Differential polyvalent passive immune protection of egg yolk antibodies (IgY) against live and inactivated Vibrio fluvialis in fish.

Egg yolk antibodies (IgY) can be prepared in large quantities and economically, and have potential value as polyvalent passive vaccines (against multiple bacteria) in aquaculture. This study prepared live and inactivated Vibrio fluvialis IgY and immunized Carassius auratus prior to infection with V. fluvialis and Aeromonas hydrophila. The results showed that the two IgY antibodies hold effective passive protective rates against V. fluvialis and A. hydrophila in C. auratus. Further, the serum of C. auratus recognized the two bacteria in vitro, with a decrease in the bacteria content of the kidney. The phagocytic activity of C. auratus plasma was enhanced, with a decrease in the expression of inflammatory and antioxidant factors. Pathological sections showed that the kidney, spleen, and intestinal tissue structures were intact, and apoptosis and DNA damage decreased in kidney cells. Moreover, the immunoprotection conferred by the live V. fluvialis IgY was higher than that of the inactivated IgY. Addition, live V. fluvialis immunity induced IgY antibodies against outer membrane proteins of V. fluvialis were more than inactivated V. fluvialis immunity. Furthermore, heterologous immune bacteria will not cause infection, so V. fluvialis can be used to immunize chickens to obtain a large amount of IgY antibody. These findings suggest that the passive immunization effect of live bacterial IgY antibody on fish is significantly better than that of inactivated bacterial antibody, and the live V. fluvialis IgY hold potential value as polyvalent passive vaccines in aquaculture.

Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy.

BACKGROUND: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP. METHODS: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites. RESULTS: An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP. CONCLUSIONS: Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

Polyvalent passive vaccine candidates from egg yolk antibodies (IgY) of important outer membrane proteins (PF1380 and ExbB) of Pseudomonas fluorescens in fish.

Polyvalent antibodies can resist multiple bacterial species, and immunoglobulin Y (IgY) antibody can be economically prepared in large quantities from egg yolk; further, IgY polyvalent antibodies have application value in aquaculture. The outer membrane proteins (OMPs) PF1380 and ExbB of Pseudomonas fluorescens were expressed and purified, and the corresponding IgY antibodies were prepared. PF1380, ExbB, and the corresponding IgY antibodies could activate the innate immune responses of chicken and Carassius auratus. The passive immunization to C. auratus showed that the IgY antibodies of PF1380 and ExbB had an immune protection rate, down-regulated the expression of antioxidant-related factors (MDA, SOD, GSH-Px, and CAT) to reduce the antioxidant reaction, down-regulated the expression of inflammation-related genes (IL-6, IL-8, TNF-α, and IL-1ß) to reduce the inflammatory reaction, maintained the integrity of visceral tissue structure, and reduced apoptosis and damage of tissue cells in relation to P. fluorescens and Aeromonas hydrophila infections. Thus, the IgY antibodies of PF1380 and ExbB could be considered as passive polyvalent vaccine candidates in aquaculture.

The identification of polyvalent protective immunogens and immune abilities from the outer membrane proteins of Aeromonas hydrophila in fish.

Among aquaculture vaccines, polyvalent vaccines (for immunoprotection against multiple bacterial species) are more efficient and can better avoid bacterial resistance and antibiotic residues in fish. Here, 15 outer membrane proteins (OMPs) of Aeromonas hydrophila were cloned and purified, and mouse antisera were prepared. Passive immunization to Carassius auratus showed that four OMPs sera (OmpW, OmpAII, P5, and AHA2685) and the entire OMPs serum held effective immunoprotection against A. hydrophila infection. Furthermore, the active immunization of four OMPs to C. auratus showed that OmpW, OmpAII, P5, and AHA2685 held effective immunoprotection against A. hydrophila, and OmpW held active cross-protection against Vibrio alginolyticus. The mechanisms of these four candidate vaccines in triggering immune responses were subsequently explored. They all could activate innate immune responses in active immunization, down-regulate (p < 0.05) the inflammation-related genes expression to reduce the inflammatory reaction induced by A. hydrophila, and down-regulate (p < 0.05) antioxidant-related factors to reduce the antioxidant reaction for bacterial infection. Noteablely, the four OMPs had protective abilities on kidney and spleen tissues of C. auratus after challenged with A. hydrophila and V. alginolyticus by histopathological observation. Collectively, our results identify OmpW as a polyvalent vaccine candidate, and OmpAII, P5, and AHA2685 as vaccine candidates against A. hydrophila infection in fish.

Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report.

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

The Effect of Crank Length Changes from Cycling Rehabilitation on Muscle Behaviors.

BACKGROUND: Many sports and physical activities can result in lower limb injures. Pedaling is an effective exercise for lower extremity rehabilitation, but incorrect technique may cause further damage. To some extent, previous experiments have been susceptible to bias in the sample recruited for the study. Alternatively, methods used to simulation activities can enable parametric studies without the influence of noise. In addition, models can facilitate the study of all muscles in the absence of the effects of fatigue. This study investigated the effects of crank length on muscle behavior during pedaling. METHODS: Six muscles (soleus, tibialis anterior, vastus medialis, vastus lateralis, gastrocnemius, and rectus femoris), divided into three groups (ankle muscle group, knee muscle group, and biarticular muscle group), were examined under three cycling crank lengths (100 mm, 125 mm, and 150 mm) in the present study. In addition, the relationship between crank length and muscle biological force was analyzed with the AnyBody Modeling System™, a human simulation modeling software based on the Hill-type model. Findings. Based on inverse kinematic analysis, the results indicate that muscle activity and muscle force decrease in varying degrees with increases in crank length. The maximum and minimum muscular forces were attained in the tibialis anterior and vastus lateralis, respectively. Interpretation. Studying the relationship between muscle and joint behavior with crank length can help rehabilitation and treating joint disorders. This study provides the pedal length distribution areas for patients in the early stages of rehabilitation.

The influence of crown coverage on the accuracy of static guided implant surgery in partially edentulous models: An in vitro study.

OBJECTIVE: To evaluate the influence of crown coverage of surgical guides on the accuracy of static computer-assisted implant surgeries (sCAISs) in different partially edentulous situations. METHODS: Acrylic models with five types of partially edentulous situations were fabricated in this study. In coDiagnostiX software (Dental Wings, Montreal, Canada), surgical templates were designed and fabricated with reduced crown coverage (RCC), standard crown coverage (SCC) and extended crown coverage (ECC). Then, fully guided implant placement into the acrylic models was performed by dental surgeons with more than 10 years of experience. In total, 120 models and 120 guides were manufactured, and 168 bone-level Straumann replica implants (4.1 × 10 mm, Institut Straumann AG, Basel, Switzerland) were inserted. Postoperative implant positions were scanned (Trios 3, 3 shape, Copenhagen, Denmark) and compared with the preplanned virtual positions via coDiagnostiX (Dental Wings, Montreal, Canada). The angular, coronal and apical deviations were measured and analyzed to evaluate the accuracy of implant insertion. Statistical analysis was performed using one-way ANOVA and Tukey's test. RESULTS: For single tooth missing situations, the RCC group was similar to the SCC group and ECC group in anterior sites. In premolar or molar sites, the SCC and ECC groups had no statistically significant difference (p > .05), while the RCC group had more coronal and apical deviation (p < .05). For multiple teeth missing situations, there was no difference among the RCC, SCC and ECC groups (p > .05). No difference was found among the five edentulous situations with different CCs (p > .05). CONCLUSION: The CC of templates can significantly affect the accuracy of guided surgeries when implants are inserted in a single gap at posterior sites. Templates with CC extended to the undercut line may be an optimal choice for static guided surgeries. CLINICAL SIGNIFICANCE: The accuracy of static guided implant surgery can be influenced by the CC of templates, and proper CC with the guide covering extending to the undercut line may contribute to improved accuracy. CC should be taken into consideration when designing surgical templates.

SH2B3, Transcribed by STAT1, Promotes Glioblastoma Progression Through Transducing IL-6/gp130 Signaling to Activate STAT3 Signaling.

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. The aberrant activation of STAT3 commonly occurs in GBM and is a key player in GBM tumorigenesis. Yet, the aberrant activation of STAT3 signaling is not fully understood. Here, we report that SH2B adaptor protein 3 (SH2B3) is highly expressed in GBM and preferentially expressed in GBM stem cells (GSCs). Moreover, SH2B3 high expression predicts worse survival of GBM patients. Targeting SH2B3 considerably impairs GBM cell proliferation, migration, and GSCs' self-renewal in vitro as well as xenograft tumors growth in vivo. Additionally, we provide evidence suggesting that STAT1 directly binds to the promoter of SH2B3 and activates SH2B3 expression in the transcriptional level. Functionally, SH2B3 facilitates GBM progression via physically interacting with gp130 and acting as an adaptor protein to transduce IL-6/gp130/STAT3 signaling. Together, our work firstly uncovers that the STAT1/SH2B3/gp130/STAT3 signaling axis plays critical roles in promoting GBM progression and provides insight into new prognosis marker and therapeutic target in GBM.

miR­124­3p inhibits the viability and motility of glioblastoma multiforme by targeting RhoG.

The mortality rate of patients with glioma is increasing worldwide per annum. This is attributed to the poor disease prognosis, most notably for high­grade gliomas (grade III and IV), which does not improve the overall patient survival. The dysregulation of microRNA (miRNA/miR)­124­3p is found in a variety of tumors. However, the association between miR­124­3p expression and its target genes in glioma has not been thoroughly elucidated. The present study aimed to explore the possible effects of miR­124­3p and its proved target, Ras homology Growth­related (RhoG), on the oncogenic events associated with glioblastoma multiforme (GBM) development. The data demonstrated an inverse association between miR­124­3p and RhoG expression levels during GBM progression in GBM tissues and cells. U87 and U251 cells were employed for the in vitro assays. Luciferase reporter assays revealed that miR­124­3p interacted with RhoG at the RhoG 3' untranslated region and inhibited RhoG expression in GBM cells. Functionally, enriched miR­124­3p repressed RhoG transcription and suppressed GBM cell proliferation and migration, promoting apoptosis and altering the expression or activity of the apoptosis­related proteins of GBM cells. By contrast, the inhibition of miR­124­3p in GBM cells upregulated RhoG levels and promoted the proliferation of GBM cells. The knock down of RhoG expression by specific small interfering RNA sequences partially neutralized the effects induced by the miR­124­3p inhibitor. In conclusion, the present study demonstrated the crucial effects of miR­124­3p on the development and deterioration of GBM by targeting RhoG.

[Composition, Characteristics, and Accumulation of Antibiotics in the Soil in Agricultural Land].

Exploring the composition and accumulation of antibiotics in agricultural land soil for soil for quality management of agricultural land and control of antibiotic pollution is of great significance. A total of 95 soil samples were collected from farmland soil in a typical agricultural and sideline production base of northern China. In this study, the concentrations of 10 antibiotics, including tetracycline antibiotics (TCs), macrolide antibiotics (MLs), and sulfonamide antibiotics (SAs), were determined in soil samples from different land use types using HPLC-MS/MS. In addition, the composition and spatial distribution of the antibiotics were compared. The relationships between the concentration distributions and the distance from livestock farms, highways, and rivers were analyzed. Moreover, the composition and accumulation of antibiotics in the soil with different planting patterns and soil properties were preliminarily discussed. The results showed that the concentrations of antibiotics in the soil were low-level, while the detection rate was high; in particular, the detection rate of the total amount of antibiotics was as high as 100%. In the study area, TCs were the dominant antibiotic types, accounting for 94% of the total. The coefficient variation (CV) was high, which reflected a significant difference in the spatial variation of these antibiotics. The spatial distribution and accumulation of antibiotics in the soil in this area were affected by the intensity of human activity. The detection rate and concentrations of the various antibiotics decreased with increasing distance between the soil sample and livestock farms, highways, and rivers. Among these, there was a significant negative correlation between the concentration of antibiotics and the distance between livestock farms and the soil samples (P<0.05). The detection rate of three types of antibiotics in soil samples from within 50 meters of a river reached 100%. The total concentration of the 10 antibiotics was the highest in orchards, followed by vegetable plots, and mixed fruit and vegetable areas. Furthermore, the sources and concentrations of antibiotics in a peach orchard and open-air vegetable field were significantly different from those in a walnut orchard, greenhouse vegetable field, and mixed field. Moreover, the soil pH, soil organic matter (SOM), cation exchange capacity (CEC), total nitrogen (TN), available phosphorus (AP), and available potassium (AK) were selected to characterize soil properties. Redundancy analysis showed that soil properties such as pH, SOM, CEC, AP, AK have a greater impact on the distribution of antibiotics. The distribution of antibiotics was most closely related to AK, and the effect of TN was relatively weak. The results of this study suggested that the composition and accumulation of soil antibiotics in the area were affected by human activities and soil properties.

Post-transplant infection improves outcome of hepatocellular carcinoma patients after orthotopic liver transplantation.

BACKGROUND: Tumor recurrence after orthotopic liver transplantation (OLT) remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma (HCC), since very few factors or measures have shown impact on overcoming HCC recurrence after OLT. Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection (PTI), a common complication, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified. AIM: To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT. METHODS: A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group (53 patients) and a non-PTI group (185 patients). Univariate analyses, including the differences of overall survival (OS), recurrence-free survival (RFS), and post-recurrence survival (PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method, and the differences were compared using the log rank test. The variables with a P-value < 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model. RESULTS: The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%, and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group (96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group (84.0%, 63.4%, and 60.2%) (P = 0.033). The absence of PTI was an independent risk factor for dismal OS (relative risk [RR] = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS (RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS (P = 0.003) and RFS (P = 0.003) rates of HCC patients with vascular invasion (IV), but did not impact on OS (P = 0.404) and RFS (P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, patients with PTI showed significantly better OS (P = 0.026) and PRS (P = 0.042) rates than those without PTI. CONCLUSION: PTI improves OS and RFS of the transplant HCC patients at a high risk for post-transplant death and tumor recurrence, which is attributed to suppressive effect of PTI on HCC recurrence.

Daytime fluctuation of intraocular pressure in patients with primary angle-closure glaucoma after trabeculectomy.

PURPOSE: To evaluate the daytime fluctuation of intraocular pressure (IOP) in patients with primary angle-closure glaucoma (PACG) after trabeculectomy. PARTICIPANTS AND METHODS: A total of 176 patients with PACG participated in a clinical trial of trabeculectomy with or without releasable sutures. Applanation IOP was measured at 5, 7, and 10 AM, and 2, 6, and 10 PM at 3 months posttrabeculectomy. We documented the mean, peak, and trough IOPs, determined the fluctuation of daytime IOP, and explored the associations of IOP fluctuation with baseline factors. RESULTS: IOP measurements were obtained in 173 patients. The mean daytime IOP was 13.2±3.7 mm Hg; mean peak IOP 15.1±4.1 mm Hg, mean trough IOP 11.3±3.5 mm Hg, and mean fluctuation 3.8±2.1 mm Hg. Fluctuation was positively correlated with peak (r=0.528, R2=0.28, P<0.001) and mean IOP (r=0.278, R2=0.08, P<0.001), but not with the trough IOP (r=0.015, P=0.843). Fluctuation was lower with extent of bleb (0.6 mm Hg/unit increase in extent; 95% CI, 0.1-1.2 mm Hg) and in blebs with microcysts (1.1 mm Hg less fluctuation; 95% CI, 0.2-1.9 mm Hg). Fluctuation was not associated with sex, age, baseline IOP, extent of peripheral anterior synechia or number of glaucoma medications before surgery, mean deviation of the visual field, vertical cup:disc ratio, or the use of releasable sutures. CONCLUSIONS: The mean fluctuation of daytime IOP after trabeculectomy for PACG was about 4 mm Hg. The fluctuation was positively associated with higher peak and mean IOP and negatively associated with extent of bleb and presence of microcysts.

Duloxetine treatment of long-term ketamine abuse-related lower urinary tract symptoms: a case report.

OBJECTIVE: To report a case of ketamine abuse-related lower urinary tract symptoms (LUTS) in a depressed patient, who was successfully treated with duloxetine. CASE REPORT: A 19-year-old woman with long-term (3 years) daily ketamine abuse had developed moderate depressive symptoms after forced cessation of ketamine use, together with severe LUTS of 3 months' duration. Urinary analysis and culture revealed negative results, and treatment with antibiotics was unsuccessful. Ketamine abuse-related LUTS were suspected and duloxetine was prescribed at 60 mg daily. After 2 weeks, the symptoms of depression and LUTS had been relieved. CONCLUSIONS: Duloxetine can be considered as one of the therapeutic drugs of choice for depressive patients with significant LUTS.