Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 infections in neonates.

Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in neonates remain unclear. This study aimed to determine whether there are differences in the main clinical, radiological, and laboratory features of early-onset and late-onset SARS-CoV-2 infections in neonates. This single-center, prospective cohort study enrolled neonates with SARS-CoV-2 infection from December 7, 2022, to January 3, 2023, and evaluated their clinical characteristics during hospitalization. All neonates (N = 58) infected with SARS-CoV-2 within 28 days of birth who were admitted to the neonatal intensive care unit of Taizhou Hospital were included. These neonates were classified into the early-onset (diagnosed within 7 days of birth) and late-onset (diagnosed more than 7 days after birth) groups. The symptoms, treatment, and prognosis of SARS-CoV-2 infection were the main study outcomes. The incidence of hospitalization attributable to SARS-CoV-2 infection was 10.6% (58 of 546 neonates) in Linhai. Sixteen (28%) of the 58 SARS-CoV-2 infections were early-onset cases, and 42 (72%) were late-onset cases. The common symptoms among the late-onset group were fever (p < 0.001) and cough (p < 0.001). Neonates with late-onset SARS-CoV-2 infection (p < 0.001) were significantly more likely to develop pneumonia.  Conclusion: The clinical symptoms and rates of pneumonia caused by SARS-CoV-2 infection in neonates differed between the early-onset and late-onset groups. Different clinical management is necessary for neonates with early-onset and late-onset SARS-CoV-2 infections. What is Known: • Neonates are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • Differences in clinical characteristics of early-onset and late-onset SARS-CoV-2 infections in neonates remain unclear. What is New: • Fever and cough were the most common symptoms among neonates with late-onset infection. • Neonates with late-onset SARS-CoV-2 infection were more likely to develop pneumonia.

Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre-metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr-1+ myeloid cells are characterized to form a pre-metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage-associated molecular patterns released from surgical resection contribute to the formation of pre-metastatic niche in lung through IL-1ß secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre-metastatic niche in lung which is with important implications for developing rational therapies during peri-operative period.

Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella.

Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. Cyclin-dependent kinases (CDK) are prominent target proteins in apicomplexan parasites. In this study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of Eimeria tenella (EtCRK2) were detected. mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. The anticoccidial drug diclazuril against E.tenella affects the expression pattern of EtCRK2 molecule, and EtCRK2 is a potential target for new drug development.

Phosphatidylserine released from apoptotic cells in tumor induces M2-like macrophage polarization through the PSR-STAT3-JMJD3 axis.

BACKGROUND: Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co-localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved. METHODS: Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography-mass spectrometry. Phosphatidylserine-containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real-time PCR, immunohistochemistry enzyme-linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies. RESULTS: The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2-like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2-like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4 (TIM4) and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression. CONCLUSIONS: This study suggest that apoptotic cell-generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.

Analysis of association between eating behaviours and childhood obesity among pre-school children: A cross-sectional study.

Background: Childhood obesity is a worldwide critical health concern. We aimed to clarify whether eating behaviours increased the risk of childhood obesity. Methods: We recruited 2,049 pre-school children aged 3-6 years between 1 December 2021 and 31 January 2022 in Taizhou, China. Children's weight status was classified according to the International Obesity Task Force criteria, and their eating behaviours were evaluated using the Children's Eating Behaviour Questionnaire. Correlation analyses, linear regressions, and one-way ANCOVA. were performed to analyse the association between children's eating behaviours and weight status. Results: In 'Food Avoidant' subscales, the scores of satiety responsiveness (P < 0.001) and slowness in eating (P = 0.001) were negatively associated with body mass index z score among pre-school children of both sexes. In 'Food Approach' subscales, the score of enjoyment of food was positively associated with body mass index z score in both boys (P = 0.007) and girls (P = 0.035), but the association of scores of food responsiveness with body mass index z score was found only in girls (P = 0.001). Conclusion: Our results supported that pre-school children with low scores in 'Food Avoidant' subscales and high scores in 'Food Approach' scales were more likely to become obese.

Anticoccidial effect of toltrazuril and Radix Sophorae Flavescentis combination: Reduced inflammation and promoted mucosal immunity.

An anticoccidial model of chicken infected with Eimeria tenella was established to investigate the effect of toltrazuril (Tol) combined with the Radix Sophorae Flavescentis (RSF) on coccidiosis. The anticoccidial index (ACI) was evaluated, and the cecal developmental parameters (i.e., villus height, [VH], crypt depth, [CD], and VH/CD) were determined. The distributions of glycoproteins and goblet cells in the cecal tissue were determined through the Periodic Acid-Schiff (PAS) and Alcian blue PAS staining methods, respectively. The mRNA expression levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17 of the cecal tissue were determined through quantitative real-time PCR. The moderate ACI was obtained using the combination of Tol and RSF. Compared with the normal control (NC) group, the infected control (IC) group showed remarkably lower VH and VH/CD at five and seven days postinfection. Compared with the IC group, the IC + RSF and IC + TolRSF groups showed remarkably higher VH and VH/CD at five and seven days postinfection. Compared with the NC group, the IC group contained fewer glycoproteins and goblet cells, but the Tol and RSF treatment promoted more glycoproteins and goblet cells at five and seven days postinfection. The mRNA expression levels of IL-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17 in the IC group were upregulated (P < 0.01) compared with those in the NC group. The IC + RSF and IC + TolRSF groups had downregulated mRNA expression levels of IL-1ß, IL-6, and IL-17 cytokines (P < 0.01), and upregulated mRNA expression levels of IL-2 and IL-4 cytokines (P < 0.01) compared with the IC group. Results showed that the combination of Tol and RSF exerts anticoccidial effect by reducing inflammation and promoting intestinal mucosal immunity.

Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors.

INTRODUCTION: Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT. PATIENTS AND METHODS: Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0-3.0 mm3 sections using a sterilized razor blade. The tumor grafts were surgically implanted into subrenal capsules of athymic mice to establish patient-derived tumor xenograft (PDTX) mouse models. Histological and response patterns to CSF1R inhibitors evaluations were analyzed. In addition, ex vivo cultures of patient-derived explants (PDEs) with endpoint analysis were used to validate TGCT graft response patterns to CSF1R inhibitors. RESULTS: The TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The "take" rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures. CONCLUSIONS: Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.

Progress of artificial intelligence in diabetic retinopathy screening.

Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide, and the limited availability of qualified ophthalmologists restricts its early diagnosis. For the past few years, artificial intelligence technology has developed rapidly and has been applied in DR screening. The upcoming technology provides support on DR screening and improves the identification of DR lesions with a high sensitivity and specificity. This review aims to summarize the progress on automatic detection and classification models for the diagnosis of DR.

Effects of diclazuril on the expression of enolase in second-generation merozoites of Eimeria tenella.

Eimeria tenella is an obligate intracellular parasite of the chicken cecum; it brings huge economic loss to the chicken industry. Enolase is a multifunctional glycolytic enzyme involved in many processes of parasites, such as infection and migration. In this study, the effect of diclazuril on the expression of enolase in second-generation merozoites of E. tenella (EtENO) was reported. The prokaryotic expression plasmid pET-28a-EtENO was constructed and transformed into Escherichia coli BL21 (DE3). Then, it was subjected to expression under the induction of isopropyl-ß-D-1-thiogalactopyranoside. The expressed products were identified and purified. The purified EtENO protein was used for antibody preparation. The EtENO mRNA and protein expression levels were analyzed via real-time PCR and Western blotting. Localization of EtENO on the merozoites was examined by immunofluorescence technique. The mRNA and protein expression levels of EtENO were decreased by 36.3 and 40.36%, respectively, by diclazuril treatment. EtENO distributed in the surface, cytoplasm, and nucleus of the infected/control group. With diclazuril treatment, it was significantly reduced in the surface and cytoplasm and even disappeared in the nucleus of the infected/diclazuril group. These observations suggested that EtENO may play an important role in mechanism of diclazuril anticoccidial action and be a potential drug target for the intervention with E. tenella infection.

Effects of Eimeria tenella infection on the barrier damage and microbiota diversity of chicken cecum.

The symbiosis of host and intestinal microbiota constitutes a microecosystem and plays an important role in maintaining intestinal homeostasis and regulating the host's immune system. Eimeria tenella, an obligate intracellular apicomplexan parasite, can cause coccidiosis, a serious intestinal disease. In this study, the effects of E. tenella infection on development parameters (villus height, crypt depth, mucosa thickness, muscularis thickness, and serosa thickness) and microbiota in chicken cecum were investigated. Fourteen-day-old male Hy-Line Variety Brown layer chickens were inoculated with sporulated oocysts of E. tenella. Cecal tissues were collected 7 d after inoculation. Relative density of goblet cells and glycoproteins were determined by Alcian blue periodic acid-Schiff staining and periodic acid-Schiff staining, respectively. Intestinal development parameters were also evaluated. Cecal contents were extracted, and the composition of cecal microflora was examined by Illumine sequencing in the V3-V4 region of the 16S rRNA gene. Results indicated that E. tenella infection destroyed the structure of cecal tissue and reduced the relative density of goblet cells and glycoproteins. Sequencing analysis indicated that E. tenella infection altered the diversity and composition of cecal microbiota. The populations of Proteobacteria, Enterococcus, Incertae, and Escherichia-Shigella decreased, and those of Bacteroidales and Rikenella significantly increased in the infected group compared with those in the control group. Hence, the pathological damage caused by E. tenella infection is associated with cecal microbiota dysbiosis, and this finding may be used to develop an alternative measure for alleviating the effect of coccidiosis on the poultry industry.

Eukaryotic elongation factor 2 is involved in the anticoccidial action of diclazuril in the second-generation merozoites of Eimeria tenella.

Eimeria tenella, an obligate intracellular parasite, can actively invade the cecal epithelial cells of chickens and cause severe enteric disease. Eukaryotic elongation factor 2 (eEF2) plays a major role in protein synthesis and cell survival. This study aims to explore the exact mechanisms underlying diclazuril inhibition in second-generation merozoites of E. tenella. The eEF2 cDNA of the second-generation merozoites of E. tenella (EtEF2) was cloned by reverse transcriptase polymerase chain reaction and rapid amplification of cDNA ends. Diclazuril-induced expression profiles of EtEF2 were also analyzed. The cloned full-length cDNA (2893 bp) of the EtEF2 nucleotide sequence encompassed a 2499 bp open reading frame (ORF) that encoded a polypeptide of 832 residues with an estimated molecular mass of 93.12 kDa and a theoretical isoelectric point of 5.99. The EtEF2 nucleotide sequence was submitted to the GenBank database with the accession number KF188423. The EtEF2 protein sequence shared 99 % homology with the eEF2 sequence of Toxoplasma gondii (GenBank XP_002367778.1). The GTPase activity domain and ADP-ribosylation domain were conserved signature sequences of the eEF2 gene family. The changes in the transcriptional and translational levels of EtEF2 were detected through quantitative real-time PCR and Western blot analyses. The mRNA expression level of EtEF2 was 2.706 fold increases and the protein level of EtEF2 was increased 67.31 % under diclazuril treatment. In addition, the localization of EtEF2 was investigated through immunofluorescence assay. Experimental results demonstrated that EtEF2 was distributed primarily in the cytoplasm of second-generation merozoites, and its fluorescence intensity was enhanced after diclazuril treatment. These findings indicated that EtEF2 may have an important role in understanding the signaling mechanism underlying the anticoccidial action of diclazuril and could be a promising target for novel drug exploration.

DNA Methylation and Uveal Melanoma.

OBJECTIVE: The objective of the study was to summarize the role of DNA methylation in the development and metastasis of uveal melanoma (UM). DATA SOURCES: The relevant studies in MEDLINE were searched. STUDY SELECTION: In this review, we performed a comprehensive literature search in MEDLINE using "uveal melanoma" AND ("DNA methylation" OR "epigenetics") for original research/review articles published before February 2018 on the relationship between DNA methylation and UM. References of the retrieved studies were also examined to search for potentially relevant papers. RESULTS: Previous studies on the relationship between DNA methylation and UM covered many genes including tumor suppressor genes (TSGs), cyclin-dependent kinase genes, and other genes. Among them, the TSG genes such as RASSF1A and p16INK4a, which encodes a cyclin-dependent kinase inhibitor, are relatively well-studied genes. Specifically, a high percentage of promoter methylation of RASSF1A was observed in UM cell lines and/or patients with UM. Promoter methylation of RASSF1A was also associated with the development of metastasis. Similarly, a high percentage of promoter hypermethylation of p16INK4a was found in UM cell lines. DNA promoter methylation can control the expression of p16INK4a, which affect cell growth, migration, and invasion in UM. Many other genes might also be involved in the pathogenesis of UM such as the Ras and EF-hand domain containing (RASEF) gene, RAB31, hTERT, embryonal fyn-associated substrate, and deleted in split-hand/split-foot 1. CONCLUSIONS: Our review reveals the complex mechanisms underlying the tumorigenesis of UM and highlights the great needs of future studies to discover more genes/5'-C-phosphate-G-3' sites contributing to the development/metastasis of UM and explore the mechanisms through which epigenetic changes exert their function in UM.

[Evaluation of profile aesthetics of skeletal Class â ¡ patients with different treatment methods].

PURPOSE: To study the aesthetic appearance of skeletal Class Ⅱ patients with maxillary protrusion and mandibular retrusion treated with different methods. METHODS: The facial profile photographs and lateral cephalometric radiographs of a Chinese woman suffering from skeletal Class Ⅱ with maxillary protrusion and mandibular retrusion was digitized.The digital images were modified to obtain orthodontic compensatory treatment, genioplasty with different advancement ranges and orthognathic treatment comprising 6 profiles by Photoshop software，orthodontic professionals and non-professionals were chosen to score the pictures. Post hoc tests were done with ANONA and the Student Keuls method to analyze the data Using SPSS22.0 software package. RESULTS: The profile with the highest score was the picture treated by orthognathic and orthodontic treatment. The profile with genioplasty (advancement of 4 mm) took the second place. When the advancement distance of genioplasty was 8 mm, the score was under the score of orthodontic compensatory treatment profile. CONCLUSIONS: Orthognathic-orthodontic treatment of skeletal Class Ⅱ is still the best treatment option to improve facial aesthetics. Genioplasty, as a adjuvant treatment, improves the appearance based on compensatory orthodontic treatment to some extent, but not comparable to orthognathic-orthodontic treatment.

Changed trends of major causes of visual impairment in Sichuan, China from 1987 to 2006.

AIM: To study the trends of major causes of visual impairment (VI) in adults in Sichuan, China and evaluate the effect of aging on the trends. METHODS: We used data from the National Sample Survey on Disabilities (NSSD) in Sichuan province conducted in 1987 and 2006. The age-adjusted prevalence of major causes of VI and the prevalence stratified by age in each cause were calculated and compared. The association between age and each cause of VI was also analyzed. RESULTS: Retinal disease increased and became the second leading cause of VI in 2006 while blinding trachoma decreased markedly. Cataract and non-trachomatous corneal diseases were among the leading causes of VI in both years. We found associations between age and causes of VI, with age showing the strongest association with cataract and relatively lower associations with other causes. CONCLUSION: In the last two decades, dramatic changes occurred in the major causes of VI with significantly increased retinal disease and decreased blinding trachoma. Aging of the population might be an important factor accounting for the changed trends of VI. Understanding the prevalence of VI, its major causes and trends over time can assist in prioritizing and developing effective interventional strategies and monitoring their impact.