rss_2.0Journal of Translational Internal Medicine FeedSciendo RSS Feed for Journal of Translational Internal Medicine of Translational Internal Medicine 's Cover variant: Partially sensitive to vaccination, but still worth global attention<abstract><title style='display:none'>Abstract</title><p>The pandemic coronavirus disease 2019 (COVID-19) has rapidly spread to all countries worldwide. The emergence of its variants has exacerbated this problem. To date, many variants have been identified across the viral genome; the variants of concern are the focus of attention due to their higher transmissibility and resistance to vaccines, especially the delta variant. The delta variant has become the dominant severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) variant worldwide, causing severe panic as it is highly infectious. A better understanding of these variants may help in the development of possible treatments and save more lives. In this study, we summarize the characteristics of the variants of concern. More importantly, we summarize the results of previous studies on the delta variant. The delta variant has a high transmissibility rate and increases the risk of hospitalization and death. However, it is partially sensitive to vaccines. In addition, nonpharmaceutical interventions are valuable during epidemics. These interventions can be used against the delta variant, but managing this variant should still be taken seriously.</p></abstract>ARTICLE2022-09-24T00:00:00.000+00:00Aberrant energy metabolism in Alzheimer’s disease<abstract><title style='display:none'>Abstract</title><p>To maintain energy supply to the brain, a direct energy source called adenosine triphosphate (ATP) is produced by oxidative phosphorylation and aerobic glycolysis of glucose in the mitochondria and cytoplasm. Brain glucose metabolism is reduced in many neurodegenerative diseases, including Alzheimer’s disease (AD), where it appears presymptomatically in a progressive and region-specific manner. Following dysregulation of energy metabolism in AD, many cellular repair/regenerative processes are activated to conserve the energy required for cell viability. Glucose metabolism plays an important role in the pathology of AD and is closely associated with the tricarboxylic acid cycle, type 2 diabetes mellitus, and insulin resistance. The glucose intake in neurons is from endothelial cells, astrocytes, and microglia. Damage to neurocentric glucose also damages the energy transport systems in AD. Gut microbiota is necessary to modulate bidirectional communication between the gastrointestinal tract and brain. Gut microbiota may influence the process of AD by regulating the immune system and maintaining the integrity of the intestinal barrier. Furthermore, some therapeutic strategies have shown promising therapeutic effects in the treatment of AD at different stages, including the use of antidiabetic drugs, rescuing mitochondrial dysfunction, and epigenetic and dietary intervention. This review discusses the underlying mechanisms of alterations in energy metabolism in AD and provides potential therapeutic strategies in the treatment of AD.</p></abstract>ARTICLE2022-09-24T00:00:00.000+00:00Crosstalk between adipose tissue and the heart: An update<abstract><title style='display:none'>Abstract</title><p>It is important to understand how different human organs coordinate and interact with each other. Since obesity and cardiac disease frequently coincide, the crosstalk between adipose tissues and heart has drawn attention. We appreciate that specific peptides/proteins, lipids, nucleic acids, and even organelles shuttle between the adipose tissues and heart. These bioactive components can profoundly affect the metabolism of cells in distal organs, including heart. Importantly, this process can be dysregulated under pathophysiological conditions. This also opens the door to efforts targeting these mediators as potential therapeutic strategies to treat patients who manifest diabetes and cardiovascular disease. Here, we summarize the recent progress toward a better understanding of how the adipose tissues and heart interact with each other.</p></abstract>ARTICLE2022-09-24T00:00:00.000+00:00Obesity and coronavirus disease 2019<abstract><title style='display:none'>Abstract</title><p>The coronavirus disease 2019 (COVID-19) pandemic has brought severe challenges to global public health. Many studies have shown that obesity plays a vital role in the occurrence and development of COVID-19. Obesity exacerbates COVID-19, leading to increased intensive care unit hospitalization rate, high demand for invasive mechanical ventilation, and high mortality. The mechanisms of interaction between obesity and COVID-19 involve inflammation, immune response, changes in pulmonary dynamics, disruptions of receptor ligands, and dysfunction of endothelial cells. Therefore, for obese patients with COVID-19, the degree of obesity and related comorbidities should be evaluated. Treatment methods such as administration of anticoagulants and anti-inflammatory drugs like glucocorticoids and airway management should be actively initiated. We should also pay attention to long-term prognosis and vaccine immunity and actively address the physical and psychological problems caused by longterm staying-at-home during the pandemic. The present study summarized the research to investigate the role of obesity in the incidence and progression of COVID-19 and the psychosocial impact and treatment options for obese patients with COVID-19, to guide the understanding and management of the disease.</p></abstract>ARTICLE2022-09-24T00:00:00.000+00:00A novel wide-band dielectric imaging system for electro-anatomic mapping and monitoring in radiofrequency ablation and cryoablation<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2022-0040_s_007"> <title style='display:none'>Background and Objectives</title> <p>A novel wide-band dielectric mapping system, named as KODEX-EPD (EPD Solutions, Philips, Best, the Netherlands), was effectively used in the EA mapping for atrial fibrillation (AF) ablation. To date, only a few studies have concentrated on the application of the KODEX-EPD system for ablating supraventricular tachycardia or ventricular premature beats (VPBs) in human models. This study aims to assess the applicability and efficiency of a novel three-dimensional electro-anatomic (EA) mapping system to improve the success rate of ablation.</p> </sec> <sec id="j_jtim-2022-0040_s_008"> <title style='display:none'>Methods</title> <p>This study included 11 consecutive patients who underwent ablation after EA mapping with the KODEX-EPD system.</p> </sec> <sec id="j_jtim-2022-0040_s_009"> <title style='display:none'>Results</title> <p>All surgeries were successfully performed using the KODEX-EPD system, including 6 cases who underwent ablation of paroxysmal supraventricular tachycardia (PSVT), 2 cases who received ablation of VPBs from right ventricular outflow tract (RVOT), and 3 cases who underwent cryoablation of AF. For ablation of PSVT or VPBs, the operation time was 31.4 (range, 24.0–38.0) min, in which a median operation time of 2.9 min was used to create anatomic images, and the median fluoroscopic dose was 7.4 mGy. For ablation of AF, the operation time was 56.0 (range, 49.0–62.0) min, in which a median of 4.3 (range, 3.4–5.2) min was used for constructing left atrium map, and the median fluoroscopic dose was 15.0 mGy. The operation time and the fluoroscopic dose were greatly shortened for all surgeries.</p> </sec> <sec id="j_jtim-2022-0040_s_010"> <title style='display:none'>Conclusion</title> <p>The KODEX-EPD system is an effective and safe tool to guide the EA mapping, leading to improvement in the success rate of ablation. It can promote the ablation process with the reduced fluoroscopic dose, and it is also a promising tool for complex surgeries.</p> </sec> </abstract>ARTICLE2022-08-31T00:00:00.000+00:00Pan-cancer landscape of the RUNX protein family reveals their potential as carcinogenic biomarkers and the mechanisms underlying their action<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2022-0013_s_006"><title style='display:none'>Background</title> <p>The RUNX family of transcription factors plays an important regulatory role in tumor development. Although the importance of RUNX in certain cancer types is well known, the pan-cancer landscape remains unclear.</p></sec> <sec id="j_jtim-2022-0013_s_007"><title style='display:none'>Materials and Methods</title> <p>Data from The Cancer Genome Atlas (TCGA) provides a pan-cancer overview of the <italic>RUNX</italic> genes. Hence, herein, we performed a pan-cancer analysis of abnormal <italic>RUNX</italic> expression and deciphered the potential regulatory mechanism. Specifically, we used TCGA multi-omics data combined with multiple online tools to analyze transcripts, genetic alterations, DNA methylation, clinical prognoses, miRNA networks, and potential target genes.</p></sec> <sec id="j_jtim-2022-0013_s_008"><title style='display:none'>Results</title> <p><italic>RUNX</italic> genes are consistently overexpressed in esophageal, gastric, pancreatic, and pan-renal cancers. The total protein expression of <italic>RUNX1</italic> in lung adenocarcinoma, kidney renal clear cell carcinoma (KIRC), and uterine corpus endometrial carcinoma (UCEC) is consistent with the mRNA expression results. Moreover, increased phosphorylation on the T14 and T18 residues of RUNX1 may represent potential pathogenic factors. The <italic>RUNX</italic> genes are significantly associated with survival in pan-renal cancer, brain lower-grade glioma, and uveal melanoma. Meanwhile, various mutations and posttranscriptional changes, including the <italic>RUNX1</italic> D96 mutation in invasive breast carcinoma, the co-occurrence of <italic>RUNX</italic> gene mutations in UCEC, and methylation changes in the <italic>RUNX2</italic> promoter in KIRC, may be associated with cancer development. Finally, analysis of epigenetic regulator co-expression, miRNA networks, and target genes revealed the carcinogenicity, abnormal expression, and direct regulation of <italic>RUNX</italic> genes.</p></sec> <sec id="j_jtim-2022-0013_s_009"><title style='display:none'>Conclusions</title> <p>We successfully analyzed the pan-cancer abnormal expression and prognostic value of <italic>RUNX</italic> genes, thereby providing potential biomarkers for various cancers. Further, mutations revealed via genetic alteration analysis may serve as a basis for personalized patient therapies.</p></sec> </abstract>ARTICLE2022-07-10T00:00:00.000+00:00Novel insights into alcoholic liver disease: Iron overload, iron sensing and hemolysis<abstract> <title style='display:none'>Abstract</title> <p>The liver is the major target organ of continued alcohol consumption at risk and resulting alcoholic liver disease (ALD) is the most common liver disease worldwide. The underlying molecular mechanisms are still poorly understood despite decades of scientific effort limiting our abilities to identify those individuals who are at risk to develop the disease, to develop appropriate screening strategies and, in addition, to develop targeted therapeutic approaches. ALD is predestined for the newly evolving translational medicine, as conventional clinical and health care structures seem to be constrained to fully appreciate this disease. This concept paper aims at summarizing the 15 years translational experience at the Center of Alcohol Research in Heidelberg, namely based on the long-term prospective and detailed characterization of heavy drinkers with mortality data. In addition, novel experimental findings will be presented. A special focus will be the long-known hepatic iron accumulation, the somewhat overlooked role of the hematopoietic system and novel insights into iron sensing and the role of hepcidin. Our preliminary work indicates that enhanced red blood cell (RBC) turnover is critical for survival in ALD patients. RBC turnover is not primarily due to vitamin deficiency but rather to ethanol toxicity directly targeted to erythrocytes but also to the bone marrow stem cell compartment. These novel insights also help to explain long-known aspects of ALD such as mean corpuscular volume of erythrocytes (MCV) and elevated aspartate transaminase (GOT/AST) levels. This work also aims at identifying future projects, naming unresolved observations, and presenting novel hypothetical concepts still requiring future validation.</p></abstract>ARTICLE2022-07-10T00:00:00.000+00:00Binding domain characterization of growth hormone secretagogue receptor<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2022-0033_s_005"> <title style='display:none'>Background and Objectives</title> <p>Activation of ghrelin receptor growth hormone secretagogue receptor (GHS-R) by endogenous or synthetic ligands amplifies pulsatile release of growth hormone (GH) and enhances food intake, very relevant to development and growth. GHS-R is a G-protein coupled receptor that has great druggable potential. Understanding the precise ligand and receptor interactions is crucial to advance the application of GHS-R.</p> </sec> <sec id="j_jtim-2022-0033_s_006"> <title style='display:none'>Materials and Methods</title> <p>We used radiolabeled ligand-binding assay and growth hormone release assay to assess the binding and functional characteristics of GHS-R to synthetic agonists MK-0677 and GHS-25, as well as to endogenous peptide ligand ghrelin. We analyzed the ligand-dependent activity of GHS-R by measuring aequorin-based [Ca<sup>++</sup>]<sub>i</sub> responses. To define a ligand-binding pocket of GHS-R, we generated a series of human/puffer fish GHS-R chimeras by domain swapping, as well as a series of mutants by site-directed mutagenesis.</p> </sec> <sec id="j_jtim-2022-0033_s_007"> <title style='display:none'>Results</title> <p>We found that the synthetic ligands have high binding affinity to GHS-R in the <italic>in vitro</italic> competitive binding assay. Remarkably, the <italic>in vivo</italic> GH secretagogue activity is higher with the synthetic agonists MK-0677 and GHS-25 than that of ghrelin. Importantly, the activity was completely abolished in GHS-R knockout mice. In GHS-R chimera analysis, we identified the C-terminal region, particularly the transmembrane domain 6 (TM6), to be critical for the ligand-dependent activity. Our site-directed mutagenesis study further revealed that amino acid residues D99 and W276 in GHS-R are essential for ligand binding. Interestingly, critical residues distinctively interact with different ligands, MK-0677 activation depends on E124, while ghrelin and GHS-25 preferentially interact with F279.</p> </sec> <sec id="j_jtim-2022-0033_s_008"> <title style='display:none'>Conclusion</title> <p>The ligand-binding pocket of human GHS-R is mainly defined by interactive residues in TM6 and the adjacent region of the receptor. This novel finding in GHS-R binding domains advances the structural/ functional understanding of GHS-R, which will help to select/design better GHS-R agonists/ antagonists for future therapeutic applications.</p> </sec> </abstract>ARTICLE2022-07-02T00:00:00.000+00:00Prevalence and risk factors of hyperuricemia and gout: a cross-sectional survey from 31 provinces in mainland China<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2022-0031_s_005"><title style='display:none'>Background and Objetives</title> <p>Hyperuricemia (HUA) and gout seriously influence patients’ quality of life. The current study was performed to investigate the prevalence of HUA and gout and the related risk factors in Chinese adults.</p></sec> <sec id="j_jtim-2022-0031_s_006"><title style='display:none'>Methods</title> <p>Data were collected from the National Survey of Thyroid Disorders and Diabetes (the Thyroid Disease, Iodine Status, and Diabetes National Epidemiological survey [TIDE]), a cross-sectional investigation conducted during 2015–2017. Using a random, multistage, and stratified sampling strategy, a representative sample (78,130 participants aged 18 years and above) was selected from the general population in 31 provinces of mainland China. The weighted prevalence rates of HUA and gout were calculated, and the related risk factors were analyzed.</p></sec> <sec id="j_jtim-2022-0031_s_007"><title style='display:none'>Results</title> <p>The weighted prevalence rates of HUA and gout in Chinese adults were 17.7% and 3.2%, respectively. The prevalence of HUA in males linearly decreased with age, while the prevalence in females showed the opposite trend (both <italic>P</italic> for trend &lt; 0.01). The prevalence rate of gout exhibited a rising tendency with age in both genders (both <italic>P</italic> for trend &lt; 0.05). The HUA and gout prevalence rates in males were the highest in Han and Tibetan nationalities, respectively. Logistic regression analysis showed that the morbidities of HUA and gout were differentially associated with age, residence location, nationality, smoking, and other complicating metabolic diseases in the two genders.</p></sec> <sec id="j_jtim-2022-0031_s_008"><title style='display:none'>Conclusions</title> <p>There are relatively high prevalence rates of gout and HUA in China, which is currently a developing country. Reducing their burden has become an urgent issue for Chinese people.</p></sec> </abstract>ARTICLE2022-07-07T00:00:00.000+00:00The potential role of the brain–gut axis in the development and progression of Alzheimer's disease ventricle remodeling in chronic thromboembolic pulmonary hypertension<abstract> <title style='display:none'>Abstract</title> <p>Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed, but potentially curable pulmonary vascular disease. The increased pulmonary vascular resistance in CTEPH is caused by unresolved proximal thrombus and secondary microvasculopathy in the pulmonary vasculature, leading to adaptive and maladaptive remodeling of the right ventricle (RV), eventual right heart failure, and death. Knowledge on the RV remodeling process in CTEPH is limited. The progression to RV failure in CTEPH is a markedly slower process. A detailed understanding of the pathophysiology and underlying mechanisms of RV remodeling may facilitate early diagnosis and the development of targeted therapy. While ultrasound, magnetic resonance imaging, right heart catheterization, and serum biomarkers have been used to assess cardiac function, the current treatment strategies reduce the afterload of the right heart, but are less effective in improving the maladaptive remodeling of the right heart. This review systematically summarizes the current knowledge on adaptive and maladaptive remodeling of the right heart in CTEPH from molecular mechanisms to clinical practice.</p></abstract>ARTICLE2022-07-02T00:00:00.000+00:00Prognostic value of serum ammonia in critical patients with non-hepatic disease: A prospective, observational, multicenter study<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2022-0021_s_005"> <title style='display:none'>Background and Objectives</title> <p>Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU).</p> </sec> <sec id="j_jtim-2022-0021_s_006"> <title style='display:none'>Materials and Methods</title> <p>This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia.</p> </sec> <sec id="j_jtim-2022-0021_s_007"> <title style='display:none'>Results</title> <p>A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia (<italic>P</italic> &lt; 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07–2.80, <italic>P</italic> = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, <italic>P</italic> &lt; 0.001) remained the most predictive factor for patient prognosis by ROC analysis.</p> </sec> <sec id="j_jtim-2022-0021_s_008"> <title style='display:none'>Conclusion</title> <p>Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.</p> </sec> </abstract>ARTICLE2022-07-02T00:00:00.000+00:00A Case of abdominal pain and diarrhea post immunotherapy: Hypophysitis associated with immune checkpoint inhibitors membrane oxygenation using a modified cardiopulmonary bypass system evaluation of intermediate coronary lesions with integrated computed tomography angiography and invasive angiography in patients with stable coronary artery disease<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2022-0018_s_007"> <title style='display:none'>Background and objectives</title> <p>The hemodynamic evaluation of coronary stenoses undergoes a transition from wire-based invasive measurements to image-based computational assessments. However, fractional flow reserve (FFR) values derived from coronary CT angiography (CCTA) and angiography-based quantitative flow ratio have certain limitations in accuracy and efficiency, preventing their widespread use in routine practice. Hence, we aimed to investigate the diagnostic performance of FFR derived from the integration of CCTA and invasive angiography (FFR<sub>CT-angio</sub>) with artificial intelligence assistance in patients with stable coronary artery disease (CAD).</p> </sec> <sec id="j_jtim-2022-0018_s_008"> <title style='display:none'>Methods</title> <p>Forty stable CAD patients with 67 target vessels (50%–90% diameter stenosis) were included in this single-center retrospective study. All patients underwent CCTA followed by coronary angiography with FFR measurement within 30 days. Both CCTA and angiographic images were combined to generate a three-dimensional reconstruction of the coronary arteries using artificial intelligence. Subsequently, functional assessment was performed through a deep learning algorithm. FFR was used as the reference.</p> </sec> <sec id="j_jtim-2022-0018_s_009"> <title style='display:none'>Results</title> <p>FFR<sub>CT-angio</sub> values were significantly correlated with FFR values (r = 0.81, <italic>P</italic> &lt; 0.001, Spearman analysis). Per-vessel diagnostic accuracy of FFR<sub>CT-angio</sub> was 92.54%. Sensitivity and specificity in identifying ischemic lesions were 100% and 88.10%, respectively. Positive predictive value and negative predictive value were 83.33% and 100%, respectively. Moreover, the diagnostic performance of FFR<sub>CT-angio</sub> was satisfactory in different target vessels and different segment lesions.</p> </sec> <sec id="j_jtim-2022-0018_s_010"> <title style='display:none'>Conclusions</title> <p>FFR<sub>CT-angio</sub> exhibits excellent diagnostic performance of identifying ischemic lesions in patients with stable CAD. Combining CCTA and angiographic imaging, FFR<sub>CT-angio</sub> may represent an effective and practical alternative to invasive FFR in selected patients.</p> </sec> </abstract>ARTICLE2022-06-10T00:00:00.000+00:00Mitochondrial damage-associated molecular patterns in chronic obstructive pulmonary disease: Pathogenetic mechanism and therapeutic target<abstract> <title style='display:none'>Abstract</title> <p>Chronic obstructive pulmonary disease (COPD) is a common inflammatory airway disease characterized by enhanced inflammation. Recent studies suggest that mitochondrial damage-associated molecular patterns (DAMPs) may play an important role in the regulation of inflammation and are involved in a serial of inflammatory diseases, and they may also be involved in COPD. This review highlights the potential role of mitochondrial DAMPs during COPD pathogenesis and discusses the therapeutic potential of targeting mitochondrial DAMPs and their related signaling pathways and receptors for COPD. Research progress on mitochondrial DAMPs may enhance our understanding of COPD inflammation and provide novel therapeutic targets.</p></abstract>ARTICLE2022-06-10T00:00:00.000+00:00Acute kidney injury associated with severe hypouricemia caused by a novel mutation: Enlightenment from rare disease to common disease bifunctional enzyme of that distinctly regulates phosphoribosyl ubiquitination of the SidE family effectors role of autophagy in triptolide-induced apoptosis of TM3 Leydig cells<abstract> <title style='display:none'>Abstract</title> <sec id="j_jtim-2021-0051_s_006"> <title style='display:none'>Background and Objectives</title> <p>Triptolide (TP) is known to impair testicular development and spermatogenesis in mammals, but the mechanism of the side effects still needs to be investigated. The aim of the research is to confirm whether TP can cause autophagy in TM3 Leydig cells and the potential molecular pathway in vitro.</p> </sec> <sec id="j_jtim-2021-0051_s_007"> <title style='display:none'>Methods</title> <p>TM3 Leydig cells are used to investigate the molecular pathway through Western blot, detection of apoptosis, transmission electron microscopy for autophagosomes and so on.</p> </sec> <sec id="j_jtim-2021-0051_s_008"> <title style='display:none'>Results</title> <p>The data show that TP treatment resulted in the decreasing of the viability of TM3 cells due to the increased apoptosis. Treated with TP, the formation of autophagosomes, the decrease in P62, and the increase in the conversion of LC3-I to LC3-II suggested the induction of autophagy. The induction of autophagy has accompanied the activation of the mTOR/P70S6K signal pathway. The viability of the TM3 cells was further inhibited when they were co-treated with autophagy inhibitor, chloroquine (CQ).</p> </sec> <sec id="j_jtim-2021-0051_s_009"> <title style='display:none'>Conclusion</title> <p>All these data suggest that autophagy plays a very important role in antagonizing TM3 cell apoptosis during the TP exposure.</p> </sec> </abstract>ARTICLE2022-05-05T00:00:00.000+00:00Inhaled antibiotics and airway bacterial decolonization for patients with chronic obstructive pulmonary disease: The rationale and future