Identification of tophi in ultrasound imaging based on transfer learning and clinical practice.

Gout is a common metabolic disorder characterized by deposits of monosodium urate monohydrate crystals (tophi) in soft tissue, triggering intense and acute arthritis with intolerable pain as well as articular and periarticular inflammation. Tophi can also promote chronic inflammatory and erosive arthritis. 2015 ACR/EULAR Gout Classification criteria include clinical, laboratory, and imaging findings, where cases of gout are indicated by a threshold score of ≥ 8. Some imaging-related findings, such as a double contour sign in ultrasound, urate in dual-energy computed tomography, or radiographic gout-related erosion, generate a score of up to 4. Clearly, the diagnosis of gout is largely assisted by imaging findings; however, dual-energy computed tomography is expensive and exposes the patient to high levels of radiation. Although musculoskeletal ultrasound is non-invasive and inexpensive, the reliability of the results depends on expert experience. In the current study, we applied transfer learning to train a convolutional neural network for the identification of tophi in ultrasound images. The accuracy of predictions varied with the convolutional neural network model, as follows: InceptionV3 (0.871 ± 0.020), ResNet101 (0.913 ± 0.015), and VGG19 (0.918 ± 0.020). The sensitivity was as follows: InceptionV3 (0.507 ± 0.060), ResNet101 (0.680 ± 0.056), and VGG19 (0.747 ± 0.056). The precision was as follows: InceptionV3 (0.767 ± 0.091), ResNet101 (0.863 ± 0.098), and VGG19 (0.825 ± 0.062). Our results demonstrate that it is possible to retrain deep convolutional neural networks to identify the patterns of tophi in ultrasound images with a high degree of accuracy.

The Effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-Analysis.

The effects of ketoanalogues (KA) on chronic kidney disease (CKD) deterioration have not yet been fully confirmed. To strengthen the evidence of the role of KA in CKD, PubMed and Embase were searched for studies published through February 2019. Effect sizes from ten randomized control trials (RCTs) and two non-RCTs comprising a total of 951 patients were pooled and analyzed. A restricted protein diet supplemented with ketoanalogues (RPKA) was found to significantly delay the progression of CKD (p = 0.008), particularly in patients with an estimated glomerular filtration rate (eGFR) > 18 mL/min/1.73 m2 (p < 0.0001). No significant change in eGFR was found when comparing a very-low-protein diet and a low-protein diet (p = 0.10). In addition, compared with the placebo, RPKA did not cause malnutrition (albumin: p = 0.56; cholesterol: p = 0.50). Moreover, RPKA significantly decreased phosphorous levels (p = 0.001), increased calcium levels (p = 0.04), and decreased parathyroid hormone (PTH) levels (p = 0.05) in patients with eGFR < 18 mL/min/1.73 m2. In conclusion, RPKA could slow down the progression of CKD in patients with eGFR > 18 mL/min/1.73 m2 without causing malnutrition and reverse CKD-MBD in patients with eGFR < 18 mL/min/1.73 m2.

Taxifolin Resensitizes Multidrug Resistance Cancer Cells via Uncompetitive Inhibition of P-Glycoprotein Function.

P-glycoprotein (P-gp) effluxes lots of chemotherapeutic agents and leads to multidrug resistance (MDR) in cancer treatments. The development of P-gp inhibitors from natural products provide a potential strategy for the beneficial clinical outcomes. This study aimed to evaluate the effects of the natural flavonoid taxifolin, luteolin, (-)-gallocatechin, and (-)-catechin on human P-gp activity. The kinetic interactions and underlying mechanisms of taxifolin-mediated transporter inhibition were further investigated. The transporter inhibition ability was evaluated in human P-gp stable expression cells (ABCB1/Flp-InTM-293) by calcein-AM uptake assays. The kinetics study for P-gp inhibition was evaluated by doxorubicin and rhodamine123 efflux assays. The MDR reversal ability of taxifolin were performed by SRB assays to detect the cell viability in sensitive cancer cell line (HeLaS3), and resistant cancer cell line (KB-vin). Cell cycle analysis and ABCB1 real-time RT-PCR were used for mechanical exploration. The results demonstrated that taxifolin decreased ABCB1 expression in a concentration-dependent manner. The function of P-gp was inhibited by taxifolin through uncompetitive inhibition of rhodamine 123 and doxorubicin efflux. The combination of taxifolin significantly resensitized MDR cancer cells to chemotherapeutic agents. These results suggested that taxifolin may be considered as a potential P-gp modulator for synergistic treatment of MDR cancers.

Impacts of GRIN3A, GRM6 and TPH2 genetic polymorphisms on quality of life in methadone maintenance therapy population.

Opioid addiction is a major public health issue worldwide. Methadone maintenance treatment (MMT) is used to detoxify users of illicit opiates, but drug relapse is common and associated with poor quality of life (QoL). This study investigated the associations between the GRIN3A, GRM6, and TPH2 genetic variants and QoL in the MMT population. A total of 319 participants were included in the study, and genotyping of GRIN3A, GRM6, and TPH2 genes was performed using the Sequenom iPLEX. Associations between genotypes and the domains of QoL were examined through posthoc analysis with LSMEANS syntax using SAS 9.1.3. The single nucleotide polymorphisms rs9325202 and rs1487275 in the TPH2 gene were significantly associated with the QoL domain of physical functioning. The least absolute shrinkage and selection operator regression model revealed that the risk allele rs1487275-G was significantly correlated with the domain of physical functioning when clinical characteristics were considered as covariates. The results of the present study illuminate the importance of the genetic basis of QoL in the MMT population, and suggest that genotypes should be considered as a potential QoL indicator.