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Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea and high mortality in neonatal piglets. Pseudorabies causes acute and often fatal infections in young piglets, respiratory disorders in growing pigs, and reproductive failure in sows. In late 2011, pseudorabies virus (PRV) variants occurred in Bartha-K61-vaccine-immunized swine herds, resulting in economic losses to the global pig industry. Therefore, it is essential to develop a safe and effective vaccine against both PEDV and PRV infections. In this study, we constructed a recombinant virus rPRV-PEDV S1 expressing the major neutralizing epitope region (COE, SS2, and SS6) of the PEDV S1 protein by homologous recombination technology and CRISPR/Cas9 gene editing technology, and then evaluated its biological characteristics in vitro and immunogenicity in pigs. The recombinant virus rPRV-PEDV S1 had similar growth kinetics in vitro to the parental rPRV NY-gE−/gI−/TK− strain, and was proven genetically stable in swine testicle (ST) cells and safe for piglets. PEDV S1-specific antibodies were detected in piglets immunized with rPRV-PEDV S1 on the 7th day post-immunization (dpi), and the antibody level increased rapidly at 14–21 dpi. Moreover, the immunized piglets receiving the recombinant virus exhibited alleviated clinical signs and reduced viral load compared to the unvaccinated group following a virulent PEDV HN2021 strain challenge. Also, piglets immunized with rPRV-PEDV S1 developed a PRV-specific humoral immune response and elicited complete protection against a lethal PRV NY challenge. These data indicate that the recombinant rPRV-PEDV S1 is a promising vaccine candidate strain for the prevention and control of PEDV and PRV infections.

Objective: A combination of glucocorticoids with mycophenolate is recommended by current guidelines to boost response to Graves’ orbitopathy (GO) therapy. This study was designed to evaluate the therapeutic effects and safety of m ethotrexate (MTX) plus reduced (3.0 g) or full-dose (4.5 g) i.v. methylprednisolone (MP) vs full-dose i.v. MP alone. Design and methods: This was a prospective, randomized, observer-masked, singlecenter clinical trial conducted in a tertiary clinical center. Ninety-seven patients with active moderate-to-severe GO were screened and 90 patients underwent randomization between April 2018 and Oct 2019. All patients completed 12 weeks of treatment and received clinical assessment. The patients received either MP 4.5 g only, MP 4.5 g plus oral MTX, or MP 3.0 g plus oral MTX. The primary outcome was th e CAS response at week 12. Secondary outcomes were adverse events and other individual ophthalmic parameters. Results: At week 12, 53.3% of MP, 76.7% of reduced MP plus MTX, and 76.7 % of MP plus MTX achieved a CAS response, although the difference was not sig nificant (P = 0.1). The overall response rates of the MP group, the reduced MP plus MTX group, and the MP plus MTX group were 43.3%, 53.3%, and 60%, respectively ( P = 0.5). Subgroup analysis found that smoking status interacted with marginal significance with treatment effect (P = 0.048). Importantly, adverse event incidence was significantly lower in the reduced MP + MTX group (P = 0.017). Conclusions: Our study shows that reduced MP plus MTX therapy is effective and safer in treating active and moderate-to-severe GO patients than 4.5 g MP monotherapy.

Background Enteral nutrition support can effectively improve the nutritional status of patients with severe brain injury, which is beneficial to the prognosis of patients. However, the relevant literature in China and abroad lacks a systematic nutritional management plan for such patients, and there is rare summary of the best evidence for enteral nutrition support. Objective To retrieve and summarize the best evidence of enteral nutrition support in adult patients with severe brain injury, and provide evidence-based evidence for the clinical nutrition management of such patients. Methods All evidence on enteral nutrition in adult patients with severe brain injury was retrieved from databases and websites including BMJ Best Practice, Up To Date, GIN, NICE, NGC, RNAO, Yimaitong, ESPEN, ASPEN, SCCM, ESICM, JBI Library, Cochrane Library, PubMed, EMBase, CINAHL, CBM, CNKI, Wanfang Data, VIP. The retrieved evidence included guidelines, evidence summaries, best practices, expert consensus, systematic reviews and meta-analysis. The retrieval period was from April 2011 to April 2021. Corresponding quality evaluation criteria were used to evaluate the quality of the included literature, and the evidence was described and summarized using the JBI Evidence-based Health Care Center Evidence Pre-grading System (2014 edition) and JBI Evidence Recommendation Rating System (2014 edition) . Results A total of 18 articles were included, including 5 clinical guidelines, 3 evidence summaries, 3 expert consensus, 2 systematic reviews, and 5 meta-analysis. Their methodological qualities were rated high overall. Finally 25 pieces of best evidence involving 8 aspects were nutrition screening, nutrition assessment, timing of initiating enteral nutrition, energy and protein requirements, enteral nutrition composition, feeding route, infusion method and complication management. Conclusion When giving enteral nutrition to adult patients with severe brain injury, medical staff need to implement it based on the best evidence. At the same time, an individualized enteral nutrition support program should be formulated in combination with the current medical status and specific treatment goals in China to improve the effect of nutritional support, thereby improving the clinical outcome of patients.

Simple Summary: This study explores a new way to control fertility in male mice by combining two substances: quinestrol, a synthetic hormone, and ketoconazole, a medication usually used to treat fungal infections. The researchers wanted to see if adding ketoconazole could make quinestrol more effective, so less of the hormone would be needed. They tested different combinations of these two substances on male mice and checked their impact on fertility-related factors like sperm count and reproductive organ size. The most promising results came from a low dose of quinestrol combined with ketoconazole, which significantly reduced sperm count and lowered testosterone levels after 10 days. Even after 30 days, this combination continued to exhibit some suppressive effects on reproductive capacity. The study also found that ketoconazole helped to slow down the body's metabolism of quinestrol, making it work more effectively. This study suggests that using ketoconazole alongside quinestrol could be a safer and more efficient way to control fertility, potentially offering a new approach for managing populations of certain animal species. This study investigates whether ketoconazole, a CYP3A4 inhibitor, can enhance the suppressive effects of quinestrol on reproductive capacity, potentially allowing for a reduced quinestrol dosage while maintaining its efficacy. A total of 104 healthy adult male mice were divided into two groups, assessed at 10 and 30 days. Within each group, six treatment categories were tested: the control (CK), quinestrol alone (Q1, Q5), and quinestrol combined with varying doses of ketoconazole (Q1 + K0.4, Q1 + K2, Q5 + K0.4). The key parameters measured included internal and reproductive organ weights, sperm density, sperm motility, sperm abnormalities, and CYP3A4 enzyme content in intestinal and liver tissues. After 10 days, the combination of a low dose of quinestrol with ketoconazole (Q1 + K0.4) showed the most significant pronounced effects in reducing reproductive potential, with notable reductions in epididymal weight, sperm density, sperm abnormality rate and vitality, serum hormone levels, and CYP3A4 content in the small intestine and liver. Although some reproductive parameters returned to near-baseline levels after 30 days, the Q1 + K0.4 regimen continued to exhibit reduced seminal vesicle weight and testosterone levels. Importantly, the combination did not significantly increase CYP3A4 enzyme content, indicating effective metabolic inhibition. The combination of quinestrol and ketoconazole, especially the Q1 + K0.4 regimen, demonstrated the most noticeable impact on reducing reproductive capacity. This regimen significantly reduced key reproductive parameters and showed strong metabolic inhibition, suggesting that ketoconazole substantially enhances the efficacy of quinestrol in fertility control. [ABSTRACT FROM AUTHOR]

Felty's syndrome (FS) is an uncommon disorder with a poor prognosis, and most patients die from infections caused by neutropenia. Currently, there is no standardized treatment strategy, and treatment options are based on case reports and clinical experience. To date, no cases of FS complicated by coronavirus disease-2019 (COVID-19) have been reported. This article reports a successful case of FS complicated by COVID-19. We emphasized treating rheumatic diseases with immunosuppressive therapy at appropriate doses based on strong and effective anti-infection when co-infected. [ABSTRACT FROM AUTHOR]

Abstract Background Actinomycosis is a rare infectious disease caused by Actinomyces, especially in children. Here, we present a case of musculoskeletal actinomycosis in a 5-year-old girl from China. Case presentation A 5-year-old girl presented with recurrent episodes of fever, pain, erythema, swelling, and festering sores on the right lower extremity, and pus was discharged from a sinus in the right foot. Magnetic resonance imaging (MRI) suggested subcutaneous soft tissue infection and osteomyelitis of the right crus. A bacterial culture of pus extracted from a festering sore on the right popliteal fossa detected the growth of Actinomycetes europaeus. The patient was cured with 7 weeks of treatment with intravenous ampicillin-sulbactam, followed by 6 weeks of treatment with oral amoxicillin-clavulanate with surgical debridement and drainage. There were no symptoms of recurrence during the 15-month period of follow-up. Conclusions Pediatric actinomycosis is a rare and challenging infectious disease. Early accurate diagnosis and optimal surgical debridement are important for the management of pediatric actinomycosis.