Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can be fatal. However, very few studies have provided comprehensive analyses and specified the differences in symptoms observed in ...different parts of the GI tract. This study aimed to comprehensively analyze clinical manifestations and management of GI CMV disease. This retrospective cohort study enrolled the patients who had CMV diseases of the GI tract proved by CMV immunohistochemistry stain from the pathology database in a 4000-bed tertiary medical center between January 2000 and May 2021. The patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors were analyzed. A total of 356 patients were enrolled, including 46 infected in the esophagus, 76 in the stomach, 30 in the small intestine, and 204 in the colon. In total, 49.4% patients were immunocompromised. The overall in-hospital mortality rate was 20.8%: CMV enteritis had the highest rate (23.3%). Sixty percent of patients received antiviral treatment and 16% were administered both intravenous and oral anti-viral drugs (Combo therapy, minimal and mean treatment duration were 14 and 39.9 ± 25 days). Prognostic factors of in-hospital mortality included age, immune status, albumin level, platelet count, GI bleeding, time-to-diagnosis, and Combo therapy. In the survival analysis, immunocompetent patients receiving Combo therapy had the best survival curve, and immunocompromised patients receiving non-Combo therapy had the worst survival curve. Combo therapy ≥14 days resulted in a better outcome for both immunocompromised and immunocompetent patients. In conclusion, CMV GI diseases affect both immunocompromised and immunocompetent hosts, and a complete treatment course should be considered for patients with poor prognostic factors.
Unplanned patient readmission (UPRA) is frequent and costly in healthcare settings. No indicators during hospitalization have been suggested to clinicians as useful for identifying patients at high ...risk of UPRA. This study aimed to create a prediction model for the early detection of 14-day UPRA of patients with pneumonia. We downloaded the data of patients with pneumonia as the primary disease (e.g., ICD-10:J12*-J18*) at three hospitals in Taiwan from 2016 to 2018. A total of 21,892 cases (1208 (6%) for UPRA) were collected. Two models, namely, artificial neural network (ANN) and convolutional neural network (CNN), were compared using the training (n = 15,324; ≅70%) and test (n = 6568; ≅30%) sets to verify the model accuracy. An app was developed for the prediction and classification of UPRA. We observed that (i) the 17 feature variables extracted in this study yielded a high area under the receiver operating characteristic curve of 0.75 using the ANN model and that (ii) the ANN exhibited better AUC (0.73) than the CNN (0.50), and (iii) a ready and available app for predicting UHA was developed. The app could help clinicians predict UPRA of patients with pneumonia at an early stage and enable them to formulate preparedness plans near or after patient discharge from hospitalization.
Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, ...very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva. We successfully produced 363 clones of mouse anti-peptide monoclonal antibodies (mAbs) against 36 of 49 selected targets, and characterized useful mAbs against 24 targets in terms of their binding affinity for peptide antigens and immuno-capture ability. Comparative analyses revealed that an equilibrium dissociation constant (KD) cut-off value < 2.82 × 10−9m could identify most clones with an immuno-capture recovery rate >5%. Using these mAbs, we assembled a 24-plex SISCAPA-MRM assay and optimized assay conditions in a 25-μg saliva matrix background. This multiplexed assay showed reasonable precision (median coefficient of variation, 7.16 to 32.09%), with lower limits of quantitation (LLOQ) of <10, 10–50, and >50 ng/ml for 14, 7 and 3 targets, respectively. When applied to a model saliva sample pooled from oral cancer patients, this assay could detect 19 targets at higher salivary levels than their LLOQs. Finally, we demonstrated the utility of this assay for quantification of multiple targets in individual saliva samples (20 healthy donors and 21 oral cancer patients), showing that levels of six targets were significantly altered in cancer compared with the control group. We propose that this assay could be used in future studies to compare the clinical utility of multiple oral cancer biomarker candidates in a large cohort of saliva samples.
Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that ...control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.
•Xanthohumol enhanced 28 microRNA expressions and downregulated 3 microRNA levels in inducing glioblastoma apoptotic death.•The miR-204-3p levels is the most significantly upregulated microRNA in xanthohumol-treated glioma cells.•Xanthohumol upregulated miR-204-3p levels via ERK/c-Fos pathway.•IGFBP2 was validated as a direct target gene of miR-204-3p.•The miR-204-3p-targeted IGFBP2/AKT/Bcl2 pathway is involved in xanthohumol cytotoxicity.
Background To comprehensively analyze the risk factors, clinical characteristics, outcomes, and prognostic factors of Cytomegalovirus (CMV) enteritis. Methods This retrospective cohort study enrolled ...patients who had undergone pathological examinations for CMV enteritis. They were divided into CMV and non-CMV groups according to immunohistochemistry staining results. The risk factors, clinical presentations, endoscopic features, treatments, outcomes, and prognostic factors of CMV enteritis were then analyzed. Results Forty-two patients (18 CMV, 24 non-CMV group) were included in the study. Major clinical presentations in the CMV group included gastrointestinal bleeding (72.2%), abdominal pain (55.6%), and fever (33.3%); ulcers (72.2%) were the most common endoscopic findings. In-hospital and overall mortality rates were 27.8% and 38.9%, respectively; and longer hospital stays and higher overall mortality rates were observed. Radiotherapy and C-reactive protein levels were prognostic factors for in-hospital mortality. The risk factors for CMV enteritis included immunocompromised status (p = 0.013), steroid use (p = 0.014), shock (p = 0.031), concurrent pneumonia (p = 0.01), antibiotic exposure (p < 0.001), radiotherapy (p = 0.027), chronic kidney disease (p = 0.041), and CMV colitis (p = 0.031). Conclusions Physicians should pay attention to the characteristics of CMV enteritis in high-risk patients to make an early diagnosis and potentially improve the clinical outcome. Keywords: Cytomegalovirus enteritis, Endoscopy, Risk factor, Prognostic factor, Immunohistochemistry staining
Diabetes‐induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin‐like growth factor II receptor α (IGF‐IIRα) is a cardiac risk ...factor. In this study, we hypothesized IGF‐IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague–Dawley rat model with specific IGF‐IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF‐IIRα in diabetic hearts. The results showed that IGF‐IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro‐inflammatory factors, such as Tumor necrosis factor‐alpha, Interleukin‐6, Cyclooxygenase‐2, Inducible nitric oxide synthase, and Nuclear factor‐kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac‐specific IGF‐IIRα overexpression. Correspondingly, IGF‐IIRα overexpression in the diabetic myocardium also reduced the PI3K‐AKT survival axis and activated mitochondrial‐dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac‐specific IGF‐IIRα overexpression. Overall, all results provid clear evidence that IGF‐IIRα can enhance cardiac damage and is a harmful factor to the heart under high‐blood glucose conditions. However, the pathophysiology of IGF‐IIRα under different stresses and its downstream regulation in the heart still require further research.
Begomoviruses frequently inflict upward or downward leaf curling symptoms on infected plants, leading to severe economic damages. Knowledge of the underlying mechanism controlling the leaf curling ...severity may facilitate the development of alternative disease management strategies. In this study, through genomic recombination between
Nan-Tou strain (AYVV-NT) and
Tai-Chung Strain (TLCV-TC), which caused upward and downward leaf curling on
, respectively, it was found that the coding region of C4 protein might be involved in the determination of leaf curling directions. Sequence comparison and mutational analysis revealed that the cysteine and glycine at position 8 and 14 of AYVV-TC C4 protein, respectively, are involved in the modulation of leaf curling symptoms. Cross-protection assays further demonstrated that
inoculated with AYVV-carrying mutations of the aforementioned amino acids exhibited attenuated leaf curling symptoms under the challenge of wild-type AYVV-NT. Together, these findings revealed a new function of begomovirus C4 proteins involved in the modulation of leaf curling severity during symptom formation and suggested potential applications for managing viral diseases through manipulating the symptoms.
The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical ...treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.
Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP ...variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC−MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 μL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.
Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ...ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance.
A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD.
The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12-0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82-0.88), 0.83 (95% CI 0.78-0.87) and 0.86 (95% CI 081-0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001).
The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. AQ3
Key messages
The prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early.
Adiponectin-leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio.
Our study found that adiponectin-leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin-leptin ratio was 0.28(95%CI: 0.12-0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82-0.88). Further rigorous investigation is necessary and should be promptly performed.
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