Case report: Aggressive progression of acute heart failure due to juvenile tuberculosis-associated Takayasu arteritis with aortic stenosis and thrombosis

BackgroundTakayasu arteritis (TA) is a chronic granulomatous vasculitis with unknown pathophysiology. TA with severe aortic obstruction has a poor prognosis. However, the efficacy of biologics and appropriate timing of surgical intervention remain controversial. We report a case of tuberculosis (TB)-associated TA with aggressive acute heart failure (AHF), pulmonary hypertension (PH), thrombosis, and seizure, who failed to survive after surgery.Case presentationA 10-year-old boy who developed a cough with chest tightness, shortness of breath, hemoptysis with reduced left ventricular ejection fraction, PH, and increased C-reactive protein and erythrocyte sedimentation rate was hospitalized at the pediatric intensive care unit of our hospital. He had strongly positive purified protein derivative skin test and interferon-gamma release assay result. Computed tomography angiography (CTA) showed occlusion of proximal left subclavian artery and stenosis of descending aorta and upper abdominal aorta. His condition did not improve after administration of milrinone, diuretics, antihypertensive agents, and intravenous methylprednisolone pulse followed by oral prednisone. Intravenous tocilizumab was administered for five doses, followed by two doses of infliximab, but his HF worsened, and CTA on day 77 showed complete occlusion of the descending aorta with large thrombus. He had a seizure on day 99 with deterioration of renal function. Balloon angioplasty and catheter-directed thrombolysis were performed on day 127. Unfortunately, the child's heart function continued to deteriorate and died on day 133.ConclusionTB infection may be related to juvenile TA. The biologics, thrombolysis, and surgical intervention failed to achieve the anticipated effect in our case with aggressive AHF due to severe aortic stenosis and thrombosis. More studies are needed to determine the role of biologics and surgery in such dire cases

Clinical efficacy of Osteoking in knee osteoarthritis therapy: a prospective, multicenter, non-randomized controlled study in China

BackgroundOsteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs).AimsTo evaluate the efficacy and safety of Osteoking in treating KOA.MethodsIn the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc.ResultsAfter 8 weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8 weeks more effectively than that by the treatment of NSAIDs. After 8 weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8 weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2 weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65 years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65 years old and with VAS 8–10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs.ConclusionOsteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4–7 scores.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR200003447

Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.</p> <p>Methods</p> <p>In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes.</p> <p>Results</p> <p>One hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (<it>P </it>< 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; <it>P </it>< 0.001) and vomiting (12.4% vs. 2.0%; <it>P </it>= 0.005).</p> <p>Conclusions</p> <p>Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00136201</p

Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells

Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation

Research on Diesel Engine Fault Diagnosis Method Based on Stacked Sparse Autoencoder and Support Vector Machine

Due to the relative insufficiencies of conventional time-domain waveform and spectrum analysis in fault diagnosis research, a diesel engine fault diagnosis method based on the Stacked Sparse Autoencoder and the Support Vector Machine is proposed in this study. The method consists of two main steps. The first step is to utilize the Stacked Sparse Autoencoder (SSAE) to reduce the feature dimension of the multi-sensor vibration information; when compared with other dimension reduction methods, this approach can better capture nonlinear features, so as to better cope with dimension reduction. The second step consists of diagnosing faults, implementing the grid search, and K-fold cross-validation to optimize the hyperparameters of the SVM method, which effectively improves the fault classification effect. By conducting a preset failure experiment for the diesel engine, the proposed method achieves an accuracy rate of more than 98%, better engineering application, and promising outcomes

Research on Diesel Engine Fault Diagnosis Method Based on Stacked Sparse Autoencoder and Support Vector Machine

Due to the relative insufficiencies of conventional time-domain waveform and spectrum analysis in fault diagnosis research, a diesel engine fault diagnosis method based on the Stacked Sparse Autoencoder and the Support Vector Machine is proposed in this study. The method consists of two main steps. The first step is to utilize the Stacked Sparse Autoencoder (SSAE) to reduce the feature dimension of the multi-sensor vibration information; when compared with other dimension reduction methods, this approach can better capture nonlinear features, so as to better cope with dimension reduction. The second step consists of diagnosing faults, implementing the grid search, and K-fold cross-validation to optimize the hyperparameters of the SVM method, which effectively improves the fault classification effect. By conducting a preset failure experiment for the diesel engine, the proposed method achieves an accuracy rate of more than 98%, better engineering application, and promising outcomes

Fault Diagnosis Method of Planetary Gearbox Based on Compressed Sensing and Transfer Learning

This paper suggests a novel method for diagnosing planetary gearbox faults. It addresses the issue of network bandwidth limitation during wireless data transmission and the problem of relying on expert experience and insufficient training samples in traditional fault diagnosis. The continuous wavelet transform was combined with the AlexNet convolutional neural network using transfer learning and the compressed theory of sense. The original vibration signal was compressed and reconstructed using the compressed sampling orthogonal matching pursuit reconstruction algorithm. A continuous wavelet transform was used to convert the compressed signal into a time&ndash;frequency image. The pretrained AlexNet model was selected as the migration object, the network model was fine-tuned and retrained, and the trained AlexNet model was used to diagnose the fault using the model-based migration method. It was demonstrated by the experimental results when the compression ratio CR = 0.5. Compared to other network models, the classification accuracy rate is 97.78%. This method has specific reference value and application prospects and good feature extraction and fault classification capabilities

Combination of Optimized Variational Mode Decomposition and Deep Transfer Learning: A Better Fault Diagnosis Approach for Diesel Engines

Extracting features manually and employing preeminent knowledge is overly utilized in methods to conduct fault diagnosis. A diagnosis approach utilizing intelligent methods of the optimized variational mode decomposition and deep transfer learning is proposed in this manuscript to deal with fault diagnosis. Firstly, the variational mode decomposition is optimized by K values of the dispersion entropy to realize an adaptive decomposition and reduce the noise of the signal. Secondly, an image with two dimensions is generated by a vibration signal with one dimension utilizing a short-time Fourier transform, after conducting noise reduction. Then, the ResNet18 network model is used to pre-train the model. Finally, the model transfer method is used to detect faults of a diesel engine. The results show that the proposed method outperforms the deep learning methods available in the literature. Besides, better noise reduction ability and higher diagnostic accuracy are attained

Combination of Optimized Variational Mode Decomposition and Deep Transfer Learning: A Better Fault Diagnosis Approach for Diesel Engines

Extracting features manually and employing preeminent knowledge is overly utilized in methods to conduct fault diagnosis. A diagnosis approach utilizing intelligent methods of the optimized variational mode decomposition and deep transfer learning is proposed in this manuscript to deal with fault diagnosis. Firstly, the variational mode decomposition is optimized by K values of the dispersion entropy to realize an adaptive decomposition and reduce the noise of the signal. Secondly, an image with two dimensions is generated by a vibration signal with one dimension utilizing a short-time Fourier transform, after conducting noise reduction. Then, the ResNet18 network model is used to pre-train the model. Finally, the model transfer method is used to detect faults of a diesel engine. The results show that the proposed method outperforms the deep learning methods available in the literature. Besides, better noise reduction ability and higher diagnostic accuracy are attained