Translation and Validation of the Chinese Language Version of the Control of Allergic Rhinitis and Asthma Test in Patients with Allergic Rhinitis.

Objective: Due to the escalating global prevalence of allergic rhinitis (AR) and its status as an independent risk factor for asthma, timely and effective control of AR is crucial. Achieving this often involves the accurate assessment of AR. Currently, the Control of Allergic Rhinitis and Asthma Test (CARAT) is widely used as an assessment tool, but its measurement effectiveness in Chinese AR patients remains unclear. Therefore, this study aims to evaluate the reliability and validity of the Chinese version of the CARAT10 scale (CARAT10-C) and analyze its application value in the assessment of allergic rhinitis and asthma control trials. Methods: The study enrolled 130 patients with AR from the Ear, Nose, and Throat (ENT) outpatient department of a comprehensive teaching hospital from March to May 2022 as participants. The reliability and validity of the CARAT10-C scale were assessed using Cronbach's alpha coefficient (CAC), Kaiser-Meyer-Olkin (KMO), and Bartlett's sphericity test. Additionally, the study analyzed the effectiveness of the CARAT10-C scale in its application within the Control of Allergic Rhinitis and Asthma Test (CARAT). Results: The Cronbach's alpha coefficient ranges between 0 and 1, with higher values indicating better reliability. Significant differences in exploratory factor analysis suggest good validity. The Cronbach's alpha coefficient of the CARAT10-C scale was 0.806. Exploratory factor analysis revealed that the eigenvalues of Component 1 (3.851) and Component 2 (2.193) were both greater than 1, with a cumulative variance contribution rate (CVCR) of 60.436%. Items 6-10 were primarily loaded on Component 1 (Asthma), while items 1-4 were mainly influenced by Component 2 (AR), with loading ranges of 0.508-0.874, all significant at P < .001. The composite reliability (CAC) of the CARAT10-C scale was 0.806, exceeding 0.8, indicating high reliability. Component 1 had a CAC of 0.834, and Component 2 had a CACs of 0.807, both exceeding 0.8, indicating high reliability for both components. Conclusion: The CARAT10-C scale demonstrates good reliability and validity in the preliminary assessment of AR. It holds potential value in the evaluation and management of AR in China, although the specific application effects still require further investigation.

The impact of preoperative serum lactate dehydrogenase on mortality and morbidity after noncardiac surgery.

Preoperative serum lactate dehydrogenase (LDH) has been reported to be associated with adverse outcomes following thoracic surgery. However, its association with outcomes in noncardiac surgery as a whole has not been investigated. We conducted a retrospective cohort study at West China Hospital, Sichuan University, from 2018 to 2020, including patients undergoing noncardiac surgery. Multivariable logistic regression and propensity score weighting were employed to assess the link between LDH levels and postoperative outcomes. Preoperative LDH was incorporated into four commonly used clinical models, and its discriminative ability, reclassification, and calibration were evaluated in comparison to models without LDH. Among 130,879 patients, higher preoperative LDH levels (cut-off: 220 U/L) were linked to increased in-hospital mortality (4.382% vs. 0.702%; OR 1.856, 95% CI 1.620-2.127, P < 0.001), myocardial injury after noncardiac surgery (MINS) (3.012% vs. 0.537%; OR 1.911, 95% CI 1.643-2.223, P < 0.001), and ICU admission (15.010% vs. 6.414%; OR 1.765, 95% CI 1.642-1.896, P < 0.001). The inverse probability of treatment-weighted estimation supported these results. Additionally, LDH contributed significantly to four surgical prognostic models, enhancing their predictive capability. Our study revealed a significant association between preoperative LDH and in-hospital mortality, MINS, and ICU admission following noncardiac surgery. Moreover, LDH provided supplementary predictive information, extending the utility of commonly used surgical prognostic scores.

Therapeutic Potential of Downregulated Interleukin-6 Signaling for the Treatment of Chronic Pain: A Mendelian Randomization Study.

Introduction: While numerous studies have emphasized the pivotal involvement of the Interleukin 6 (IL-6) pathway in the development of chronic pain, the causal nature of this relationship remains uncertain. Methods: In this study, we opted to include genetic variants situated within the locus of the IL-6 receptor (IL-6R) that exhibited associations with C-reactive protein (CRP) levels. CRP serves as a downstream effector in the IL-6 pathway. Utilizing these variants as genetic proxies, we aimed to modulate IL-6 signaling. Employing a two-sample Mendelian randomization (MR) approach, we investigated the potential link between the genetic proxy and seven distinct subtypes of chronic pain, categorized based on their corresponding body locations. Moreover, we examined the relationship between chronic pain and an alternative instrument of IL-6 signaling that was weighted based on s-IL-6R levels. Furthermore, we conducted exploratory analyses to estimate the plausible causal association between CRP, gp130, and the subtypes of chronic pain. Results: Our analysis showed that genetic proxied downregulation of IL-6 signaling, weighted on CRP levels, was linked to a reduced risk of chronic back and knee pain. The sensitivity analyses across various MR methods confirmed the consistency of the findings and showed no evidence of horizontal pleiotropy or heterogeneity. Moreover, the results remained robust with different sets of instrument variables. A genetically increased level of s-IL-6R was also negatively associated with chronic back and knee pain. However, there was no causal relationship between CRP and gp130 with chronic pain. Conclusion: Based on our findings, there is evidence to suggest a potential causal relationship between IL-6 signaling and chronic back and knee pain. Consequently, the downregulation of IL-6 signaling holds promise as a potential therapeutic target for addressing chronic back and knee pain.

Assessment of the prognostic value of preoperative high-sensitive troponin T for myocardial injury and long-term mortality for groups at high risk for cardiovascular events following noncardiac surgery: a retrospective cohort study.

Background: Few studies explored the association between high-sensitive cardiac troponin T (hs-cTnT) and long-term mortality for patients after surgery. This study was conducted to assess the association of hs-cTnT with long-term mortality and to investigate the extent to which this association is mediated via myocardial injury after noncardiac surgery (MINS). Methods: This retrospective cohort study included all patients with hs-cTnT measurements who underwent non-cardiac surgery at Sichuan University West China Hospital. Data were collected from February 2018 and November 2020, with follow-up through February 2022. The primary outcome was all-cause mortality within 1 year. As secondary outcomes, MINS, length of hospital stay (LOS), and ICU admission were analyzed. Results: The cohort included 7,156 patients (4,299 [60.1%] men; 61.0 [49.0-71.0] years). Among 7,156 patients, there were 2,151 (30.05%) with elevated hs-cTnT(>14 ng/L). After more than 1 year of follow-up, more than 91.8% of mortality information was available. During one-year follow-up after surgery, there were 308 deaths (14.8%) with a preoperative hs-cTnT >14 ng/L, compared with 192 deaths (3.9%) with a preoperative hs-cTnT <=14 ng/L(adjusted hazard ratio [aHR] 1.93, 95% CI 1.58-2.36; p < 0.001). Elevated preoperative hs-cTnT was also associated with several other adverse outcomes (MINS: adjusted odds ratio [aOR] 3.01; 95% CI, 2.46-3.69; p < 0.001; LOS: aOR 1.48, 95%CI 1.34-1.641; p < 0.001; ICU admission: aOR 1.52, 95%CI 1.31-1.76; p < 0.001). MINS explained approximately 33.6% of the variance in mortality due to preoperative hs-cTnT levels. Conclusion: Preoperative elevated hs-cTnT concentrations have a significant association with long-term mortality after noncardiac surgery, one-third of which may by accounted for by MINS.

Pharmacological properties and derivatives of saikosaponins-a review of recent studies.

OBJECTIVES: Saikosaponins (SSs) constitute a class of medicinal monomers characterised by a triterpene tricyclic structure. Despite their potential therapeutic effects for various pathological conditions, the underlying mechanisms of their actions have not been systematically analysed. Here, we mainly review the important anti-inflammatory, anticancer, and antiviral mechanisms underlying SS actions. METHODS: Information from multiple scientific databases, such as PubMed, the Web of Science, and Google Scholar, was collected between 2018 and 2023. The search term used was saikosaponin. KEY FINDINGS: Numerous studies have shown that Saikosaponin A exerts anti-inflammatory effects by modulating cytokine and reactive oxygen species (ROS) production and lipid metabolism. Moreover, saikosaponin D exerts antitumor effects by inhibiting cell proliferation and inducing apoptosis and autophagy, and the antiviral mechanisms of SSs, especially against SARS-CoV-2, have been partially revealed. Interestingly, an increasing body of experimental evidence suggests that SSs show the potential for use as anti-addiction, anxiolytic, and antidepressant treatments, and therefore, the related molecular mechanisms warrant further study. CONCLUSIONS: An increasing amount of data have indicated diverse SS pharmacological properties, indicating crucial clues for future studies and the production of novel saikosaponin-based anti-inflammatory, efficacious anticancer, and anti-novel-coronavirus agents with improved efficacy and reduced toxicity.

Assessment of prognostic value of preoperative neutrophil-to-lymphocyte ratio for postoperative mortality and morbidity.

Background: The preoperative elevated neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with poorer outcomes after cancer and cardiovascular surgeries. It is unclear, however, if the predictive value is particular or if it may be applied to other types of surgery. We aimed to assess the prognostic value of preoperative NLR levels for morbidity and mortality after various surgery and determine an optimal threshold for NLR. Methods: We conducted a cohort analysis on patients receiving surgery at Sichuan University West China Hospital between 2018 and 2020. Multivariable piecewise regression analysis were used to determine the optimal cutoff value of NLR. Subgroup analysis were performed to verify the correlation. Sensitivity analysis was used to explore the effect of different thresholds. Results: We obtained data from 136,347 patients. The optimal cutoff of NLR was determined as 3.6 [95% CI (3.0, 4.1)] by piecewise regression method. After multivariable adjustment, preoperative high NLR remained significantly associated with increased in-hospital mortality (aOR, 2.19; 95% CI, 1.90-2.52; p < 0.001) and ICU admission after surgery (aOR, 1.69; 95% CI, 1.59-1.79; p < 0.001). Subgroup analyses confirmed the predictive value of high NLR in multiple surgical subgroups, including general, orthopedic, neurosurgical, and thoracic surgery subgroups, otorhinolaryngology, head and neck surgery, and burn plastic surgery. A NLR threshold of 3.6 gave excellent predictive value, whether employed alone or added in an extended model. Conclusions: In conclusion, the association of elevated NLR with higher mortality and ICU admission can be extended to a wider range of procedures. NLR threshold of 3.6 could provide good prognostic value for the prognostic model.

Preoperative serum alpha-hydroxybutyrate dehydrogenase level as a predictor of postoperative mortality and morbidity after noncardiac surgery: A propensity-adjusted analysis.

BACKGROUND: Preoperative serum alpha-hydroxybutyrate dehydrogenase is reportedly associated with myocardial infarction. Myocardial injury after noncardiac surgery is independently associated with postoperative mortality. However, the association between preoperative alpha-hydroxybutyrate dehydrogenase and outcomes after noncardiac surgery has not been researched. We aimed to assess the association between preoperative serum alpha-hydroxybutyrate dehydrogenase levels and mortality and morbidity after noncardiac surgery. METHODS: We conducted a retrospective cohort study on patients undergoing noncardiac surgery from 2018 to 2020 in Sichuan University West China Hospital. After multivariate adjustment, the alpha-hydroxybutyrate dehydrogenase level was verified to be associated with postoperative outcomes by logistic regression analyses and propensity score weighting methods. RESULTS: We obtained data from 130,880 patients. An elevated preoperative serum alpha-hydroxybutyrate dehydrogenase level was associated with increasing mortality (odds ratio 1.244, 1.190-1.300; P < .001), myocardial injury after noncardiac surgery (odds ratio 1.198, 1.141-1.257; P < .001), and intensive care unit admission (odds ratio 1.138, 1.111-1.166; P < .001) in logistic regression analyses. The covariate balancing generalized propensity score methodology demonstrated similar results. After classifying alpha-hydroxybutyrate dehydrogenase as a binary variable with a cut-off value of 182, we found that mortality, myocardial injury after noncardiac surgery, and intensive care unit admission >24 hours were significantly higher in the elevated alpha-hydroxybutyrate dehydrogenase group (5.458% vs 0.737%; odds ratio 1.771, 1.533-2.046; P < .001), (3.598% vs 0.572%; odds ratio 1.636, 1.393-1.922; P < .001), and (18.182% vs 6.442%; odds ratio 1.430, 1.327-1.542; P < .001), respectively. Similarly, the inverse-probability-of-treatment weighted estimation demonstrated similar results. CONCLUSION: Our results suggest that the preoperative serum alpha-hydroxybutyrate dehydrogenase level was associated with in-hospital mortality, myocardial injury after noncardiac surgery, and intensive care unit admission after noncardiac surgery.

Diagnostic Errors in Initial Misdiagnosis of Foreign Body Aspiration in Children: A Retrospective Observational Study in a Tertiary Care Hospital in China.

Background: Foreign body aspiration (FBA) in children is a common emergency that can easily be missed, leading to delays in treatment. Few large cohort studies have focused on errors in diagnostic assessment. The main purpose of this study was to analyze factors contributing to the initial misdiagnosis of FBA in children. Methods: We retrospectively reviewed the charts of 226 children diagnosed with FBA at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2018 to November 2020. Cases were divided into two groups according to whether or not patients were initially misdiagnosed. The clinical characteristics of the two groups were then compared. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was applied to cases with initial misdiagnosis. Results: Of the 226 included children with a final diagnosis of FBA, 153 (67.7%) were boys. Ninety percent of patients were under 3 years old. More than half (61.9%) of the children were referred from primary institutions, and 38.1% visited tertiary hospitals directly. A total of 80 (35.4%) patients were initially misdiagnosed. More than half of misdiagnosed children received an alternative diagnosis of bronchiolitis (51.3%), the most common alternative diagnosis. Test failures (i.e., errors in test ordering, test performance, and clinician processing) were primarily responsible for the majority of initial diagnostic errors (76.3%), followed by failure or delay in eliciting critical case history information (20.0%). Characteristics significantly associated with initial misdiagnosis were: presentation over 24 h (OR 9.2, 95% CI 4.8-17.5), being referred from primary institutions (OR 8.8, 4.1-19.0), no witnessed aspiration crisis (OR 7.8, 3.0-20.3), (4) atypical signs or symptoms (OR 3.2, 1.8-5.7), foreign body not visible on CT (OR 36.2, 2.1-636.8), foreign body located in secondary bronchi (OR 4.8, 1.3-17.2), organic foreign body (OR 6.2, 1.4-27.2), and history of recurrent respiratory infections (OR 2.7, 1.4-5.3). Children with misdiagnosis tended to have a longer time from symptom onset to the definitive diagnosis of FBA (P < 0.001). Conclusions: More than one-third of children with FBA were missed at first presentation. Errors in diagnostic testing and history taking were the main reasons leading to initial misdiagnosis.

Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines.

Colorectal cancer is a common malignant tumor of the gastrointestinal tract. Currently, the main treatment is surgical resection, which can be combined with other treatments. However, treatment efficacy is poor, and colorectal cancer is prone to relapse and metastasis; thus, identifying an effective anti-cancer drug is an urgent requirement. The present study examined the antagonistic effect of penicillin on cultured colorectal cancer cells and the related mechanism. A MTT assay was used to assess the growth of the colorectal cancer cells treated with penicillin and to determine the optimal drug concentration. The wound healing and Transwell invasion assays were performed to investigate the effect of penicillin on the migration and invasion of the colorectal cancer cells. Live cell mitochondrial energy metabolism analysis was performed to detect changes in mitochondrial energy metabolism of the colorectal cancer cells, while western blot analysis was used to measure the expression of cytochrome c and autophagy-related protein, LC3. RFP-GFP-LC3 lentivirus was used to detect autophagic flux, and autophagosomes were observed using a transmission electron microscope, while flow cytometry was used to analyze the effect of penicillin on cell cycle progression and apoptosis of the colorectal cancer cells. After penicillin treatment, the growth, migration and invasion ability of the colorectal cancer cells were inhibited. The mitochondrial energy metabolism of the cell was impaired, and the basic respiratory capacity, maximum respiratory capacity, respiratory potential, and ATP production were all reduced. The protein expression levels of the autophagy-related proteins, LC3-II/LC3-I increased in a dose- and time-dependent manner. In addition, autophagy flux and the number of autophagosomes increased, and mitochondrial structural damage was observed. The cell cycle was arrested at the G1 phase, the number of early apoptotic cells increased and the protein expression level of cleaved caspase-3 increased, while penicillin-induced apoptosis was blocked by the autophagy inhibitor 3-MA. In conclusion, penicillin disrupted mitochondrial function and energy metabolism in the colorectal cancer cells, which resulted in the induction of autophagic apoptosis and ultimately the inhibition of cancer cell growth and metastasis.

Assessing the applications of transitional care and its impact on the quality of life in patients after total laryngectomy.

OBJECTIVE: To explore the effect of transitional care and its impact on quality of life (QoL) in patients who underwent total laryngectomy. METHODS: The study enrolled 68 patients who were admitted to our hospital and underwent total laryngectomy from January 2017 to January 2019. The subjects were randomly divided into an observation group and a control group. Conventional care was given to the control group (34 cases), while conventional and transitional care was given to the observation group (34 cases). The study sought to compare the self-care ability, health knowledge, satisfaction with nursing, and QoL between the two groups at discharge and 6 months after discharge. RESULT: Compared with the control group, the observation group showed higher scores in self-care ability, more extensive health knowledge, greater satisfaction, and better QoL at 6 months after discharge from the hospital. The differences were statistically significant (P < 0.05). CONCLUSION: Transitional care can effectively improve the following performance in patients, including self-care activity after hospital discharge, health knowledge, and satisfaction with care, medication adherence, and QoL. Transitional care can be considered in a broader application.

Erector spinae plane block for postoperative analgesia in spine surgery: a systematic review and meta-analysis.

PURPOSE: Although in recent years some randomized controlled trails (RCTs) have explored the analgesic effect of erector spinae plane block (ESPB) in spine surgery, their results are controversial. Our study aimed to examine the analgesic effect of preoperative ESPB in spine surgery by a meta-analysis of RCTs. METHODS: The articles of RCTs that compared preoperative ESPB with no block in terms of the analgesic effect in adult patients following spine surgery were eligible for inclusion. The primary outcome was the pain scores reported by Visual Analog Scale or Numerical Rating Scale of pain at different time intervals in 48 h after surgery. The secondary outcomes included postoperative opioid consumption, rescue analgesia requirement, opioid-related side effects and complications associated with ESPB. RESULTS: Twelve studies involving 828 patients were eligible for our study. Compared with no block, ESPB had a significant effect on reducing postoperative pain scores at rest and at movement at different time intervals except at movement at 48 h. ESPB significantly decreased opioid consumption in 24 h after surgery (SMD - 1.834; 95%CI - 2.752, - 0.915; p < 0.001; I2 = 89.0%), and reduced the incidence of rescue analgesia (RR 0.333; 95%CI 0.261, 0.425; p < 0.001; I2 = 0%) and postoperative nausea and vomiting (RR 0.380; 95%CI 0.272, 0.530; p < 0.001; I2 = 9.0%). Complications associated with ESPB were not reported in the included studies. CONCLUSION: Our meta-analysis demonstrates that ESPB is effective in decreasing postoperative pain intensity and postoperative opioid consumption in spine surgery. Therefore, for the management of postoperative pain following spine surgery, preoperative ESPB is a good choice.

Aspirin restores endothelial function by mitigating 17ß-estradiol-induced α-SMA accumulation and autophagy inhibition via Vps15 scaffold regulation of Beclin-1 phosphorylation.

AIMS: Previous studies have shown that the widespread use of estrogen preparations can cause adverse outcomes such as thrombosis and cardiovascular disease. Autophagy is a biochemical process necessary to maintain cell homeostasis. The present study investigated whether E-2 mediates autophagy-induced endothelial cell dysfunction. The role of aspirin in this process was then studied. MAIN METHODS: Western blot, fluorescence microscopy, electron transmission microscopy, plasma construction and transfection, vasoreactivity study in wire myograph are all used in this study. KEY FINDINGS: We found that E-2 activated the PI3K/mTOR signaling pathway and inhibited the formation of the Atg14L-Beclin1-Vps34-Vps15 complex, thereby inhibiting autophagy. Aspirin promoted Beclin1 phosphorylation in autophagy initiation complexes and enhanced autophagy. Furthermore, E-2 treatment of HAECs resulted in endothelial dysfunction by inhibiting autophagy and leading to accumulation of α-smooth muscle actin (α-SMA). E-2 inhibited the activation of eNOS and reduced the expression of eNOS protein. In the mouse aortic vascular function test, E-2 disrupted endothelium-dependent vasodilation. An α-SMA-shRNA lentivirus eliminated the disruption to endothelium-dependent vasodilation by E-2. Aspirin inhibited α-SMA accumulation by enhancing autophagy, reversed endothelial functional impairment caused by E-2, and promoted endothelium-dependent vasodilation. SIGNIFICANCE: This study provides new evidence that E-2 inhibits autophagy and induces abnormal accumulation of α-SMA, resulting in endothelial cell dysfunction and affecting vasodilation. Aspirin can effectively restore the endothelial cell function disrupted E-2.

Influences of Daily Life Habits on Risk Factors of Stroke Based on Decision Tree and Correlation Matrix.

PURPOSE: To explore the influences of smoking, alcohol consumption, drinking tea, diet, sleep, and exercise on the risk of stroke and relationships among the factors, present corresponding knowledge-based rules, and provide a scientific basis for assessment and intervention of risk factors of stroke. METHODS: The decision tree C4.5 algorithm was optimized and utilized to establish a model for stroke risk assessment; then, the main risk factors of stroke (including hypertension, dyslipidemia, diabetes, atrial fibrillation, body mass index (BMI), history of stroke, family history of stroke, and transient ischemic attack (TIA)) and daily habits (e.g., smoking, alcohol consumption, drinking tea, diet, sleep, and exercise) were analyzed; corresponding knowledge-based rules were finally presented. Establish a correlation matrix of stroke risk factors and analyze the relationship between stroke risk factors. RESULTS: The accuracy of the established model for stroke risk assessment was 87.53%, and the kappa coefficient was 0.8344, which was superior to that of the random forest and Logistic algorithm. Additionally, 37 knowledge-based rules that can be used for prevention of risk factors of stroke were derived and verified. According to in-depth analysis of risk factors of stroke, the values of smoking, exercise, sleep, drinking tea, alcohol consumption, and diet were 6.00, 7.00, 8.67, 9.33, 10.00, 10.60, and 10.75, respectively, indicating that their influence on risk factors of stroke was reduced in turn; on the one hand, smoking and exercise were strongly associated with other risk factors of stroke; on the other hand, sleep, drinking tea, alcohol consumption, and diet were not firmly associated with other risk factors of stroke, and they were relatively tightly associated with smoking and exercise. CONCLUSIONS: Establishment of a model for stroke risk assessment, analysis of factors influencing risk factors of stroke, analysis of relationships among those factors, and derivation of knowledge-based rules are helpful for prevention and treatment of stroke.

Diagnosis of coronary artery disease in patients with atrial fibrillation using low tube voltage coronary CT angiography with isotonic low-concentration contrast agent.

This prospective study evaluated the image quality and accuracy of coronary computed tomography angiography (CCTA) for diagnosing coronary artery disease (CAD) in patients with atrial fibrillation (AF), in which CCTA used adaptive iterative dose reduction (AIDR) with a low tube voltage and low concentration of isotonic contrast agent. Sixty-eight consecutive patients with AF and suspected CAD were equally and randomly apportioned to two groups and underwent CCTA. In the experimental group, the contrast agent was iodixanol (270 mg I/mL), patients were scanned with 100 kV, and reconstruction was by AIDR. In the conventional scanning (control) group, the contrast agent was iopromide (370 mg I/mL), patients were scanned with 120 kV, and reconstruction was by filtered back projection. The image quality, effective radiation dose (E), and total iodine intake of the groups were compared. Thirty-nine patients with coronary artery stenosis later were given invasive coronary angiography (ICA). The groups were similar with regard to mean CT value, noise, and signal-to-noise and contrast-to-noise ratios. The figure of merit of the experimental group was significantly higher than that of the control group, while the E and total iodine were significantly lower. Using ICA as the diagnostic reference, the groups shared similar sensitivity, specificity, and false positive and false negative rates for diagnosing coronary artery stenosis. For determining CAD in patients with AF, CCTA with isotonic low-concentration contrast agent and low-voltage scanning is a feasible alternative that improves accuracy and reduces radiation dose and iodine intake.

Aberrant expression of serum circANRIL and hsa_circ_0123996 in children with Kawasaki disease.

BACKGROUND: Kawasaki disease is a childhood systemic vasculitis that causes coronary artery abnormalities. The etiology remains unknown and there are no specific diagnostic tests. Circular non-coding RNAs are a special class of endogenous RNAs that display some characteristics of an ideal biomarker. However, few studies have examined the expression of circRNAs in the serum of Kawasaki disease (KD) patients. The aim of this study was to identify circRNAs in the serum that can serve as potential biomarkers for KD diagnosis. METHODS: The cases were children diagnosed with KD (n = 56). The controls comprised healthy children (n = 56). Blood was collected from the patients before and after intravenous immunoglobulin therapy, and from the healthy controls. Levels of circANRIL and hsa_circ_0123996 in the serum were measured by quantitative reverse transcription PCR. Then, the potential relationship between serum circRNA levels and patients' biochemical parameter levels was investigated. Receiver operating characteristic curves were constructed for evaluating the diagnostic value of these circRNAs. RESULTS: The serum levels of circANRIL were lower in patients with KD before therapy than in the controls, but became higher in the patients after therapy than before therapy. The serum levels of hsa_circ_0123996 were higher in patients with KD before therapy than in healthy controls. CONCLUSION: Our study indicated that the circANRIL and hsa_circ_0123996 levels in the serum of patients with KD were significantly different from those in healthy individuals. circANRIL and hsa_circ_0123996 may become potential biomarkers for early KD diagnosis.

Hsa_circRNA_0054633 is highly expressed in gestational diabetes mellitus and closely related to glycosylation index.

BACKGROUND: Circular RNA (circRNA) is involved in the pathological processes of various diseases. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM). METHODS: A retrospective case-control study was conducted using data and samples from women treated at a hospital in China between July 10, 2017, and February 15, 2018. We collected serum samples from 40 healthy pregnant women (controls) and 40 women with GDM (cases) during the second trimester as well as 65 controls and 65 cases during the third trimester of pregnancy. Placenta tissues and neonatal cord blood were each from another 20 cases and 20 controls. We selected six circRNAs (hsa_circRNA_0054633, hsa_circRNA_103410, hsa_circRNA_063981, hsa_circRNA_102682, hsa_circRNA_0018508, and hsa_circRNA_406918) as candidate biomarkers and used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to measure their concentrations in the serum and placental tissues. The Pearson correlation test was used to assess the correlation between various circRNAs and between circRNA and clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs for GDM at each stage. RESULTS: Hsa_circRNA_0054633 was highly expressed in the blood during the second and third trimesters; its expression was also high in the placenta but low in the cord blood (P < 0.05). Hsa_cirRNA_0054633 was highly correlated with GHBA1 and GHBA1c levels in maternal blood samples at various stages of the GDM group (including placental tissue and umbilical cord blood) (P < 0.05). Hsa_circRNA_063981, hsa_circRNA_102682, and hsa_circRNA_103410 were also differentially expressed between the case and control groups at different stages (P < 0.05). There was a strong correlation between hsa_circRNA_0054633 and hsa_circRNA_103410 levels in third-trimester maternal blood (P = 0.000, r = 0.554) and in neonatal umbilical cord blood (P = 0.000, r = 0.866). Hsa_circRNA_0054633 showed a significant diagnostic value in the second and third trimesters of pregnancy, placenta, and cord blood (AUC = 0.793, 0.664, 0.747, and 0.783, respectively, P < 0.001). CONCLUSION: This study suggests that hsa_cirRNA_0054633 is abnormally expressed in GDM patients and may play a potential role in the development of GDM. The possibility of using circRNAs for the diagnosis of GDM requires additional investigation in future studies.

Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2-induced PSMB5 in endothelial cells.

Atherosclerosis (AS) is one of important events involving in the pathological process of coronary artery disease. Many traditional Chinese medicines have been widely used for the treatment of AS. Previous studies have demonstrated that Ilexgenin A (IA) obtained from Ilex hainanensis Merr. could improve AS development. However, its underlying mechanism is still unknown. This study was conducted to explore the possible targets and mechanisms involving in the anti-atheroclerosis effect of IA. The results showed IA significantly promoted NO production, reduced reactive oxygen species (ROS) generation, and inflammatory cytokine production induced by palmitate (PA) in endothelial cells, demonstrating IA could improve endothelial dysfunction. Meanwhile, IA dramatically inhibited dynamin-related protein 1 (Drp1) expression and mitochondrial fission induced by PA whereas proteasome inhibitor epoxomicin attenuated its effect on Drp1 expression, indicating IA decreased Drp1 expression with regulation of proteasome. Furthermore, IA also could increase the expression of proteasome subunit beta type5 (PSMB5) and activate nuclear factor-like 2 (Nrf2). Nrf2 knockdown eliminated the induction effect of IA on PSMB5 expression while abrogated its inhibition on ROS generation and mitochondrial fission stimulated by PA. These results demonstrated that IA could promote PSMB5 expression in an Nrf2-dependent manner, resulting in the suppression of mitochondrial fission, and thus improve endothelial dysfunction. These findings laid a foundation to the future development of IA as an agent to the prevention and treatment of AS.

Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics.

Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.

Identification of similarities and differences between myeloid and lymphoid acute leukemias using a gene-gene interaction network.

Acute myeloid leukemia (AML) is a cancer that affects the myeloid line of blood cells. Acute lymphoid leukemia (ALL) is a type of leukemia that targets the lymphoid line of blood cells. As the comparison of these two types facilitates in the understanding of their molecular pathology, exploring the similarities and differences in the mechanisms of them is worthwhile. We identified 28 novel AML- and ALL-related genes shared in both of them using a short path algorithm. By integrating gene ontology (GO) and KEGG pathway annotations, we revealed the underlying molecular features of AML and ALL. We finally obtained 160 optimal GO terms that could satisfactorily distinguish two types. Further analysis revealed that the results agree well with previous knowledge. Determining the common and different features between AML and ALL facilitates the classification of leukemia and is thus clinically relevant for exploring the molecular markers.

Integrating GO and KEGG terms to characterize and predict acute myeloid leukemia-related genes.

BACKGROUND/OBJECTIVE: Acute myeloid leukemia (AML) is a progressive and malignant cancer of myelogenous blood cells, which disturbs the production of normal blood cells. Although several risk and genetic factors (AML-related genes) have been investigated, the concrete mechanism underlying the development of AML remains unclear. In view of this, it is crucial to develop an effective computational method for meaningfully characterizing AML genes and accurately predicting novel AML genes. METHODS: In this study, we integrated gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations as features to characterize AML genes. We also provided an optimal set of features for predicting AML-related genes by using the minimum redundancy maximum relevance (mRMR) algorithm and dagging metaclassifier. RESULTS: We obtained 26 optimal GO terms that characterized AML genes well. Finally, we predicted 464 novel genes to provide clinical researchers with additional candidates and useful insights for further analysis of AML. DISCUSSION: An in-depth feature analysis indicated that the results are quite consistent with previous knowledge. We developed a systematic method to identify the possible underlying mechanism of AML by analyzing the related genes. Our method has the ability to identify the types of features that are optimal to meaningfully interpret AML and accurately predict more AML genes for further clinical researches.