Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin.

Background: With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism. Methods: The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague-Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3. Results: PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3'-UTR and significantly downregulated NR1I3 expression. Conclusion: Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

Early predictive value of ultrasound measurements of rectus femoris cross-sectional area to diagnose ICU-acquired weakness in patients undergoing invasive mechanical ventilation: a prospective cohort study.

BACKGROUND: The diagnosis of ICU-acquired weakness (ICUAW) may be delayed due to the complexity of critically ill patients. This study aimed to investigate the value of ultrasound measurements of rectus femoris cross-sectional area (RFCSA) in predicting ICUAW in patients undergoing invasive mechanical ventilation. METHODS: This was a prospective cohort study of patients undergoing mechanical ventilation for at least 48 h. RFCSA was measured using ultrasound in patients upon ICU admission and followed until discharge. Using the Medical Research Council score as the gold standard, we evaluated the diagnostic value of ultrasound measurements in predicting ICUAW. Kaplan-Meier curves were constructed to evaluate and compare the length of ICU stay and duration of invasive mechanical ventilation between patients with and without ICUAW. RESULTS: Among the 76 patients, 34 (44.7%) were diagnosed with ICUAW using the Medical Research Council score as the gold standard. The RFCSA atrophy rate between day 1 and day 3 was significantly higher in the ICUAW group (7.9 ± 2.8% vs. 4.3 ± 2.1%, p < 0.001). By utilizing a cutoff point of 6.9%, we discovered that the RFCSA atrophy rate exhibited excellent diagnostic accuracy in predicting ICUAW, with a sensitivity of 76.5% and specificity of 92.9%. In ICUAW patients diagnosed based on an RFCSA atrophy rate, the proportion of patients with an ICU stay longer than 14 days was 42.9%, which was significantly higher compared to 22.9% in the non-ICUAW group (HR: 1.768; 95% CI 1.128-2.772; p = 0.006). Similarly, the proportion of patients continuing mechanical ventilation at 14 days was 28.6% versus 4.2% between the two groups (HR: 1.988; 95% CI 1.266-3.120; p < 0.001). CONCLUSION: Ultrasound measurements of RFCSA provide a reliable method for diagnosing ICUAW and indicating prognosis in patients undergoing invasive mechanical ventilation.

FB-EEGNet: A fusion neural network across multi-stimulus for SSVEP target detection.

BACKGROUND: Steady-state visual evoked potential (SSVEP) is a prevalent paradigm of brain-computer interface (BCI). Recently, deep neural networks (DNNs) have been employed for SSVEP target recognition. However, current DNN models can not fully extract information from SSVEP harmonic components, and ignore the influence of non-target stimuli. NEW METHOD: To employ information of multiple sub-bands and non-target stimulus data, we propose a DNN model for SSVEP target detection, i.e., FB-EEGNet, which fuses features of multiple neural networks. Additionally, we design a multi-label for each sample and optimize the parameters of FB-EEGNet across multi-stimulus to incorporate the information from non-target stimuli. RESULTS: Under the subject-specific condition, FB-EEGNet achieves the average classification accuracies (information transfer rate (ITR)) of 76.75 % (50.70 bits/min) and 89.14 % (70.45 bits/min) in a time widow of 0.7 s under the public 12-target dataset and our experimental 9-target dataset, respectively. Under the cross-subject condition, FB-EEGNet achieved mean accuracies (ITRs) of 81.72 % (67.99 bits/min) and 92.15 % (76.12 bits/min) on the public and experimental datasets in a time window of 1 s, respectively. COMPARISON WITH EXISTING METHODS: FB-EEGNet shows superior performance than CCNN, EEGNet, CCA and FBCCA both for subject-dependent and subject-independent SSVEP target recognition. CONCLUSION: FB-EEGNet can effectively extract information from multiple sub-bands and cross-stimulus targets, providing a promising way for extracting deep features in SSVEP using neural networks.

Risk factors for brain metastases from non-small-cell lung cancer: A protocol for observational study.

ABSTRACT: Brain metastasis is a common site of distant metastasis of non-small-cell lung cancer (NSCLC) that greatly reduces the prognosis of patients. In this study, we explored the correlation between different clinical factors and secondary brain metastases in NSCLC in an attempt to identify NSCLC patient populations at high risk of metastasis to the central nervous system.We collected data for 350 NSCLC patients from the medical record system of the First Affiliated Hospital of Nanchang University from June 2015 to June 2019, and these patients had pathologically verified diagnoses. The correlations between age at the time of diagnosis, sex, histological type, calcium concentration, hemoglobin (HB), fibrinogen (Fbg), activated partial thromboplastin time (APTT), alkaline phosphatase (ALP), carcinoembryonic antigen (CEA), CA125, and CA199 levels and brain metastasis were analyzed. Multivariate logistic regression analysis was used to identify risk factors for NSCLC brain metastasis. A receiver operating characteristic (ROC) curve was used to calculate the cutoff, sensitivity, and specificity of the independent related factors.Of the 350 patients, 57 were diagnosed with brain metastases. Univariate and multivariate logistic regression analysis indicated that lesion diameter, calcium concentration, and CEA level were independent risk factors correlated with brain metastasis (P < .05). There were no significant differences in age, sex, type of histopathology, presence or absence of mediastinal lymph node metastasis, HB, Fbg, APTT, ALP, cancer antigen 125 (CA-125), or cancer antigen 199 (CA-199) levels between patients with brain metastases and patients without brain metastases (P > .05, respectively). ROC curves demonstrated that these factors had comparable accuracy in predicting brain metastasis (area under the curve [AUCs] were 0.620, 0.661, and 0.729, respectively). The cutoff values for lesion diameter, calcium, and CEA were 5.050 cm, 2.295 mmol/L, and 11.160 ng/mL, respectively. The sensitivities for prediction brain metastasis were 59.6%, 64.9%, and 73.3%, with specificities of 63.1%, 59.2%, and 70.3%, respectively.According to our study, lesion diameter, calcium concentration, and CEA level are independent risk factors for brain metastases in NSCLC patients. Thus, we can strengthen the regular follow-up of NSCLC patients with tumor diameter > 5.050 cm, calcium > 2.295 mmol/L, CEA > 11.160 ng/mL, and use these factors as a reference for preventive treatments.

Increased red blood cell distribution width might predict left ventricular hypertrophy in patients with atrial fibrillation.

The presence of left ventricular hypertrophy has been confirmed to be an independent risk factor for stroke and death in patients with atrial fibrillation. This retrospective study aimed to evaluate the potential risk factors for left ventricular hypertrophy in patients with atrial fibrillation.A series of consecutive patients diagnosed with atrial fibrillation between June 2018 and December 2019 were included. The patients' clinical data were analyzed. The cut-off values, sensitivity and specificity of the independent risk factors were calculated using a receiver operating characteristic curve.Among 87 patients with atrial fibrillation, 39 patients with left ventricular hypertrophy and 48 patients without left ventricular hypertrophy were included. Multivariate logistic regression analysis showed that red blood cell distribution width (odds ratio [OR] 4.89, 95% confidence interval [CI]: 1.69-14.13, P < .05) was an independent risk factor, while the concentration of low-density lipoprotein (OR 0.37, 95% CI: 0.17-0.83, P < .05) and left ventricular ejection fraction (OR 0.88, 95% CI: 0.82-0.95, P < .05) were inversely associated with left ventricular hypertrophy in atrial fibrillation patients. The receiver operating characteristic curve demonstrated that the area under the curve was 0.80 (95% CI: 0.71-0.90, P < .05) with a cut-off value of 13.05, and the red blood cell distribution width predicted left ventricular hypertrophy status among atrial fibrillation patients with a sensitivity of 72.1% and a specificity of 76.9%.Red blood cell distribution width was associated with left ventricular hypertrophy in patients with atrial fibrillation.

Atypical primary pulmonary amyloidosis: A rare case report.

RATIONALE: Pulmonary amyloidosis is a rare respiratory disease characterized by amyloid deposition in the lungs. The clinical manifestations of pulmonary amyloidosis are variable and without specific symptoms. PATIENT CONCERNS: We report a rare case of tracheobronchial amyloidosis to improve our understanding of the disease. DIAGNOSES: The diagnosis of tracheobronchial amyloidosis was finally established by transbronchoscopic lung biopsy and histological examination. INTERVENTIONS: The patient significantly improved with methylprednisolone sodium succinate for injection (40 mg/day) for 5 days and low-dose oral prednisone for 10 days. OUTCOMES: After treatment, discomfort, such as cough, stridor, dyspnea, and chest tightness, disappeared, and he was discharged. The patient was in good clinical condition after 8 months of follow-up. CONCLUSION: This case clearly shows that it is difficult to distinguish tracheobronchial amyloidosis from other diseases with manifestations of cough, dyspnea and chest tightness because of their similar symptoms and imaging findings. Thus, the role of transbronchoscopic lung biopsy and histological examination in the diagnosis of tracheobronchial amyloidosis is very important.

Risk factors for depression in patients with chronic obstructive pulmonary disease.

BACKGROUND: The prevalence of depression in patients with chronic obstructive pulmonary disease (COPD) ranges from 10% to 42%, but the diagnosis of depression in patients with COPD is often unrecognized and untreated. Unrecognized depression has major implications for compliance with medical treatment, prolonged lengths of stay, increased frequency of hospital admissions, and increased consultations with primary care physicians. Many studies have attempted to identify risk factors for progression, prognosis and response to therapy in patients with depression. However, few studies have examined the risk factors for depression in patients with COPD, and some results remain controversial. AIM: To identify the potential risk factors to define patients with COPD who are at "high risk" of depression. METHODS: The clinical data of 293 patients with COPD were reviewed from January 2017 to December 2018. The correlations between demographics, clinical characteristics and depression were analyzed. The risk factors for depression in patients with COPD were identified by multivariate logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated with a receiver operating characteristic curve. RESULTS: Of the 293 patients included, 65 (22.18%) individuals were identified to have depression. Significant differences were detected between patients with and without depression in terms of body mass index (BMI), forced expiratory volume in 1 s (FEV1), and COPD assessment test (CAT) score (all P < 0.05). Low BMI, low FEV1, and high CAT were independent risk factors for depression in patients with COPD and the cutoff values of BMI, FEV1, and CAT scores were 21.373 kg/m2, 0.855 L and 12.5, respectively. CONCLUSION: Low BMI, low FEV1, and high CAT score were identified as independent risk factors for depression in patients with COPD.

Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5.

Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes the death of patients, but the pathophysiological mechanisms under these adverse effects are not clear. Here, two solanidine-type VAs (isorubijervine and rubijervine) isolated from Veratrum taliense exhibited strong cardiovascular toxicity. A pathophysiological study indicated that these VAs blocked sodium channels Na(V)1.3-1.5 and exhibited the strongest ability to inhibit Na(V)1.5, which is specifically expressed in cardiac tissue and plays an essential role in cardiac physiological function. This result reveals that VAs exert their cardiovascular toxicity via the Na(V)1.5 channel. The effects of VAs on Na(V)1.3 and Na(V)1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively.

[Factors associated with retention in a community-based methadone maintenance treatment among heroin addicts].

OBJECTIVE: To explore factors associated with retention in a community-based methadone maintenance treatment (MMT) among heroin addicts in Xichang of Sichuan province. METHODS: All 206 heroin addicts were first admitted to MMT community-based program between March to September 2004. Baseline data of patients characteristics, social function, drug using behaviors, sexual behaviors, dose of methadone and retention were collected. RESULTS: Up to Oct, 2005, all 206 patients contributed 8.98 +/- 5.74 person-months of following-up. The retention rates were 58.7% after 6 months and 34.6% after 12 months respectively. Cox proportional hazard regression model indicated that the employed (HR, 0.60; 95% CI, 0.39 - 0.92), helping family to do housework in past 30 days more than once a day (HR, 0.59; 95% CI, 0.42 - 0.82) and previous self-detoxification > or = 3 times (HR, 0.65; 95% CI, 0.47 - 0.91) were independently associated with retention. CONCLUSION: We should give individual counseling to help heroin addicts increasing compliance.

[Incidence rates of human immunodeficiency virus and syphilis as well as the rate of retention in a 6-month follow-up study of female sex workers in areas with heavy drug use in Xichang of Sichuan province, China].

OBJECTIVE: To investigate the human immunodeficiency virus (HIV) and syphilis incidence rates as well as the retention rate in a cohort with 6-month follow-up study among female sex workers (FSWs). METHODS: From December, 2004, to January, 2005, a community-based baseline survey was conducted to recruit 343 FSWs for a prospective cohort study in Xichang county of Sichuan province, China. Follow-up visits were conducted at 6 months to analyze risk factors associated with cohort retention for subjects' baseline sociodemographic and sexual behavioral characteristics. Blood specimens were also collected to test antibodies against HIV and syphilis. RESULTS: During the 6-month follow-up period, HIV and syphilis incidence appeared to be 1.00 per 100 person-years and 6.23 per 100 person-years, respectively. The rate of retention in the cohort was 53.6% (184/343). Results from multivariate logistic regression model showed that factors were significantly associated with cohort retention including people with minority ethnic background (OR = 0.36; 95% CI: 0.18-0.74), people having participated in AIDS prevention program (OR = 1.83; 95% CI: 1.17-2.86) or being clients in the last 6 months > or = 50 (OR = 1.75; 95% CI: 1.11-2.77) and having changed living/working place (OR = 0.56; 95% CI: 0.33-0.94). CONCLUSION: The results of this study showed that the syphilis incidence and unprotected sex behavior were high among local FSWs. People belonged to Han nationality, having participated in AIDS prevention program and having a steady living/working place were associated with cohort retention at 6-month follow-up study among FSWs, respectively.