Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.
Humans ; Gene Expression Profiling ; Neoplasms/genetics* ; Organ Specificity ; RNA, Long Noncoding/genetics* ; Transcriptome

MicroRNAs (miRs) are single-stranded RNAs of 18-25 nucleotides. These molecules regulate gene expression at the post-transcriptional level; several of these are differentially expressed in asthma as well as in viral acute respiratory infections (ARIs), the main triggers of acute asthma exacerbations. In recent years, miRs have been studied in order to discover drug targets as well as biomarkers for diagnosis, disease severity and prognosis. We describe recent findings on miR expression and function in asthma and their role in the regulation of viral ARIs, according to cell tissue specificity and asthma severity. By combining the above information, we identify miRs that may be important in virus-induced asthma exacerbations. This is the first attempt to link miR profiles of asthmatic patients and ARI-induced miRs, addressing the question of whether there might be a specific miR deficit in asthmatic subjects that make them more susceptible and/or reactive to infection.
Asthma ; Biomarkers ; Diagnosis ; Disease Progression ; Gene Expression ; Humans ; Inflammation ; MicroRNAs ; Nucleotides ; Organ Specificity ; Prognosis ; Respiratory Tract Infections ; RNA

Objective To investigate the epidemiological and forensic characteristics of multiple organ dysfunction syndrome （MODS） after severe trauma and explore the reference indexes for determining traumatic MODS. Methods In terms of the number of organs or systems involved in MODS, the number of failures of each organ or system, the first failing organ and the survival time after organ failure, 72 cases of MODS death caused by traffic accidents were retrospectively analyzed. The cases were divided into two groups according to the mean injury severity score （ISS）. The t test was used to analyze the differences in the number of organs or systems involved in MODS in the two groups. Chi-square test was used to analyze the differences in the types of first failing organs and the differences between the two groups in the number of cases of organ or system failure involved in MODS. Wilcoxon signed-rank test was used to analyze the differences between the two groups in survival time of MODS after trauma. Kaplan-Meier survival curve was drawn and Log-Rank test was performed. Results The number of MODS involved organs or systems after trauma in ISS≤35 group was 3-5, and 2-4 in the ISS>35 group （P<0.05）. The cases of MODS organ or system failure after trauma occurred more in brain and lung in the two groups. The first failing organ after trauma was mainly the lung or kidney. The median time of first organ failure after trauma was 2.00 d, the median survival time of MODS after trauma in ISS≤35 group was 6.00 d, and 2.33 d in ISS>35 group （P<0.05）. The survival curve of ISS≤35 group was relatively high and declined gradually, while the survival curve of ISS>35 group was relatively low and the decline was steep （P<0.05）. Conclusion The epidemiological and forensic characteristics of MODS caused by traffic accidents have certain specificity. The ISS and the forensic characteristics of MODS at ISS>35 can be used as reliable reference indexes for evaluation of the causal relationship among trauma, MODS and death.
Accidents, Traffic ; Humans ; Injury Severity Score ; Multiple Organ Failure/etiology* ; Retrospective Studies ; Sensitivity and Specificity ; Wounds and Injuries/complications*

OBJECTIVE: Community-acquired pneumonia (CAP) is a major cause of sepsis, and sepsis-related acute organ dysfunction affects patient mortality. Although the quick Sequential Organ Failure Assessment (qSOFA) is a new screening tool for patients with suspected infection, its predictive value for the mortality of patients with CAP has not been validated. Lactate concentration is a valuable biomarker for critically ill patients. Thus, we investigated the predictive value of qSOFA with lactate concentration for in-hospital mortality in patients with CAP in the emergency department (ED).METHODS: From January 2015 to June 2015, 443 patients, who were diagnosed with CAP in the ED, were retrospectively analyzed. We defined high qSOFA or lactate concentrations as a qSOFA score ≥2 or a lactate concentration >2 mmol/L upon admission at the ED. The primary outcome was all-cause in-hospital mortality.RESULTS: Among the 443 patients, 44 (9.9%) died. Based on the receiver operating characteristic (ROC) analysis, the areas under the curves for the prediction of mortality were 0.720, 0.652, and 0.686 for qSOFA, CURB-65 (confusion, urea, respiratory rate, blood pressure, and age), and Pneumonia Severity Index, respectively. The area under the ROC curve of qSOFA was lower than that of SOFA (0.720 vs. 0.845, P=0.004). However, the area under the ROC curve of qSOFA with lactate concentration was not significantly different from that of SOFA (0.828 vs. 0.845, P=0.509). The sensitivity and specificity of qSOFA with lactate concentration were 71.4% and 83.2%, respectively.CONCLUSION: qSOFA with lactate concentration is a useful and practical tool for the early prediction of in-hospital mortality among patients with CAP in the ED.
Blood Pressure ; Critical Illness ; Emergencies ; Emergency Service, Hospital ; Hospital Mortality ; Humans ; Lactic Acid ; Mass Screening ; Mortality ; Organ Dysfunction Scores ; Pneumonia ; Respiratory Rate ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Sepsis ; Urea

Although the foundations and evolution of Chinese medicine and Western medicine are very different, an increasing amount of research has revealed that those Eastern medicine principles practiced over thousands of years are confirmed by new technologies applied to the basic science of the human body. Recent scientific discoveries present enticing opportunities to reconcile Chinese medicine theories with Western biomedicine. Is there a trend toward the convergence of Eastern and Western medicine? Four studies which exemplify the potential for convergence are described in this article. The studies present findings in regard to mesentery, interstitium, a gut-lung axis, and lung-centered hematopoiesis, and were published recently in leading journals such as Science, Nature, and Lancet.
Hematopoiesis ; Humans ; Medicine, Chinese Traditional ; Meridians ; Organ Specificity

PURPOSE: We aimed to investigate organ-specific recurrence or the metastatic pattern of breast cancer according to biological subtypes and clinical characteristics. METHODS: We retrospectively analyzed the medical records of 168 patients with recurrent breast cancer who were diagnosed between January 1, 2000 and April 30, 2017. Four biological subtypes were classified according to estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 expression: luminal A, luminal B, HER2-enriched, and triple negative breast cancer (TNBC). To analyze recurrence patterns according to biological subtypes, we accessed clinical variables including age at diagnosis, TNM stage, type of surgery in the breast and axilla, histologic grade, nuclear grade, lymphatic, vascular, and neural invasion, Ki-67 expression and recurrence to distant organs. RESULTS: The biological subtypes of recurrent breast cancer comprised the following luminal A (n=33, 19.6%), luminal B (n=95, 56.5%), HER2 enriched (n=19, 11.3%), and TNBC (n=21, 12.5%). Luminal A (7.7%) and B (6.5%) subtypes were associated with the increased rate of local recurrence compared to HER2-enriched (2.4%) and TNBC subtypes (1.8%) (p=0.005). The bone (53.6%) was the most common metastatic organ, followed by the lung (34.5%), liver (29.8%), brain (17.9%), and other visceral organ (7.7%). Bone metastasis was commonly observed in individuals with luminal B (63.2%), HER2-enriched (57.9%), and luminal A (42.4%) subtypes (p=0.005). Most liver metastases occur in individuals with luminal B (40.0%) and HER2-enriched subtypes (31.6%) (p=0.002). CONCLUSION: Luminal B subtype was commonly observed in individuals with recurrent breast cancer, and the bone is the most common target organ for breast cancer metastasis, followed by the lungs and liver.
Axilla ; Brain ; Breast Neoplasms ; Breast ; Diagnosis ; Estrogens ; Humans ; Liver ; Lung ; Medical Records ; Neoplasm Metastasis ; Organ Specificity ; Phenobarbital ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Recurrence ; Retrospective Studies ; Triple Negative Breast Neoplasms

Chemokine (C-X3-C motif) ligand 1 (CX₃CL1, also known as fractalkine) and its receptor chemokine (C-X3-C motif) receptor 1 (CX₃CR1) are widely expressed in immune cells and non-immune cells throughout organisms. However, their expression is mostly cell type-specific in each tissue. CX₃CR1 expression can be found in monocytes, macrophages, dendritic cells, T cells, and natural killer (NK) cells. Interaction between CX3CL1 and CX₃CL1 can mediate chemotaxis of immune cells according to concentration gradient of ligands. CX₃CL1 expressing immune cells have a main role in either pro-inflammatory or anti-inflammatory response depending on environmental condition. In a given tissue such as bone marrow, brain, lung, liver, gut, and cancer, CX₃CL1 expressing cells can maintain tissue homeostasis. Under pathologic conditions, however, CX₃CL1 expressing cells can play a critical role in disease pathogenesis. Here, we discuss recent progresses of CX3CL1/CX₃CL1 in major tissues and their relationships with human diseases.
Bone Marrow ; Brain ; Chemokine CX3CL1 ; Chemotaxis ; Dendritic Cells ; Homeostasis ; Humans ; Ligands ; Liver ; Lung ; Macrophages ; Monocytes ; Organ Specificity ; T-Lymphocytes

Sex differences are widely observed under various circumstances ranging from physiological processes to therapeutic responses, and a myriad of sex-biased genes have been identified. In recent years, transcriptomic datasets of microRNAs (miRNAs), an important class of non-coding RNAs, become increasingly accessible. However, comprehensive analysis of sex difference in miRNA expression has not been performed. Here, we identified the differentially-expressed miRNAs between males and females by examining the transcriptomic datasets available in public databases and conducted a systemic analysis of their biological characteristics. Consequently, we identified 73 female-biased miRNAs (FmiRs) and 163 male-biased miRNAs (MmiRs) across four tissues including brain, colorectal mucosa, peripheral blood, and cord blood. Our results suggest that compared to FmiRs, MmiRs tend to be clustered in the human genome and exhibit higher evolutionary rate, higher expression tissue specificity, and lower disease spectrum width. In addition, functional enrichment analysis of miRNAs show that FmiR genes are significantly associated with metabolism process and cell cycle process, whereas MmiR genes tend to be enriched for functions like histone modification and circadian rhythm. In all, the identification and analysis of sex-biased miRNAs together could provide new insights into the biological differences between females and males and facilitate the exploration of sex-biased disease susceptibility and therapy.
Biological Evolution ; Female ; Genome, Human ; Humans ; Male ; MicroRNAs ; blood ; genetics ; Organ Specificity ; Sex Characteristics ; Transcriptome

The mA modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of mA regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by mA modification (mAfreq genes) and those occasionally regulated by mA modification (mAocca genes). Compared to the mAocca genes, the mAfreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the mAfreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the mAfreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between mA epitranscriptomic regulation and other gene expression regulatory machineries.
Adenosine ; analogs & derivatives ; metabolism ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; MicroRNAs ; metabolism ; Organ Specificity ; Signal Transduction

BACKGROUND: Basic National Institute of Health (NIH) and sensitive antihuman globulin (AHG) methods are widely used for T-cell complement-dependent cytotoxicity crossmatch (XM) tests. Whereas NIH-negative, AHG-positive (NIH⁻/AHG⁺) results are caused by weak antibodies, NIH⁺/AHG⁻ results are usually due to autoantibodies. We found that solid organ transplantation candidates with NIH⁺/AHG⁻ XM results are repeatedly excluded from allocation of deceased donor organs by the Korean Network for Organ Sharing (KONOS) allocation system. Here, we attempted to demonstrate that these patients do not have donor-specific HLA antibodies (DSAs). METHODS: Sera showing NIH⁺/AHG⁻ results in the analysis of 1,668 KONOS T-cell XM tests were screened for panel reactive antibody (PRA) using a Luminex test. For screen-positive samples, antibody identification was conducted using a Luminex single antigen assay and the presence or absence of class I DSAs was determined. For positive controls, 42 KONOS XM tests showing probable true-positive (NIH⁻/AHG⁺ or NIH⁺/AHG⁺) results were reviewed for PRA results based on electronic medical records and the presence or absence of DSAs was determined. RESULTS: NIH⁺/AHG⁻ results were observed in 1.3% (21/1,668) of KONOS XM tests analyzed. Most of these (18/21, 85.7%) were negative for PRA or DSAs. All probable true-positive cases were either positive for DSAs (24/42, 57.1%) or had high PRA (mean, 92% [range; 42%~100%]), complicating accurate identification of antibody specificities. CONCLUSIONS: NIH⁺/AHG⁻ results are not rare (1.3%) in KONOS XM tests. Most of these results are not due to DSAs, and these patients should not be excluded from organ allocation.
Antibodies ; Antibody Specificity ; Autoantibodies* ; Electronic Health Records ; Humans ; Organ Transplantation ; T-Lymphocytes* ; Tissue Donors ; Transplants