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Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.

Intracerebral hemorrhage (ICH) is a dangerous neurological disease. The mechanism of ferroptosis in ICH remains unclear. Using bioinformatics analysis, we aimed to identify the key molecules involved in ferroptosis and provide treatment targets for ICH to further explore the mechanism of ferroptosis in ICH. GSE24265 was downloaded from the Gene Expression Omnibus (GEO) dataset and intersected with ferroptosis genes. A total of 45 differentially expressed genes (DEGs) were selected, most of which were involved in the TNF signaling pathway and oxidative stress response. Key modules constructed by the protein–protein interaction (PPI) network analysis and screening of genes related to the TNF signaling pathway led to the confirmation of the following genes of interest: MAPK1, MAPK8, TNFAIP3, ATF4, and SLC2A1. Moreover, MAPK1 was one of the key genes related to TNF signaling and oxidative stress, and it may play an important role in ferroptosis after cerebral hemorrhage. The MAPK1-related molecules included hsa-miR-15b-5P, hsa-miR-93-5P, miR-20b-5p, SNHG16, XIST, AC084219.4, RP11-379K17.11, CTC-444N24.11, GS1-358P8.4, CTB-89H12.4, RP4-773N10.5, and FGD5-AS1. We also generated a hemorrhage rat model, which was used to conduct exercise intervention in ICH rats, and qRT-PCR was used to assess the expression levels of our genes of interest. The mRNA levels after cerebral hemorrhage showed that MAPK1, ATF4, SLC2A1, and TNFAIP3 were upregulated, whereas MAPK8 was downregulated. Treadmill training increased the expression of anti-inflammatory molecules TNFAIP3 and SLC2A1 and reduced the expression of MAPK1, ATF4, and MAPK8, indicating that treadmill training may be utilized as antioxidant therapy to decrease neuronal ferroptosis. The results of this study indicated that the MAPK1-related mRNA–miRNA–lncRNA interaction chain could be potentially employed as a biomarker of the inception and progression of ferroptosis after cerebral hemorrhage.

Background: This study aims to evaluate the therapeutic effect of intra-articular injection of different doses of exosomes derived from mesenchymal stem cells(MSC) and the effect on nerve and cartilage repair in a monoiodoacetate (MIA) model of knee osteoarthritis(OA) in rats. Methods: The pain rat model was established by injection of sodium monoiodate (MIA) into the knee joint of the rats, the knee joint and dorsal root ganglion (DRG) of rats were collected for histologic analyses. For pain assessment, On 1 day before MIA injection, 7, 14 days after MIA injection and 7, 14,28 days after Exosome injection,paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) was measured. Articular cartilage were assessed on HE by ORASI grade and the expression of ATF-3 and GAP-43 in dorsal root ganglion (DRG) using immunohistochemistry and western blotting in MIA-induced rats. Results: In our study, exosome significantly improved PWT and PWL value with a dose-dependent manner on 7, 14, and 28 days after intra-articular Exosome compared with the MIA group. Exosome injection therapy also has a repairing effect on cartilage on 28 days after intra-articular Exosome compared with the MIA group. Moreover, exosome treatment significantly upregulated GAP-43 protein and downregulated ATF-3 protein in the DRG with a dose-dependent manner of the OA rat. Conclusion: Intraarticular injection of different doses of mesenchymal stem cell derived exosomes in MIA-induced rats osteoarthritis, the analgesic effect of exosome was dose-dependent. Moreover, the repair of nerve by exosomes is earlier than that of cartilage.

The effective utilization and assessment of medical resources have become a common concern for scholars in various countries due to the impact of the COVID-19 pandemic. This study deals with a method to monitor medical resource allocation in real-time and verify the effectiveness of the proposed method with actual data. In this work, we selected Iwate Prefecture in northeastern Japan based on the geographical characteristics and social environment. By collecting data from the Japanese Ministry of Land, Infrastructure, Transport, and Tourism and Welfare (MLIT), we clustered population centers in Iwate Prefecture, and found the clustering centers in densely populated areas from the k-means algorithm. Subsequently, to compare the distribution of county-level medical resources across different secondary care areas, we selected the indicators of Iwate Prefectural Hospitals from the Hospital Intelligence Agency. We classified 19 prefectural hospitals in Iwate Prefecture into four different clusters using the spectral clustering algorithm. The clustering results revealed that all hospitals close to the " clustering centers in densely populated areas" were Iwate prefectural disaster stronghold hospitals. Moreover, we found that these hospitals performed well in operational indicators. Only the Ninohe prefectural hospital in the Ninohe medical area was found not located in a population center. However, it still performs well in terms of business indicators since the Ninohe medical area has a high proportion of public hospitals and the Ninohe prefectural hospital plays an important role. Hence, the government should fully consider geographical characteristics when considering hospital restructuring. We used a real data set to demonstrate the validity of the proposed technique, providing a theoretical basis for the government's healthcare policy.

Attention is a psychological and neurophysiological phenomenon, and associated with task difficulty. With the development of electroencephalography (EEG) detection tools, mature and affordable mobile brainwave sensors have become available. Therefore, this study aims to predict attentional status with the difficulty of work based on the EEG signals, and apply the process of prediction to an Android application. In the study, 10 participants performed different tasks with NeuroSky's MindWave EEG device, which can collect participants' EEG signals. K-means clustering algorithm was used to estimate the boundary of different attentional status. Moreover, Q-value was used to evaluate the question difficulty. 20 participants were recorded gender, the EEG signals, question difficulty, results, and answer time, which were participant predictors. The attentional status was predicted by support vector machine (SVM) classifier. The findings indicated that early identity of attentional status is essential to the learning efficiency, and provided a guide to the design of task.

Objective In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). Methods PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Results Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Conclusion Our results indirectly suggest that BP-stainless DESs may offer more benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is better.

Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5–146.8%, and 241.5–255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate.

With the help of ABAQUS and its subroutine DLOAD calculated the asphalt pavement response of different pothole area and combination of pavement structural from moving load. So as to arrive the law of development to pothole and the best combination of pavement structure to resist the pothole .Results show that the inflection point in the development of pothole is 53.25cm×53.25cm of pothole area; The best combination of pavement structure to resist the pothole is 4.5cm+6cm+9.5cm.The results could use to define the best time to repair pothole, and provide the best combination of pavement structural to resist pothole.

We investigated the effect of different concentrations of elastase on the aneurysm formation rate in the abdominal aortic aneurysm (AAA) model induced by low-pressurized abdominal aortic perfusion of elastase in rabbits. Fifty male New Zealand white rabbits were randomly divided into five groups (