Abstract Objectives Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, gut microbiota and its metabolites contribute to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear. In this study, we aimed to investigate whether gut microbiota and their metabolites alter the effects of high fat diet (HFD) on the severity of collagen-induced arthritis (CIA) in mice. Methods Briefly, mice were divided into normal group (N), CIA model group (C), HFD group (T), and HFD CIA group (CT). Hematoxylin and Eosin staining(HE) and Safranin O-fast green staining were conducted, and levels of blood lipid and inflammatory cytokines were measured. 16S rDNA sequencing technique and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics were performed to explore changes in the microbiota structure to further reveal the pathomechanism of HFD on CIA. Results HFD aggravated the severity of CIA in mice. The CT group had the highest proportion of microbial abundance ofBlautia, Oscillibacter, Ruminiclostridium-9, andLachnospiraceaeUCG 006 at the genus level, but had a lower proportion of Alistipes. Additionally, the fecal metabolic phenotype of the combined CT group shows significant changes, with differential metabolites enriched in 9 metabolic pathways, including primary bile acid biosynthesis, arginine biosynthesis, sphingolipid metabolism, purine metabolism, linoleic acid metabolism, oxytocin signaling pathway, aminoacyl-tRNA biosynthesis, the pentose phosphate pathway, and sphingolipid signaling pathway. Correlation analysis revealed that some of the altered gut microbiota genera were strongly correlated with changes in fecal metabolites, total cholesterol (TC), triglyceride (TG), and inflammatory cytokine levels. Conclusions This study shows that HFD may aggravate inflammatory reaction in CIA mice by altering the gut microbiota and metabolic pathways. RA. . (RA) addition However unclear (HFD collageninduced collagen induced (CIA Briefly N, N , (N) C, C (C) T, T (T) CT. (CT) stainingHE HE staining(HE Ofast O fast conducted measured S chromatographymass chromatography mass LCMSbased LC MS based ofBlautia Oscillibacter Ruminiclostridium9, Ruminiclostridium9 Ruminiclostridium 9, Ruminiclostridium-9 00 level Alistipes Additionally pathways biosynthesis metabolism pathway aminoacyltRNA aminoacyl tRNA TC, TC (TC) TG, TG (TG) (RA (N (C (T (CT Ruminiclostridium- 0 (TC (TG

ABSTRACT Objective: To explore the factors affecting short-term prognosis of circulatory failure patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Methods: A total of 136 patients undergoing VA-ECMO were enrolled in this study and subsequently divided into the death group (n=35) and the survival group (n=101) based on whether death occurred during hospitalisation. Extracorporeal membrane oxygenation (ECMO) running time, length of intensive care unit stay, length of hospital stay, costs, and ECMO complications were then compared between the two groups. Results: The average age of all patients undergoing ECMO was 47.64±16.78 years (53.2±16.20 years in the death group and 45.713±16.62 years in the survival group) (P=0.022). Patients in the survival group exhibited a clear downward trend in lactic acid value following ECMO treatment compared to those in the death group. Total hospitalisation stay was longer in the survival group (35 days) than in the death group (15.5 days) (P<0.001). In the analysis of ECMO complications, the incidence of neurological complications, renal failure, limb complications, and infection were higher in the death group than in the survival group (P<0.05 for all). Specifically, as a risk factor for patient survival and discharge, the occurrence of infection will lead to increased hospitalisation stays and costs (P<0.05 for both). Conclusion: Complications such as kidney failure and infection are associated with in-hospital death, and ECMO-related complications should be actively prevented to improve the survival rate of VA-ECMO treatment. Objective shortterm short term VAECMO VA (VA-ECMO Methods 13 n=35 n35 n 35 (n=35 n=101 n101 101 (n=101 (ECMO time groups Results 47641678 47 64 16 78 47.64±16.7 53.2±16.20 5321620 53 2 20 (53.2±16.2 457131662 45 713 62 45.713±16.6 P=0.022. P0022 P P=0.022 . 0 022 (P=0.022) (3 days 15.5 155 15 5 (15. P<0.001. P0001 P<0.001 001 (P<0.001) P<0.05 P005 05 (P<0.0 all. all) Specifically discharge both. both both) Conclusion inhospital ECMOrelated related 1 n=3 n3 3 (n=3 n=10 n10 10 (n=10 4764167 4 6 7 47.64±16. 53.2±16.2 532162 (53.2±16. 45713166 71 45.713±16. P002 P=0.02 02 (P=0.022 ( 15. (15 P000 P<0.00 00 (P<0.001 P<0.0 P00 (P<0. n= (n= n=1 n1 (n=1 476416 47.64±16 53.2±16. 53216 (53.2±16 4571316 45.713±16 P=0.0 (P=0.02 (1 (P<0.00 P<0. P0 (P<0 (n 47641 47.64±1 53.2±16 5321 (53.2±1 457131 45.713±1 P=0. (P=0.0 P<0 (P< 4764 47.64± 53.2±1 532 (53.2± 45713 45.713± P=0 (P=0. P< (P 476 47.64 53.2± (53.2 4571 45.713 P= (P=0 47.6 53.2 (53. 457 45.71 (P= 47. 53. (53 45.7 (5 45.

ABSTRACT Objective: To compare health-related quality of life (HRQoL) of patients primarily treated with a no-touch saphenous vein graft with that of patients who received a conventional graft. Methods: The study included all individuals treated with a percutaneous coronary intervention (PCI) on a saphenous vein graft (SVG) between January 2006 and June 2020. The RAND-36 health survey was used to assess HRQoL. The Mann-Whitney U test was used to test differences in HRQoL between the two groups. Effect size was estimated via Cohen’s d. The average treatment effect between the groups was tested by propensity score matching (PSM). Results: Of the 346 patients treated with a PCI in a stenosed or occluded SVG, 165 responded to RAND-36 (no-touch: n=48; conventional: n=117). Patients with a no-touch graft reported better mean values on seven of the eight health survey domains. Statistically significant differences were observed for four of the domains, all in favour of the no-touch group. The effect size estimates indicated a small difference for five domains, with the highest values (>0.40) seen for the general health and energy/fatigue domains. PSM confirmed a statistically significant difference for the physical functioning and general health domains. Conclusion: At a mean follow-up of 5.4 years, patients who received a PCI in no-touch vein grafts showed significantly better HRQoL than those who received a PCI in conventional vein grafts. Objective healthrelated related (HRQoL notouch no touch Methods (PCI SVG (SVG 200 2020 RAND36 RAND 36 RAND-3 MannWhitney Mann Whitney Cohens Cohen s d PSM. . (PSM) Results 34 16 (no-touch n=48 n48 n 48 n=117. n117 n=117 117 n=117) domains group >0.40 040 0 40 (>0.40 energyfatigue energy fatigue Conclusion followup follow up 54 5 4 5. years 20 202 RAND3 3 RAND- (PSM 1 n=4 n4 n11 n=11 11 >0.4 04 (>0.4 2 n= n1 n=1 >0. (>0. >0 (>0 > (> (

Abstract Objectives This study was to compare the effects of different local analgesia protocols on osteoarthritis patients undergoing total knee arthroplasty (TKA). Methods Medical records of 148 osteoarthritis patients who underwent unilateral TKA between October 2016 and October 2017 in our hospital were retrospectively analyzed. All these patients were divided into three groups according to the pain management protocol (morphine, morphine + cocktail [100 mg ropivacaine, 10 mg morphine, and 30 mL 0.9% sodium chloride solution containing 2 mL betamethasone (4 mg)], or cocktail). The postoperative visual analog scale (VAS) score, muscle strength, and complications were compared between the groups. Results At 6 and 12 hours post-operation, the VAS score in group C was significantly higher than that in group A or group B. In addition, the muscle (quadriceps femoris) strength score of group C (3.7 ± 2.8) was significantly higher than that in groups A and B at 6 and 12 hours post-operation. The VAS score and muscle strength score showed no significant differences among the three groups at 24 and 36 hours post-operation. The time of postoperative first void of group C was significantly shorter than that of groups A and B. Groups A or B had a significantly higher incidence of nausea and emesis compared with group C. The incidence of pruritus was higher in groups A or B than that in group C. Conclusion Epidural anesthesia combined with local analgesic cocktail injection is a preferable effective multimodal analgesia for TKA.

SUMMARY OBJECTIVE: The aim of this study is to analyze the relations of heart-type fatty acid-binding protein (H-FABP) and brain-type fatty acid-binding protein (B-FABP) with postoperative cognitive dysfunction (POCD) in elderly patients undergoing spinal surgery. METHODS: One hundred and twenty-five patients who underwent spinal surgery were enrolled in this study. According to whether patients had POCD within 5 days after surgery, the participants were divided into POCD group and non-POCD group. Before surgery and 6 h after surgery, the serum H-FABP and B-FABP contents were detected. RESULTS: There were 33 (26.4%) patients in POCD group, and 92 (73.60%) patients in non-POCD group. After surgery, the serum H-FABP and B-FABP contents in POCD group were significantly higher than those before surgery, respectively (p<0.05), and those in non-POCD group were significantly lower than those before surgery, respectively (p<0.05). After surgery, the serum H-FABP and B-FABP contents in POCD group were significantly higher than those in non-POCD group, respectively (p<0.05). CONCLUSION: The serum H-FABP and B-FABP contents are positively related to the occurrence of POCD in elderly patients undergoing spinal surgery.

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.

ABSTRACT Purpose: To make a further evaluation of perioperative outcomes between the robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we conducted a comparison and trend analysis by using the Nationwide Inpatient Sample (NIS) from 2009 to 2014. Materials and Methods: Adult prostate cancer patients with radical prostatectomy were abstracted from the NIS. RARP and ORP were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The perioperative outcomes included blood transfusion, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Propensity score matching method and multivariable logistic regression model were performed to adjust for the pre-defined covariates. The annual percent change (APC) was used to detect the change trend of rates for outcomes. Results: A total of 77.054 patients were included in our study. According to the results of propensity score matching analyses, RARP outperformed ORP in blood transfusion (1.96% vs. 9.40%), intraoperative complication (0.73% vs. 1.25%), overall postoperative complications (8.87% vs. 11.97%), and pLOS (13.39% vs. 36.70%). We also found that there was a significant decreasing tendency of incidence in blood transfusion (APC=-9.81), intraoperative complication (APC=-12.84), and miscellaneous surgical complications (APC=-14.09) for the RARP group. The results of multivariable analyses were almost consistent with those of propensity score matching analyses. Conclusions: The RARP approach has lower incidence rates of perioperative complications than the ORP approach, and there is a potential decreasing tendency of complication incidence rates for the RARP.

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.

Abstract Background: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. Results: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (lECs) to investigate the communication between MCs and lECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into lECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. Conclusions: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.

OBJECTIVES: To investigate the effects of an intratympanic injection of dexamethasone combined with gentamicin on the expression level of serum P0 protein antibodies in patients with Meniere’s disease (MD). METHODS: A total of 136 patients with MD treated in our hospital were enrolled in this study. Among them, 68 patients were treated with an intratympanic injection of dexamethasone combined with gentamicin (observation group). Another 68 patients were treated with gentamicin alone (control group). RESULTS: After treatment, the expression levels of IgG and IgM in the two groups significantly decreased (p<0.05); the levels in the observation group were significantly lower than those in the control group (p<0.05). The incidences of vertigo, tinnitus, and gait instability in the observation group were significantly lower than those in the control group (p<0.05). Vestibular symptom index (VSI) scores in the observation group were significantly lower than those in the control group (p<0.05). We observed no significant difference between the two groups in the number of vertigo attacks 6 months after treatment (p>0.05). CONCLUSION: For patients with MD, dexamethasone combined with gentamicin can reduce the incidence of vertigo, tinnitus, and gait instability, but it has no effect on the efficacy or number of vertigo attacks 6 months after treatment. Therefore, the levels of myelin P0 protein antibodies after treatment can be used as predictors of vertigo at 6 months after treatment.

ABSTRACT In this study, we examined the effects of lactic acid bacteria (LAB) inoculant and beet pulp (BP) on the quality of yacon (Smallanthus sonchifolius) residue silage. Yacon silage was prepared using a small-scale system of silage fermentation, and the treatments were as follows: control silage without any additive and silages with LAB inoculant Chikuso-1 (Lactobacillus plantarum, 5 mg/kg, fresh matter basis), BP (30% fresh matter basis), and LAB+BP. Silages were opened on days 3, 5, 7, 15, 30, and 60 of fermentation. The chemical composition, organic acid content, and in vitro ruminal digestion of the 60-day silage were determined. The pH of LAB-treated silage was lower than that of the silage without LAB. Furthermore, the LAB-treated silage presented the lowest ammonia-N concentration among the four types of silages, and it inhibited the growth of harmful bacteria including molds and clostridia during the early stages of fermentation. The BP-treated silage had lower contents of crude protein and ether extract than the silage without BP. The 60-day silage inoculated with LAB had the highest in vitro dry matter (DM) digestibility among the four silages, and the production of methane was lower than that of the silage treated with BP. The pH showed a tendency toward stabilization after 30 days of fermentation, although the concentration of lactic acid exhibited fluctuations during fermentation. The results suggest that the addition of LAB and BP can improve the fermentation quality of yacon silage, and the yacon silage with LAB might increase in vitro DM digestibility, but decrease in vitro ruminal methane production.

This study explores the safety and effect of acute cerebral infarction treatment by microcatheter injection of tirofiban combined with a Solitaire AB stent and/or stent implantation. Emergency cerebral angiograms showing the responsible vascular occlusion of 120 acute cerebral infarction patients who underwent emergency endovascular thrombectomy were included in the study. These patients were randomly divided into two groups using the random number table method: treatment group (n=60) that received thrombectomy (with cerebral artery stents) combined with intracerebral injection of tirofiban and control group (n=60) that only received thrombectomy (with cerebral artery stents alone). The baseline data, cerebral angiography before and after surgery, hospitalization, and follow-up results of patients in these two groups were compared. Furthermore, the incidence of major adverse cerebrovascular events of these two groups was compared (90-day modified Rankin scale, a score of 0–2 indicates a good prognosis). The difference between baseline clinical data and brain angiography between these two groups was not statistically significant. Patients in the treatment group had a higher prevalence of thrombolysis in cerebral infarction grade 2b/3 than patients in the control group (88.3% (53/60) vs 66.7% (40/60), P=0.036). Moreover, the National Institutes of Health Stroke Scale scores 7 days after surgery and the 90-day prognosis were all better for the patients who received tirofiban (P=0.048 and P=0.024). Mechanical thrombectomy with Solitaire AB stents in combination with the injection of tirofiban through a microcatheter appears to be safe and effective for the endovascular treatment of acute ischemic stroke.

Abstract Background: Gastric cancer is a common malignant tumor with high morbidity and mortality worldwide, which seriously affects human health. Gramicidin is a short peptide antibiotic which could be used for treating infection induced by bacteria or fungi. However, the anti-cancer effect of gramicidin on gastric cancer cells and its underlying mechanism remains largely unknown. Results: Gastric cancer cells SGC-7901, BGC-823 and normal gastric mucosal cells GES-1 were treated with different concentrations of gramicidin respectively. The results of CCK-8 experiment revealed cellular toxicity of gramicidin to cancer cells while cell colony formation assay showed that gramicidin significantly inhibited the proliferation of gastric cancer cells, but had little effect on normal gastric mucosal cells. In addition, the wound healing assay showed that gramicidin inhibited the migration of SGC-7901 cell. Meanwhile, apoptosis and cell cycle analysis revealed that gramicidin induced cell apoptosis with G2/M cell cycle inhibition. Furthermore, western blot analysis demonstrated that gramicidin down-regulated the expression of cyclinD1 and Bcl-2 as well as the FoxO1 phosphorylation. Conclusions: The current study illustrated the anti-tumor activity of gramicidin on gastric cancer cells, providing a possibility for gramicidin to be applied in clinical practice for the treatment of gastric cancer.

We introduce a novel approach in simple and highly sensitive fluorometric determination of ammonium nitrogen. The proposed method is based on a fluorescence derivatization with benzyl chloride. The benzyl chloride was converted to a new fluorescent derivative by reaction with ammonium ion (NH4+) in the presence of sodium bicarbonate. The excitation and emission wavelengths were 258 and 284 nm, respectively. The effects of benzyl chloride concentration, sodium bicarbonate concentration, reaction temperature and time, and hydrochloric acid concentration were studied in detail. Under the optimal conditions of the experiment, the linear range for determination of ammonium nitrogen was 0.01-0.60 mg L-1, and the detection limit was 0.008 mg L-1. Relative standard deviation of eleven measurements for 0.40 mg L-1 NH4+-N was 2.6%. The method was successfully applied to the determination of ammonium nitrogen concentration in different water samples. The mechanism of the derivatization was further confirmed by Fourier transform infrared (FTIR) spectra.

Abstract In the bauxite flotation process, concentrate grade and tailings grade are key production indicators; however, they are difficult to measure online. It is also difficult to develop an effective mathematical model for the process because of the complex non-linear and uncertain relationship among the feed parameters (feed grade, pulp density, slurry particle size, etc.), froth features and production indicators. Therefore, an online hybrid modeling method is proposed by analyzing the multiple parameters that affect the production indicators. First, according to the correlation and redundancy in the feed and froth feature parameters, the kernel principle component analysis (KPCA) is used to reduce the number of the parameters. Then, a neutral network model of the regular extreme learning machine (RELM), which is based on wavelet function, is presented to predict these two indicators. To improve generalization capability and prediction accuracy, information entropy is used to distribute the weight of the two models based on their predicting error. At last, an on-line updating strategy of the hybrid model is constructed in order to investigate the influence of the working conditions. The proposed method is tested on the diasporic-bauxite flotation process and shows high predictive accuracy and generalization capability. It lays the foundation for optimal control of the operation parameters based on mineral grade in the flotation process.