Assessing professional behaviors: a self-administered scale for medical students during clerkships.

BACKGROUND: Medical professionalism is a core competency for medical students during clerkships for further professional development. Given that the behavior-based framework could provide clear insight and is easy to assess, the study aimed to create a self-administered scale to measure the professional behaviors of medical students during their clerkships. METHODS: A comprehensive literature review on medical professional behaviors in English or Chinese and Delphi interviews were used to develop the initial version of the Self-Administered Scale for Professional Behavior of Medical Students During Clerkships. The reliability and validity analysis based on a survey of medical students from China, Cronbach's α calculations, and Confirmatory Factor Analysis (CFA) specifically were conducted to finalize the scale. The associations of professional behaviors with gender, medical programs, and clerkship duration were examined using Wilcoxon rank-sum tests. RESULTS: We included 121 studies and extracted 57 medical professionalism assessment tools, initially forming a pool of 48 items. To refine these items, eighteen experts participated in two rounds of Delphi interviews, ultimately narrowing down the item pool to 24 items. A total of 492 participants effectively completed the questionnaire. One item was removed due to its correlated item-total correlation (CITC) value, resulting in a final scale containing 23 items with six domains: Respect, Altruism, Communication and Collaboration, Integrity, Duty, and Excellence. The overall Cronbach's alpha value was 0.98, ranging from 0.88 to 0.95 for each domain. The fit indices (χ2/df = 4.07, CFI = 0.96, TLI = 0.95, RMSEA = 0.08, and SRMR = 0.02) signified a good fit for the six-domain model. Medical students' professional behavior was significantly associated with gender (p = 0.03) and clerkship duration (p = 0.001). CONCLUSION: The scale was demonstrated to be reliable and valid in assessing the professional behaviors of Chinese medical students during clerkships.

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages.

Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 1011 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host's immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-ɑ, IL-1ß, IL-6, IL-10, and TGF-ß1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. KEY POINTS: • Preparation and characterization of P. multocida OMVs. • P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. • P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro.

Impact of industry-university-research collaboration and convergence on economic development: Evidence from chengdu-chongqing economic circle in China.

Collaboration among industry, universities, and research is crucial for building an innovative nation. Although industry-university-research collaborative innovation (IURCI) and time-space convergence can drive innovation, increase productivity, and spur economic development, their effects on the regional economy have not been thoroughly examined in existing literature. Therefore, this study investigates the impact of industry-university-research collaborative innovation (IURCI) and time-space convergence on economic development in China. Specifically, we focus on local-level cities in the Chengdu-Chongqing Economic Circle (CCEC) and construct an evaluation index system and time-space convergence model to measure the effects of IURCI and time-space convergence on economic development from 2007 to 2021. Our findings indicate that the efficacy of IURCI on economic development in China follows an inverted U-shaped curve, meaning that the marginal impact of IURC may decrease as more creative funds are deployed. Furthermore, the positive marginal effect of inventive talent input may decrease when it surpasses a certain value in an open innovation environment. The spatiotemporal convergence of collaborative innovation and development levels of IURCI in the CCEC shows significant differences. Regionally, the development level of IURCI in different regions exhibits significant differences in state and speed of convergence. In the southern Sichuan urban agglomeration, the collaborative innovation level of industry, education, and research follows an evolutionary process from convergence to divergence and then to convergence. Policymakers should pay close attention to the spatial effect of high-level development of regional IURCI and promote regions with higher development to drive regions with relatively weak development levels.

Isolation, Identification and Drug Resistance Rates of Bacteria from Pigs in Zhejiang and Surrounding Areas during 2019-2021.

This study aimed to determine the prevalence of bacterial diseases in pig farms in various regions of Zhejiang Province and surrounding areas. A total of 526 samples were collected from 85 pig farms in Zhejiang Province and surrounding areas. In this study, samples were analyzed using bacterial isolation and purification, Gram staining, PCR amplification, and antimicrobial susceptibility testing. A total of 36 Pasteurella multocida (Pm) isolates were detected, with an isolation rate of 6.84%; 37 Bordetella bronchiseptica (Bb) isolates were detected, with an isolation rate of 7.03%; 60 Glasserella parasuis (G. parasuis) isolates were detected, with an isolation rate of 11.41%; 170 Escherichia coli (E. coli) isolates were detected, with an isolation rate of 32.32%; 67 Streptococcus suis (SS) isolates were detected, with an isolation rate of 12.74%; 44 Actinobacillus pleuropneumoniae (APP) isolates were detected, with an isolation rate of 8.37%; and 7 Salmonella enteritis (SE) isolates were detected, with an isolation rate of 1.33%. Antimicrobial drug susceptibility testing against 21 types of antibiotics was carried out on the isolated strains, and the results showed that 228 strains had varying degrees of resistance to 21 antibiotics, including Pm, Bb, E. coli, and APP, with the highest resistance to lincomycin, at 100%. Pm and APP were the most sensitive to cephalothin, with resistance rates of 0. In terms of strains, Pm had the highest overall sensitivity to 21 antibiotics, and E. coli had the highest resistance. In short, bacterial diseases in Zhejiang and the surrounding areas were harmful, and the drug resistance situation was severe. This study provides scientific guidance for the clinical treatment of bacterial diseases.

Enhancing effect of chitosan nanoparticles on the immune efficacy of Bordetella bronchiseptica outer membrane vesicles.

The outer membrane vesicle (OMV) of bacteria is a bilayer membrane vesicle with a diameter of about 10-300 nm that is secreted during the growth of Gram-negative bacteria. OMV is considered as a high-quality vaccine candidate antigen because of its natural immunogenicity and non-replicability. Although the excellent antigenicity of OMV has been widely confirmed, its instability and heterogeneity greatly affect its immune effect. Many studies have demonstrated that in combination with nanoparticles can enhance the stability of OMV. In this study, OMVs were used to coat chitosan nanoparticles (CNPs) and obtain a stable OMV vaccine. The characteristics, including morphology, hydrodynamic size, and zeta potential were evaluated. The immune protection of CNP-OMV and anti-infection efficacy were examined and compared in vivo and in vitro. The results showed that the CNP-OMV were homogenous with a size of 139 nm and a stable core-shell structure. And CNP-OMV could significantly increase the cell proliferation, phagocytosis and TNF-α, IL-6 and IL-10 secretion of RAW264.7 in vitro. In vivo, CNP-OMV could significantly increase the levels of anti-Bb and OMV IgG antibodies. Levels of blood lymphocyte, and Th1 (IFN-γ, IL-12), Th2 (IL-4, IL-5), and Th17 (IL-17, TNF-α) type cytokines in the serum were all significantly increased. At the same time, CNP-OMV could significantly reduce the bacterial invading the lungs of challenged rabbits. And CNP-OMV could largely protect the lungs from injury. The above results showed that CNP-OMV had a good immune efficacy and could resist the infection of Bordetella bronchiseptica. This study provided a scientific basis for the development of novel effective and safe vaccine against Bordetella bronchiseptica, and also provided a new idea for the development of new bacterial vaccine.

Mechanism of fibroblast growth factor 21 in cardiac remodeling.

Cardiac remodeling is a basic pathological process that enables the progression of multiple cardiac diseases to heart failure. Fibroblast growth factor 21 is considered a regulator in maintaining energy homeostasis and shows a positive role in preventing damage caused by cardiac diseases. This review mainly summarizes the effects and related mechanisms of fibroblast growth factor 21 on pathological processes associated with cardiac remodeling, based on a variety of cells of myocardial tissue. The possibility of Fibroblast growth factor 21 as a promising treatment for the cardiac remodeling process will also be discussed.

Adjuvant Efficacy of the ECMS-Oil on Immune Responses against Bordetella bronchiseptica in Mice through the TLR2/MyD88/NF-κB Pathway.

Bordetella infection can be efficiently prevented through vaccination. The current study investigated the effects of an extract of Cochinchina momordica seed (ECMS) combined with oil on the immune responses to the inactivated Bordetella vaccine in mice. Serum IgG and IgG1 level was significantly increased in ECMS-oil group compared to any other group (P < 0.05) 2 weeks after immunization, while groups ECMS200 µg/400 µg-oil had a markedly higher level of serum IgG2b and IgG3 than any other groups (P < 0.05). Moreover, lipopolysaccharide/ConA-stimulated proliferation of splenocytes was significantly enhanced in ECMS 400 µg-oil immunized mice in comparison with mice in any other group (P < 0.05). RT-PCR assay revealed that while ECMS800 µg-oil group had significantly higher levels of serum IL-4, IL-10, Toll-like receptor (TLR)2, and IL-1 beta than any other group (P < 0.05), the levels of serum IL-2, IL-4, and IL-10 were markedly increased in ECMS 400 µg-oil group as compared to any other groups (P < 0.05). Blood analysis showed that ECMS800 µg-oil and oil groups had a significantly higher number of immunocytes than any other groups (P < 0.05). There were significant differences in the number of IgG+, IgG2b+, and IgA+ cells in the lung between ECMS800 µg-oil group and any other groups (P < 0.05). Western blot analysis demonstrated that stimulation with ECMS 25 µg/mL or 50 ng/mL led to a significant increase in the expression of TLR2, MyD88, and NF-κB in Raw264.7 cells (P < 0.05). Compared with any other group, the expression of MyD88 was markedly increased in the cells stimulated with ECMS 50 ng/mL, as indicated by the RT-PCR analysis (P < 0.05). Overall, we observed that ECMS-oil efficiently enhanced the humoral or cellular immune responses against Bordetella and suggested that the mechanism of adjuvant activity of ECMS-oil might involve TLR2/MyD88/NF-κB signaling pathway.

Chemical Vapor Transport Synthesis of Fibrous Red Phosphorus Crystal as Anodes for Lithium-Ion Batteries.

Red phosphorus (RP) is considered to be the most promising anode material for lithium-Ion batteries (LIBs) due to its high theoretical specific capacity and suitable voltage platform. However, its poor electrical conductivity (10-12 S/m) and the large volume changes that accompany the cycling process severely limit its practical application. Herein, we have prepared fibrous red phosphorus (FP) that possesses better electrical conductivity (10-4 S/m) and a special structure by chemical vapor transport (CVT) to improve electrochemical performance as an anode material for LIBs. Compounding it with graphite (C) by a simple ball milling method, the composite material (FP-C) shows a high reversible specific capacity of 1621 mAh/g, excellent high-rate performance and long cycle life with a capacity of 742.4 mAh/g after 700 cycles at a high current density of 2 A/g, and coulombic efficiencies reaching almost 100% for each cycle.

Significant differences in the electrochemical activity of black phosphorus anodes prepared under different atmospheres.

The effects of atmosphere and temperature on the electrochemical reversibility of black phosphorus (BP) anodes were investigated. BP anodes prepared in ambient air exhibited much-enhanced electrochemical activity due to the newly formed Cu3P phase. This work highlights the importance of maintaining intragranular electronic conduction for developing advanced BP-based anodes with high reversible capacities.

Effects of Dietary Coated Lysozyme on the Growth Performance, Antioxidant Activity, Immunity and Gut Health of Weaned Piglets.

The purpose of this study was to evaluate the effects of dietary coated lysozyme on growth performance, serum biochemical indexes, antioxidant activity, digestive enzyme activity, intestinal permeability, and the cecal microbiota in weaned piglets. In total, 144 weaned Large White × Landrace piglets were divided into six treatment groups, with 3 replicates and 8 piglets per replicate: CN, a basal diet; CL-L, CL-M, and CL-H, basal diet supplemented with 100, 150, 500 mg/kg coated lysozyme; UL, basal diet supplemented with 150 mg/kg lysozyme; and Abs, basal diet supplemented with 150 mg/kg guitaromycin for 6 weeks. Compared with the CN and UL diets, dietary CL-H inclusion increased the average daily gain (ADG) and decreased the feed/gain (F/G) ratio of piglets (p < 0.05). The addition of 500 mg/kg coated lysozyme to the diet significantly increased the total protein (TP) and globulin (Glob) plasma levels of weaned piglets (p < 0.05). Supplementation with 500 mg/kg coated lysozyme significantly increased the serum IgM concentration and increased lipase activity in the duodenum (p < 0.05). The addition of coated lysozyme and lysozyme significantly decreased the malondialdehyde (MDA) content, while the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels all increased (p < 0.05). High-throughput sequencing results showed that CL-H treatment effectively improved the intestinal microbiome. The relative abundance of Terrisporobacter in the CL-H and CL-M groups was significantly lower than that in the other groups (p < 0.05). LEfSe analysis results showed that the relative abundance of Coprococcus_3 was higher in the CL-M treatment group. The marker species added to the CL-H treatment group was Anaerofilum. In summary, as a potential substitute for feed antibiotics, lysozyme is directly used as a dietary additive, which is inefficient. Therefore, we used palm oil as the main coating material to coat lysozyme. Lysozyme after coating can more effectively improve the growth performance of piglets by improving the intestinal flora, improving the activity of digestive enzymes, reducing the damage to intestinal permeability and oxidative stress in piglets caused by weaning stress, and improving the immunity of piglets.

Safety and Efficacy of the Bordetella bronchiseptica Vaccine Combined with a Vegetable Oil Adjuvant and Multi-Omics Analysis of Its Potential Role in the Protective Response of Rabbits.

Infectious respiratory diseases caused by Bordetella bronchiseptica (Bb) are seriously endangering the development of the rabbit industry in China. Unfortunately, no licensed vaccines are available for this pathogen. The present study was designed to determine whether the inactivated Bb antigen formulated with vegetable oil adjuvant (named E515) which contains soybean oil, vitamin E, and ginseng saponins, functions as a safe and effective vaccine (E515-Bb) against Bb infection in rabbits. Based on local and systemic reactions, both the E515 adjuvant alone and the E515-Bb vaccine exhibited good safety in rabbits. Immune response analysis implies that rabbits immunized with the E515-Bb vaccine produced significantly higher, earlier, and longer-lasting specific antibody responses and activated Th1/Th2/Th17 cell responses than those immunized with the aluminum hydroxide (Alum)-adjuvanted Bb vaccine (Alum-Bb) or Bb antigen alone. Moreover, the E515-Bb vaccine effectively protected rabbits from Bb infection. Additionally, integrated multi-omics analysis revealed that the immunoprotective effect of the E515-Bb vaccine was achieved through upregulation of the complement and coagulation cascades and cell adhesion molecule (CAM) pathways, and the downregulation of the P53 pathway. Overall, these results indicate that the E515-Bb vaccine is safe, elicits an efficient immune response and provides good protection against Bb infection in rabbits. Thus, the E515-adjuvanted Bb vaccine can be considered a promising candidate vaccine for preventing Bb infection.

Effects of Clostridium butyricum and a Bacteriophage Cocktail on Growth Performance, Serum Biochemistry, Digestive Enzyme Activities, Intestinal Morphology, Immune Responses, and the Intestinal Microbiota in Rabbits.

The objective of this study was to assess the effects of dietary supplementation with Clostridium butyricum (CB) and a bacteriophage cocktail (BP) on growth performance, serum biochemical parameters, intestinal digestive and oxidase enzymes, intestinal morphology, immune responses, and the cecum microbiota in rabbits. In total, 108 New Zealand rabbits (5 weeks old) were randomly and equally allotted into three dietary treatment groups (four replicates per treatment, n = 36/treatment): (1) the control (CN) group-rabbits fed the basal diet; (2) CB group-rabbits fed the basal diet supplemented with 100 mg/kg diet Clostridium butyricum; and (3) BP group-rabbits fed the basal diet supplemented with 200 mg/kg diet BP cocktail, respectively, for 6 weeks. Compared with the CN diet, dietary CB and BP inclusion increased the average daily gain (ADG) and average daily feed intake (ADFI) and decreased the feed/gain (F/G) ratio of rabbits. Furthermore, CB increased the digestive enzyme activity (α-amylase and trypsin in the ileum); the chymotrypsin activity was also significantly increased in the duodenum and jejunum. Supplementation with CB significantly enhanced antioxidant capacity (SOD and GSH-Px) in the jejunum and ileum and reduced MDA levels. Additionally, rabbits fed CB had significantly elevated villus height (V) and (V/C) ratios but reduced crypt depth (C). Moreover, dietary CB supplementation markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) and increased secretory immunoglobulin A (sIgA) production. High-throughput sequencing indicated that the microbiota in the rabbit intestine was altered by CB and BP. Venn diagrams and heatmap plots revealed that the gut microbial community composition varied obviously among rabbits fed different diets. Specifically, CB increased the relative abundance of beneficial bacteria to maintain intestinal barrier homeostasis, whereas BP decreased the relative abundance of Gammaproteobacteria, which included a plenty of pathogenic bacteria.

Preliminary study of the relationship between career choice motivation and understanding of professionalism in newly enrolled medical students in China: a cross-sectional study.

OBJECTIVES: Early professionalism education for first-year students is important for generating sound knowledge and attitudes towards medical professionalism. Of the many factors affecting professionalism and professional identity formation in medical students, career choice motivation is an understudied one. This study aimed to explore the relationship between the career choice motivations of first-year medical students and their understanding of professionalism. SETTINGS AND PARTICIPANTS: A cross-sectional survey of 940 first-year clinical medicine students was conducted at China Medical University in September 2017 to explore students' motivation to study medicine and its relationship with students' understanding of professionalism. Demographics, career choice motivation and professionalism were obtained through paper questionnaires. Logistic regression analysis was used to analyse the association between career choice motivation and understanding of professionalism while controlling for potential demographic confounders. RESULTS: The most common career choice motivations for first-year medical students (N=843) were interested in the health sciences, income and social status and advocating altruism. The most mentioned subdimensions of professionalism were accountability, pursuit of excellence and compassion. There were significant differences in the understanding of professionalism among students with different career choice motivations. CONCLUSION: First-year medical students with different motivations to study medicine also have different understandings of professionalism. Medical educators can explore motivations to learning medicine as a new entry point to providing professionalism education for newly enrolled medical students.

Ginseng Stem-Leaf Saponins in Combination with Selenium Promote the Immune Response in Neonatal Mice with Maternal Antibody.

Neonates acquire from their mothers maternal antibody (MatAb) which results in poor immune response to vaccination. We previously demonstrated that ginseng stem-leaf saponins in combination with selenium (GSe) had adjuvant effect on the immune response to an attenuated pseudorabies virus (aPrV) vaccine. The present study was to evaluate GSe for its effect on the immune response to aPrV vaccine in neonatal mice with MatAb. Results showed that GSe had adjuvant effect on the immune response to aPrV vaccine in neonates. When GSe was co-administered with aPrV vaccine (aP-GSe), specific gB antibody, Th1 cytokines (IL-2, IL-12 and IFN-γ) and Th2 cytokines (IL-4, IL-6 and IL-10) responses were significantly increased in association with enhanced protection of vaccinated neonates against the lethal PrV challenge even though MatAb existed when compared to the neonates immunized with aPrV vaccine alone. GSe-enhanced immune response depended on its use in the primary immunization. The mechanisms underlying the adjuvant effect of GSe may be due to more innate immune related pathways activated by GSe. Transcriptome analysis of splenocytes from neonates immunized with aP-GSe, aPrV or saline solution showed that there were 3976 differentially expressed genes (DEGs) in aP-GSe group while 5959 DEGs in aPrV group when compared to the control. Gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that innate immune responses and cytokine productions related terms or pathways were predominantly enriched in aP-GSe group, such as "NOD-like receptor signaling pathway", "Natural killer cell mediated cytotoxicity", "NF-κB signaling pathway", "cytokine-cytokine receptor interaction", and "Th1 and Th2 cell differentiation". Considering the potent adjuvant effect of GSe on aPrV vaccine in neonatal mice with MatAb, it deserves further investigation in piglets.

Sunflower seed oil combined with ginseng stem-leaf saponins as an adjuvant to enhance the immune response elicited by Newcastle disease vaccine in chickens.

The present study was to evaluate the adjuvant effect of sunflower seed oil containing saponins extracted from the stem and leaf of Panax ginseng C.A. Meyer (E515-D) on the immune response induced by an inactivated Newcastle disease virus (NDV) in chickens. The results showed that E515-D promoted significantly higher serum NDV-specific HI and neutralizing antibody responses, IFN-γ and IL-4 levels, and lymphocyte proliferative responses to Con A, LPS, and NDV antigen than the conventional adjuvant Marcol 52. Different adjuvant effect between E515-D and Marcol 52 may be attributed to different genes expressed in two groups. Transcriptome analysis of splenocytes showed that there were 1198 differentially expressed genes (DEGs) with 539 up and 659 down regulated in E515-D group while 1395 DEGs with 697 up and 698 down regulated in Marcol 52 group in comparison with the control group. Analysis of gene ontology (GO) term and kyoto encyclopedia of Genes and Genomes (KEGG) pathways showed that the predominant immune related pathways included "Toll-like receptor signaling pathway", "NOD-like receptor signaling pathway", "C-type lectin receptor signaling pathway", and "Phosphatidylinositol signaling system" in E515-D group while Marcol 52 were "NOD-like receptor signaling pathway", "Phagosome", and "Lysosome", and the most relevant DEGs in E515-D group were STAT1, STAT2, PI3K, and IL-6. Considering the excellent adjuvant activity and vegetable origin, E515-D deserves further study as an adjuvant for vaccines used in food animals.

Enhanced Immune Responses with Serum Proteomic Analysis of Hu Sheep to Foot-and-Mouth Disease Vaccine Emulsified in a Vegetable Oil Adjuvant.

Our previous study demonstrated that a vegetable oil consisting of soybean oil, vitamin E, and ginseng saponins (SO-VE-GS) had an adjuvant effect on a foot-and-mouth disease (FMD) vaccine in a mouse model. The present study was to compare the adjuvant effects of SO-VE-GS and the conventional ISA 206 on an FMD vaccine in Hu sheep. Animals were intramuscularly (i.m.) immunized twice at a 3-week interval with 1 mL of an FMD vaccine adjuvanted with SO-VE-GS (n = 10) or ISA 206 (n = 9). Animals without immunization served as control (n = 10). Blood was sampled prior to vaccination and at 2, 4, 6, and 8 weeks post the booster immunization to detect FMD virus (FMDV)-specific IgG. Blood collected at 8 weeks after the booster was used for the analyses of IgG1 and IgG2, serum neutralizing (SN) antibody, IL-4 and IFN-γ production, and proteomic profiles. The results showed that IgG titers rose above the protection level (1:128) in SO-VE-GS and ISA 206 groups after 2 and 4 weeks post the booster immunization. At 6 weeks post the booster, the ISA 206 group had 1 animal with IgG titer less than 1:128 while all the animals in the SO-VE-GS group retained IgG titers of more than 1:128. At 8 weeks post the booster, 6 of 9 animals had IgG titers less than 1:128 with a protective rate of 33.3% in the ISA 206 group, while only 1 of 10 animals had IgG titer less than 1:128 with a protective rate of 90% in the SO-VE-GS group, with statistical significance. In addition, IgG1, IgG2, SN antibodies, IL-4, and IFN-γ in the SO-VE-GS group were significantly higher than those of the ISA 206 group. Different adjuvant effects of SO-VE-GS and ISA 206 may be explained by the different proteomic profiles in the two groups. There were 39 and 47 differentially expressed proteins (DEPs) identified in SO-VE-GS compared to the control or ISA 206 groups, respectively. In SO-VE-GS vs. control, 3 immune related gene ontology (GO) terms and 8 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were detected, while 2 immune related GO terms and 5 KEGG pathways were found in ISA 206 vs. control. GO and KEGG analyses indicated that 'positive regulation of cytokine secretion', 'Th1/Th2 cell differentiation', and 'Toll-like receptor signaling pathways', were obviously enriched in the SO-VE-GS group compared to the other groups. Coupled with protein-protein interaction (PPI) analysis, we found that B7TJ15 (MAPK14) was a key DEP for SO-VE-GS to activate the immune responses in Hu sheep. Therefore, SO-VE-GS might be a promising adjuvant for an FMD vaccine in Hu sheep.

Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder with a genetic origin. The purpose of the present study was to analyze the mutation spectrum of CH patients in China. A targeted next­generation sequencing panel covering all exons of 29 CH­related causative genes was used in 43 Han Chinese patients with CH [11 dysgenesis and 32 glands in situ (GIS)]. The functional impact and pathogenicity of detected variants were analyzed using a comprehensive bioinformatics approach and co­segregation studies. A total of 47 rare non­polymorphic variants in 9 target genes associated with thyroid hormone synthesis (DUOX2, DUOXA2, TPO, TG, SLC26A4 and SLC5A5), thyroid stimulating hormone resistance (TSHR) and central hypothyroidism (PROP1 and TRHR) were identified in 31 patients (31/43, 72%). Of these variants, 8 were novel, including 3 in DUOX2, 2 in TPO, 3 in TSHR and 1 in SLC5A5. Variants were mostly affected by DUOX2, TG, TPO and TSHR. Approximately 44% of the patients (19/43) carried DUOX2 variants. The mutation detection rates in patients with GIS were higher compared with patients with dysgenesis [25/32 (78%) vs. 6/11 (54%)]. Oligogenic mutations were detected in 25.6% of the total cases and 35% of the mutated cases. Genetic basis was ascertained in 13 patients, reaching a diagnosis detection rate of 30%. In conclusion, genetic defects in dyshormonogenesis, mainly in DUOX2, were the main genetic cause of CH in the Chinese population. Oligogenicity is highly involved in CH pathogenesis and may thus be an important factor in common phenotypic variability observed in patients with CH.

A Solution with Ginseng Saponins and Selenium as Vaccine Diluent to Increase Th1/Th2 Immune Responses in Mice.

Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4+/CD8+ ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.

Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant.

The present study evaluated soybean oil (SO) containing vitamin E (VE) and ginseng saponins (GS) (SO-VE-GS) for their adjuvant effect on foot-and-mouth disease (FMD) vaccine. Since mineral oil ISA 206 is a common adjuvant used in the FMD vaccine, it was used as a control adjuvant in this study. VE and GS were found to have a synergistic adjuvant effect. When mice were immunized with the FMD vaccine emulsified in SO with VE and GS, significantly higher serum IgG, IgG1, and IgG2a were found than VE and GS used alone. SO-VE-GS and ISA 206 behaved differently in adjuvant activities. When mice were immunized with the FMD vaccine adjuvanted with SO-VE-GS, significantly higher and earlier production of serum IgG was found than that adjuvanted with ISA 206. Although both adjuvants significantly increased the number of bone marrow plasma cells, a stimulation index of lymphocytes (SI) as well as the production of IL-4 and IL-6, SO-VE-GS promoted significantly higher SI and the ratio of CD4+/CD8+ T cells with production of increased IFN-γ and decreased TGF-ß1 as compared with the ISA 206 group. The data suggested that SO-VE-GS activated Th1/Th2 immune responses. Transcriptome analysis of splenocytes showed that differentially expressed genes (DEGs), immune-related gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the SO-VE-GS group. Therefore, the potent adjuvant effect of SO-VE-GS on the FMD vaccine may be attributed to the immune-related gene profile expressed in lymphocytes. Due to its plant origin and due to being much cheaper than imported mineral oil ISA 206, SO-VE-GS deserves further study in relation to vaccines used in food animals.

Immunomodulatory effect of thymopentin on lymphocytes from supramammary lymph nodes of dairy cows.

Previous study showed that injection of thymopentin (TP 5) in the area of supramammary lymph nodes (SMLN) had therapeutic effect on the intramammary infection (IMI) in cows. This study was to explore the underlying mechanisms by investigating the immunomodulatory effect of TP 5 on SMLN lymphocytes. Lymphocyte proliferation, cell cycle distribution and cytokine mRNA expression were determined by MTT, FCM and RT-qPCR, respectively. Laser scanning confocal microscope (LSCM) was used to observe the binding between TP 5 and SMLN lymphocytes. Moreover, RNA-sequencing (RNA-seq) was performed to observe the difference between the lymphocytes with and without TP 5 treatment. The results showed that TP 5 significantly promoted lymphocyte proliferation, accelerated cell cycle progression, and enhanced mRNA expression of IL-17A and IL-17F. Laser scanning confocal microscopic analysis revealed the binding of TP 5 to the surface of SMLN lymphocytes. A total of 1094 genes were identified as differentially expressed genes (DEGs) using RNA-seq with 692 up- and 402 down-regulated genes. 48 significantly enriched GO terms were identified by RNA-seq. In KEGG analysis, 1/3 of DEGs were enriched in the immune system pathway, including IL-17 signaling pathway, cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, T cell receptor signaling pathway, Th17 cell differentiation. Among them, IL-17 signaling pathway was the most prominent. This study suggested that the therapeutic benefit of TP 5 in the treatment of bovine mastitis might be attributed to its immunomodulatory activity in SMLN lymphocytes.