Dme-Hsa Disease Database (DHDD): Conserved Human Disease-Related miRNA and Their Targeting Genes in Drosophila melanogaster.

Abnormal expressions of microRNA (miRNA) can result in human diseases such as cancer and neurodegenerative diseases. MiRNA mainly exert their biological functions via repressing the expression of their target genes. Drosophila melanogaster (D. melanogaster) is an ideal model for studying the molecular mechanisms behind biological phenotypes, including human diseases. In this study, we collected human and D. melanogaster miRNA as well as known human disease-related genes. In total, we identified 136 human disease-related miRNA that are orthologous to 83 D. melanogaster miRNA by mapping "seed sequence", and 677 human disease-related genes that are orthologous to 734 D. melanogaster genes using the DRSC Integrative Ortholog Prediction Tool Furthermore, we revealed the target relationship between genes and miRNA using miRTarBase database and target prediction software, including miRanda and TargetScan. In addition, we visualized interaction networks and signalling pathways for these filtered miRNA and target genes. Finally, we compiled all the above data and information to generate a database designated DHDD This is the first comprehensive collection of human disease-related miRNA and their targeting genes conserved in a D. melanogaster database. The DHDD provides a resource for easily searching human disease-related miRNA and their disease-related target genes as well as their orthologs in D. melanogaster, and conveniently identifying the regulatory relationships among them in the form of a visual network.

[A retrospective analysis of 105 drowning victims with psychiatric disorders].

OBJECTIVE: To analyze the features of drowning victims with psychiatric disorders to support further investigation on such cases. METHODS: One hundred and five archives of drowning victims with psychiatric disorders from January 2010 to June 2014 in Harbor Public Security Subbureau, Shanghai Public Security Bureau were reviewed. The decedents' general information, autopsy findings, case investigation data and disease histories were statistically analyzed. RESULTS: Of the 105 cases, 104 were suicides. Most decedents were poorly educated. Most suicides occurred in warm climate, and the corpses were usually found within 2 days. Most decedents had no suicide history and notes, but had abnormal mental or behavior changes before suicide. Depression, depression status and schizophrenia were the main types of psychiatric disorders, and only 9 decedents had received regular therapies before their deaths. CONCLUSION: Mental disorder is a high risk factor in the drowning victims. Guardians should be aware of psychotic abnormal behaviors, especially during warm climate seasons.

Methodology exploration and reproducibility evaluation of TAI and TSI for quantitative ultrasound assessment of hepatic steatosis.

Background and aim: New quantitative ultrasound techniques can be used to quantify hepatic steatosis, including tissue attenuation imaging (TAI), tissue scatter -distribution imaging (TSI), and the hepatorenal index (HRI). However, the measurement norms and the effects of fasting on these measurements remain unclear. The present study performed a methodological exploration and investigated the reliability of these measurements. Methods: In total, 103 participants were prospectively recruited for ultrasonography and magnetic resonance imaging (MRI) scans. For the TAI and TSI data, the upper (2 cm), middle (4 cm) and lower (6 cm) areas determined according to the depth of the region of interest from the liver capsule, were sampled three times. Correlation analyses were performed to compare the measurements of TAI, TSI, and HRI with the controlled attenuation parameter (CAP) or MRI-proton density fat fraction (MRI-PDFF). Intra- and inter-operator repeatability was assessed using intraclass correlation coefficients. The effects of fasting on these measurements were then compared. Results: The TAI and TSI measurements obtained from the upper and middle depths exhibited stronger correlations with the CAP measurements than those obtained from the lower depth. Specifically, the mean TAI had a significant positive correlation with MRI-PDFF (r = 0.753, P < 0.0001). TAI and TSI measurements exhibited excellent intra- (0.933 and 0.925, respectively) and inter- (0.896 and 0.766, respectively) examiner reliability. However, the correlation between HRI and CAP measurements was only 0.281, with no significant correlation with MRI-PDFF, and intra- and inter-examiner reproducibility of 0.458 and 0.343, respectively. Fasting did not affect these measurements. Conclusions: TAI and TSI measurements demonstrated good intra- and interobserver reliability and correlated well with CAP and MRI-PDFF measurements. However, in practice-based clinical applications, the sampling depth should be controlled within 2-4 cm of the hepatic capsule; no fasting is required before the examination.

Morphological risk of acute type A aortic dissection in the mildly to moderately dilated aorta.

OBJECTIVES: This study aimed to analyse and determine the role of aortic length and curvature in the pathogenesis of acute type A aortic dissection (ATAAD) with ascending aortic diameters (AADs) <5 cm. METHODS: We reviewed the clinical and imaging data of patients with ATAAD (n = 201) and ascending aortic dilation (n = 83). Thoracic aortic bending index (TABI) was used to quantify aortic curvature and analyse its role in ATAAD below the diameter risk threshold. RESULTS: The AAD was <5.0 and <4.0 cm in 78% and 37% of patients with ATAAD, respectively. The median ascending aortic length (AAL) was 104.6 mm (Q1-Q3, 96.5-113.6 mm), and in 62.7% of patients, it was <11 cm. The median TABI was 14.99 mm/cm (Q1-Q3, 14.18-15.86 mm/cm). Patients with ATAAD and those with aortic dilation were matched for AAD, age, sex, height and other clinical factors. After matched, the dissection group had higher AALs (median, 102.9 mm; Q1-Q3, 96.0-112.5 mm vs median, 88.2 mm; Q1-Q3, 83.7-95.9 mm; P < 0.001) and TABI (median, 14.84 mm/cm; Q1-Q3, 14.06-15.83 mm/cm vs median, 13.55 mm/cm; Q1-Q3, 13.03-14.28 mm/cm; P < 0.001). According to the regression analysis, the area under the curve required to distinguish patients with ATAAD from those with aortic dilation was 0.831 in AAL, 0.837 in TABI and 0.907 when AAL was combined with TABI. CONCLUSIONS: The patients with ATAAD had higher AAL and TABI than those with aortic dilation. The combination of TABI and AAL might be a potential morphological marker for determining ATAAD risk below the current aortic diameter risk threshold.

Efficacy of low-intensity pulsed ultrasound for the treatment of viral pneumonia: study protocol for a randomized controlled trial.

BACKGROUND: Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of therapeutic LIPUS in improving lung inflammation in hospitalized patients with viral pneumonia. METHODS: Sixty eligible participants with clinically confirmed viral pneumonia will be assigned to either (1) intervention group (LIPUS stimulus), (2) control group (null stimulus), or (3) self-control group (LIPUS stimulated areas versus non-stimulated areas). The primary outcome will be the difference in the extent of absorption and dissipation of lung inflammation on computed tomography. Secondary outcomes include changes in lung inflammation on ultrasonography images, pulmonary function, blood gas analysis, fingertip arterial oxygen saturation, serum inflammatory factor levels, the sputum excretion volume, time to the disappearance of pulmonary rales, pneumonia status score, and course of pneumonia. Adverse events will be recorded. DISCUSSION: This study is the first clinical study of the efficacy of therapeutic LIPUS in the treatment of viral pneumonia. Given that the current clinical recovery mainly depends on the body's self-limiting and conventional symptomatic treatment, LIPUS, as a new therapy method, might be a major advance in the treatment of viral pneumonia. TRIAL REGISTRATION: ChiCTR2200059550 Chinese Clinical Trial Registry, May 3, 2022.

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives.

An efficient access to the tetracyclic-fused quinoline systems, 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives 4a-l, is described, involving the intramolecular Friedel-Crafts acylation reaction of 2-(phenoxymethyl)-4-phenylquinoline-3-carboxylic acid derivatives 3a-l aided by the treatment with PPA (polyphosphoric acid) or Eaton's reagent. The required starting compound (2) was obtained by Friedländer reaction of 2-aminobenzophenone (1) with 4-chloroethylacetoacetate by using CAN (cerium ammonium nitrate, 10 mol %) as catalyst at room temperature. The substrates 3a-l were prepared through one-pot reaction of ethyl 2-(chloromethyl)-4-phenylquinoline-3-carboxylate (2) and substituted phenols. Our developed strategy, involving a three-step route, offers easy access to tetracyclic-fused quinoline systems in short reaction times, and the products are obtained in moderate to good yields.

A Prediction Equation to Estimate Vascular Endothelial Function in Different Body Mass Index Populations.

Objective: Vascular endothelial dysfunction is considered an early predictor of endothelial injury and the initiating factor of atherosclerosis (AS). Brachial artery flow-mediated dilation (FMD) can detect endothelial injury early and provide important prognostic information beyond traditional cardiovascular (CV) risk factors. This study aimed to find the influencing factors of FMD and develop a simple prediction model in populations with different body mass indices (BMIs). Methods: In total, 420 volunteers with different BMIs were recruited in our study. Subjects were randomly assigned to the derivation and validation cohorts (the ratio of the two was 1:2) with simple random sampling. The former was used for influencing factors searching and model construction of FMD and the latter was used for verification and performance evaluation. Results: The population was divided into two groups, i.e., 140 people in the derivation group and 280 people in the verification group. Analyzing in the training data, we found that females had higher FMD than males (p < 0.05), and FMD decreased with age (p < 0.05). In people with diabetes, hypertension or obesity, FMD was lower than that in normal individuals (p < 0.05). Through correlation analysis and linear regression, we found the main influencing factors of FMD: BMI, age, waist-to-hip radio (WHR), aspartate aminotransferase (AST) and low-density lipoprotein (LDL). And we developed a simple FMD prediction model: FMD = -0.096BMI-0.069age-4.551WHR-0.015AST-0.242LDL+17.938, where R2 = 0.599, and adjusted R2 = 0.583. There was no statistically significant difference between the actual FMD and the predicted FMD in the verification group (p > 0.05). The intra-class correlation coefficient (ICC) was 0.77. In a Bland-Altman plot, the actual FMD and the predicted FMD also showed good agreement. This prediction model had good hints in CV risk stratification (area under curve [AUC]: 0.780, 95 % confidence intervals [95% CI]: 0.708-0.852, p < 0.001), with a sensitivity and specificity of 73.8 and 72.1%, respectively. Conclusions: Males, older, obesity, hypertension, diabetes, smoking, etc. were risk factors for FMD, which was closely related to CV disease (CVD). We developed a simple equation to predict FMD, which showed good agreement between the training and validation groups. And it would greatly simplify clinical work and may help physicians follow up the condition and monitor therapeutic effect. But further validation and modification bears great significance.

Metagenomic Assessment of the Pathogenic Risk of Microorganisms in Sputum of Postoperative Patients With Pulmonary Infection.

Respiratory infections are complicated biological processes associated with an unbalanced microbial community and a wide range of pathogens. To date, robust approaches are still required for distinguishing the pathogenic microorganisms from the colonizing ones in the clinical specimens with complex infection. In this study, we retrospectively analyzed the data of conventional culture testing and metagenomic next-generation sequencing (mNGS) of the sputum samples collected from 50 pulmonary infected patients after cardiac surgery from December 2020 and June 2021 in Ruijin Hospital. Taxonomic classification of the sputum metagenomes showed that the numbers of species belonging to bacteria, fungi, and viruses were 682, 58, and 21, respectively. The full spectrum of microorganisms present in the sputum microbiome covered all the species identified by culture, including 12 bacterial species and two fungal species. Based on species-level microbiome profiling, a reference catalog of microbial abundance detection limits was constructed to assess the pathogenic risks of individual microorganisms in the specimens. The proposed screening procedure detected 64 bacterial pathogens, 10 fungal pathogens, and three viruses. In particular, certain opportunistic pathogenic strains can be distinguished from the colonizing ones in the individual specimens. Strain-level identification and phylogenetic analysis were further performed to decipher molecular epidemiological characteristics of four opportunistic etiologic agents, including Klebsiella pneumoniae, Corynebacterium striatum, Staphylococcus aureus, and Candida albicans. Our findings provide a novel metagenomic insight into precision diagnosis for clinically relevant microbes, especially for opportunistic pathogens in the clinical setting.

Relationship Between Length and Curvature of Ascending Aorta and Type a Dissection.

Background: Type A aortic dissection (TAAD) has a rapid onset and high mortality. Currently, aortic diameter is the major criterion for evaluating the risk of TAAD. We attempted to find other aortic morphological indicators to further analyze their relationships with the risk of type A dissection. Methods: We included the imaging and clinical data of 112 patients. The patients were divided into three groups, of which Group 1 had 49 patients with normal aortic diameter, Group 2 had 22 patients with ascending aortic aneurysm, and Group 3 had 41 patients with TAAD. We used AW Server software, version 3.2, to measure aorta-related morphological indicators. Results: First, in Group 1, the univariate analysis results showed that ascending aortic diameter was correlated with patient age (r 2 = 0.35) and ascending aortic length (AAL) (r 2 = 0.43). AAL was correlated with age (r 2 = 0.12) and height (r 2 = 0.11). Further analysis of the aortic morphological indicators among the three groups found that the median aortic diameter was 36.20 mm in Group 1 (Q1-Q3: 33.40-37.70 mm), 42.5 mm in Group 2 (Q1-Q3: 41.52-44.17 mm) and 48.6 mm in Group 3 (Q1-Q3: 42.4-55.3 mm). There was no significant difference between Groups 2 and 3 (P > 0.05). Group 3 had the longest AAL (median: 109.4 mm, Q1-Q3: 118.3-105.3 mm), followed by Group 2 (median: 91.0 mm, Q1-Q3: 95.97-84.12 mm) and Group 1 (81.20 mm, Q1-Q3: 76.90-86.20 mm), and there were statistically significant differences among the three groups (P < 0.05). The Aortic Bending Index (ABI) was 14.95 mm/cm in Group 3 (Q1-Q3: 14.42-15.78 mm/cm), 13.80 mm/cm in Group 2 (Q1-Q3: 13.42-14.42 mm/cm), and 13.29 mm/cm in Group 1 (Q1-Q3: 12.71-13.78 mm/cm), and the difference was statistically significant in comparisons between any two groups (P < 0.05). Regression analysis showed that aortic diameter + AAL + ABI differentiated Group 2 and Group 3 with statistical significance (area under the curve (AUC) = 0.834), which was better than aortic diameter alone (AUC = 0.657; P < 0.05). Conclusions: We introduced the new concept of ABI, which has certain clinical significance in distinguishing patients with aortic dissection and aneurysm. Perhaps the ascending aortic diameter combined with AAL and ABI could be helpful in predicting the occurrence of TAAD.

Simple surrogate equations to predict controlled attenuation parameter values for screening non-alcoholic fatty liver disease in a Chinese population.

Objective: Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease. The controlled attenuation parameter (CAP) obtained by FibroScan reflects the level of liver steatosis in patients with obesity. Our study aimed to construct a simple equation to predict the CAP, to facilitate the screening and monitoring of patients at high risk for NAFLD. Methods: A total of 272 subjects were randomly divided into derivation and validation cohorts at a ratio of 1:2. The derivation set was used for constructing a multiple linear regression model; the validation set was used to verify the validity of the model. Results: Several variables strongly correlated with the CAP were used to construct the following equation for predicting CAP values:CAP1 = 2.4 × BMI + 10.5 × TG+ 3.6 × NC + 10.3 × CP +31.0, where BMI is body mass index, TG is triglyceride, NC is neck circumference and CP is C-peptide. The CAP1 model had an R 2 of 0.764 and adjusted R 2 of 0.753. It was then simplified to derive CAP2 included only simple anthropometric parameters: CAP2 = 3.5 × BMI + 4.2 × NC + 20.3 (R 2 = 0.696, adjusted R 2 = 0.689). The data were well fitted by both models. In the verification group, the predicted (CAP1 and CAP2) values were compared to the actual CAP values. For the CAP1 equation, R 2 = 0.653, adjusted R 2 = 0.651. For the CAP2 equation, R 2 = 0.625, adjusted R 2 = 0.623. The intra-class correlation coefficient (ICC) values were 0.781 for CAP1 and 0.716 for CAP2 (p < 0.001). The actual CAP and the predicted CAP also showed good agreement in Bland-Altman plot. Conclusion: The equations for predicting the CAP value comprise easily accessible variables, and showed good stability and predictive power. Thus, they can be used as simple surrogate tools for early screening and follow-up of NAFLD in the Chinese population.

Intracranial solitary fibrous tumor: Report of two cases.

RATIONALE: Intracranial solitary fibrous tumor (ISFT) is a rare spindle cell tumor derived from dendritic mesenchymal cells expressing CD34 antigens, which are widely distributed in human connective tissues. PATIENT CONCERNS: In two case reports, we describe a 61-year-old woman and a 42-year-old man who present with intracranial malignant SFTs. Computed tomography or magnetic resonance imaging of head revealed that the largest size is about 3.3 × 3.0 cm in left occipital part and 4.0 × 3.0 cm in right skull base. DIAGNOSIS: Postoperative pathological results demonstrated that all of two cases are SFT. Case one: Immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation (CD)34, B-cell lymphoma 2 (Bcl-2) and Vimentin (Vim). Case two: The tumor was distinctively positive for Bcl-2, but not for CD34 and Vim. INTERVENTIONS: One of the two patients recurred 6 years after the first tumor resection. After the recurrence, two gamma knife treatments were given, and another operation was performed about five years later. In one case, only tumor resection was performed. OUTCOMES: Case one: The postoperative neurological status was substantially improved and regular follow-up examinations for 6 months postsurgery have shown that the patient is currently disease-free. Case two: The patient achieved a good outcome, with no epilepsy or other neurological symptoms experienced on a regular 6-month follow-up. The patient is currently disease free. LESSONS: Imaging findings can be used to assist the diagnosis. The diagnostic method is pathology, and total surgical resection is the most effective treatment. The main treatment methods were total resection, supplemented by radiotherapy and chemotherapy if necessary.

Dynamic miRNA-mRNA regulations are essential for maintaining Drosophila immune homeostasis during Micrococcus luteus infection.

Pathogen bacteria infections can lead to dynamic changes of microRNA (miRNA) and mRNA expression profiles, which may control synergistically the outcome of immune responses. To reveal the role of dynamic miRNA-mRNA regulation in Drosophila innate immune responses, we have detailedly analyzed the paired miRNA and mRNA expression profiles at three time points during Drosophila adult males with Micrococcus luteus (M. luteus) infection using RNA- and small RNA-seq data. Our results demonstrate that differentially expressed miRNAs and mRNAs represent extensively dynamic changes over three time points during Drosophila with M. luteus infection. The pathway enrichment analysis indicates that differentially expressed genes are involved in diverse signaling pathways, including Toll and Imd as well as orther signaling pathways at three time points during Drosophila with M. luteus infection. Remarkably, the dynamic change of miRNA expression is delayed by compared to mRNA expression change over three time points, implying that the "time" parameter should be considered when the function of miRNA/mRNA is further studied. In particular, the dynamic miRNA-mRNA regulatory networks have shown that miRNAs may synergistically regulate gene expressions of different signaling pathways to promote or inhibit innate immune responses and maintain homeostasis in Drosophila, and some new regulators involved in Drosophila innate immune response have been identified. Our findings strongly suggest that miRNA regulation is a key mechanism involved in fine-tuning cooperatively gene expressions of diverse signaling pathways to maintain innate immune response and homeostasis in Drosophila. Taken together, the present study reveals a novel role of dynamic miRNA-mRNA regulation in immune response to bacteria infection, and provides a new insight into the underlying molecular regulatory mechanism of Drosophila innate immune responses.

Drosophila miR-964 modulates Toll signaling pathway in response to bacterial infection.

Recent studies suggest that microRNA (miRNA) plays important roles in the control of immune response and tolerance. We previously found that the expression level of antimicrobial peptide gene Drosomycin (Drs) is decreased in miR-964 overexpressing flies. Here, we further verified that miR-964 deficiency leads to hyper-activation of Drs. In addition, we employed three widely-used bioinformatic algorithms to screen potential miR-964 targets. Finally, we identified that miR-964 modulates Toll signaling pathway, at least in part, by repressing the expression of Drs. Taken together, our study identifies miR-964 as a modulator of Toll signaling and enriches the repertoire of immune-modulating miRNAs in Drosophila.

Transcriptome-wide analysis of microRNAs in Branchiostoma belcheri upon Vibrio parahemolyticus infection.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that participate in diverse biological processes via regulating expressions of target genes at post-transcriptional level. Amphioxus, as modern survivor of an ancient chordate lineage, is a model organism for comparative genomics study. However, miRNAs involved in regulating immune responses in Branchiostoma belcheri are largely unclear. Here, we systematically investigated the microRNAs (miRNAs) involved in regulating immune responses in the cephalochordate amphioxus (Branchiostoma belcheri) through next-generation deep sequencing of amphioxus samples infected with Vibrio parahemolyticus. We identified 198 novel amphioxus miRNAs, consisting of 12 conserved miRNAs, 33 candidate star miRNAs and 153 potential amphioxus-specific-miRNAs. Using microarray profiling, 14 miRNAs were differentially expressed post infection, suggesting they are immune-related miRNAs. Eight miRNAs (bbe-miR-92a-3p, bbe-miR-92c-3p, bbe-miR-210-5p, bbe-miR-22-3p, bbe-miR-1∼bbe-miR-133 and bbe-miR-217∼bbe-miR-216 clusters) were significantly increased at 12 h post-infection, while bbe-miR-2072-5p was downregulated at 6 h and 12 h. Three miRNAs, bbe-miR-1-3p, bbe-miR-22-3p and bbe-miR-92a-3p, were confirmed to be involved in immune responses to infection by qRT-PCR. Our findings further clarify important regulatory roles of miRNAs in the innate immune response to bacterial infection in amphioxus.

Small RNA-Seq analysis reveals microRNA-regulation of the Imd pathway during Escherichia coli infection in Drosophila.

Drosophila have served as a model for research on innate immunity for decades. However, knowledge of the post-transcriptional regulation of immune gene expression by microRNAs (miRNAs) remains rudimentary. In the present study, using small RNA-seq and bioinformatics analysis, we identified 67 differentially expressed miRNAs in Drosophila infected with Escherichia coli compared to injured flies at three time-points. Furthermore, we found that 21 of these miRNAs were potentially involved in the regulation of Imd pathway-related genes. Strikingly, based on UAS-miRNAs line screening and Dual-luciferase assay, we identified that miR-9a and miR-981 could both negatively regulate Drosophila antibacterial defenses and decrease the level of the antibacterial peptide, Diptericin. Taken together, these data support the involvement of miRNAs in the regulation of the Drosophila Imd pathway.