BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective To analyze the correlations of D-dimer and the Global Registry of Acute Coronary Events (GRACE) score with long-term heart failure (HF) in patients with acute myocardial infarction (AMI). Methods A total of 398 patients with AMI were selected as research objects and divided into normal D-dimer group (n=309) and elevated D-dimer group (n=89) based on the D-dimer level. Cox proportional hazard model was used to analyze the risk factors for long-term HF in both groups. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the values of D-dimer, GRACE score and their combination in predicting long-term HF. According to the GRACE score and D-dimer level, 398 patients were divided into low-value group (181 patients with normal D-dimerand low GRACE score), high-value group (70 patients with elevated D-dimer and high GRACE score), and middle-value group (147 patients did not meet the conditions of the low-value and high-value groups). Kaplan-Meier method was used to analyze the occurrence of long-term HF in the three groups. Point-biserial analysis was used to analyze the correlation between elevated D-dimer and the occurrence of long-term HF. Results The number of patients with long-term HF in the elevated D-dimer group was 2.3 times of the normal group. D-dimer and GRACE score were independent risk factors for long-term HF in patients with AMI (P < 0.05). Both D-dimer and GRACE score had certain predictive values for the occurrence of HF at 5 years after AMI, but the predictive efficiency of GRACE score was better. The incidence of long-term HF in the high-value group was significantly higher than that in the low-value group and the middle-value group (P < 0.01). D-dimer was significantly positively correlated with the occurrence of long-term HF after AMI (P < 0.001). Conclusion Both D-dimer and GRACE score are independent risk factors for long-term HF in patients with AMI, and the two indexes have certain predictive value for the occurrence of long-term HF. Patients with both elevated indicators are high-risk groups for long-term HF.

In this paper, an image mosaic algorithm based on feature points was proposed by making a study of the image mosaic methods and the characteristics of pathological image. Points of interest were firstly extracted by Moravec operator in this method, and the corresponding feature matches of the original images were achieved by correlation coefficient. The parameters of affine transformation were calculated by the matching feature points, and weighted average method was used to fuse images. The experimental results show that, as for the pathological image with translation and rotation, the algorithm can extract the matching feature points accurately and realize the image seamless mosaic.
Algorithms ; Image Enhancement ; methods ; Image Processing, Computer-Assisted ; methods ; Pathology ; methods ; Pattern Recognition, Automated ; methods

To implement the network printing in PACS (Picture Archiving and Communication System), each level of DICOM (Digital Imaging and Communication in Medicine) print management service is defined by means of object oriented method, and the corresponding events and properties are implemented with C++ language. It is tested on laser printers of AGFA, KODAK and FUJI to determine whether the network environment supports the print management service and implements the presentation LUT (Look Up Table) correctly. The quality control of printing at the level of data flow is also assessed. The program finally succeeds in realizing the network printing based on DICOM in hospital environment.
Computer Communication Networks ; instrumentation ; Image Processing, Computer-Assisted ; standards ; Medical Records Systems, Computerized ; organization & administration ; standards ; Printing ; methods ; Radiology Information Systems ; standards

In accordance with the character of heart rate variability(HRV) signal, we have divided HRV signal into 1/f fractal component and 1/f non-fractal component by use of wavelet transform. This division will be beneficial to the acqusition of the character of HRV signal as well as to the quantitative analysis of 1/f fractal component.
Algorithms ; Electrocardiography ; Heart Rate ; physiology ; Humans ; Nonlinear Dynamics ; Signal Processing, Computer-Assisted

Objective To reduce information loss in the refining processing of photoplethysmographic (PPG) pulse waveform. Method A novel PPG pulse waveform refining processing technique, named truncation/extrapolation technique was proposed. The key point of the proposed technique was to preserve the shape pattern of the most significant parts of the waveform at the expense of the distortion of the insignificant part. Thus, as compared with the conventional time-normalization method, the proposed technique ensured the accumulation coherent of the signal energy could be. Result Waveform analysis and comparison of experimental data between two methods verified the effectiveness of the proposed method in maintaining the most significant time domain features of the pulse waveform over a relatively wide range of the heart rate change, especially the shape and width of the dominant peak and the position of the dicrotic notch of the first derivative of PPG(dPPG). Conclusion The proposed method reduces the information loss in PPG pulse waveform refining processing, thus helps further processing of the PPG signal using some advanced signal processing techniques, such as waveform modeling and pattern recognition.

By use of fractal analysis indexes-correlation dimension, fractal dimension and scaling exponent, the heart rate variability signals obtained from 38 subjects' ECG during anesthesia are analyzed. The results show that there is an obvious change of fractal characteristic of heart rate variability during anesthesia. The correlation dimension (P < 0.000001) during anesthesia is evidently less than that during consciousness, while the short-range scaling exponent a (P < 0.0001) during consciousness is evidently less than that during anesthesia. These illustrate that the difference in fractal characteristic between anesthesia and well-balanced state can be detected by the fractal analysis of heart rate variability. In the end, the paper poses that the analysis of heart rate variability is fit for monitoring the depth of anesthesia by detrended fluctuation analysis.
Anesthesia ; Electrocardiography ; Heart Rate ; physiology ; Humans ; Monitoring, Physiologic ; methods

Anesthesia as a necessary procedure in the process of surgical operation could restrain the response of patients to the damage stimulation; However, improper anesthesia could also result in severe misfortune for patients. At the present time, one kind of monitor technology assuring highly effectual anesthesia is exigently required in clinical practice and many researchers have actively undertaken investigations to seek the parameters predicting the depth of anesthesia (DOA). Electroencephalogram (EEG) assumes a dominant position in the current researches on detecting the depth of anesthesia. In this paper, the achievements of detecting the depth of anesthesia by means of EEG are systematically reviewed and the potentials are anticipated.
Anesthesia ; Anesthesiology ; methods ; Electroencephalography ; Humans ; Monitoring, Physiologic

By use of the complexity analysis indices (approximate entropy, complexity), the heart rate variability signals obtained from 38 subjects' ECG during anesthesia were analyzed. The results showed that there is an obvious chaos change of heart rate variability during anesthesia, both the complexity and approximate entropy of heart rate variability during anesthesia are evidently less than those during consciousness (P<0.05). In this dissertation, we decompose the heart rate variability during anesthesia into 1/f part and non-fractal part, and then analyze these parts. The results reveal that the sensitivity of the complexity indices can be improved by decomposing the heart rate variability.
Adult ; Anesthesia ; Autonomic Nervous System ; drug effects ; Electrocardiography ; Entropy ; Heart Rate ; physiology ; Humans ; Middle Aged ; Models, Statistical ; Signal Processing, Computer-Assisted