[Etanercept combined with Tripterygium wilfordii polyglycoside for treatment of rheumatoid arthritis in the elderly: a clinical study].

OBJECTIVE: To evaluate the efficacy and safety of etanercept plus Tripterygium wilfordii polyglycoside (TWP) in elderly patients with active rheumatoid arthritis (RA). METHODS: Totally 46 elderly patients with active RA were randomly assigned to the treatment group (22 cases) and the control group (24 cases). All patients received subcutaneous injection of etanercept, 25 mg each time, twice per week. The dosage was reduced to once per week 3 months later. Patients in the treatment group took TWP Tablet (10 mg each time, three times per day), while those in the control group took methotrexate (MTX), 10 mg each time, once per week. The whole course lasted for 24 weeks. Patients' rest pain, tender joint number, swollen joint number, health assessment questionnaire (HAQ), patients' global assessment, physicians' global assessment, erythrocyte sediment rate (ESR), C reactive protein (CRP), rheumatic factor were assessed at week 0, 4, 8, 12, and 24. The curative effect was statistically evaluated by the United States Institute of Rheumatology ACR20, ACR50, and ACR70 improvement criteria. Meanwhile, any adverse event was recorded and evaluated. RESULTS: Totally 41 completed the trial, and 5 dropped off (3 in the treatment group and 2 in the control group). Compared with the control group, there was no statistical difference in ACR20, ACR50, or ACR70 in the treatment group (P > 0.05). Compared with before treatment in the same group, there was some improvement in tender joint number, swollen joint number, visual analogue scale (VAS) for patients' global assessment, VAS for physicians' global assessment, ESR, CRP, and HAQ between the two groups, showing statistical difference (P < 0.05). Compared with the control group in the same phase, there was no statistical difference in the treatment group (P > 0.05). There was no statistical difference in the occurrence of adverse events between the two groups. CONCLUSIONS: Etanercept plus TWP could achieve equivalent therapeutic effect to that of Etanercept plus MTX. The two regimens could improve clinical signs, symptoms, and QOL related to RA. They were well tolerated in the treatment of elderly patients with active RA.

Serum level of eight cytokines in Han Chinese patients with systemic lupus erythematosus using multiplex fluorescent microsphere method.

AIM OF THE STUDY: To investigate the role of 8 cytokines and their correlation with clinical characteristics in systemic lupus erythematosus (SLE) in Han Chinese population by detecting their serum levels using the multiplex fluorescent microsphere method. MATERIAL AND METHODS: Serum was separated from 79 patients with SLE and 40 healthy controls. The serum cytokine detection was conducted according to the instruction of MILLIPLEX MAP human cytokine detection kit on the Luminex liquid phase array platform with 0.01 pg/ml detectable level. The 8 cytokines were interferon α2 (IFN-α2), IFN-γ, interleukin 6 (IL-6), IL-8, IL-10, IFN-γ-inducible protein 10 (IP-10), tumor necrosis factor α (TNF-α) and IL-17. Variable data were in skewed distribution and were expressed with median (P25, P75). Mann-Whitney analysis was used in statistical analysis. RESULTS: At the baseline level without any stimulus, the level of IP-10 expression was the highest among the 8 cytokines and the second highest was IL-8. The level of IL-17 was too low to be detected. The level of 7 cytokines was higher in SLE patients than in healthy controls (p < 0.01). The level of dsDNA antibody, C3, CRP, ESR and anti-nucleosome antibody was correlated with IL-10. Proteinuria was not correlated with any cytokine. CONCLUSIONS: Eight cytokines were measured in our study, while not all of them were detected. The most important finding was the usefulness of IL-10 as a disease activity biomarker for Han Chinese patient with SLE. None of cytokines reflected kidney injury.

A real-world pharmacovigilance study of FDA adverse event reporting system events for diazepam.

Background: Diazepam, one of the benzodiazepines, is widely used clinically to treat anxiety, for termination of epilepsy, and for sedation. However, the reports of its adverse events (AEs) have been numerous, and even fatal complications have been reported. In this study, we investigated the AEs of diazepam based on real data from the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS). Methods: Disproportionality in diazepam-associated AEs was assessed through the calculation of reporting odds ratios (RORs), proportional reporting ratios (PRRs), Bayesian confidence-propagation neural networks (BCPNNs), and gamma-Poisson shrinkage (GPS). Results: Among the 19,514,140 case reports in the FAERS database, 15,546 reports with diazepam as the "principal suspect (PS)" AEs were identified. Diazepam-induced AEs occurred targeting 27 system organ categories (SOCs). Based on four algorithms, a total of 391 major disproportionate preferred terms (PTs) were filtered out. Unexpectedly significant AEs such as congenital nystagmus, developmental delays, and rhabdomyolysis were noted, which were not mentioned in the drug insert. Conclusion: Our study identified potential signals of new AEs that could provide strong support for clinical monitoring and risk identification of diazepam.

Association between atorvastatin and erectile dysfunction: a comprehensive analysis incorporating real-world pharmacovigilance and Mendelian randomization.

Background: Atorvastatin is a commonly prescribed medication for the prevention of cardiovascular diseases. Recent observational studies have suggested a potential association between atorvastatin use and the occurrence of Erectile Dysfunction (ED). In this study, we aimed to explore the relationship between atorvastatin and ED using real-world data from the FAERS database and employed Mendelian randomization to assess causality. Methods: To evaluate the disproportionality of atorvastatin in relation to ED, we conducted several pharmacovigilance analyses, including odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence propagation neural network (BCPNN), and gamma-Poisson contractile apparatus (GPS). Additionally, we employed Mendelian randomization to investigate the causal relationship between atorvastatin and ED. Results: Pharmacovigilance disproportionality analysis revealed a significant association between atorvastatin and ED, as indicated by the following results: ROR [3.707078559, 95% CI (3.33250349, 4.123756054)], PRR [3.702969038, χ2 (669.2853829)], IC [1.870490139, IC025 (1.702813857)], and EBGM [3.656567867, EBGM05 (3.28709656)]. Furthermore, the two-sample Mendelian randomization analysis provided evidence supporting a causal relationship between atorvastatin use and ED, with an inverse variance weighted estimate of ß = 3.17 (OR = 23.91, p = 0.02 < 0.05). Conclusion: Based on comprehensive analyses incorporating pharmacovigilance and Mendelian randomization, our findings suggest that atorvastatin use is associated with an increased risk of ED and indicate a causal relationship. These results emphasize the importance of considering potential adverse effects, such as ED, when prescribing atorvastatin for cardiovascular disease prevention. Further research and clinical monitoring are warranted to better understand the underlying mechanisms and develop appropriate strategies to mitigate this side effect.

Inclusion of guanidinoacetic acid in a low metabolizable energy diet improves broilers growth performance by elevating energy utilization efficiency through modulation serum metabolite profile.

This study was aimed to explore the elevating energy utilization efficiency mechanism for the potentially ameliorative effect of guanidinoacetic acid (GAA) addition on growth performance of broilers fed a low metabolizable energy (LME) diet. A total of 576 d old broilers were randomly allocated to one of the six treatments: a basal diet (normal ME, positive control, PC), or an LME diet (50 kcal/kg reduction in ME, negative control, NC) supplemented with 0.02%, 0.04%, 0.06%, and 0.08% GAA from 1 to 42 d of age, respectively. The GAA fortification in LME diet linearly or quadratically dropped (P < 0.05) the feed conversion ratio (FCR) from 22 to 42 and 1 to 42 d of age, abdominal fat rate on day 42, serum alanine aminotransferase (ALT) on day 21, and serum creatinine (CREAN) on days 21 and 42, elevated (P < 0.05) breast muscle rate and leg muscle rate on day 42, serum creatine kinase (CK) on days 21 and 42, as well as alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) on day 21. The dietary optimal GAA levels were 0.03%-0.08% based on the best-fitted quadratic models (P < 0.03) of the above parameters. Thus, the PC, LME, and 0.04% GAA-LME groups were selected for further analysis. Serum essential amino acids (EAA) tryptophan, histidine and arginine, non-essential amino acids (NEEA) serine, glutamine and aspartic acid were significantly decreased (P < 0.05), compared to PC diet by LME or 0.04% GAA-LME diet. 0.04% GAA-LME group reversed (P < 0.05) the reduction of arginine, 3-methyhistidine, and 1-methylhistidine by LME diet. Besides, six birds at 28 d of age from LME and 0.04% GAA-LME groups were selected for energy utilization observation in calorimetry chambers. The results demonstrated that 0.04% GAA-LME group significantly improved (P < 0.05) the ME intake (MEI) and net energy (NE) compared to the LME diet. Overall, these findings suggest that 0.04% GAA is the ideal dose of broilers fed the LME diet, which can significantly improve the growth performance and carcass characteristics by modulation of creatine metabolism through elevating serum CK activity and arginine concentration.

Guanidinoacetic acid (GAA) has been found to elevate energy utilization efficiency in broilers; however, the underlying mechanisms remain unclear. We investigated the effects of GAA addition in low metabolizable energy (LME) diet on growth performance, carcass characteristics and serum biochemical indices of broilers, and found that GAA addition linearly or quadratically dropped the feed conversion ratio from 22 to 42 and 1 to 42 d of age, abdominal fat rate on day 42, serum alanine aminotransferase on day 21, and serum creatinine on days 21 and 42, elevated breast muscle and leg muscle rate on day 42, serum creatine kinase, alkaline phosphatase, as well as lactate dehydrogenase on days 21 or 22. The dietary optimal GAA levels were 0.03%-0.08% based on the best-fitted quadratic models of the above parameters. Thus, further analysis was conducted and found that 0.04% GAA reversed the reduction of arginine, 3-methyhistidine, and 1-methylhistidine and improved the ME intake and net energy compared to the LME diet. These findings suggested that 0.04% GAA is the ideal dose for enhancing the energy utilization of broilers fed the LME diet, GAA addition can significantly improve the growth performance by elevating energy utilization efficiency through modulation serum metabolite profile.

Freehand 3D Ultrasound Imaging Based on Probe-mounted Vision and IMU System.

OBJECTIVES: Freehand three-dimensional (3D) ultrasound (US) is of great significance for clinical diagnosis and treatment, it is often achieved with the aid of external devices (optical and/or electromagnetic, etc.) that monitor the location and orientation of the US probe. However, this external monitoring is often impacted by imaging environment such as optical occlusions and/or electromagnetic (EM) interference. METHODS: To address the above issues, we integrated a binocular camera and an inertial measurement unit (IMU) on a US probe. Subsequently, we built a tight coupling model utilizing the unscented Kalman algorithm based on Lie groups (UKF-LG), combining vision and inertial information to infer the probe's movement, through which the position and orientation of the US image frame are calculated. Finally, the volume data was reconstructed with the voxel-based hole-filling method. RESULTS: The experiments including calibration experiments, tracking performance evaluation, phantom scans, and real scenarios scans have been conducted. The results show that the proposed system achieved the accumulated frame position error of 3.78 mm and the orientation error of 0.36° and reconstructed 3D US images with high quality in both phantom and real scenarios. CONCLUSIONS: The proposed method has been demonstrated to enhance the robustness and effectiveness of freehand 3D US. Follow-up research will focus on improving the accuracy and stability of multi-sensor fusion to make the system more practical in clinical environments.

Application of double-stent assisted coil embolization in intracranial vertebral artery dissecting aneurysms with mass effect.

BACKGROUND: Unruptured intracranial vertebral artery dissecting aneurysms (IVADAs) with mass effect have an extremely poor natural course, and treatment of these aneurysms remains a challenge for endovascular and surgical strategies. The aim of this study was to analyze the role of double-stent-assisted coil embolization in preventing rupture and bleeding of intracranial vertebral artery dissecting aneurysm with brainstem compression by reducing mass effect and preventing the recurrence of the aneurysm. METHODS: A total of 25 patients (mean age, 56.04±13.0 years) with unruptured IVADAs with mass effect received dual-stent-assisted coil embolization. The baseline characteristics, the change of aneurysm size on MR, the rate of retreatment, and the improvement rate of clinical symptoms and signs were analyzed retrospectively. RESULTS: All patients completed the surgical procedures successfully. No aneurysm bleeding or perforating artery occlusion occurred during the perioperative and follow-up periods. The initial maximum diameter of the aneurysm on MR was 17.5±3.6 mm. One year after treatment, the maximum diameter of the aneurysm on MR was 15.8±4.9 mm. The reduction rate of the maximum diameter of the aneurysm was 10.7±12.7%. The change of the maximum diameter before and after treatment of aneurysm was statistically significant (P<0.001). In terms of the improvement rate of clinical symptoms, 15 cases were completely improved (60.0%), 6 cases were partially improved (24.0%), and the total clinical improvement rate was 84%. Four cases (16.0%) showed no improvement or even had aggravation of clinical symptoms. In 5 cases (20.0%), aneurysms recurred. Among 4 cases involving posterior inferior cerebellar artery origin, 3 cases had the recurrence (75%). 5 recurred cases were treated with single-stent-assisted coil embolization. No residual aneurysm and recurrence were found on the follow-up angiography. CONCLUSIONS: The double-stent-assisted coil embolization procedure is very safe and reliable. It can effectively prevent the aneurysm from continuing to grow and rupture and thereby reduce the clinical symptoms caused by the mass effect.

Advantages of using Ti-mesh type electrodes for flexible dye-sensitized solar cells.

We used Ti meshes for both the photoanodes and counter electrodes of dye-sensitized solar cells (DSSCs) to improve the flexibility and conductivity of the electrodes. These mesh type electrodes showed good transparency and high bendability when subjected to an external force. We demonstrated the advantages of cells using such electrodes compared to traditional transparent conducting oxide based electrodes and back side illuminated DSSCs, such as low sheet resistance, elevated photo-induced current and enhanced sunlight utilization. Nanotube layers of different thicknesses were investigated to determine their effect on the photovoltaic parameters of the cell. The overall efficiency of the best cells was approximately 5.3% under standard air mass 1.5 global (AM 1.5 G) solar conditions. Furthermore, the DSSCs showed an efficiency of approximately 3.15% due to the all Ti-mesh type electrodes even after illumination from the back side.

Bio-Fermented Malic Acid Facilitates the Production of High-Quality Chicken via Enhancing Muscle Antioxidant Capacity of Broilers.

Malic acid, an intermediate of the tricarboxylic acid (TCA) cycle, is a promising acidifier with strong antioxidant capacity. This study aimed to evaluate the effects of bio-fermented malic acid (BFMA) on promoting the body health, performance and meat quality of broilers. A total of 288 one-day-old Arbor Acres male broiler chicks were randomly divided into four treatments with six replicates in each. Every replicate had 12 chicks. Four experimental diets contained 0, 4, 8, and 12 g/kg BFMA, respectively. During the 42-day trial, mortality was recorded daily, feed intake and body weight of each replicate being recorded every week. Blood samples were collected on days 21 and 42 for chemical analysis. After slaughter at the age of 42 days, the carcass traits and meat quality of the broilers were measured, breast muscle samples were collected for the determination of antioxidant capacity, and cecal digesta were pretreated for microbiota analysis. Dietary BFMA significantly increased feed intake and daily gain, and decreased feed conversion ratio and death and culling ratio of the broilers at the earlier stage. The water-holding capacity of breast muscle indicated by the indexes of dripping loss and cooking loss was significantly increased by BFMA, especially at the addition level of 8 g/kg. Dietary BFMA significantly decreased the activity of superoxide dismutase and contents of immunoglobulin A and glutathione, and increased contents of immunoglobulin G and M in serum of the broilers. The contents of glutathione, inosinic acid, and total antioxidant capacity and the activities of glutathione-Px and superoxide dismutase were significantly increased by dietary BFMA, with the level of 8 g/kg best. The diversity of cecal microbiota of broilers was obviously altered by BFMA. In conclusion, as one of several acidifiers, addition of BFMA in diets could improve the performance and body health of broilers, probably by reinforcing immunity and perfecting cecal microbiota structure. As one of the intermediates of the TCA cycle, BFMA increases the water-holding capacity of breast muscle of broilers, probably through reducing lactate accumulates and enhancing antioxidant capacity.

Open-source algorithm and software for computed tomography-based virtual pancreatoscopy and other applications.

Pancreatoscopy plays a significant role in the diagnosis and treatment of pancreatic diseases. However, the risk of pancreatoscopy is remarkably greater than that of other endoscopic procedures, such as gastroscopy and bronchoscopy, owing to its severe invasiveness. In comparison, virtual pancreatoscopy (VP) has shown notable advantages. However, because of the low resolution of current computed tomography (CT) technology and the small diameter of the pancreatic duct, VP has limited clinical use. In this study, an optimal path algorithm and super-resolution technique are investigated for the development of an open-source software platform for VP based on 3D Slicer. The proposed segmentation of the pancreatic duct from the abdominal CT images reached an average Dice coefficient of 0.85 with a standard deviation of 0.04. Owing to the excellent segmentation performance, a fly-through visualization of both the inside and outside of the duct was successfully reconstructed, thereby demonstrating the feasibility of VP. In addition, a quantitative analysis of the wall thickness and topology of the duct provides more insight into pancreatic diseases than a fly-through visualization. The entire VP system developed in this study is available at https://github.com/gaoyi/VirtualEndoscopy.git .