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This study aims to clarify the specific anti-fatigue components of Schizophyllum commune (S.commune) and analyze its potential anti-fatigue mechanism. The main anti-fatigue active ingredient of S.commune was locked in n-butanol extract (SPE-n) by activity evaluation. Twelve compounds were identified by high performance liquid chromatography-electrospray tandem mass spectrometry (LC–ESI–MS/MS). The anti-fatigue effect of morusin is the most predominant among these 12 ingredients. The determination of biochemical indices showed that morusin could increase liver glycogen reserves, improve the activity of antioxidant enzymes in liver, and reduce reactive oxygen species (ROS) content in muscle tissue, thereby reducing myocyte damage. Further studies revealed that morusin could reduce the level of oxidative stress by activating Nrf2/HO-1 pathway, thus alleviating the fatigue of mice caused by exhaustive exercise. The current findings provide a theoretical basis for the development of natural anti-fatigue functional food. [Display omitted] • The anti-fatigue active components was mainly n-butanol extract of Schizophyllum commune through activity screening. • Morusin was identified as the major active anti-fatigue substance in Schizophyllum commune by LC–ESI–MS/MS. • Morusin could relieve fatigue by regulating the Nrf2/HO-1 pathway and down-regulating oxidative stress. [ABSTRACT FROM AUTHOR]

The physical status of humans can be estimated by observing the appearance of the tongue coating, known as tongue diagnosis. The goals of this study were to reveal the relationship between tongue coating appearance and the oral microbiota in patients with gastric cancer and to open a novel research direction supporting tongue diagnosis. We used a tongue manifestation acquisition instrument to analyse the thickness of the tongue coating of patients with gastric cancer and that of healthy controls, and high-throughput sequencing was used to describe the microbial community of the tongue coating by sequencing the V2-V4 region of the 16S rDNA. The tongue coatings of 74 patients with gastric cancer were significantly thicker than those of 72 healthy controls (343.11 ± 198.22 versus 98.42 ± 48.25, P < 0.001); 51.35% of the patients were assessed as having thick tongue coatings, whereas all healthy controls were assessed as having thin tongue coatings. Thick tongue coatings presented lower microbial community diversity than thin tongue coatings. The tongue coating bacterial community is associated with the appearance of the tongue coating. The tongue coating may be a potential source for diagnosing gastric cancer, but its sensitivity needs to be further improved. [ABSTRACT FROM AUTHOR]

Background: To investigated the effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine for patient-controlled intravenous analgesia (PCIA) on patients after open gastrointestinal tumor surgery, and compared this combination with traditional PCIA with pure opioids or epidural analgesia (PCEA). Methods: Patients (n = 640) who underwent open gastrointestinal tumor surgery and received patient-controlled analgesia (PCA) were included. According to the type of PCA, patients were assigned to three groups: MPCIA (PCIA with sufentanil, flurbiprofen axetil, dexmedetomidine and metoclopramide), OPCIA (PCIA with sufentanil, tramadol and metoclopramide) and PCEA group (PCEA with sufentanil and ropivacaine). The characteristics of patients, intraoperative use of analgesics, postoperative visual analogue scale (VAS), postoperative adverse reactions and postoperative recovery were collected. The primary outcome was postoperative VAS score. One-way ANOVA, Kruskal-Wallis H test, Fisher exact probability method, and binary logistic regression analysis were used for analysis. Results: There were no significant differences in the characteristics of patients, operation time, tumor site and the use of postoperative rescue analgesics among the groups. In the first two days after open gastrointestinal tumor surgery, the VAS (expressed by median and interquartile range) of MPCIA (24th h, resting: 1,1; movement: 3,2. 48th h, resting: 0,1; movement: 2,1.) and PCEA (24th h, resting: 0,1; movement: 2,1. 48th h, resting: 0,1; movement: 2,2.) groups were significantly lower than those of OPCIA group (24th h, resting: 2.5,2; movement: 4,2. 48th h, resting: 1.5,1.75; movement: 3,1.) (all p < 0.01). The incidence of postoperative nausea and vomiting in MPCIA group was 13.6% on the first day after surgery, which was significantly higher than that in PCEA group. There was no significant difference in the incidence of other postoperative adverse events. Higher intraoperative sufentanil dosage (OR (95%CI) = 1.017 (1.002–1.031), p = 0.021), lower body mass index (OR (95%CI) = 2.081 (1.059–4.089), p = 0.033), and tumor location above duodenum (OR (95%CI) = 2.280 (1.445–3.596), p < 0.001) were associated with poor postoperative analgesia. Conclusions: The analgesic effects of PCIA with sufentanil in combination with flurbiprofen axetil and dexmedetomidine on postoperative analgesia was better than that of traditional pure opioids PCIA, and similar with that of PCEA. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore elderly patients with end-stage renal disease (ESRD) white matter changes, the relationship between white matter (WM) abnormalities and emotional regulation strategies, coping styles in elderly ESRD patients. Methods: Twenty-eight elderly ESRD patients and twenty-eight sex and age matched healthy controls (HC) were included in this study. Tract-based spatial statistic (TBSS) was used to investigate the microstructural changes of WM. Two questionnaires were used to measure emotional regulation strategies and coping styles. Results: Neuroimaging analysis showed that the damage of WM structure was widespread in elderly ESRD patients. Psychological test results showed that there were differences in emotional regulation strategies and coping styles between elderly ESRD patients and HC. Furthermore, mediating analysis showed that the mean diffusivity (MD) of the significantly different brain regions played a complete mediating role between group and positive coping style. Conclusion: These results suggest that the integrity of WM, emotional regulation strategies and coping styles play an important role in ESRD patients. Our findings provide evidence that positive coping style may be fully mediated by MD. These results may help us develop new ways to treat and prevent physical and psychological problems in elderly ESRD hemodialysis patients. [ABSTRACT FROM AUTHOR]

Objective: Defects in the human solute carrier family 26 member 4 (SLC26A4) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC26A4 mutations in Chinese patients with CH and analyze the function of the mutations. Methods: Patients with primary CH were screened for 21 CH candidate genes mutations by targeted next-generation sequencing. All the exons and exon-intron boundaries of SLC26A4 were identified and analyzed. The function of six missense mutation in SLC26A4 were further investigated in vitro. Results: Among 273 patients with CH, seven distinct SLC26A4 heterozygous mutations (p.S49R, p.I363L, p.R409H, p.T485M, p.D661E, p.H723R, c.919-2A>G) were identified in 10 patients (3.66%, 10/273). In vitro experiments showed that mutation p.I363L, p.R409H, p.H723R affect the membrane location and ion transport of SLC26A4, while p.S49R did not. Mutation p.T485M and p.D661E only affected ion transport, but had no effect on the membrane location. Conclusion: The prevalence of SLC26A4 mutations was 3.66% in Chinese patients with CH. Five mutations (p.I363L, p.R409H, p.T485M, p.D661E and p.H723R) impaired the membrane location or ion transport function of SLC26A4, suggesting important roles for Ile363, Arg409, Thr485, Asp661, and His723 residues in SLC26A4 function. As all variants identified were heterozygous, the pathogenesis of these patients cannot be explained, and the pathogenesis of these patients needs further study. [ABSTRACT FROM AUTHOR]

This study sought to assess the differences in mental health conditions among the general population, quarantined population and healthcare workers during the COVID-19 outbreak in China. An online rapid assessment captured depressive and anxiety symptoms, and sleep quality data. A total of 2689 participants (n=374 general population, n=403 healthcare workers, n=1912 quarantined population) were included in the final statistical analysis. The proportion of individuals with mild and/or serious depression and anxiety were higher in the general population when compared to the quarantined population and healthcare workers (58.6% vs. 25.1%vs. 48.6%, P<0.001; 41.2% vs. 18.5% vs. 35.7%, P<0.001). The prevalence of sleep disturbance was higher among healthcare workers than the general population and quarantined population (29.8% vs. 24.1% vs. 22.7%, P=0.013). Logistic regression analysis showed that, perceived effect on daily life was associated with depression, anxiety and sleep disturbance in the general population, quarantined population and the healthcare workers. The general population had a greater risk of developing psychological problems. The healthcare workers suffered the poorest sleep quality. Future research must further explorethe targeted measures for the general population and healthcare workers while combating COVID-19. [ABSTRACT FROM AUTHOR]

Background: The effects of circadian rhythms on drug metabolism and efficacy are being increasingly recognized. However, the extent to which they affect general anesthesia remains unclear. This study aims to investigate the effects of circadian rhythms on anesthetic depth and the concentrations of propofol target-controlled infusion (TCI). Methods: Sixty patients undergoing laparoscopic surgeries were sequentially assigned to four groups. Group ND (n = 15): Propofol TCI with Narcotrend monitor during the day (8:00–18:00), Group NN (n = 15): Propofol TCI with Narcotrend monitor during the night (22:00–5:00), Group CLTD (n = 15): Propofol closed-loop TCI guided by bispectral index (BIS) during the day (8:00–18:00), Group CLTN (n = 15): Propofol closed-loop TCI guided by BIS during the night (22:00–5:00). The Narcotrend index, mean arterial pressure (MAP) and heart rate (HR) were compared between group ND and NN at 7 time points, from 5 min before induction to the end of operation. The propofol TCI concentrations, MAP and HR were compared between group CLTD and CLTN at 7 time points, from 5 min after induction to the end of operation. Results: The Narcotrend index, MAP, and HR in group NN were lower than those in group ND from the beginning of mechanical ventilation to the end of operation (p < 0.05). The propofol TCI concentrations in group CLTN were lower than those in group CLTD from the beginning of operation to the end of operation (p < 0.05). Conclusion: Circadian rhythms have a significant effect on the depth of anesthesia and drug infusion concentrations during propofol TCI. When using general anesthesia during night surgery, the propofol infusion concentration should be appropriately reduced compared to surgery during the day. Trial registration: The present study was registered on the ClinicalTrials.gov website (NCT02440269) and approved by the Medical Ethics Committee of Southwest Hospital of Third Military Medical University (ethics lot number: 2016 Research No. 93). All patients provided informed written consent to participate in the study. [ABSTRACT FROM AUTHOR]

Objective  We aimed to describe changes in cesarean delivery (CD) rates after the change of the one-child policy in China by using the Robson classification in a large Chinese population. Study Design  This retrospective cohort study included 91,015 women who delivered at ≥24 weeks of gestation at a large tertiary obstetric center in Shanghai, China from 2011 to 2016. We analyzed CD rate trend and CD contribution trend in each Robson group. Logistic regression was used to calculate the odds of CD while adjusting for confounding variables. Results  The overall CD rate decreased from 49.0% in 2011 to 40.6% in 2016. In nulliparous women with singleton cephalic term pregnancy and planned CD, the CD contribution rate was reduced significantly from 29.3% in 2011 to 16.4% in 2016 (p  < 0.001). In multiparous with a scarred uterus, the CD contribution rate began to increase from 3.8% in 2011 to 9.1% in 2016 (p  < 0.001). Compared with delivery in 2011, delivery in 2016 was associated with a 37% (adjusted odds ratio [aOR]: 0.63; 95% confidence interval [CI]: 0.60–0.66) reduction in CD. This reduction was observed in both nulliparous women with singleton cephalic term pregnancy (aOR: 0.57; 95% CI: 0.54–0.60), and multiparous women with singleton cephalic term pregnancy without scar (aOR: 0.41; 95% CI: 0.30–0.55). Conclusion  The rate of cesarean delivery in our Chinese population has declined significantly in the past few years. [ABSTRACT FROM AUTHOR]

Existing research has established that openness to experience can enhance dispositional awe. For the first time, the current study examines whether subjective socioeconomic status (SSES) moderates and a Zhong‐Yong thinking style mediates this effect. A sample of 2,377 Chinese undergraduates (mean age 20.7, ranging from 18 to 26) was recruited. As shown in previous research, openness was found to be positively associated with dispositional awe. As predicted, the relationship was moderated by familial and school SSES. The positive correlation was significantly larger in cases of lower familial and school SSES. The mediating effect of Zhong‐Yong thinking style was also supported in the relationship between openness and dispositional awe, as was the moderating effect of familial SSES; however, a suppressive effect was found for school SSES. The implications of this study are discussed herein. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of video-based nursing education on perioperative anxiety and depression. A total of 128 patients scheduled for minimally invasive gastrectomy were randomly divided into intervention (n = 64) and control (n = 64) group. The. The anxiety and depression scores, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were assessed before the intervention, 1 h before surgery and 24 h after surgery. And the cortisol levels were measured before the intervention and 1 h before surgery. No significant difference was observed in baseline anxiety score, depression score, vital signs and cortisol level (P > 0.05). The anxiety level, depression level, SBP, DBP and HR of patients in intervention group was significantly lower than that in control group at 1 h before surgery and 24 hs after surgery (P < 0.05). The serum cortisol in the intervention group was also significantly lower than that in the control group 1 h before surgery (p < 0.001). Video-based nursing education was effective in decreasing the perioperative anxiety and depression of patients undergoing minimally invasive gastrectomy. It could also keep vital signs and serum cortisol levels in normal limits. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a 16-week Tai Chi (TC) intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss. Thirty-six older adults were divided into sensory loss and control groups, and they underwent a 16-week TC intervention. Significant interactions were detected in heel cutaneous sensitivity (p = 0.046, F = 4.419) and knee flexion (p = 0.043, F = 4.580), extension (p = 0.027, F = 5.529) and ankle plantar-flexion proprioception (p = 0.037, F = 4.860). The post hoc test indicated that in the sensory loss group, heel cutaneous sensitivity threshold (p = 0.034) and knee flexion (p = 0.004), extension (p = 0.002) and ankle plantar-flexion (p = 0.023) proprioception threshold decreased at week 17, whereas in the control group, knee flexion (p = 0.029) proprioception threshold decreased at week 17. TC intervention improved cutaneous sensitivity at more sites and proprioception in more joints among the older adults with sensory loss. TC intervention is a good option for older adults to exercise, and it is more effective among older adults with sensory loss. [ABSTRACT FROM AUTHOR]

Background: Hypertension and overweight are independent risk factors for cardiovascular disease, and overweight increase the risk of developing high blood pressure. ERBB3(also known as HER3) plays a considerable role in the development of cardiovascular diseases. However, the effect of ERBB3 levels in hypertensive overweight patients is unknown. The aim of this study was to assess the association between ERBB3 levels and hypertension in overweight Chinese patients. Methods: We evaluated the height,weight, blood pressure, biochemical indicators, and ERBB3 levels in 128 Chinese adults aged 33–79 years. Plasma ERBB3 levels were assessed by the enzyme-linked immunosorbent assay, and body mass index(BMI) was calculated as body weight divided by height squared. Participants were allocated into three groups according to blood pressure and BMI: healthy control (CNT, n = 31; normotensive and non-overweight), hypertension (HT, n = 33; hypertension and non-overweight), and hypertension with overweight (HTO, n = 64; hypertension and overweight). Statistical significance was defined as a two-tailed P < 0.05. Results: There was no significant difference in mean ERBB3 levels among the three groups, although a linear decrease from CNT (1.13 ± 0.36), HT (1.03 ± 0.36), to HTO (0.84 ± 0.26 ng/mL) was observed in men (P = 0.007). Among the drinking population, the ERBB3 level was significantly reduced in the HTO group as compared with those of the CNT and HT groups (0.76 ± 0.23 versus 1.18 ± 0.37 and 1.20 ± 0.30, respectively). ERBB3 levels were negatively correlated with diastolic blood pressure in men (r= − 0.293, P = 0.012), smoking (r= − 0.47, P = 0.004), and drinking (r = − 0.387, P = 0.008). BMI in men and among drinkers, and uric acid among drinkers were negatively correlated with ERBB3 levels. Multivariate conditional logistic regression showed that plasma ERBB3 levels were associated with a reduced risk of HTO in men [odds ratio (OR) 0.054; 95 % confidence interval (CI): 0.007–0.412) and drinkers (OR 0.002; 95 % CI: 0.000–0.101). Conclusions: ERBB3 may contribute to the pathogenesis of hypertension in overweight patients, with BMI, gender, and drinking all potentially modulating the process. [ABSTRACT FROM AUTHOR]

Objective. Interleukin- (IL-) 34 is a new type of cytokine with neuroprotective effects discovered in recent years. However, the relationship between IL-34 and vascular dementia (VaD) has not yet been elucidated. The purpose of this study is to determine whether IL-34 is involved in cognitive impairment of VaD. Methods. From January 2017 to December 2020, 84 VaD patients and 60 healthy controls who attended Qingpu Branch of Zhongshan Hospital were prospectively included in the study. Once included in the study, demographic features of all research subjects are collected. They include age, gender, education, white blood cells (WBC), neutrophil, lymphocyte, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Meanwhile, the Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function of participants. The serum IL-34 level was determined by enzyme-linked immunosorbent assay (ELISA). Results. There was no significant difference between the demographic features of VaD patients and healthy controls (p > 0.05). However, the serum IL-34 levels of VaD patients and healthy controls are 27.6 ± 3.9 pg / ml and 41.8 ± 6.0 pg / ml , respectively, and there is a significant statistical difference between them (p < 0.001). The results of bivariate correlation analysis showed that serum IL-34 levels were significantly positively correlated with MoCA scores (r = 0.371 , p = 0.023). Further regression analysis showed that IL-34 was still correlated with MoCA after adjusting for demographic features (β = 0.276 , p = 0038). Conclusions. Serum IL-34 levels in VaD patients were significantly reduced, which may be an independent predictor of cognitive impairment in VaD patients. [ABSTRACT FROM AUTHOR]

Objective: This study aims to develop an artificial intelligence‐based method to screen patients with left ventricular ejection fraction (LVEF) of 50% or lesser using electrocardiogram (ECG) data alone. Methods: Convolutional neural network (CNN) is a class of deep neural networks, which has been widely used in medical image recognition. We collected standard 12‐lead ECG and transthoracic echocardiogram (TTE) data including the LVEF value. Then, we paired the ECG and TTE data from the same individual. For multiple ECG‐TTE pairs from a single individual, only the earliest data pair was included. All the ECG‐TTE pairs were randomly divided into the training, validation, or testing data set in a ratio of 9:1:1 to create or evaluate the CNN model. Finally, we assessed the screening performance by overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: We retrospectively enrolled a total of 26 786 ECG‐TTE pairs and randomly divided them into training (n = 21 732), validation (n = 2 530), and testing data set (n = 2 530). In the testing set, the CNN algorithm showed an overall accuracy of 73.9%, sensitivity of 69.2%, specificity of 70.5%, positive predictive value of 70.1%, and negative predictive value of 69.9%. Conclusion: Our results demonstrate that a well‐trained CNN algorithm may be used as a low‐cost and noninvasive method to identify patients with left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Zanthoxylum armatum DC. (Z. armatum) is an herbal medicine with various active ingredients and pharmacological effects. However, modern studies found that Z. armatum is hepatotoxic. The liver is the target organ for toxic effects and an important site for lipid metabolism. The effects of Z. armatum on lipid level and metabolism in the liver are still unclear. This study aimed to analyze hepatic lipid levels, lipid metabolites and metabolic pathways of action of Z. armatum based on lipidomics, to investigate the potential hepatotoxic mechanism of Z. armatum. Different doses (62, 96, and 150 mg/kg) of the methanolic extract of Z. armatum (MZADC) were administered to ICR mice by gavage. The hepatotoxicity of MZADC was assessed by the liver index, serum biochemical measurements, and histopathological examination. Lipid levels measured by the serum lipid index were evaluated in the mice. Lipidomics was used to screen for differential lipid metabolism markers and lipid metabolism pathways in the liver. Western blot analysis was performed to investigate the effects of MZADC on the liver. Liver index values and serum alanine transaminase and aspartate transaminase levels were increased in the MZADC group. Histopathology examination revealed hepatocyte necrosis, watery degeneration of the hepatocytes, and hepatic cord rupture in the livers of mice. Serum levels of low-density lipoprotein cholesterol, cholesterol, and triglycerides were elevated, and high-density lipoprotein cholesterol levels were decreased. Lipidomics screening for markers of differential lipid metabolism in the liver, and altered profiles of differential metabolites indicated that glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol-anchored biosynthesis, sphingolipid metabolism and arachidonic acid metabolic pathways were significantly associated with MZADC-induced liver injury. Western blots confirmed that the protein expression of LC3, Beclin-1, ATG5, ATG12 and ATG16L1 was decreased, and p62 was increased in the MZADC group. The proportion of p-PI3K/PI3K and p-AKT/AKT was increased. The liver injury induced by MZADC involved many different lipid metabolites and lipid metabolic pathways, which may be related to autophagy. This study provides a new perspective on the hepatotoxicity study of Z. armatum and provides a reference for the safe application of Z. armatum in the medicine and food fields. [Display omitted] • Based on lipidomics, this study revealed hepatotoxicity induced by Zanthoxylum armatum DC. • The metabolites of liver lipid difference induced by Zanthoxylum armatum DC. may serve as potential biomarkers. • Glycerophospholipid metabolism pathways were significantly associated with Zanthoxylum armatum DC. induced liver injury. [ABSTRACT FROM AUTHOR]

Background. It is generally considered that traditional Chinese medicine (TCM) therapy postpones the progression of some chronic kidney diseases (CKDs). Chinese medicine herbs are widely applied in TCM therapy. We aimed to evaluate clinical efficacy and safety of Chinese herbal formula granules in patients with CKD stage 3 through a prospective randomized controlled study. Methods. A total of 343 participants with CKD stage 3 were recruited from 9 hospitals in Jiangsu Province between April 2014 and October 2016. Participants were randomly assigned to a treatment or control group. Patients in the treatment group orally took Chinese herbal formula granules twice a day, while controls received placebo granules. The duration of intervention was 24 weeks. Primary outcomes were 24-hour proteinuria, serum creatinine, and eGFR, which were measured every 4 weeks. Results. There was no statistical difference in 24-hour proteinuria between the two groups (0.97 ± 1.14 g/d vs. 0.97 ± 1.25 g/d). Patients in the treatment group had significantly lower serum creatinine level (130.78 ± 32.55 μmol/L versus 149.12 ± 41.27 μmol/L) and significantly higher eGFR level (55.74 ± 50.82 ml/min/1.73·m2 versus 44.46 ± 12.60 ml/min/1.73·m2) than those in the control group (P < 0.05). There was no significant difference between two groups in the incidence of adverse events. Conclusion. The treatment adopting Chinese herbal formula granules for 24 weeks improved kidney function of patients with CKD stage 3. [ABSTRACT FROM AUTHOR]

Background: H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. Aims: To describe the clinical features of H7N9 avian influenza and the response to treatment. Methods: Clinical, radiological and histopathological data, and treatment‐related of H7N9‐infected patients hospitalised during 2014–2017 were extracted and analysed. Results: A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground‐glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252‐C/C interferon‐induced transmembrane protein‐3 (IFITM3) genotype, while the others had the C/T genotype. Conclusions: H7N9 virus infection causes human influenza‐like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high‐risk patients. The presence of the IFITM3 rs12252‐C genotype may predict severe illness. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of superior vena cava (SVC) isolation using second‐generation cryoballoon (CB) ablation remain unknown. Methods: A total of 26 (3.2%) patients with SVC‐related paroxysmal atrial fibrillation (AF) from a consecutive series of 806 patients who underwent second‐generation CB were included. Pulmonary vein isolation was initially achieved by CB ablation. If the SVC trigger was determined, the electrical isolation of SVC isolation was performed using the second‐generation CB. Results: Real‐time SVC potential was observed in all patients. Isolation of the SVC was successfully accomplished in 21 (80.8%) patients. The mean number of freeze cycles in each patient was 2.1 ± 1.1. The mean time to isolation and ablation duration were 22.5 ± 14.2 seconds and 94.5 ± 22.3 seconds, respectively. A transient phrenic nerve (PN) injury was observed in five patients (19.2%). There were two patients (7.7%) experienced reversible sinus node injury during the first application. During a mean follow‐up period of 13.2 ± 5.8 months, four patients (15.4%) had atrial arrhythmia recurrences. Conclusion: Isolation of SVC using the second‐generation 28‐mm CB is feasible when SVC driver during AF is identified. Vigilant monitoring of PN function during CB ablation of SVC is needed to avoid PN injury. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in the treatment of neonatal infection, mortality rates and comorbidities associated with neonatal sepsis remain high. Hypocalcemia has been reported in critically ill patients, especially in as-sociation with sepsis. However, the importance of hypo-calcemia in neonatal sepsis has not been explored in detail. Objectives: The purpose of this study was to evaluate the prognostic value of hypocalcemia in neonatal sepsis patients and to identify the risk factors associated with sepsis-related mortality. Methods: This retrospective study examined perinatal data from patients in a level IV neonatal in-tensive care unit between January 2010 and June 2016. Univariate analysis was performed to understand the differences in clinical and laboratory characteristics between patients with and without neonatal sepsis. Neonates with sepsis were further stratified as having ionized hypocalcemia (if serum ionized calcium [iCa] <1.0 mmol/L) or not. Uni- and multivariate logistic regression analyses were utilized to evaluate the predictive potential of iCa for identifying sepsis-related mortality. Results: A total of 472 neonates were enrolled in this study, including 169 neonates diagnosed with culture-proven sepsis and 303 neonates without infection (control group). The comparison of neonates with and without sepsis highlighted significant differences in levels of iCa (0.97 ± 0.26 vs. 1.12 ± 0.25 mmol/L), magnesium (0.75 ± 0.22 vs. 0.89 ± 0.12 mmol/L), and phosphate (2.26 ± 1.08 vs. 1.65 ± 0.85 mmol/L; all p < 0.001). When neonates with sepsis were stratified into 2 subgroups based on serum iCa, neonates with hypocalcemia showed higher rates of organ dysfunction than those with normal iCa, as well as higher rates of cardiovascular system dysfunction (37.35 vs. 17.44%), renal dysfunction (34.94 vs. 30.95%), disseminated intravascular coagulation (26.51 vs. 11.63%), and seizure (16.04 vs. 5.8%; all p < 0.05). Among all neonates who had sepsis, the mortality rate was 13.61%, and this rate was higher among neonates with hypocalcemia than among those with normal iCa (20.48 vs. 6.98%, p < 0.05). Uni- and multivariate analyses showed that acidosis, hypoalbuminemia, hypocalcemia, and hyperphosphatemia were independent prognostic markers of sepsis-related mortality. In receiver-operating characteristic curve analysis, the areas under the curve were 0.70 (95% CI 0.624–0.768; p = 0.0004), 0.74 (95% CI 0.671–0.808; p < 0.0001), 0.73 (95% CI 0.653–0.792; p = 0.0002), and 0.67 (95% CI 0.59–0.737; p = 0.0154) for serum albumin, iCa, phosphate, and acidosis, respectively. Based on these findings, we developed a nomogram to predict sepsis-related mortality. Conclusions: Hypocalcemia is common in neonates with sepsis and is significantly associated with organ dysfunction and sepsis-related mortality. [ABSTRACT FROM AUTHOR]

Background. Qixuehe capsule (QXH), a Chinese patent medicine, has been demonstrated to be effective in the treatment of menstrual disorders. In traditional Chinese medicine (TCM) theory, qi stagnation and blood stasis syndrome (QS-BSS) is the main syndrome type of menstrual disorders. However, the pharmacodynamic effect of QXH in treating QS-BSS is not clear, and the main active compounds and underlying mechanisms remain unknown. Methods. A rat model of QS-BSS was established to evaluate the pharmacodynamic effect of QXH. Thereafter, a network pharmacology approach was performed to decipher the active compounds and underlying mechanisms of QXH. Results. QXH could significantly reduce the rising whole blood viscosity (WBV) and plasma viscosity (PV) but also normalize prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) content in QS-BSS rats. Based on partial least-squares-discriminant analysis (PLS-DA), the low-dose QXH-intervened (QXH-L) and the high-dose QXH-intervened (QXH-H) groups seemed the most effective by calculating the relative distance to normality. Through network pharmacology, QXH may improve hemorheological abnormality mainly via 185 compounds-51 targets-28 pathways, whereas 184 compounds-68 targets-28 pathways were associated with QXH in improving coagulopathy. Subsequently, 25 active compounds of QXH were verified by UPLC-Q/TOF-MS. Furthermore, 174 active compounds of QXH were shared in improving hemorheological abnormality and coagulopathy in QS-BSS, each of which can act on multiple targets to be mainly involved in complement and coagulation cascades, leukocyte transendothelial migration, PPAR signaling pathway, VEGF signaling pathway, and arachidonic acid metabolism. The attribution of active compounds indicated that Angelicae Sinensis Radix (DG), Paeoniae Radix Rubra (CS), Carthami Flos (HH), Persicae Semen (TR), and Corydalis Rhizoma (YHS) were the vital herbs of QXH in treating QS-BSS. Conclusion. QXH can improve the hemorheology abnormality and coagulopathy of QS-BSS, which may result from the synergy of multiple compounds, targets, and pathways. [ABSTRACT FROM AUTHOR]

Purpose: To determine the dose-response of vitamin D3 supplementation on serum 25-hydroxyvitamin D [25(OH)D] among Chinese adults. Methods: In this 5-arm, randomized, double-blinded controlled trial, 76 healthy participants were assigned to orally administrate 0, 400, 800, 1200 or 2000 IU/d of vitamin D3 for 16 weeks. Serum 25(OH)D, parathyroid hormone, calcium, biomarkers of liver and renal function were measured at multiple time points. Results: The mean (SD) serum 25(OH)D at baseline was 31.6 (8.7) nmol/L, and the dose-response relationship was curvilinear with a plateau around 6 weeks for all doses. At week 16, 25(OH)D was increased by 6.0 (6.5), 21.7 (15.8), 26.3 (12.6), 32.0 (12.8) and 36.3 (26.0) nmol/L for 0, 400, 800, 1200 and 2000 IU/d (all P ≤ 0.002), corresponding to approximately 19, 53, 67, 77 and 80 % of reversion of vitamin D deficiency, respectively. Daily intake of 800 IU vitamin D3 reached a targeted 25(OH)D ≥ 30 nmol/L in at least 97.5 % of Chinese, but not a targeted 25(OH)D ≥ 50 nmol/L even with 2000 IU/d. Change of 25(OH)D was inversely associated with change of PTH concentration ( r = −0.39, P < 0.001) after controlling for age and sex. No between-group differences were observed in terms of the change in serum calcium, alanine transaminase, aspartate aminotransferase, gamma-glutamyltransferase and creatinine ( P ≥ 0.22). Conclusions: Supplementation with 400, 800, 1200 or 2000 IU/d vitamin D could improve the vitamin D deficiency with various degrees. Whether 2000 IU/d vitamin D3 would generate a better result without side effect requires more studies with larger samples in future. [ABSTRACT FROM AUTHOR]

Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC–MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design. [ABSTRACT FROM AUTHOR]

Guizhi Fuling Capsule (GFC) is a famous traditional Chinese medicine (TCM) formula recorded in Synopsis of the Golden Chamber, which has achieved obvious effects in the treatment of uterine fibroids (UFs). Mediator complex subunit 12 (Med12) mutations were closely related to UFs in 85% of fibroid cases. The Wnt/β-Catenin signaling pathway plays an important role in the occurrence and development of UFs. This study aims to explore the pharmacological mechanism of GFC against UFs in which the Med12-mediated Wnt/β-Catenin pathway is involved. Med12 was silenced in uterine fibroid cells (UFCs) using a lentivirus-based Med12 gene-specific RNA interference (RNAi) strategy. Cell proliferation was performed by CCK-8 assay, cell apoptosis and cell cycle were measured by flow cytometry. The rat model of UFs was established by injecting estradiol benzoate and progesterone. Forty-eight rats were divided into six groups, the low-dose GFC (L-GFC) group, the medium-dose GFC (M-GFC) group and the high-dose GFC (H-GFC) group were intragastrically treated with GFC solution at 0.25 g/kg, 0.50 g/kg and 1.00 g/kg per day for 8 weeks, the positive control (PC) group was administrated with mifepristone (2.70 mg/kg/day), the normal control (NC) group and the model control (MC) group were given equal volume of normal saline once a day for 8 weeks. The histopathological changes of uterine tissues were evaluated by H&E staining. The expression of Med12 in uterine tissues were detected by immunohistochemistry. The protein and mRNA levels of associated genes were evaluated by western bolt and real time-PCR, respectively. Related indicators involved in Wnt/β-Catenin pathway, such as Wnt1, β-Catenin, Cyclin D1, TCF1/TCF7 and C-myc, were compared among different groups. The Wnt/β-Catenin signaling pathway was inhibited after Med12 gene was knocked out in UFCs. GFC-containing serum could induce cell apoptosis, make the cell cycle stagnated in G0/G1 phase to inhibiting the proliferation and reduce the expression of Wnt1, β-Catenin, Cyclin D1, TCF1/TCF7, and C-myc in control-shRNA cells, while had no significant effect on Med12-shRNA cells. Compared with the MC group, the weight, endometrial thickness, and pathological structure of the uterus in the GFC treated groups were significantly improved. The expression of Med12, Wnt1, β-Catenin, Cyclin D1, TCF1/TCF7, and C-myc that related to Wnt/β-Catenin pathway in the GFC treated groups were decreased with the increase of dosage administration. GFC inhibited UFs growth, which was directly associated with Med12 modulated Wnt/β-Catenin signaling pathway. This study provided new perspective to understand the therapeutic mechanism of UFs. [Display omitted] • Guizhi Fuling Capsule (GFC) inhibited the proliferation of uterine fibroid cells by disrupting the normal Med12 expression. • GFC induced apoptosis and made the cell cycle stagnated in G0/G1 phase of uterine fibroid cells. • GFC improved the weight, endometrial thickness, and pathological structure of the uterus in uterine fibroids model rats. • GFC regulated the Med12-mediated Wnt/β-Catenin pathway to treating uterine fibroids in model rats. [ABSTRACT FROM AUTHOR]

Fifteen new seco-pregnane steroidal glycosides cynanosides A-O (1-15) together with twenty-seven known ones were isolated from the roots of Cynanchum atratum. The structures of 1-15 were determined by extensive analysis of spectroscopic data. The anti-tobacco mosaic virus (TMV) activity of these steroidal glycosides was screened by the conventional half-leaf method, enzyme-linked immunosorbent assay, and Western blot methods, most of them showed potent anti-TMV activity. Among them, compounds 1, 7, 13, 28 and 31 showed significantly anti-TMV activity with an IC50 value of 20.5, 18.6, 22.0, 19.2 and 22.2 μg/mL, respectively, and were much more effective than the positive control, ningnanmycin (IC50 = 49.6 μg/mL). [ABSTRACT FROM AUTHOR]

Evidence shows that asthma originates in early life. Studies have found that phototherapy and/or neonatal jaundice may be associated with asthma. We investigated the association between neonatal bilirubin levels and childhood asthma without phototherapy intervention in the Collaborative Perinatal Project, a multicenter prospective cohort study conducted in the United States from 1959 to 1965. A total of 54,795 livebirths were included, and 40,063 children were followed up until 7 years of age or older. Total serum bilirubin (TSB) levels were examined at 48 hours postpartum in newborns with birthweights of 2,250 g or more. Information on asthma and other diseases through age 7 years was summarized and confirmed by a group of pediatricians and child neurologists. Among 28,807 term infants, the overall prevalence of asthma was 5.26%. Risks of asthma increased with both maximum TSB levels and TSB levels at 48 hours postpartum (P for trend < 0.01). Neonatal maximum TSB levels greater than 15 mg/dL were associated with a 61% increase in the risk of childhood asthma (odds ratio = 1.61, 95% confidence interval: 1.04, 2.08) after adjustment for confounders. In this prospective cohort study of infants born at a time when phototherapy was unavailable, neonatal hyperbilirubinemia was associated with an increased risk of childhood asthma. [ABSTRACT FROM PUBLISHER]

Abstract: Four new C18-diterpenoid alkaloids, weisaconitines A–D (1–4), were isolated from Aconitum weixiense. Based on extensive UV, IR, MS, 1D and 2D NMR analyses, their structures were elucidated as 8-O-ethyldolaconine (1), 4-demethylgenicunine B (2), 14-oxoaconosine (3), and 8-O-ethylaconosine (4). The analgesic activity of compound 4 was studied with CH3COOH-induced writhing model in mice. Compound 4 showed writhing inhibitions of 24% (50mg/kg), 26% (100mg/kg) and 34% (200mg/kg), respectively, as compared to the reference drug aspirin (63%) at a dose of 200mg/kg. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Ginkgo biloba extract (EGb 761) is widely used to treat cerebral disorders. Clinical trials have demonstrated therapeutic benefits of EGb 761 in various vascular diseases. Because the potential pathophysiological mechanisms appear similar to those involved in aneurysmal degeneration, we postulated that EGb 761 might affect the development and progression of experimental abdominal aortic aneurysm (AAA). This study was aimed to investigate whether EGb 761 influences the development of experimental AAAs, and to explore the underlying mechanisms. Material and methods: C57/BL6 mice underwent abluminal application of CaCl2 to the abdominal aorta followed by gavages with either 200mg/kg EGb 761 per day or vehicle. Six weeks after AAA induction, aortic tissue was excised for further examinations. Results: EGb 761 treatment reduced the aneurysm size compared with vehicle-treated controls. EGb 761 had no effect on hemodynamics or macrophage infiltration in the aortic wall. However, nuclear factor κB protein levels were decreased in the aortas of EGb 761 treated animals. The increased ROS production, SOD and CAT activities, and mRNA expression of p47phox nicotinamide adenine dinucleotide phosphate oxidase were attenuated by EGb 761 treatment. Moreover, administration of EGb 761 preserved the destruction of the wavy morphology of the elastin during AAA formation. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lowered in EGb 761 treated mice. Conclusions: These results suggest that treatment with EGb 761 in mice prevented the development of CaCl2-induced AAA. The possible mechanisms include decreased oxidative damage and inflammation, preservation of aortic wall architecture, and altered MMPs activities. [Copyright &y& Elsevier]

Background: Statins are widely prescribed to reduce cholesterol levels in the prevention of atherosclerotic cardiovascular disease. However, the debate about the effect of statins on cancer risk remains unsettled. The aim of this study was to investigate the association of utilization of statins with the risk of gastric cancer by carrying out a meta-analysis. Methods: A literature search was performed on PubMed and EMBASE up to March 2013 to identify the cohort or case-control studies or randomized controlled trials (RCTs) that examined the relationship between statins use and the risk of gastric cancer. The bibliographies of the retrieved articles were also reviewed to identify additional studies. A random-effects model was used to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs). Results: Three post-hoc analyses of 26 RCTs involving 290 gastric cancers and eight observational studies totaling 7,321 gastric cancers were included. Statins use was shown to be significantly associated with a 27 % reduction in the risk of gastric cancer (RR = 0.73, 95 % CI = 0.58-0.93), with considerable heterogeneity among studies ( I = 88.9 %). Excluding one study in which all subjects are diabetic patients obtained an attenuated, but homogeneous result (RR = 0.85, 95 % CI = 0.80-0.91, I = 0.0 %). These findings were consistent in the subgroup analysis. Conclusion: A meta-analysis of existing evidence, primarily from observational studies, indicates that use of statins reduces the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Polybrominated diphenyl ethers (PBDEs), commonly used in building materials, electronics, plastics, polyurethane foams, and textiles, are health hazards found in the environment. Objective: In this study we investigated the effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells as well as the underlying protein alterations. Methods: We used MCF-7 and MCF-7/ADR (multidrug-resistant MCF-7) breast cancer cell lines, the HeLa cervical cancer cell line, the OVCAR-3 ovarian cancer cell line, and the normal CHO (Chinese hamster ovary) cell line to assess the effects of PBDE-209 using cell viability, immunofluorescence, and flow cytometric assays. Western blot assays were used to detect changes in protein expression. To assess the effects of PBDE-209 on apoptosis, we used the protein kinase Cα (PKCα) inhibitor Gö 6976, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and tamoxifen. Results: Our data indicate that PBDE-209 increased viability and proliferation of the tumor cell lines and in CHO cells in a dose- and time-dependent manner. PBDE-209 also altered cell cycle distribution by inducing the S phase or G2/M phase. Furthermore, PBDE-209 partially suppressed tamoxifen-induced cell apoptosis in the breast cancer cell lines (MCF-7 and MCF-7/ADR) but suppressed Gö 6976- and PD98059-induced apoptosis in all cell lines. At the molecular level, PBDE-209 enhanced PKCα and ERK1/2 phosphorylation in the cell lines. Conclusions: Our data demonstrate that PBDE-209 is able to promote proliferation of various cancer cells from the female reproductive system and normal ovarian CHO cells. Furthermore, it reduced tamoxifen, PKCα, and ERK inhibition-induced apoptosis. Finally, PBDE-209 up-regulated phosphorylation of PKCα and ERK1/2 proteins in tumor cells and in CHO cells. [ABSTRACT FROM AUTHOR]

Green tea is the most ancient and popular beverage worldwide and its main constituent epigallocatechin-3-gallate (EGCG) has a potential role in the management of cancer through the modulation of cell signaling pathways. However, EGCG is frangible to oxidation and exhibits low lipid solubility and bioavailability, and we synthesized a derivative of EGCG in an attempt to overcome these limitations. The anthracycline antibiotic daunorubicin (DNR) is a potent anticancer agent. However, its severe cardiotoxic limits its clinical efficacy. Human carbonyl reductase 1 (CBR1) is one of the most effective human reductases for producing hydroxyl metabolites and thus may be involved in increasing the cardiotoxicity and decreasing the antineoplastic effect of anthracycline antibiotics. Accordingly, in this study, we investigated the co-therapeutic effect of Y6, a novel and potent adjuvant obtained by optimization of the structure of EGCG. The cellular concentrations of DNR and its metabolite DNRol were measured by HPLC to determine the effects of EGCG and Y6 on the inhibition of DNRol formation. The cytotoxic effects of EGCG and Y6 were tested by MTT assay in order to identify non-toxic concentrations of them. To understand their antitumor and cardioprotective mechanisms, hypoxia-inducible factor-1α (HIF-1α) and CBR1 protein expression was measured via Western blotting and immunohistochemical staining while gene expression was analyzed using RT-PCR. Moreover, PI3K/AKT and MEK/ERK signaling pathways were analyzed via Western blotting. HepG2 xenograft model was used to detect the effects of EGCG and Y6 on the antitumor activity and cardiotoxicity of DNR in vivo. Finally, to obtain further insight into the interactions of Y6 and EGCG with HIF-1α and CBR1, we performed a molecular modeling. Y6(10 μg/ml or 55 mg/kg) decreased the expression of HIF-1α and CBR1 at both the mRNA and protein levels during combined drug therapy in vitro as well as in vivo , thereby inhibiting formation of the metabolite DNRol from DNR, with the mechanisms being related to PI3K/AKT and MEK/ERK signaling inhibition. In a human carcinoma xenograft model established with subcutaneous HepG2 cells, Y6(55 mg/kg) enhanced the antitumor effect and reduced the cardiotoxicity of DNR more effectively than EGCG(40 mg/kg). Y6 has the ability to inhibit CBR1 expression through the coordinate inhibition of PI3K/AKT and MEK/ERK signaling, then synergistically enhances the antitumor effect and reduces the cardiotoxicity of DNR. Image 1 [ABSTRACT FROM AUTHOR]