The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination. 相似文献
Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation. 相似文献
ObjectiveTo construct deep learning (DL) models to improve the accuracy and efficiency of thyroid disease diagnosis by thyroid scintigraphy.MethodsWe constructed DL models with AlexNet, VGGNet, and ResNet. The models were trained separately with transfer learning. We measured each model’s performance with six indicators: recall, precision, negative predictive value (NPV), specificity, accuracy, and F1-score. We also compared the diagnostic performances of first- and third-year nuclear medicine (NM) residents with assistance from the best-performing DL-based model. The Kappa coefficient and average classification time of each model were compared with those of two NM residents.ResultsThe recall, precision, NPV, specificity, accuracy, and F1-score of the three models ranged from 73.33% to 97.00%. The Kappa coefficient of all three models was >0.710. All models performed better than the first-year NM resident but not as well as the third-year NM resident in terms of diagnostic ability. However, the ResNet model provided “diagnostic assistance” to the NM residents. The models provided results at speeds 400 to 600 times faster than the NM residents.ConclusionDL-based models perform well in diagnostic assessment by thyroid scintigraphy. These models may serve as tools for NM residents in the diagnosis of Graves’ disease and subacute thyroiditis. 相似文献
Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.
Objective
To investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo.
Methods
One hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry.
Results
The serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells.
Conclusion
CCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo. 相似文献
Background: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population.
Methods: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool.
Results: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR?=?0.76, 95% CI?=?0.58–0.99 and OR?=?0.76, 95% CI?=?0.58–0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR?=?0.63, 95% CI?=?0.45–0.88), no hypertension (OR?=?0.66, 95% CI?=?0.46–0.94), diabetes (OR?=?0.33, 95% CI?=?0.17–0.64), and smoking (OR?=?0.65, 95% CI?=?0.44–0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR?=?4.48; 95% CI?=?2.98–6.72) increased risk of AS.
Conclusion: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population. 相似文献
Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury. 相似文献