Development and validation of a nomogram to predict postsurgical intra-abdominal infection in blunt abdominal trauma patients: A multicenter retrospective study.

BACKGROUND: Intra-abdominal infection is a common complication of blunt abdominal trauma. Early detection and intervention can reduce the incidence of intra-abdominal infection and improve patients' prognoses. This study aims to construct a clinical model predicting postsurgical intra-abdominal infection after blunt abdominal trauma. METHODS: This study is a retrospective analysis of 553 patients with blunt abdominal trauma from the Department of General Surgery of 7 medical centers (2011-2021). A 7:3 ratio was used to assign patients to the derivation and validation cohorts. Patients were divided into 2 groups based on whether intra-abdominal infection occurred after blunt abdominal trauma. Multivariate logistic regression and least absolute shrinkage and selection operator regression were used to select variables to establish a nomogram. The nomogram was evaluated, and the validity of the model was further evaluated by the validation cohort. RESULTS: A total of 113 were diagnosed with intra-abdominal infection (20.4%). Age, prehospital time, C-reactive protein, injury severity score, operation duration, intestinal injury, neutrophils, and antibiotic use were independent risk factors for intra-abdominal infection in blunt abdominal trauma patients (P < .05). The area under the receiver operating curve (area under the curve) of derivation cohort and validation cohort was 0.852 (95% confidence interval, 0.784-0.912) and 0.814 (95% confidence interval, 0.751-0.902). The P value for the Hosmer-Lemeshow test was .135 and .891 in the 2 cohorts. The calibration curve demonstrated that the nomogram had a high consistency between prediction and practical observation. The decision curve analysis also showed that the nomogram had a better potential for clinical application. To facilitate clinical application, we have developed an online at https://nomogramcgz.shinyapps.io/IAIrisk/. CONCLUSION: The nomogram is helpful in predicting the risk of postoperative intra-abdominal infection in patients with blunt abdominal trauma and provides guidance for clinical decision-making and treatment.

Talaromyces Marneffei Infection in an HIV-Negative Patient in a Non-Endemic Area: a Case Report and Literature Review.

BACKGROUND: Talaromyces marneffei infection is insidious and occurs in immunocompromised or deficient populations, particularly in patients with acquired immune deficiency syndrome (AIDS). It is less commonly found in HIV-negative individuals, but is more likely to present with increased leukocytes (increased CD4+ cell counts), negative blood cultures, respiratory distress, and bone destruction. Therefore, we report a case of an HIV-negative patient infected with Talaromyces marneffei. METHODS: After percutaneous lung aspiration biopsy, infectious agent macrogenomics assay (NGS) was done. RESULTS: The patient's chest CT suggested a pulmonary infection but failed to accurately confirm the diagnosis, and a lung puncture biopsy with NGS was performed which suggested the presence of Talaromyces marneffei, and the patient was given symptomatic treatment. CONCLUSIONS: For fungal infections with non-respiratory symptoms as the first manifestation, we should clarify the infectious agent as early as possible, and it is necessary to improve chest CT in a timely manner. When blood culture cannot be clearly diagnosed, timely percutaneous lung biopsy should be performed to obtain pathological tissue and perform NGS to further clarify the condition.

[Bioinformatics analysis and prokaryotic expression of Strongyloides stercoralis serine protease inhibitor 1].

OBJECTIVE: To predict the structure and antigenic epitope of the Strongyloides stercoralis serine protease inhibitor 1 (Ss-SRPN-1) protein using bioinformatics tools, and to construct prokaryotic expression plasmids for expression of recombinant Ss-SRPN-1 protein, so as to provide the basis for unraveling the function of the Ss-SRPN-1 protein. METHODS: The amino acid sequence of the Ss-SRPN-1 protein was downloaded from the NCBI database, and the physicochemical properties, structure and antigenic epitopes of the Ss-SRPN-1 protein were predicted using bioinformatics tools, including ExPASy, SWISS-MODEL and Protean. Primers were designed according to the nucleotide sequences of Ss-SRPN-1, and the Ss-SRPN-1 gene was amplified, cloned and sequenced with genomic DNA extracted from the infective third-stage larvae of S. stercoralis as a template. The Ss-SRPN-1 protein sequence was cloned into the pET28a (+) expression vector and transformed into Escherichia coli BL21 (DE) cells for induction of the recombinant Ss-SRPN-1 protein expression. The recombinant Ss-SRPN-1 protein was then purified and identified using Western blotting and mass spectrometry. RESULTS: Bioinformatics analysis showed that the Ss-SRPN-1 protein, which was composed of 372 amino acids and had a molecular formula of C1948H3046N488O575S16, was a stable hydrophilic protein, and the subcellular localization of the protein was predicted to be extracellular. The Ss-SRPN-1 protein was predicted to contain 11 dominant B-cell antigenic epitopes and 20 T-cell antigenic epitopes. The Ss-SRPN-1 gene with a length of 1 119 bp was successfully amplified, and the recombinant plasmid pET28a (+)/Ss-SRPN-1 was constructed and transformed into E. coli BL21(DE) cells. The expressed recombinant Ss-SRPN-1 protein had a molecular weight of approximately 43 kDa, and was characterized as a Ss-SRPN-1 protein. CONCLUSIONS: The recombinant Ss-SRPN-1 protein has been expressed successfully, and this recombinant protein may be a potential vaccine candidate against strongyloidiasis.

Mechanized Pneumonia Secondary to Legionella Infection with Diarrhea as the First Manifestation: a Case Report.

BACKGROUND: Legionella is a Gram-negative bacterium, and Legionella pneumonia is an atypical pneumonia, clinically similar to Streptococcus pneumoniae or other bacterial pneumonia, with respiratory symptoms as the most common clinical manifestation, but very few patients have a predominantly GI symptom presentation, which often leads to delayed treatment; timely and effective standardized treatment has a good prognosis, and individual patients can develop mechanized pneumonia. Therefore, we report a case of Legionella infection with diarrhea as the first manifestation secondary to mechanized pneumonia. METHODS: bronchoscopy, percutaneous lung aspiration biopsy, infection pathogen macrogenomics next-generation assay (mNGS). RESULTS: The patient was examined by bronchoscopy and NGS was performed suggesting the presence of Legionella and poorly absorbed by the treated pulmonary lesion condition. Therefore, we further improved the pathology of percutaneous lung puncture biopsy suggesting the presence of mechanized pneumonia and gave the patient symptomatic treatment. CONCLUSIONS: For severe pneumonia with non-respiratory symptoms as the first manifestation, we need to clarify the infecting pathogen as early as possible, and we also need to evaluate the anti-infective efficacy in a timely manner. After a full course of treatment with active pathogen coverage and imaging suggesting poor absorption, bronchoscopy or percutaneous lung biopsy should be perfected in a timely manner to obtain pathological tissue to further clarify the condition.

"You Can't Be Too Skinny. You Can't Be Too Fat. I Don't Know What You Are Supposed To Be.": A qualitative focus group study exploring body image experiences of South Asian women in the UK.

British South Asian women may experience unique appearance pressures associated with their intersecting (racialised and gendered) identities; yet qualitative investigations of intersectional understandings of their body image are scarce. The aim of this study was to explore sociocultural factors influencing British South Asian women's body image using an intersectional framework. Seven focus groups were conducted with 22 women of South Asian heritage living in the UK between the age of 18 and 48 years old who were comfortable speaking in English. Data were analysed using reflexive thematic analysis. We generated four themes (1) navigating (often marriage-related) appearance pressures from South Asian elders and aunties (2) negotiating cultural and societal standards across different aspects of one's identity (3) representation of South Asian women in the wider context and (4) forms of healing from the pressures imposed on South Asian women. The findings have important implications for the body image experiences of South Asian women by acknowledging the need for tailored and nuanced responses to their complex needs in the sociocultural, political and relational context such as family, peers, education, health, media and the wider consumer landscape.

[Progress of researches on Strongyloides stercoralis co-infection with other pathogens].

Strongyloides stercoralis is an opportunistic pathogenic parasite that can cause severe strongyloidiasis and even death among immunocompromised individuals. Previous clinical studies have reported cases co-infected with S. stercoralis and other pathogens, such as parasites, viruses, bacteria and fungi. This review summarizes strongyloidiasis patients co-infected with pathogens, and analyzes the impact of co-infection on strongyloidiasis, so as to provide insights into the reduction of the morbidity and mortality of disorders associated with S. stercoralis infections.

[Single-cell transcriptome analysis reveals development atlas of mouse molar pulp cells].

Objective: Single-cell RNA sequencing (scRNA-seq) was used to analyze the developing mouse molars, in order to construct a spatiotemporal development atlas of pulp cells, and further to reveal the developmental process and regulatory mechanism of tooth development. Methods: Ten mandibular first molars from C57BL/6 mice in postnatal day (PN) 0 and 3 were respectively dissected and digested to obtain single-cell suspensions. scRNA-seq was performed on 10× Genomics platform. PN 7 mouse molar scRNA-seq data were obtained from our previous study. PN 0, 3, and 7 scRNA-seq data were integrated for following analysis. The initial quality control, mapping and single cell expression matrix construction were performed by Cell Ranger. Quality control, standardization, dimensional reduction and cluster analysis were performed by using Seurat. Monocle was used to generate the pseudotime trajectory. Scillus was used to perform gene ontology analysis. In order to detect the spatiotemporal change of different population of pulp cells, the marker genes of each cluster were demonstrated by RNAscope in situ hybridization. Results: There were twenty-six cell clusters within mouse molars, which were identified as eight different cell types, including dental pulp cells, dental follicle cells, epithelial cells, immune cells, endothelial cells, perivascular cells, glial cells and erythrocytes. We further re-clustered and analyzed dental pulp cells. Cluster 0 were mature pulp cells, which located at the upper portion of crown. The main functions of cluster 0 were osteogenesis and extracellular structure organization. Cluster 1 were apical papilla cells, which located at the apical part of roots, whose main functions were extracellular structure organization and organ development. Cluster 2 were cycling cells, which were actively proliferated, resided in the lower portion of the crown. Cluster 3 and 4 were preodontoblasts and odontoblasts, respectively. Their functions were closely related to biomineralization. The proportion of mature pulp cells increased with the development process, while the proportion of cycling cells and odontoblast lineage decreased. According to the expression pattern of marker genes of each cluster, we constructed a cell atlas of dental pulp. Pseudotime trajectory analysis found there were two development trajectories within dental pulp. They both started from SPARC related modular calcium binding 2 (Smoc2)+ dental papilla cells, then went through DNA topoisomerase Ⅱ alpha (Top2a)+ cycling cells, and finally divided into coxsackie virus and adenovirus receptor (Cxadr)+ mature pulp cells or dentin sialophosphoprotein (Dspp)+ odontoblasts two lineages. Conclusions: scRNA-seq could fully discover the intercellular heterogeneity of cells on transcriptome level, which provides a powerful tool to study the process and regulatory mechanism of organ development.

Scorpion venom component: AGAP exhibits local anaesthetic effects and attenuates nociceptive pain

The incidences of systemic toxicity and other complications associated with existing local anaesthetics can occur at clinical concentration level and vary with the anaesthetic techniques, types of surgery and patient factors. This evidence suggests the need for therapeutic interventions in peripheral and regional anaesthesia. Buthus martensii Karsch (BmK) scorpion venom is a compound that contains mixtures of peptides that have analgesic properties. This study aimed to investigate the local anaesthetic activity of scorpion venom peptide, AGAP (analgesic-antitumor peptide) in mechanical hyperalgesia or acute inflammatory pain. Method: Formalin was injected into the left hind paw after 20 minutes of infiltration of drugs. The time of licking or flinching of the injected hind paw was recorded as indicative of nociceptive or acute inflammatory pain. Paw flinching or quick withdrawal was considered a positive response to pain in the partial sciatic nerve ligation. The paw-withdrawal threshold (PWT) was determined by consecutively increasing and decreasing the magnitude of the stimulus. Results: The results indicated that AGAP exhibited a 67.9% inhibition in licking or flinching time and an 88.1% inhibition in paw withdrawal in mechanical hyperalgesia. The addition of AGAP to lidocaine showed an 89.5% inhibition in paw withdrawal. Conclusion: The data presented in this study suggest that local infiltration of AGAP significantly reduced mechanical hyperalgesia and acute inflammatory pain

[Characteristics of daytime napping and its correlation with chronic diseases in Chinese adults].

Objective: To describe the prevalence of daytime nap habit in participants of the China Kadoorie Biobank (CKB) study, across 10 study regions and explore its correlation with prevalence of major chronic diseases. Methods: Participants with a self-reported pre-diagnosis of any cancer at baseline survey were excluded. Logistic regression models were used to analyze the differences in study regions and age distribution of the prevalence daytime nap habit, and its correlation with the prevalence of diabetes, hypertension, coronary heart disease (CHD), stroke, chronic obstructive pulmonary disease (COPD), and chronic liver diseases. Results: Among 510 145 participants, 39.9% had daytime nap habit in summer and 20.8% had daytime nap habit all the year round. Urban-rural differences were observed in the prevalence of summer nap habit and perennial nap habit. Daytime nap in summer was common in rural areas and Suzhou, with prevalence ranged from 32.9% to 73.3%. Haikou and Liuzhou had higher prevalence of perennial nap (60.4% and 63.3%). The proportion of people with daytime nap habit all the year round increased with age (P for trend <0.001), the proportion was highest in those aged 70- years (31.9%). Daytime nap habit in summer was positively correlated with the prevalence of diabetes, hypertension, CHD and chronic liver disease with OR of 1.10 (95%CI: 1.07-1.14), 1.03 (95%CI:1.02-1.05), 1.07 (95%CI: 1.02-1.12) and 1.07 (95%CI:1.00-1.14), respectively. Daytime nap habit all the year round was positively correlated with the prevalence of diabetes, hypertension, CHD, stroke, COPD and chronic liver disease with OR of 1.33 (95%CI: 1.29-1.37), 1.11 (95%CI: 1.09-1.13), 1.39 (95%CI: 1.33-1.45), 1.33 (95%CI: 1.26-1.41), 1.12 (95%CI: 1.08-1.16) and 1.27 (95%CI:1.18-1.37) respectively. Conclusion: There were regional and age differences in prevalence of daytime nap habit among CKB participants. Daytime nap habit, especially daytime nap habit all the year round, was positively correlated with the prevalence of major chronic diseases.

[Associations between multimorbidity patterns of 4 chronic diseases and physical activity with all-cause mortality].

Objective: To identify the prevalence of multimorbidity among a Chinese population, analyze the risk of all-cause mortality with different multimorbidity patterns, and the impact of exercise on the risk of multimorbidity-related mortality and life lost. Methods: The study was based on 437 408 MJ Health Management Center participants. The classification decision tree was used to explore multimorbidity patterns composed of hypertension, diabetes, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). The Cox proportional hazards model was used to calculate the all-cause mortality hazard ratio (HR) for different multimorbidity patterns. Using Chiang's life table method, years of life lost were the difference in life expectancy for those with and without multimorbidity. Results: The prevalence rate of multimorbidity was 8.7%. Among multivariate patterns, the most common ones were "hypertension+CKD" (3.6%), "hypertension + diabetes + CKD" (1.1%) and "hypertension+diabetes+CKD+COPD" (0.1%). Compared with a healthy population, patterns with the highest mortality risk were "diabetes+CKD" (HR=3.80, 95%CI: 3.45-4.18), "diabetes+CKD+COPD" (HR=4.34, 95%CI: 3.43-5.49) and "hypertension+ diabetes+CKD+COPD" (HR=4.75,95%CI:4.15-5.43). Through low-intensity and moderate to high-intensity exercise, the increased HRs were attenuatedcompared with the inactive population. People with single disease and multimorbidity shortened life by 4.6 and 13.4 years, while exercise attenuated 2.3 and 4.6 years of life lost, of which low-intensity and moderate to high-intensity exercise saved 1.5 and 3.7 years of life lost due to chronic diseases. Conclusions: Multimorbidity patterns based on "diabetes + CKD" cause the highest mortality risk, and physical activity in reducing mortality was significant for either with or without multimorbidity. Higher exercise intensity leads to a greater relative reduction of mortality risk.

[Exploring the effects of entecavir treatment on the degree of liver fibrosis in patients with non-alcoholic fatty liver combined with chronic hepatitis B in Tibet region].

Objective: To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with chronic hepatitis B (CHB) in Tibet region. Methods: HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people's Hospital between January 2018 to December 2019 were retrospectively analyzed. Among the 140 subjects with CHB, 95 cases were CHB alone, and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound. All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks. HBeAg negative conversion rate, blood glucose, blood lipid, liver function and the degree of liver fibrosis were compared between the two groups at the 12th, 24th and 48th weeks of treatment to evaluate the virological response. SPSS 19.0 statistical software was used to process the data. Measurement data were expressed as mean ± standard deviation (x¯±s). Descriptive statistical analysis was used for t-test, and the categorical variables were expressed as percentage (%) and χ2 test. A p-value < 0.05 was considered as statistically significant. Results: After 48 weeks of treatment, the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone (group B) than CHB combined with NAFLD (group A), that is to say, HBeAg negative conversion rate in group A and B patients were 28.90% and 40%, respectively, and group B was better than group A. HBV DNA negative conversion rate was significantly elevated in group B (83.2%) than group A (64.4%), with statistical significance (P<0.05), and the difference between the both groups was statistically significant. Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD. Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients, and the depletion was more pronounced in CHB alone group. Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group. Moreover, liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors, and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53, respectively; however, group B was not affected by fat attenuation factors, so LSM value reduction in group A was more obvious, and the differences were statistically significant. There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups. Conclusion: NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB, i.e., the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD. Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone. Therefore, it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.

Brain functional changes in individuals with bulimia nervosa: a protocol for systematic review and meta-analysis.

INTRODUCTION: Bulimia nervosa (BN) is a disorder with high health and socioeconomic burdens that typically arises in late adolescence and early adulthood. Previous neuroimaging studies have found functional brain changes in patients with BN. This study aims to review the latest neurobiological evidence from studies of individuals with BN, examine the consistency of these findings and evaluate the food addiction hypothesis of the disease. METHODS AND ANALYSIS: A systematic search will be performed using the Cochrane Library, PubMed, Embase and Web of Science databases, covering the period from database inception to 30 November 2021. Two researchers will be responsible for study selection, quality assessment and data extraction. The anisotropic effect size version of the signed differential mapping method will be used to conduct a coordinate-based meta-analysis. Publication bias will be examined with the Egger test. The quality of studies will be evaluated using the Newcastle-Ottawa Scale. ETHICS AND DISSEMINATION: No ethics approval is required for this is a systematic review protocol and does not require the collection of primary data. Findings will be disseminated through peer-reviewed journal or related conferences. PROSPERO REGISTRATION NUMBER: CRD42022307233.

[The correlation of physical activity and sedentary leisure time with low muscle mass, strength, and quality in Chinese adults].

Objective: To explore the relationship of physical activity and sedentary leisure time with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of physical activity and sedentary leisure time with low muscle mass, grip strength, and muscle quality. Results: A total of 24 245 participants were included in the analysis. The average daily physical activity level was (18.3±13.8) MET-h/d, and the sedentary leisure time was (4.4±1.9) hours. We took the lowest physical activity quartile as the reference and found that the participants' physical activity was negatively correlated to low muscle mass, strength, and quality. The ORs (95%CIs) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low arm muscle quality (AMQ) were 0.68 (0.60-0.77), 0.66 (0.58-0.75), 0.82 (0.72-0.94) and 0.84 (0.74-0.95), respectively. The subtypes of physical activity, including those related to work, transportation, housework, and leisure, also showed negative correlations with low muscle mass, strength, and quality to varying degrees. Compared with participants with the shortest sedentary leisure time, those who had the longest were more likely to have low TSMI (OR=1.13, 95%CI: 0.99-1.30). Conclusions: Physical activity was negatively correlated with a lower risk of low muscle mass and strength, while longer sedentary leisure time positively correlated with low muscle mass.

[Spicy food consumption and risk of lip, oral cavity and pharynx cancers: a prospective cohort study of Chinese adults].

Objective: To explore the association of spicy food consumption and risk of lip, oral cavity, and pharynx cancers (LOCPs) in Chinese adults. Methods: Based on the baseline survey and long-term follow-up of the China Kadoorie Biobank (CKB) study, Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for associations between spicy food consumption and LOCPs incidence. Results: Of the 510 145 participants included at baseline, 30.1% reported daily spicy food consumption. During a mean follow-up of 10.8 (2.0) years, we documented 767 LOCPs cases. Multivariate adjusted analyses showed that the risk of LOCPs incidence decreased with the frequency of spicy food intake (trend P=0.003), with HR of 0.69 (95%CI:0.54-0.88) for daily spicy food consumers, compared with never or occasional consumers. Participants who preferred moderate pungency degrees had the lowest risk of LOCPs, with a 33%[0.67(95%CI:0.52-0.87)] reduced risk compared to those who consumed spicy food less than once per week. The later the starting age, the lower the risk (trend P=0.004). Those who started eating spicy food after 18 years old had the lowest risk of LOCPs incidence, with adjusted HR (95%CI) of 0.70(0.54-0.92). Conclusions: Spicy food intake might be associated with a decreased risk of LOCPs incidence. Such association was independent of healthy lifestyles. Advocating moderate-pungency spicy food consumption and healthy lifestyles might help prevent LOCPs.

[The correlation of sleep duration and insomnia with low muscle mass, strength and quality in Chinese adults].

Objective: To explore the relationship of sleep duration and insomnia with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of sleep duration, insomnia, and its duration with low muscle mass, handgrip strength, and muscle quality. Results: The average sleep duration of the study population was (7.4±1.5) hours. Morbidities of short sleep duration (<6 hours), long sleep duration (≥9 hours), and insomnia were 9.3%,17.4%,and 29.9%,respectively. Compared with those who slept for 7- hours, those who slept for ≥9 hours were more likely to have low muscle mass, low handgrip strength,and low arm muscle quality (AMQ), and the OR (95%CI) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low AMQ were 1.32 (1.18-1.48),1.26 (1.13-1.41), 1.33 (1.18-1.49) and 1.16 (1.03-1.30), respectively. Compared with participants without insomnia, insomnia patients were more likely to have low muscle mass,and the longer the duration of insomnia,the higher the risk (P for trend <0.001). Participants who reported <6 hours sleep duration and insomnia had a higher proportion of low ASMI and low TSMI,compared with those who slept for 7- hours and without insomnia, the OR (95%CI) were 1.26 (1.08-1.47) and 1.25 (1.07-1.46), respectively. Conclusions: Participants who reported ≥9 hours sleep duration were more likely to have low muscle mass,low handgrip strength,and low AMQ. Participants with insomnia had lower muscle mass, and the longer the duration of insomnia, the higher the proportion of low ASMI and low TSMI.

ILF3-AS1 promotes the aerobic glycolysis and proliferation of melanoma cells by regulating miR-493-5p/PDK1 pathway.

BACKGROUND: The aim of this study was to investigate the role of ILF3-AS1 in regulating the survival of melanoma and its molecular mechanism. METHODS: The relative expression level of ILF3-AS1 in melanoma was assessed by qPCR. The effect of ILF3-AS1 and PDK1 on the cell viability was tested by MTT assay. Glucose uptake colorimetric assay, lactate assay, the measurements of extracellular acidification rate (ECAR) and Oxygen consumption rate (OCR) were performed to test the effect of ILF3-AS1 and PDK1 on the cellular glycolysis. Luciferase assay was conducted to detect the interactions of ILF3-AS1, miR-493-5p and PDK1. RNA immunoprecipitation chip (RIP) assay was used to detect the enrichments of ILF3-AS1 and miR-493-5p in the complex. Protein level of PDK1 was detected by western blot analysis. RESULTS: qPCR revealed that ILF3-AS1 was upregulated in human melanoma cell lines. MTT assay showed that ILF3-AS1 knockdown blunted cell proliferation, which was rescued by the overexpression of PDK1. Glucose uptake colorimetric assay, lactate assay, the measurements of ECAR and OCR indicated that ILF3-AS1 promoted glycolysis through PDK1. Western blotting results showed that ILF3-AS1 overexpression promoted PDK1 expression, which was prevented by miR-493-5p overexpression in SK-MEL-1 cells. CONCLUSIONS: ILF3-AS1 promotes the aerobic glycolysis and survival of melanoma cells involving miR-493-5p/PDK1 pathway.

Transcriptome profiling reveals morphogenesis-related candidate genes and pathways in the chick embryonic small intestine.

1. A better understanding of intestinal development is essential for the intestinal health of poultry. Intestinal villification starts on embryo day E15 and is generally completed before hatching (E21). The development of lymphoid organs in the intestine starts during embryogenesis. However, transcriptional information on the processing of intestinal morphogenesis and immune development during chick embryogenesis is limited.2. In this work, RNA-sequencing was performed using 12 biological replicates to investigate Hy-Line brown chick embryonic small intestinal transcription at E15 and E21. Differentially expressed genes (DEGs) between E15 and E21 were identified. GO and KEGG enrichment analyses, based on the DEGs, were performed to identify key GO terms in the biological process category and key KEGG pathways. PPI networks were constructed based on the DEGs in the key pathways to screen hub genes. The embryonic small intestinal morphology and IgA distribution were observed by histological processing. The serum levels of IgA and lysozyme were measured by ELISA.3. A total of 76.38 Gb of high-quality RNA-sequencing data were generated and uploaded. A total of 2,676 DEGs, between E15 and E21, were identified. Structural development and villification of the small intestine at E15 tended to proceed via the expression of nervous system development-related genes. A combination of the histological and serological results with the transcriptome data indicated that the identified genes and pathways may be strong candidates for intestinal morphogenesis-regulation.4. The small intestine appears to have developed a relatively complete morphology and transport, metabolism, digestion and immunity functions by E21. This work provided a transcriptome profile of the chick embryonic small intestine and provided insights into the intestinal development and health of poultry.

iPSC-derived cortical neurons to study sporadic Alzheimer disease: A transcriptome comparison with post-mortem brain samples.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by the progressive impairment of cognition and memory loss. Sporadic AD (sAD) represents approximately 95 % of the AD cases and is induced by a complex interplay between genetic and environmental factors called "Alzheimerogens". Heavy metals (e.g. copper) and pesticides (e.g. fipronil) can affect many AD-related processes, including neuroinflammation (considered as AD-inducing factor). Research would benefit from in vitro models to investigate effects of Alzheimerogens. We compared transcriptomics changes in sAD induced pluripotent stem cell (iPSC) derived cortical neurons to differentially expressed genes (DEGs) identified in post-mortem AD brain tissue. These analyses showed that many AD-related processes could be identified in the sAD iPSC-derived neurons, and furthermore, could even identify more DEGs functioning in these processes than post-mortem AD-brain tissue. Thereafter, we exposed the iPSCs to AD-inducing factors (copper(II)chloride, fipronil sulfone and an inflammatory cytokine cocktail). Cytokine exposure induced expression of immune related genes while copper-exposure affected genes involved in lipid and cholesterol metabolism, which are known AD-related processes. Fipronil-exposure did not result in significant transcriptomic changes, although prolonged exposures or higher doses may be necessary. Overall, we show that iPSC-derived cortical neurons can be beneficial in vitro models to identify Alzheimerogens and AD-related molecular mechanisms.

[Correlation between chronic diseases and low muscle mass, strength and quality in adults in China].

Objective: To explore the correlation between chronic diseases and muscle mass, strength and quality in adults in China. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of different types, number and duration of chronic diseases with low muscle mass, handgrip strength and muscle quality. Results: The prevalence rate of diabetes, coronary heart disease (CHD), stroke and chronic obstructive pulmonary disease (COPD) were 9.6%, 5.8%, 3.2% and 26.8%, respectively, and 38.8% of the participants had at least one disease, and they were more likely to have low handgrip strength and low arm muscle quality (AMQ), and the longer the chronic diseases duration, the higher the risk. The ORs (95%CIs) for low handgrip strength and low AMQ in patients with 1 chronic disease for more than 10 years was 1.64 (1.42-1.90) and 1.83 (1.60-2.10), respectively. The ORs (95%CIs) for low handgrip strength were 1.26 (1.17-1.37), 1.42 (1.23-1.64) and 2.27 (1.55-3.32) and the ORs (95%CIs) for low AMQ were 1.28 (1.18-1.38), 1.67 (1.46-1.92) and 2.41(1.69-3.45), respectively, in patients with 1, 2, ≥3 chronic diseases, the correlation showed a linear trend (P for trend <0.001). Diabetes, CHD and stroke were positively correlated with low handgrip strength and low AMQ. Compared with participants without COPD, COPD patients were more likely to have low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI) and low handgrip strength, and the risk was positively correlated with disease duration. Conclusions: Patients with chronic diseases were more likely to have lower muscle strength and muscle quality, especially the patients with multi diseases and longer disease duration. The proportion of low handgrip strength and low AMQ was higher in patients who reported multi-prevalence and longer duration of chronic diseases.