reduced in OA and the expression of FBP1 was also reduced. We treated the chondrocytes with IL-1ß to cause OA in vitro, and then made chondrocytes overexpress FBP1 with plasma. It shows that FBP1 alleviated the degeneration and senescence of chondrocytes in vitro and that it also showed the same effects in vivo experiments. To further understand the mechanism of FBP1, we screened the downstream protein of FBP1 and found that CRB3 was significantly downregulated. And we confirmed that CRB3 suppressed the degeneration and delayed senescence of chondrocytes. CONCLUSIONS: FBP1 promoted the polysaccharide synthesis in cartilage and alleviated the degeneration of cartilage by regulating CRB3, so FBP1 is a potential target in treating OA.

[Risk Analysis and Study of Post-marketing Adverse Events for Absorbable Sutures].

Objective To investigate, analyze, and evaluate the risk data associated with the clinical use of absorbable sutures by retrieving and summarizing information from the databases of the US FDA and CNKI, as well as the adverse event reports related to absorbable sutures from January 2019 to October 2022 within Zhejiang province. The adverse event reports are obtained from both incident locations and monitoring organizations affiliated with the registrant. The aim is to identify the main risk factors associated with the clinical use of absorbable sutures. The key risk factors are potential product quality defects, product design and material selection, clinical selection and application, and postoperative recovery care including patient's self-care. Risk control strategies are further proposed to reduce or minimize the risk of adverse events caused by this product.

High-Antimicrobial Gallium-Doped Zinc Oxide Thin Films on Bio-Based Poly(Ethylene Furanoate) Substrates for Food Packaging Application.

Thin films of gallium-doped zinc oxide (GZO), with a thickness of around fifty nanometers were deposited on bio-based poly(ethylene furanoate) (PEF) substrates by radio-frequency sputtering. By optimizing the Ga concentration in the target, the optics, water vapor barrier and antibacterial properties of PEF/GZO composite films can be adjusted. The highest visible light transmittance of the samples was around 85.1%. Furthermore, by introducing some GZO films with typical concentrations, the water vapor barrier and antibacterial properties of PEF films were improved. The optimized water vapor permeability of PEF/GZO composite film was 5.3 × 10-12 g·m/m2·s·Pa, and the highest antibacterial rate can reach 99.85% after 4 h. By XPS analysis, the antibacterial mechanism in the samples is envisaged to be mainly due cytotoxicity of Ga ions. The above results indicate that PEF/GZO films have great potential in the field of antibacterial food packaging.

Volumetric Analysis of Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting the Response to Chemotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: We aimed to prospectively investigate intravoxel incoherent motion parameters to predict the response to chemotherapy in locally advanced non-small cell lung cancer (NSCLC) patients. METHODS: From July 2016 to March 2018, 30 advanced NSCLC patients were enrolled and underwent chest intravoxel incoherent motion-diffusion-weighted imaging at Siemens 3T magnetic resonance imaging before and at the end of the first cycle of chemotherapy. Regions of interest were drawn including the whole tumor volume to derive the apparent diffusion coefficient value, D, D*, and f, respectively. Time-dependent receiver operating characteristic curves were generated to evaluate the cutoff values of continuous variables. A Cox proportional hazards model was used to assess the independent predictors of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were generated. RESULTS: Among the 30 patients, 28 cases (93.3%) died and 2 cases (6.7%) survived till the closeout date. Univariate Cox regression analyses revealed that the significant predictors of PFS and OS were the tumor size reduction rate, the change rates of D and apparent diffusion coefficient values, and the D value before therapy (PFS: P = 0.015, hazard ratio [HR] = 2.841; P < 0.001, HR = 5.840; P = 0.044, HR = 2.457; and P = 0.027, HR = 2.715; OS: P = 0.008, HR = 2.987; P < 0.001, HR = 4.357; P = 0.006, HR = 3.313; and P = 0.013, HR = 2.941, respectively). Multivariate Cox regression analysis suggested that △D% was identified as independent predictors of both PFS and OS (P = 0.003, HR = 9.200 and P = 0.016, HR = 4.617). In addition, the cutoff value of △D% was 21.06% calculated by receiver operating characteristic curve analysis. In the Kaplan-Meier analysis, the PFS and OS were significantly greater in the group of patients with △D% larger than 21.06% (log-rank test, χ2 = 16.453, P < 0.001; χ2 = 13.952, P < 0.001). CONCLUSIONS: Intravoxel incoherent motion-diffusion-weighted imaging was preferred for predicting the prognosis of advanced NSCLC patients treated with chemotherapy. A D increase more than 21.06% at 1 month was associated with a lower rate of disease progression and death.

[Study of Adverse Events of Endotracheal Intubation].

OBJECTIVE: In order to further decrease and reduce the serious adverse events of silicone rubber endotracheal intubation in clinical use, especially in anesthesia and intensive care. METHODS: Through the first stage analysis on the registration and certification of endotracheal intubation products in China, adverse events of products in recent five years in Zhejiang province, domestic and foreign literature of adverse events of products, retrieval of product citation standards, content integrity of product instructions, and expert seminar on serious adverse events, combined with the air leakage of endotracheal intubation products in recent two years, product material and clinical application with normative aspects. RESULTS: Silicone rubber endotracheal intubation products in clinical intensive care have certain clinical safety risks, especially for long-term use of critically ill patients. CONCLUSIONS: According to the four cases of serious adverse events of silicone rubber endotracheal intubation in the clinical intensive care unit, we put forward some suggestions for the manufacturers, clinical users and regulatory agencies to further decrease and reduce the serious adverse events of silicone rubber endotracheal intubation.

[Study on Adverse Events of Infant Incubator Products].

OBJECTIVE: To investigate the risk of adverse events in the clinical use of infant incubators of three kinds of national medical devices in Zhejiang Province. METHODS: Semi-quantitative matrix analysis was used to analyze the risk of adverse events related to incubator products in Zhejiang province from August 2018 to August 2019. RESULTS: Through the risk analysis of 213 cases of adverse events of infant incubator product, the risk point and degree of the product in practical clinical application were evaluated. CONCLUSIONS: Through the evaluation results of the production enterprises, medical institutions put forward relevant recommendations to reduce the risk of product use to prevent the recurrence of serious adverse events in the use of the product and spread.

The EZMTT cell proliferation assay provides precise measurement for drug combinations and better correlation between in vitro and in vivo efficacy.

The rate of drug-induced proliferation (DIP) has been proposed as an unbiased alternative drug effect metric. However, current assays are not easy and precise enough to track minor changes in cell growth. Here, we report the optimized EZMTT based detection method which can continuously measure time-dependent growth after drug treatment and reliably detect partial drug resistance for cancer cells. Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments. In conclusion, this simple EZMTT method provided precise measurement of loss of susceptibility after drug treatment and has great potential to be developed for drug efficacy and drug combination studies to solve the unmet medical need.

The value of diffusion-weighted imaging based on monoexponential and biexponential models for the diagnosis of benign and malignant lung nodules and masses.

OBJECTIVES: The objective is to compare the efficacy of diffusion-weighted imaging (DWI) parameters of mean and minimum apparent diffusion coefficient (ADCmean and ADCmin) and intravoxel incoherent motion (IVIM) in the differentiation of benign and malignant lung nodules and masses. METHODS: Lung lesions measured larger than 1.5 cm on CT were included between August 2015 and September 2018. DWI (10 b-values, 0-1000 s/mm2) scans were performed, and the data were post-processed to derive the ADCmean, ADCmin and IVIM parameters of true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f). An independent sample t-test or Mann-Whitney U test was used to compare benign and malignant parameters. Receiver operating characteristic curves were generated and a Z test was used. RESULTS: 121 patients were finally enrolled, each with one lesion. Examined 121 lesions were malignant in 88 (72.7%) and benign in 33 (27.3%). The ADCmean of malignant pulmonary nodules was significantly lower than that of benign pulmonary nodules (t = 3.156, p = 0.006), whereas the other parameters revealed no significant differences (p = 0.162-0.690). Receiver operating characteristic curve analysis revealed that an ADCmean threshold value of 1.43 × 10-3 mm2/s yielded 88.57% sensitivity and 64.29% specificity. While for lung masses, the ADCmean, ADCmin, D and D* values in malignant pulmonary masses were significantly lower (P﹤0.001-0.011). Among them, the D value exhibited the best diagnostic performance when the threshold of D was 1.23 × 10-3mm2/s, which yielded a sensitivity of 90.57% and a specificity of 89.47% (Z = 2.230, 3.958, 2.877 and p = 0.026, ﹤0.001 and 0.004, respectively). CONCLUSION: ADC is the most robust parameter to differentiate benign and malignant lung nodules, whereas D is the most robust parameter to differentiate benign and malignant lung masses. ADVANCES IN KNOWLEDGE: This is the first study to compare all the quantitative parameters of DWI and IVIM mentioned in the literatures for assessing lung lesions; Second, we divided the lesions into lung nodules and lung masses with the size of 3 cm as the boundary.

A primary analysis on measuring repeatability of the maximum diameter between CT and MR imaging for lung cancers.

OBJECTIVE: To investigate the measurement reproducibility of the maximum diameter on MRI routine sequence (T1WI, T2WI, DWI) and CT in peripheral and central lung cancer, and to provide reference standard for evaluating treatment responses for lung cancer. METHODS: 53 patients with lung cancer underwent CT and 3.0T MR scanning. The maximum diameter was measured according to the RECIST1.1 standard on images of CT (lung and enhanced mediastinal window), MRI T2-BLADE, axial T1-VIBE and DWIb0, DWIb300, DWIb800, respectively. The reproducibility of the diameters was analyzed with intraclass correlation coefficient (ICC), and the distribution of measurement points with the Bland-Altman method. The difference analysis was assessed by paired samples t-test and nonparametric rank sum test, P < 0.05 is considered statistically significant. RESULTS: Reproducibility of diameters derived from routine MRI and CT was good (ICC > 0.75). For peripheral lung cancer, there was no significant difference in diameters between CT and MRI. While for central lung cancer, there was significant difference in diameters measured between using CT and each MRI sequence. However, the diameters derived from T1-VIBE and T2-BLADE were not significantly different from all DWI sequences. CONCLUSIONS: For peripheral lung cancer, the measurement on CT and routine MRI sequences can potentially replace each other after comprehensive consideration of examination purposes, but for central lung cancer, alternative use of CT and MRI in evaluating treatment responses for lung cancer should needs extra attention. The diameter measurement of lung cancer on DWI is consistent with that on T1WI and T2WI, suggesting that DWI can provide functional and morphological information.

Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process.

Pulmonary fibrosis (PF) is a chronic and ultimately fatal interstitial lung disease of various causes. The advent of nintedanib and pirfenidone provides treatment options for PF patients for the first time. However, the adverse effects of the two drugs such as gastrointestinal disorders and hepatic dysfunction often lead to treatment discontinuation. Gentiopicroside (GPS) is a natural secoiridoid glycoside from gentian species of medicinal plants, and has a variety of pharmacological activities, including hepatoprotective and cholagogic, anti-inflammatory, antinociceptive, and smooth muscle relaxing activities. The present study aimed to investigate the therapeutical effects of GPS on bleomycin (BLM)-induced PF in mice. Severe lung inflammation and fibrosis were observed in BLM-treated mice. GPS significantly ameliorated inflammatory and fibrotic responses in lungs of PF mice which were confirmed by histopathological examinations including light microscopy and transmission electron microscopy. Additionally, GPS significantly decreased the levels of inflammatory cytokines including TNF-α and IL-1ß in bronchoalveolar lavage fluid and reduced the content of hydroxyproline in lungs of PF mice. Furthermore, GPS significantly downregulated the expression of TGF-ß1 and CTGF in lungs of PF mice. In vitro, GPS inhibited epithelial-mesenchymal transition of A549 cells stimulated by TGF-ß1, in a dose-dependent manner. Our findings suggest that GPS has the potential as an ideal drug candidate for PF, as it has both anti-inflammatory and anti-fibrotic effects. Alveolar epithelial cells and TGF-ß1 may be the main target cells and molecule of GPS on BLM-induced PF, respectively.

Bioinformatics analysis of key genes and pathways for hepatocellular carcinoma transformed from cirrhosis.

OBJECTIVE: We aimed to identify some pivotal genes and pathways for hepatocellular carcinoma (HCC) transformation from cirrhosis and explore potential targets for treatment of the disease. METHODS: The GSE17548 microarray data were downloaded from Gene Expression Omnibus database, and 37 samples (20 cirrhosis and 17 HCC samples) were used for analysis. The differentially expressed genes (DEGs) in HCC tissues were compared with those in cirrhosis tissues and analyzed using the limma package. Gene ontology-biological process and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using ClueGO and CluePedia tool kits, and the key KEGG pathway was analyzed using the R package pathview. The regulatory factor miRNA of DEGs was extracted from 3 verified miRNAs-target databases using the multiMiR R package. Moreover, a protein-protein interaction (PPI) network was constructed using the Cytoscape software. RESULTS: DEGs including cyclin-dependent Kinase 1 (CDK1), PDZ-binding kinase (PBK), ribonucleotide reductase M2 (RRM2), and abnormal spindle homolog, and microcephaly-associated drosophila (ASPM) were the hub proteins with higher degrees in the PPI network. The cell cycle pathway (CDK1 enriched) and p53 signaling pathway (CDK1 and RRM2 enriched) were significantly enriched by DEGs. CONCLUSION: CDK1, PBK, RRM2, and ASPM may be key genes for HCC transformation from cirrhosis. Furthermore, cell cycle and p53 signaling pathways may play vital mediatory roles; CDK1 may play crucial roles in HCC transformed from cirrhosis via cell cycle and p53 signaling pathways, and RRM2 might be involved in HCC transformed from cirrhosis via the p53 signaling pathway.

Inter- and intraobserver agreement of ADC measurements of lung cancer in free breathing, breath-hold and respiratory triggered diffusion-weighted MRI.

OBJECTIVE: To prospectively evaluate the inter- and intraobserver agreement of apparent diffusion coefficient (ADC) measurements in free breathing, breath-hold, and respiratory triggered diffusion-weighted imaging (DWI) of lung cancer. METHODS: Twenty-two patients with lung cancer (tumor size >2cm) underwent DWIs (3.0T) in three imaging methods. Lesion ADCs were measured twice by both of the two independent observers and compared. RESULTS: No statistical significance was found among methods, though respiratory-triggered DWI tended to have higher ADCs than breath-hold DWI. Great inter- and intraobserver agreement was shown. CONCLUSION: ADCs had good inter- and intraobserver agreement in all three DWI methods.

[Analysis of Adverse Events in Clinical Use of Catheter].

In recent years, with the extensive use of various clinical catheter, Adverse events in the clinical catheter products also showed an upward trend. Here we wil review the common adverse event performance, risk point and reasons of AEs adverse events about the catheter during the clinical use, through a large number of clinical research, visit and literature review, in order to provide evidence to support in reducing the incidence of catheter clinical adverse events, and prevent recurrence and spread of the serious adverse events during the using of process.

[Analysis of Adverse Events of Disposable Umbilical Cord Clamp].

To investigate and analysis the multiple medical adverse events about disposable umbilical cord clamp during clinical using in Zhejiang province, and put forward some opinions some suggestions to improve the processing technology, to strengthen the professional training of medical staff in medical institutions of umbilical cord clamp using, and to take precautions against more adverse events.