[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

[Best evidence summary for awake prone positioning in treating hypoxemic due to COVID-19 infection].

Objective: To retrieve, evaluate, and summarize the best evidence for the treatment of hypoxemia in patients with COVID-19 infection using the awake prone positioning, with the aim of guiding healthcare professionals in the standardized implementation of this therapy. Methods: A systematic search was conducted in databases including UpToDate, BMJ Best Practice, JBI Evidence-Based Healthcare Center, American Association of Critical-Care Nurses, Intensive Care Society, European Respiratory Society, World Health Organization website, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang. The retrieved literature was subjected to quality assessment and evidence extraction. Results: A total of ten publications were included, consisting of one thematic evidence summary, one guideline, two systematic reviews, three randomized controlled trials, and three expert consensus statements. This summary synthesizes thirty key pieces of evidence in five categories: organizational management and training, risk assessment, preparatory operations, implementation key points, and risk control. Conclusions: Awake prone positioning is beneficial for improving hypoxemia in patients with COVID-19 and is easy to implement. Medical institutions should develop nursing management systems, operational standards, and best practices for awake prone positioning based on evidence-based evidence in order to improve the quality of care management for such patients.

Limosilactobacillus reuteri peptidoglycan alleviates aflatoxin B1-induced toxicity through adsorbing toxins and improving growth, antioxidant status, immunity and liver pathological changes in chicks.

1. The objective of this study was to investigate the protective effects of a peptidoglycan produced by Limosilactobacillus reuteri against aflatoxin B1 (AFB1) induced toxicity in vitro and in vivo in broiler chicks.2. Toxin adsorption experiments were carried out firstly in vitro. These experiments indicated that the absorption efficiency of the peptidoglycan for AFB1 was 64.3-75.9%.3. In the in vivo experiments, Hy-Line Brown chicks were fed a diet containing AFB1 at 71.43 µg/kg with and without peptidoglycan supplementation at concentrations of 100, 200, or 300 g/kg feed from 0-42 d of age.4. The peptidoglycan supplementation in AFB1-contaminated diets resulted in significant improvements in terms of average daily gain, feed intake, feed conversion ratio, white blood cell count, haemoglobin content, glutathione peroxidase activity, immunoglobulin (Ig) A, IgG, IgM and Newcastle disease virus antibody titres (p < 0.05) and diminished liver steatosis.5. In conclusion, peptidoglycan supplementation alleviated AFB1-induced toxicity through adsorbing toxins and improving growth performance, antioxidant ability, immunity and liver pathological changes in chicks. The optimal supplemental dose was 200 mg/kg in feed.

p-CREB-1 at Ser 133 is a potential marker for breast cancer.

OBJECTIVE: Dysregulation of numerous oncogenes and their downstream signaling pathways, among others in the signaling transduction molecule p-CREB-1 (p-cAMP responsive element binding protein-1), is an essential feature of different types of cancer. To investigate whether p-CREB-1 is also pivotal in tumorigenesis and metastogenesis of breast cancer, we conducted a prospective study with long-term follow-up on 96 patients with breast cancer. PATIENTS AND METHODS: Pathway array and tissue microarray (TMA) were used to detect the differential expression of CREB (cAMP-responsive element binding protein) and p-CREB-1 in breast cancer cells, breast cancer stem cells (BCSCs), human breast cancer tissues (BCTs), and adjacent normal tissues (ANTs). The associations between p-CREB-1 expression, clinicopathological variables, and survival rates of the patients were analyzed and calculated. RESULTS: Our results revealed that p-CREB-1 and CREB expression in cancerous cell lines and tissues were significantly upregulated compared with non-cancerous cell lines and tissues. Most statistically significant overexpression was detected in BCSCs (p<0.01). In TMA and immunohistochemical analyses, BCTs exhibited significantly higher expression of p-CREB-1 and CREB than ANTs (p<0.001). Clinicopathological variable and survival analysis revealed a correlation between high expression (++/+++) of p-CREB-1 and the presence of axillary lymph node metastasis (p<0.05) and poorer disease-free and overall survival. CONCLUSIONS: p-CREB-1 is a potential predictive and prognostic biomarker and a promising therapeutic target in breast cancer.

[Identification, molecular structure and expression characteristics of Torso like gene in Anopheles dirus].

OBJECTIVE: To characterize Torso-like (tsl) gene and investigate its expression characteristics in Anopheles dirus, so as to provide a theoretical basis for subsequent functional studies of the tsl gene. METHODS: According to the coding sequences of Drosophila melanogaster and An. gambiae tsl genes, the complete genome of An. dirus was retrieved and the An. dirus tsl gene was characterized. Specific primers were designed and the target gene was amplified using PCR and reverse-transcription PCR assays. The physicochemical properties, signal peptide, transmembrane structure, secondary structure and tertiary structure of the encoded protein TSL were analyzed using bioinformatics tools, and a phylogenetic analysis was performed. In addition, the specific expression of the tls gene was detected in various tissues of An. dirus using a quantitative real-time PCR assay. RESULTS: The An. dirus tsl gene was 16 751 bp in length with a CDS region of 1 134 bp, encoding 377 amino acids, and the encoded TSL protein was a stably hydrophilic protein. The TSL protein was predicted to be a secretory protein that was located in extra-membrane regions containing signal peptides. The secondary structure of the TSL protein contained α-helix (51.72%), extended strand (12.20%), ß-bridge (4.78%) and random coil (31.30%) in the secondary structure, and a 3D homology model was generated using 5cj9.1.A as a template. Phylogenetic analysis revealed a close genetic relationship in the TSL protein between An. dirus and An. farauti. In addition, quantitative real-time PCR assay detected the tsl gene expression in the head, chest, abdomen and foot of An. dirus, with the highest expression in the head and low expression in the foot. CONCLUSIONS: The tsl gene is characterized in An. dirus at a genomic level, and the prediction of the TSL protein structure and the elucidation of the tissue-specific tsl gene expression in An. dirus provide a basis for the further studies on the gene functions.

[Effect of customized zirconia abutment on peri-implant tissue: a one-year prospective study].

Objective: To observe the changes of peri-implant tissue around the individualized abutment that was grinded from zirconia provisional crown in one year. Methods: In this research, a prosthodontic-driven virtual implant planning and immediate provisionalization were conducted in computer assisted design software. And computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate the zirconia provisional crown and surgical guide template before surgery. The implant was accurately placed with the surgical guide, and the zirconia provisional crown was immediately delivered after surgery. Three months later, the implant osseointegration was completed, and zirconia provisional crown was prepared intraorally to generate customized zirconia abutment for final prosthesis. The study included 30 patients with single anterior tooth loss, including 18 males and 12 females, aged from 26 to 50 years old, and the mean age was (36.2±6.1) years old. The patients were from the Center of Oral Implantology, The First Affiliated Hospital of Zhejiang University Medical College from January 2017 to February 2018. After cementation of the final prosthesis, the cases were followed up at 6 and 12 months time intervals. Implant survival rate, probing depth, bleeding on probing, marginal bone level loss and papilla index score (PIS) were recorded in every appointment. Results: The survival rate of 30 implants was 100%, and the probing depths were less than 5 mm. The bone resorption at 6 and 12 months follow-up after the final delivery was 0 (0, 0) mm and 0 (-0.2, 0) mm, respectively, and the difference was not statistically significant (P>0.05). The PIS was 3.0 (2.0, 4.0), 3.0 (2.8, 4.0) and 3.0 (3.0, 4.0) on the final delivery, 6 and 12 months after final delivery, respectively. Conclusions: Marginal bone level and bone loss were stable with this new implant clinical protocol at the one-year follow-up.

Effects of in ovo injection of vitamin C on heat shock protein and metabolic genes expression.

Some studies have shown that the excessive metabolic heat production is the primary cause for dead chicken embryos during late embryonic development. Increasing heat shock protein (HSP) expression and adjusting metabolism are important ways to maintain body homeostasis under heat stress. This study was conducted to investigate the effects of in ovo injection (IOI) of vitamin C (VC) at embryonic age 11th day (E11) on HSP and metabolic genes expression. A total of 320 breeder eggs were randomly divided into normal saline and VC injection groups. We detected plasma VC content and rectal temperature at chick's age 1st day, and the mRNA levels of HSP and metabolic genes in embryonic livers at E14, 16 and 18, analysed the promoter methylation levels of differentially expressed genes and predicted transcription factors at the promoter regions. The results showed that IOI of VC significantly increased plasma VC content and decreased rectal temperature (P < 0.05). In ovo injection of VC significantly increased heat shock protein 60 (HSP60) and pyruvate dehydrogenase kinase 4 (PDK4) genes expression at E16 and PDK4 and secreted frizzled related protein 1 (SFRP1) at E18 (P < 0.05). At E16, IOI of VC significantly decreased the methylation levels of total CpG sites and -336 CpG site in HSP60 promoter and -1137 CpG site in PDK4 promoter (P < 0.05). Potential binding sites for nuclear factor-1 were found around -389 and -336 CpG sites in HSP60 promoter and potential binding site for specificity protein 1 was found around -1137 CpG site in PDK4 promoter. Our results suggested that IOI of VC increased HSP60, PDK4 and SFRP1 genes expression at E16 and 18, which may be associated with the demethylation in gene promoters. Whether IOI of VC could improve hatchability needs to be further verified by setting uninjection group.

[Relationship between inflammatory indexes of amniotic fluid and pregnancy outcome of women with cervical incompetence].

Objective: To investigate the relationship between the level of amniotic fluid inflammatory factor and the pregnancy outcome in patients with cervical incompetence. Methods: A retrospective case-control study was conducted. Totally 110 cases of pregnant women were diagnosed as cervical incompetence for cervical dilation at the medical examination in Sun Yat-sen Memorial Hospital of Sun Yatsen University, from January 1st, 2015 to December 31th, 2016. A total of 32 patients (29.1%, 32/110) were performed cervical cerclage. According to their neonatal outcomes, they were divided into live infant group (23 cases, 72%) and dead infant group (9 cases, 28%) . The demographic and clinical data of two groups were analyzed and compared. Results: The mean peripheral blood leucocyte counts, the median amniotic tumor necrosis factor-α (TNF-α) and the median interleukin-8 (IL-8) level of two groups were (10.5±2.8) ×10(9)/L vs (13.6±3.1) ×10(9)/L, 23.80 ng/L (14.9-85.5 ng/L) vs 379.00 ng/L (70.2-418.5 ng/L) , and 3 354 ng/L (1 020-7 500 ng/L) vs 7 500 ng/L (4 210-7 500 ng/L) respectively. The differences were statistically significant (all P<0.05) . The amniotic fluid IL-1ß, IL-2 receptor, IL-6, IL-10, C-reactive protein and procalcitonin were not significantly different (all P>0.05) between two groups. Conclusions: The peripheral blood leucocyte counts, amniotic fluid TNF-α and IL-8 level are the factors affecting the pregnancy outcome in women with cervical incompetence before cervical cerclage. When IL-8 is higher than 3 580 ng/L and TNF-α is higher than 105 ng/L, the death of perinatal infants could be predicted.

Effects of dietary Lactobacillus rhamnosus CF supplementation on growth, meat quality, and microenvironment in specific pathogen-free chickens.

The probiotic effects of Lactobacillus rhamnosus strain CF (Chen Fu) on growth performance, meat quality, and microenvironment in specific pathogen-free (SPF) chickens were investigated and compared with Enterococcus faecium. One-hundred-eighty 7-day-old SPF chickens were randomly assigned into 3 groups with 3 replicate pens of 20 chickens each. Group 1 served as a control that was fed a basal diet without probiotics supplementation. Groups 2 and 3 were fed the basal diet supplemented with L. rhamnosus CF and E. faecium, respectively. On d 12 and 24, BW, ADG, feed conversion ratio (FCR), dressing percentage (DP), and apparent digestibility of crude protein (AD-CP) were calculated. Meat color, fat content, shear force, water content, and pH value of breast and thigh muscles; ammonia, urea nitrogen, and uric acid content in plasma; pH value, Enterococcus, Lactobacillus, and E. coli in ceca; and ammonia emission were determined. Compared with group 1, group 2 exhibited higher BW, ADG, AD-CP, DP, cecal Lactobacilli, and muscle fat content (P < 0.05) as well as lower FCR, muscle water content, plasma ammonia, pH value, E. coli, and Enterococcus in ceca, and ammonia emission (P < 0.05), and group 3 exhibited higher BW, ADG, AD-CP, DP, and muscle fat content (P < 0.05), as well as lower FCR, meat color, plasma ammonia, E. coli and Enterococcus in ceca, and ammonia emission (d 24) (P < 0.05). Compared with group 3, group 2 exhibited lower plasma ammonia level, E. coli, and pH value in ceca and ammonia emission (P < 0.05) and higher AD-CP, meat color, pH value in thigh muscles, fat content in breast muscles, and number of Lactobacillus in ceca (P < 0.05). Thus, L. rhamnosus CF improves growth performance, meat quality, and microenvironment and is a potential probiotic additive in chickens.

A novel mechanism of memory loss in Alzheimer's disease mice via the degeneration of entorhinal-CA1 synapses.

The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer's disease (AD). Here, we report that the synaptic terminals of pyramidal neurons in the EC layer II (ECIIPN) directly innervate CA1 parvalbumin (PV) neurons (CA1PV) and are selectively degenerated in AD mice, which exhibit amyloid-ß plaques similar to those observed in AD patients. A loss of ECIIPN-CA1PV synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECIIPN using a theta burst paradigm rescues ECIIPN-CA1PV synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECIIPN-CA1PV pathway.

First report of peste des petits ruminants virus lineage II in Hydropotes inermis, China.

In this study, we investigated an outbreak of peste des petits ruminants (PPR) at a Hydropotes inermis (water deer) farm in Anhui Province, China. These results demonstrated that PPR viruses (PPRVs) can infect H. inermis and also revealed that virulent lineage II PPRVs exist in China, where they have been responsible for the deaths of wild animals. The government should pay close attention to the threat of PPRV epidemiology in China.

Association between adiponectin gene T45G polymorphism and nonalcoholic fatty liver disease risk: a meta-analysis.

Numerous epidemiological investigations have evaluated the association between adiponectin gene T45G polymorphism and risk of nonalcoholic fatty liver disease (NAFLD). However, the results of these studies have proven to be inconsistent. Therefore, we conducted a meta-analysis to obtain a more accurate estimation of this association. Published articles were retrieved from PubMed and Web of Science databases and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effect models. Five case-control studies incorporating 597 cases and 701 controls were included in this meta-analysis. No association between adiponectin gene T45G polymorphism and NAFLD was established (TT vs GG: OR = 0.83, 95%CI = 0.37-1.86; TG vs GG: OR = 0.76, 95%CI = 0.33-1.79; dominant model: OR = 0.83, 95%CI = 0.37-1.84; recessive model: OR = 1.10, 95%CI = 0.69-1.76). Moreover, in a subgroup analysis, no significant correlation was found among Asian subjects. In conclusion, the T45G polymorphism of the adiponectin gene may not constitute an NAFLD risk factor. However, this needs to be further validated in single large well-designed future studies.

Cloning and functional analysis of goat SWEET1.

SWEETs are a recently discovered class of sugar transporters that mediate glucose uptake in the intestine and mammary glands. Our objectives were to clone goat SWEET1 and conduct a functional analysis of its effect on glucose efflux in goat mammary gland epithelial cells. We cloned and sequenced the goat SWEET1 gene from goat mammary glands, then conducted an analysis of the structure of goat SWEET1, including a prediction of the transmembrane helices and potential N-glycosylation sites. To investigate the biological function of goat SWEET1, we also generated goat SWEET1-transfected goat mammary gland epithelial cells using the eukaryotic expression vector pcDNA3.1-gSWEET1. Goat SWEET1 overexpression can reduce glucose absorption in mammary gland epithelial cells with increasing expression of GLUT1, GLUT4, and GLUT12, which may be attributed to glucose efflux arising from the leading role played by goat SWEET1. This study will improve our understanding of the glucose balance in mammary glands and the level of glucose in milk.

The MT2 receptor stimulates axonogenesis and enhances synaptic transmission by activating Akt signaling.

The MT2 receptor is a principal type of G protein-coupled receptor that mainly mediates the effects of melatonin. Deficits of melatonin/MT2 signaling have been found in many neurological disorders, including Alzheimer's disease, the most common cause of dementia in the elderly, suggesting that preservation of the MT2 receptor may be beneficial to these neurological disorders. However, direct evidence linking the MT2 receptor to cognition-related synaptic plasticity remains to be established. Here, we report that the MT2 receptor, but not the MT1 receptor, is essential for axonogenesis both in vitro and in vivo. We find that axon formation is retarded in MT2 receptor knockout mice, MT2-shRNA electroporated brain slices or primary neurons treated with an MT2 receptor selective antagonist. Activation of the MT2 receptor promotes axonogenesis that is associated with an enhancement in excitatory synaptic transmission in central neurons. The signaling components downstream of the MT2 receptor consist of the Akt/GSK-3ß/CRMP-2 cascade. The MT2 receptor C-terminal motif binds to Akt directly. Either inhibition of the MT2 receptor or disruption of MT2 receptor-Akt binding reduces axonogenesis and synaptic transmission. Our data suggest that the MT2 receptor activates Akt/GSK-3ß/CRMP-2 signaling and is necessary and sufficient to mediate functional axonogenesis and synaptic formation in central neurons.

Relationship between RUNX3 methylation and hepatocellular carcinoma in Asian populations: a systematic review.

Runt-related transcription factor 3 (RUNX3) is a potential tumor suppressor that is frequently hypermethylated in hepatocellular carcinoma (HCC). The present meta-analysis of case-control studies was carried out to determine whether RUNX3 hypermethylation is associated with HCC. The PubMed, Embase, and Chinese National Knowledge Infrastructure databases were searched for all relevant studies published between May 2000 and May 2012. A total of 11 studies were identified, and 8 studies involving 491 patients with HCC and 409 patients without tumors were found to satisfy the inclusion criteria for the meta-analysis. All tissue samples were from Asian populations. There was significant heterogeneity between the studies. Over the entire sample, the odds ratio (OR) of RUNX3 promoter methylation was 18.5 [95% confidence interval (CI), 11.6-29.6] for HCC tissues relative to control tissues. The ORs of RUNX3 methylation were 16.6 (95%CI = 6.5-42.4) for tumor tissues relative to tumor-adjacent tissues in patients with HCC, 67.3 (95%CI = 13.0-348.5) for tumor tissues from patients with HCC relative to liver tissues from patients with non-neoplastic liver diseases, and 3.26 (95%CI = 1.54-6.90) for tissues from patients with hepatitis C virus (HCV)- related HCC relative to liver tissues from patients with HCC unrelated to HCV. There was no association between RUNX3 methylation and age, gender, pathological stage, or hepatitis B virus infection in HCC tissues. Methylation of the RUNX3 promoter strongly correlated with HCC in Asian populations, especially in individuals with HCV-related HCC, and may be a useful marker for HCC diagnosis in these populations.

Liver injury possibly related to drug interaction after liver transplant: a case report.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced hepatotoxicity is potentially lethal. Liver transplant patients receive a large number of medications and adverse drug reactions, and drug-drug interactions must be closely monitored. CASE SUMMARY: We report a case of a 29-year-old liver transplant patient who suffered liver injury most likely induced by drug interaction between capecitabine and warfarin. Vitamin K1 caused skin rash possibly because of the distribution and metabolism characteristic of the drug in this patient. WHAT IS NEW AND CONCLUSION: Close monitoring and prompt discontinuation of the drugs with high volume of distribution and metabolized through the liver are necessary to avoid drug-drug interaction in liver transplant patients.

Reduction and the intracellular translocation of EphB2 in Tg2576 mice and the effects of ß-amyloid.

AIMS: EphB2 is a member of receptor tyrosine kinases (RTKs) family that is essential for the cell adhesion, neural crest migration, axon guidance and synaptogenesis in the nervous system. Recent studies show that preservation of EphB2 in a transgenic mouse model of Alzheimer's disease (AD) rescues the cognitive deficit, suggesting a crucial role of EphB2 in AD. However, the expression and distribution profiles of EphB2 in the early stage of AD have not been reported. METHODS: Immunohistochemistry, immunoblot and immunofluorescence were used to analyse the level of EphB2 in Tg2576 mice at different ages and in cultured neurones with Aß treatment at different times. RESULTS: EphB2 was reduced in an age-dependent manner in the olfactory bulb and the hippocampus of Tg2576 mice. The decrease of EphB2 appeared earlier in the olfactory bulb than the hippocampus, and reduction of EphB2 appeared earlier than that of MAP2, a dendritic cytoskeleton marker. In the cortex, EphB2 displayed a significant translocation from the neuronal processes to the cell bodies with ageing. In primary hippocampal neuronal cultures, Aß42 treatment also induced the decrement of EphB2 that was prior to the decline of MAP2. CONCLUSIONS: Our findings provide the first evidence for an age- and region-dependent reduction and intracellular translocation of EphB2 in Tg2576 mice, and the foremost decrement of EphB2 in the olfactory bulb may represent an early sign of AD.