Search

Objective. Remote ischemic conditioning (RIC) is a cardioprotective method in ischemia/reperfusion (I/R) injury. This study investigated the mechanism of Rho-kinase-mediated autophagy in RIC. Methods. Sixty male Sprague–Dawley rats were randomly divided into six groups: sham, I/R, RIC, I/R+fasudil, RIC+wortmannin, and RIC+fasudil+wortmannin. Throughout the experiment, mean arterial pressure and heart rate were continuously monitored. Histopathology and ultrastructure and myocardial enzymes’ expression were evaluated to determine the degree of cardiac injury. The protein expression of the Rho-kinase substrates myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1), autophagy-related protein light chain 3-II (LC3-II) and Beclin 1, and protein kinase B (AKT) was measured in the myocardial tissue. Results. Compared with the sham group, the mean arterial pressure and heart rate were decreased, myocardial enzyme levels were increased, and myocardial damage was aggravated in the I/R group; however, RIC improved these alterations. The expression of phosphorylated MLC and MYPT1 was lower, while LC3-II, Beclin 1, and phospho-AKT expression levels were higher in the RIC group compared with the I/R group. Obviously, treatment of the I/R group rats with fasudil, a Rho-kinase inhibitor, significantly ameliorated the I/R effects, whereas treatment of the RIC group rats with wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor, inhibited the RIC protective effects. Moreover, the rats in the RIC+fasudil+wortmannin group showed similar changes to those in the RIC+wortmannin group. Conclusion. These results showed that RIC protected the myocardium from I/R injury by suppressing Rho-kinase and the underlying mechanism may be related to enhancing autophagy via the PI3K/AKT pathway.

To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population.Cross-sectional study.The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines.The study included 7,719 participants (mean age: 60.5 ± 8.1 years; range: 50-97 years). The prevalence of any, early, intermediate, and late AMD was 1,607 of 7,719 (20.8%; 95% confidence interval [CI]: 20.1%, 21.9%), 832 of 7,719 (10.8%; 95% CI: 10.1%, 11.5%), 733 of 7,719 (9.5%; 95% CI: 8.9%, 10.2%), and 42 of 7,719 (0.50%; 95% CI: 0.40%, 0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio [OR]:3.49; 95% CI: 2.26, 5.38; P.001), after adjusting for older age (OR: 1.06; 95% CI: 1.05, 1.07; P.001), higher serum concentration of calcium (OR: 2.52; 95% CI: 1.32, 4.84; P = .005), high-density lipoproteins (OR: 1.39; 95% CI: 1.19, 1.61; P.001), and lower lipoprotein a (OR: 0.99; 95% CI: 0.98, 0.99; P = .02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD: OR: 4.35, P.001; intermediate and late AMD: OR: 6.14, P.001). Individuals with a monocyte count of ≥0.5 × 10A higher prevalence of early AMD, intermediate AMD, late AMD, and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD.

RNA interference (RNAi) was used to investigate the role of epididymal vascular endothelial growth factor (VEGF) gene expression on sperm hyaluronidase (HYD) in a rat model of arsenic poisoning and to identify a new gene therapy target for male infertility caused by arsenic poisoning. The Rat model of chronic arsenic poisoning was established. And we found that positive expression of VEGF and VEGF receptor 2 (VEGFR2) was observed by Immunohistochemical staining in the epididymal tissues of arsenic-exposed rats. Subsequently, VEGF-shRNA-1, VEGF-shRNA-2 and VEGF shRNA-3 expression vectors containing epididymal VEGF-shRNA lentivirus were constructed and injected into the bilateral epididymis of each group of rats (Control group, NC-shRNA negative infection group, VEGF-shRNA-1 group, VEGF-shRNA-2 group, VEGF-shRNA-3 group) (n = 10 per group). Compared with the negative infection group and the normal control group, the expression of VEGF and VEGFR2 mRNA and protein levels were significantly decreased following epididymal infection. In addition, the HYD activity was all significantly lower than that in the normal control group and the negative infection group. Taken together, epididymal VEGF gene silencing may inhibit the activity of sperm HYD through downregulating VEGFR2., Graphical abstract

Previous studies have indicated that neighborhood disorganization affects child-rearing beliefs in the United States, but few studies have focused on such influences among Asian American parents. Largely due to Asian American parents' immigration experiences, neighborhood disorganization factors inevitably intersect with their traditional cultures, which may lead to different patterns in their parental beliefs. Using structural equation modeling, this study found that neighborhood disorganization factors directly influenced Asian American parents' beliefs toward physical punishment and parenting stress mediated this relationship. These findings suggest that the integration of family and neighborhood-level practices in social services may reduce the risk of physical abuse.

Owing to the small number of patients with tyrosine hydroxylase (TH) deficiency, no genotype-phenotype correlations have yet been identified. To investigate the genotype-phenotype correlation of R233H mutation in TH deficiency, we analyzed the clinical manifestations and treatment responses of four patients with the R233H homozygous mutation. Thirty-eight additional patients, available from the literature, known to be homozygous or heterozygous for the R233H mutation, were combined with the four cases from our hospital. Data for a total of 42 patients were retrieved. Our four patients showed clinical presentation consistent with Type A TH deficiency, and responded well to levodopa therapy, with an improvement in clinical symptoms within 1–2 weeks. In the 42 patients, 20 of 42 patients (48%) were homozygous and 22 (52%) were heterozygous for the R233H mutation. Of the 20 patients who were homozygous for the R233H mutation, a majority (80%) suffered from Type A TH deficiency. Of the 8 patients that were heterozygous for the R233H/the mutation located downstream of exon 11, 7 patients (86%) suffered from Type B TH deficiency. Of the 7 patients who were heterozygous for the R233H/nonsense mutation, 6 (86%) suffered from Type B TH deficiency. Genotype-phenotype correlation of R233H mutation was observed in TH deficiency. The homozygous R233H mutation frequently manifests as Type A TH deficiency, whereas R233H/nonsense mutation or any mutation located downstream of exon 11 manifests as Type B TH deficiency.

Serum ferritin (SF) and haemoglobin (Hb) are widely used in clinical practice to assess iron status. Studies exploring the relationship of SF and Hb with atherosclerotic cardiovascular disease (ASCVD) risk have yielded conflicting results, and some indicated sex specificity. Hypertensive patients have abnormal iron status. However, research on patients with hypertension is limited. We aim to investigate the sex-specific links of SF and Hb with the predicted 10-year ASCVD risk in hypertensive patients. This cross-sectional study included 718 hypertensive men and 708 hypertensive women. The predicted 10-year ASCVD risk was calculated based on the China-PAR equation. The dose–response curves were illustrated by fitting linear and quadratic models. In hypertensive men, the iron status fits for a quadratic model for ASCVD risk, showing a U-shape. After adjusting for potential confounding factors, the regression coefficients and 95% confidence intervals (95% CI) across tertile of SF were 0.0 (reference), − 0.99 (− 1.65, − 0.33) and − 0.22 (− 0.88, 0.44), and of Hb were 0.0 (reference), − 0.74 (− 1.41, − 0.08) and − 0.77 (− 1.46, − 0.08). In hypertensive women, iron status was linearly and positively associated with ASCVD risk. Per one unit increment of log-transformed SF as well as Hb was associated with a 1.22 (95% CI: 0.97, 1.48) and 0.04 (95% CI: 0.02, 0.07) increased in ASCVD risk score, respectively. A significant interaction between iron status and inflammation on ASCVD risk was observed in hypertensive women. SF and Hb showed a U-shape with ASCVD risk in hypertensive men; however, a positive linear relationship was observed in hypertensive women.

Spontaneous mutations introduce uncertainty into COVID-19 control procedures and vaccine development. Here, we perform spatio-temporal analysis on intra-host single-nucleotide variations (iSNVs) in 402 clinical samples from 170 patients, which reveals an increase in genetic diversity over time post-symptoms onset within individual patients. Nonsynonymous mutations are over-represented in the pool of iSNVs, but underrepresent at the single nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated within the host (positive selection), and these substitutions tend to be unfixed as SNPs in population (negative selection). Dynamic iSNVs changes in subpopulations of different gender, age, illness severity and viral shedding time displayed a varied fitness selection process among populations. Taken together, our study highlights iSNVs provide a mutational pool shaping the virus rapid global evolution., Graphical Abstract, The Intra-host variations in SARS-CoV-2 provide a mutational pool shaping the virus rapid global evolution. Here, Li et al. illustrate dynamic changes of iSNVs in a longitudinal cohort, and explored a two-step fitness selection process of within-host viral evolution.

Drawing from regulatory fit theory and the literature on persuasion, the current study is the first to explore whether the fit between explanation framing and applicants' regulatory foci could enhance applicant reaction. We hypothesized that a positively framed explanation fits with applicants' promotion foci and that a negatively framed explanation fits with applicants' prevention foci. Three studies were conducted in which participants with different regulatory foci rated their perceived procedural fairness and organizational attractiveness after reading differently framed recruitment advertisements, rejection letters, and job offer letters. The results supported our hypothesis by showing significant interactions between explanation framing and participants' regulatory foci on procedural fairness and organizational attractiveness perception in the contexts of recruitment advertising and rejection letters. In these contexts, compared with receiving a negatively framed explanation, promotion-focused recipients reported higher levels of perceived fairness and organizational attractiveness after receiving a positively framed explanation, and promotion-focused recipients' fairness and attractiveness perceptions were higher than prevention-focused recipients', after receiving a positively framed explanation. Moreover, perceived procedural fairness mediated the relationship between regulatory fit and perceived organizational attractiveness. However, regulatory fit effects were not found in the context of job offer letters.

Prostate cancer (PCa) screening using serum prostate-specific antigen (PSA) testing has caused unnecessary biopsies and overdiagnosis owing to its low accuracy and reliability. Therefore, there is an increased interest in identifying better PCa biomarkers. Studies showed that trained dogs can discriminate patients with PCa from unaffected men by sniffing urine. We hypothesized that urinary volatile organic compounds (VOCs) may be the source of that odor and could be used to develop urinary VOC PCa diagnosis models.Urine samples from 55 and 53 biopsy proven PCa-positive and -negative patients respectively were initially obtained for diagnostic model development. Urinary metabolites were analyzed by gas chromatography-mass spectrometry. A PCa diagnosis model was developed and validated using innovative statistical machine-learning techniques. A second set of samples (53 PCa-positive and 22 PCa-negative patients) were used to evaluate the previously developed PCa diagnosis model.The analysis resulted in 254 and 282 VOCs for their significant association (P .05) with either PCa-positive or -negative samples respectively. Regularized logistic regression analysis and the Firth method were then applied to predict PCa prevalence, resulting in a final model that contains 11 VOCs. Under cross-validation, the area under the receiver operating characteristic curve (AUC) for the final model was 0.92 (sensitivity, 0.96; specificity, 0.80). Further evaluation of the developed model using a testing cohort yielded an AUC of 0.86. As a comparison, the PSA-based diagnosis model only rendered an AUC of 0.54.The study describes the development of a urinary VOC-based model for PCa detection.

Background Resilience has been linked to psychological adaptation to many challenging life events. The present study aims to explore the level of resilience in oral cancer patients and the key factors associated with resilience, and to evaluate the relationship between resilience and anxiety. Methods A multiple center cross-sectional study was carried out for Chinese patients with oral cancer between May 2016 and October 2017 in the Stomatology Hospital of China Medical University and Department of Stomatology, Shengjing Hospital of China Medical University. Two hundred and thirty oral cancer patients replied to the questionnaires on resilience, hope, perceived social support, optimism, perceived stress and anxiety which were measured with Resilience Scale-14 (RS-14), Herth Hope Index (HHI), Multidimensional Scale of Perceived Social Support (MSPSS), Revised Life Orientation Test (LOT-R), Perceived Stress Scale-10 (PSS-10) and Zung Self-Rating Anxiety Scale (SAS), respectively. Univariate one-way ANOVA/t-test, Pearson’s r and hierarchical linear regression analysis were conducted to explore the influence factors of resilience and the relationship between resilience and anxiety. Results The level of resilience was 67.93 ± 12.65. Resilience was positively correlated with hope, optimism and perceived social support, and negatively correlated with perceived stress. Hierarchical linear regression analysis showed that hope (β = 0.386, P

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up. Magnetic resonance (MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China. AIM To investigate the accuracy of MR imaging (MRI) in quantifying liver fat with MR spectroscopy (MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents. METHODS There were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction (PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by Bland-Altman analysis. RESULTS The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ± 10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%, respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5% (40/86) of all participants, all of whom belonged to the overweight and obese group. Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS (r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods. CONCLUSION Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.

Obesity increases the risk of developing cardiovascular disease and other metabolic diseases. We intended to compare three different anthropometric indicators of obesity, in predicting the incidence of cardiovascular events in Chinese type 2 diabetes. Beijing Community Diabetes Study was a prospective multi-center study conducted in Beijing community health centers. Type 2 diabetes patients from fourteen community health centers were enrolled at baseline. The primary endpoint was cardiovascular events. The upper quartile of neck circumference (NC) was set as greater NC. A total of 3299 diabetes patients were enrolled. In which, 941 (28.52%) had cardiovascular disease at baseline. Logistic analysis showed that central obesity (waist circumference (WC) above 90 cm in men and 85 cm in women) and greater NC were all related to baseline cardiovascular disease (adjusted OR = 1.49, and 1.55). After 10-year follow-up, 340 (10.31%) had cardiovascular events. Compared with patients without cardiovascular events, those having cardiovascular events had higher BMI, larger WC and NC. Cox regression analysis showed that greater WC and NC were all associated with the occurrence of cardiovascular events (adjusted HR = 1.41, and 1.38). A higher NC and WC might increase the risk of cardiovascular events by about 40% in type 2 diabetes patients in Beijing communities.

To observe the mechanism of myocardial injury in diabetic rats after irbesartan intervention and analyze the role of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory pathway. The experiment was divided into four groups: normal control group (CON), high glucose and high caloric diet group (HC), diabetes group (DM) and diabetes+irbesartan group (DM+Ir). Compared with CON group, in HC group, triglyceride, total cholesterol and fasting blood glucose levels were increased; however, there was no significant difference of the cardiac function, the degree of myocardial fibrosis, NLRP3, ASC, Caspase-1 mRNA and protein expressions and the releasing of inflammatory factors interleukin (IL)-1β and IL-18. Compared with HC group, in DM group, triglyceride, total cholesterol, fasting blood glucose, IL-1β and IL-18 levels, NLRP3, ASC, Caspase-1 mRNA and protein expressions and the degree of myocardial fibrosis were increased, but the cardiac function was decreased. Compared with DM group, there were no changes in total cholesterol and fasting blood glucose, the degree of myocardial fibrosis cardiac function was attenuated, NLRP3, ASC, Caspase-1 expressions, IL-1β and IL-18 levels were reduced in DM+Ir group. The results suggested that irbesartan may exert myocardial protection by inhibiting the expression of the NLRP3/ASC/Caspase-1 pathway in diabetic rats.

This study aims to identify the causes of coordination breakdowns among control crews and to understand their coordination-behaviour patterns during emergencies in nuclear power plants (NPPs). On the basis of in-depth interviews with 18 control-crew operators, we identified 25 causes of coordination breakdown related to work processes, personnel, and situation and organisation. In addition, we observed 12 control-crew training sessions that dealt with emergencies and conducted lag-sequential analysis. The levels of coordination effectiveness were evaluated using the proportion of coordination breakdowns and the anticipation ratio. We found that higher-performing teams exhibited more non-random coordination behavioural patterns than did lower-performing teams. Coordination-behaviour patterns specific to the higher-performing teams included adaptive workload management (from senior operators) and proactive seeking performance monitoring (from junior operators). The findings of the study enrich our understanding of the critical factors and processes that influence coordination effectiveness of NPP control crews.

Vitamin D deficiency has been reported to be associated with respiratory tract infection (RTI). However, evidence regarding the effects of vitamin D supplementation on susceptibility of infants to RTI is limited. In this prospective birth cohort study, we examined whether vitamin D supplementation reduced RTI risk in 2,244 infants completing the follow‐up from birth to 6 months of age. The outcome endpoint was the first episode of paediatrician‐diagnosed RTI or 6 months of age when no RTI event occurred. Infants receiving vitamin D supplements at a daily dose of 400–600 IU from birth to the outcome endpoint were defined as vitamin D supplementation and divided into four groups according to the average frequency of supplementation: 0, 1–2, 3–4, and 5–7 days/week. We evaluated the relationship between vitamin D supplementation and time to the first episode of RTI with Kaplan–Meier plots. The associations of vitamin D supplementation with infant RTI, lower RTI (LRTI), and RTI‐related hospitalization were assessed using modified Poisson regression. The median time to first RTI episode was 60 days after birth (95% CI [60, 90]) for infants without supplementation and longer than 6 months of age for infants with supplementation (p < .001). We observed inverse trends between supplementation frequency and risk of RTI, LRTI, and RTI‐related hospitalization (p for trend < .001), with the risk ratios in the 5–7 days/week supplementation group of 0.46 (95% CI [0.41, 0.50]), 0.17 (95% CI [0.13, 0.24]), and 0.18 (95% CI [0.12, 0.27]), respectively. These associations were significant and consistent in a subgroup analysis stratified by infant feeding.

OBJECTIVE: To observe the expression of NLRP1 inflammasomes in myocardial tissues in rats with a high-fat and highsugar diet and in diabetic rats analyze the role of NLRP1 inflammasomes in the pathogenesis of diabetic cardiomyopathy. METHODS: Male SD rats were divided into normal control group, high-sugar and high-fat diet (HC) group and diabetes group. Rat models of diabetes were established by intraperitoneal injection of streptozotocin (STZ; 30 mg/kg). Serum levels of cholesterol (TC), triglyceride (TG), and fasting insulin (FINS) were measured after 8 weeks of feeding, and the insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated; Echocardiographic evaluation of cardiac structure and function was performed, and Western blotting and real-time fluorescent quantitative PCR (RT-qRCP) were used to detect the protein and mRNA expressions of NLRP1, ASC, and caspase 1 in the myocardial tissue. RESULTS: Compared with the control rats, the rats in the HC group had significantly increased body weight (BW), serum levels of TG and TC, mRNA expressions of NLRP1 and caspase 1, and the protein expression of NLRP1 (P < 0.01) without significant changes in FINS, IRI, ISI, or cardiac ultrasound findings (P > 0.05) or in myocardial ASC and caspase 1 protein expressions or serum levels of IL-1β and IL-18 (P > 0.05). In the diabetic rats, TC, TG, and FBG levels increased and FINS, ISI decreased significantly (P < 0.01); the left ventricular end-diastolic diameter (LVID) and the left ventricular end-systolic diameter (LVSD) increased while the ejection fraction (LVEF), short axis shortening rate (FS), and E/A ratio all decreased. The expressions of NLRP1/ASC/caspase 1 pathway mRNA and NLRP1 and caspase 1 proteins also increased but myocardium ASC protein expression did not show significant changes in the diabetic rats (P > 0.05). IL-1β and IL-18 levels were also significantly higher in the diabetic rats than in the control group (P < 0.05). Compared with those in HC group, the diabetic rats showed significantly increased serum FBG and decreased FINS, ISI and BW (P < 0.01) with decreased LVSD, LVEF and E/A ratio and increased levels of NLRP1 and caspase 1 protein expressions and serum L-1β and IL-18 levels (P < 0.01). CONCLUSION: Diabetes can cause abnormal changes in cardiac structure and functions and induce inflammatory response in the myocardium, which may be related to the activation of NLRP1/ASC/ caspase 1 inflammasomes.

Background Maternal iodine status has been suggested to affect birth outcomes. Few studies have focused on its effects on fetal growth during pregnancy. Objective This study aimed to assess maternal iodine status during early pregnancy and further examine the relation between maternal iodine status and fetal growth. Methods A total of 2087 singleton-pregnant women participating in the Tongji Maternal and Child Health Cohort study were involved. Urinary iodine concentration (UIC) and creatinine concentration were measured in spot urine samples collected in early pregnancy (

Irisin, a myokine produced by skeletal muscle in response to physical exercise, promotes trans-differentiation of white adipose tissue into brown adipose tissue. Recent evidences suggested that irisin also plays an important role in the control of bone metabolism. This study aimed to ascertain the relationship between plasma irisin and bone mineral density (BMD) in Chinese population by adoption of an extreme sampling method. Based on a large and screened Chinese elderly population (N = 6308), two subgroups with extremely high and low hip BMD were selected for discovery (N = 80, high vs. low BMD = 44:36) and validation (N = 60, high vs. low BMD = 30:30), respectively. Plasma irisin, P1NP, and β-CTx were measured using commercially available ELISA kits. Other metabolic parameters (e.g., blood glucose, total cholesterol and triglycerides) were collected. Student's t test and Spearman correlation analyses were conducted in SPSS. Significant difference was discovered for plasma irisin between females and age-matched males (N = 80, male vs. female = 42:38, P = 0.002). The plasma irisin levels were significantly higher in high BMD subjects than in low BMD subjects, which was observed in both discovery (P = 0.012) and validation samples (P = 0.022). However, such observation was limited to males only. Further correlation analyses in males showed that plasma irisin was correlated with BMD (r = 0.362, P = 0.025) and triglyceride (r = - 0.354, P = 0.032). Plasma irisin levels were associated with hip BMD in Chinese elderly men. This study represented the first effort of investigating the relationship of plasma irisin and BMD in elderly population. The positive correlation between plasma irisin and BMD hints intrinsic communication between muscle and bone.

Myostatin is mainly secreted by skeletal muscle and negatively regulates skeletal muscle growth. However, the roles of myostatin on bone metabolism are still largely unknown. Here, we recruited two large populations containing 6308 elderly Chinese and conducted comprehensive statistical analyses to evaluate the associations among lean body mass (LBM), plasma myostatin, and bone mineral density (BMD). Our data revealed that total myostatin in plasma was mainly determined by LBM. The relative abundance of mature myostatin (mature/total) was significantly lower in high versus low BMD subjects. Moreover, the relative abundance of mature myostatin was positively correlated with bone resorption marker. Finally, we carried out in vitro experiments and found that myostatin has inhibitory effects on the proliferation and differentiation of human osteoprogenitor cells. Taken together, our results have demonstrated that the relative abundance of mature myostatin in plasma is negatively associated with BMD, and the underlying functional mechanism for the association is most likely through inhibiting osteoblastogenesis and promoting osteoclastogenesis.

In the main control rooms of nuclear power plants, operators frequently have to switch between procedure displays and system information displays. In this study, we proposed an operation-unit-based integrated design, which combines the two displays to facilitate the synthesis of information. We grouped actions that complete a single goal into operation units and showed these operation units on the displays of system states. In addition, we used different levels of visual salience to highlight the current unit and provided a list of execution history records. A laboratory experiment, with 42 students performing a simulated procedure to deal with unexpected high pressuriser level, was conducted to compare this design against an action-based integrated design and the existing separated-displays design. The results indicate that our operation-unit-based integrated design yields the best performance in terms of time and completion rate and helped more participants to detect unexpected system failures. Practitioner Summary: In current nuclear control rooms, operators frequently have to switch between procedure and system information displays. We developed an integrated design that incorporates procedure information into system displays. A laboratory study showed that the proposed design significantly improved participants' performance and increased the probability of detecting unexpected system failures.

Numerous esophageal squamous cell carcinoma (ESCC) patients exhibit tumor recurrence following radical resection. Invasion and metastasis are key factors in poor prognosis following esophagectomy. In the present study, two‑dimensional gel electrophoresis (2-DE) and matrix‑assisted laser desorption/ionization time-of-flight mass spectrometry were used to define patterns of protein expression in ESCC tissues at different pathological stages. The expression levels of identified proteins were determined by immunohistochemistry and western blotting. A total of fifteen protein spots with >2-fold differences were observed when comparing results of 2-DE for stage III and stage I ESCC tissue sample. A total of 12 proteins were identified by mass spectrometry analysis and database searches. The results of immunohistochemistry and western blotting demonstrated expression levels of tropomyosin 3 (TPM3) were higher in stage III ESCC tissue compared with stage I (P

We aimed to assess protein nutrition status during pregnancy by maternal plasma total protein (MTP) levels in urban pregnant women and to explore the association between the trimester‐specific MTP levels and risk of preterm birth (PTB). A prospective design was conducted in 3,382 mother‐newborn pairs with the second‐trimester maternal MTP information and in 3,478 mother‐newborn pairs with the third‐trimester MTP information. Multiple Cox proportional hazard regression and multiple linear regression were used to analyse the associations between MTP levels and PTB risk as well as gestational duration, respectively. Nearly all the second‐trimester MTP levels were within the clinical reference range, but more than 40% of the third‐trimester MTP levels were less than the lower limit of normal. No significant association was found between the second‐trimester MTP level and PTB risk. However, the adjusted hazard ratios (HRs) of PTB across increasing quartiles of the third‐trimester MTP levels were 1.00 (reference), 0.59 (0.36, 0.95), 0.35 (0.20, 0.60), and 0.32 (0.19, 0.53) (p for trend < 0.001), respectively. Each standard deviations increment of the third‐trimester MTP was associated with increase of 0.13 weeks in gestational duration. Moreover, stratified analyses showed that the effects of third‐trimester MTP on PTB risk and gestational duration were stronger in pregnant women carrying female offspring than those carrying male offspring (p for interaction < 0.05). The third‐trimester MTP level was inversely associated with PTB risk and was positively associated with gestational duration. Improving third‐trimester MTP level may be helpful for preventing PTB.

Background. Neck circumference (NC) was found to be related to the risk factors of cardiovascular disease. However, the effects of NC on cardiovascular disease are still controversial. A prospective study of Chinese patients with type 2 diabetes was performed to evaluate the relationship between NC and cardiovascular disease. Methods. A multicenter prospective study with eight-year follow-up was conducted in Beijing communities. Cardiovascular events were defined as myocardial infarction, unstable angina pectoris, hospitalization for heart failure, coronary revascularization, cardiac death, stroke, transient ischemic attack, and cerebral hemorrhage. Results. A total of 3,009 diabetic patients were recruited. Following an eight-year follow-up, 211 patients with cardiovascular events (105 in men and 106 in women) were identified. All patients were categorized into two groups according to the upper quartile of NC (43 cm in men and 39 cm in women). The prevalence of cardiovascular events in men with an NC >43 cm (16.48%) was higher than that in the group with an NC p=0.007). The prevalence of cardiovascular events in women with the NC >39 cm (10.67%) was higher compared to the group with NC p=0.004). The longitudinal prevalence of cardiovascular events in groups with different NC increased with the increasing duration of follow-up (p<0.001). Cox regression analysis showed that higher NC was associated with the occurrence of cardiovascular events after adjusting for confounding variables (adjusted HR = 2.305 (1.535–3.460)). Conclusions. NC was associated with the occurrence of cardiovascular events in type 2 diabetes in Chinese communities, and greater NC may increase the risk of cardiovascular events by about 2.3-fold.

Background: Treacher Collins syndrome (TCS) is a clinically and genetically heterogeneous disorder of craniofacial development mainly caused by variants in TCOF1, POLR1D, and POLR1C. Objectives: This study examined the causative genes of five TCS cases. Materials and Methods: In this study, two familial cases and three sporadic cases clinically diagonsed with TCS are described. Mutational analysis in probands was performed by targeted next-generation sequencing (NGS). Mutations identified by NGS were further confirmed by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). Results: A novel gross deletion (exons 9–13), a novel small deletion (c.381_382delAG), and two known deletions (c.4131_4135delAAAAG and c.2394_2395delAG) within TCOF1 as well as a known mutation (c.91C > T) in POLR1D were identified. These five cases exhibited high inter- and intra-familial phenotypic heterogeneity. Conclusion: This is the first report of Chinese TCS cases caused by a gross deletion within TCOF1 and mutations in POLR1D. In addition to expanding the spectrum of TCS-associated mutation in the Chinese population, our findings present the diversity of its clinical presentation. It is recommended that analyses such as NGS or MLPA capable of detecting large deletions be undertaken as a part of TCS molecular diagnosis.

Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.

Ginkgolide B (GB), a main constituent of Ginkgo biloba extracts, reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease (NAFLD) in obese mice, but the potential mechanism is unclear. Here we investigated the attenuated effects of GB on the disorder of lipid metabolism, oxidative stress and iron deposition in NAFLD and its potential mechanism associated with ferroptosis. Our preliminary research focused on high fat diet (HFD)-induced ApoE-/-mice gavaged with GB (20 and 30 mg kg-1•d-1, approximately equal to the human dose of 2 and 3 mg kg-1•d-1, respectively) and palmitic acid and oleic acid (PA/OA)-induced HepG2 cells treated with GB (4, 8, 16 μg/mL), respectively. Hepatic injury was assessed via biochemical, histopathological and immunohistochemical evaluations. In order to examine the mechanism of GB on ferroptosis-regulated pathway, we analyzed the expression levels of ferroptosis-related proteins, including nuclear factor erythroid 2 (Nrf2), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), transferrin receptor-1 (TFR1) and ferritin heavy chain-1 (FTH1) in vivo and vitro experiments by Western blotting. In order to further verify the correlation pathway of ferroptosis, after Nrf2 short hairpin RNA interference, we analyzed the effects of GB on Nrf2 pathway. Both HFD-fed mice and PA/OA-induced HepG2 cells displayed ferroptosis-based panel of biomarkers such as iron overload with the up-regulation of TFR1 and the down-regulation of FTH1, lipid peroxidation and inhibition of Nrf2 activity, which further induced GPX4 and HO-1 levels. Remarkably, after Nrf2 interference, GB treatment significantly increased Nrf2 expression, indicating that GB exerted anti-ferroptosis effects by activation of Nrf2 pathway. Our results are preliminarily illustrated that GB treatment has a specific effect on lipid accumulation and oxidative stress caused ferroptosis in NAFLD, possibly through Nrf2 signaling pathway.

Background Abnormal DNA methylation can cause gene silencing in colorectal cancer (CRC) patients. A gene that is suspected to have a crucial role in various types of cancers is the suppressor of cytokine signaling 1 (SOCS-1). Thus, this study will analyze the ramifications of SOCS-1 promoter methylation in CRC patients. This study will also test the therapeutic effects of hypomethylation as a possible CRC therapy. Methods First, 97CRC patients’ tumor and adjacent normal tissues were collected. Next, the methylation status of the SOCS-1 promoter region was assessed by methylation-specific polymerase chain reaction (MS-PCR); SOCS-1 protein and mRNA expression were also measured. A 48-month median follow-up period was used for the survival analysis of research participants. Lastly, to analyze the changes in cell invasion and migration in conjunction with protein and mRNA expression, the demethylating agent 5-azacytidine was applied in vitro to human CRC cells. Results The results showed increased SOCS-1 hypermethylation in CRC samples compared to controls. Methylated SOCS-1 was associated with significant suppression of SOCS-1 expression in tumors. Additionally, SOCS-1 hypermethylation was significantly correlated with lymph node metastasis and TNM stage. The study also found a poor overall survival rate to be significantly correlated with reduced expression of SOCS-1. After 5-azacytidine treatment, reduced in vitro DNA methylation and increased SOCS-1 expression were observed, and decreased cell migration and epithelial-mesenchymal transition biomarker expression alteration were further confirmed. Conclusions In colorectal cancer tissues, the rate of methylation in the SOCS-1 promoter region is high. Through promoter hypermethylation, the SOCS-1 gene was severely down-regulated in the CRC tissue samples, thereby revealing a plausible therapeutic target for CRC therapy.

Pharmacokinetic/pharmacodynamic studies of artemether-lumefantrine and 3 antiretroviral regimens were conducted in malaria-infected Ugandan children. Efavirenz-based treatment was associated with significant reductions in antimalarial exposure and higher risks of recurrent malaria. Caution in their concurrent use is warranted., Background. The optimal treatment of malaria in human immunodeficiency virus (HIV)–infected children requires consideration of critical drug–drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes. Methods. We conducted an intensive and sparse pharmacokinetic/pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on 3 different first-line antiretroviral therapy (ART) regimens were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin, and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated. Results. One hundred forty-five and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared with no ART, efavirenz (EFV) reduced exposure to all antimalarial components by 2.1- to 3.4-fold; lopinavir/ritonavir (LPV/r) increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on EFV vs LPV/r-based ART, changes that were associated with an approximate 4-fold higher odds of recurrent malaria by day 28 in those on EFV vs LPV/r-based ART. Conclusions. The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. EFV-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on EFV, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure, is warranted.

The present study aimed to determine whether post-ischemic treatment with dexmedetomidine (DEX) protected the heart against acute myocardial ischemia/reperfusion (I/R)-induced injury in rats. The phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)-dependent signaling pathway was also investigated. Male Sprague Dawley rats (n=64) were subjected to ligation of the left anterior descending artery (LAD), which produced ischemia for 25 min, followed by reperfusion. Following LAD ligation, rats were treated with DEX (5, 10 and 20 µg/kg) or underwent post-ischemic conditioning, which included three cycles of ischemic insult. In order to determine the role of the PI3K/Akt signaling pathway, wortmannin (Wort), a PI3K inhibitor, was used to treat a group of rats that had also been treated with DEX (20 µg/kg). Post-reperfusion, lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzymes (CK-MB), superoxide dismutase (SOD) and malondialdehyde (MDA) serum levels were measured using an ultraviolet spectrophotometer. The protein expression levels of phosphorylated (p)-Akt, Ser9-p-glycogen synthase kinase-3β (p-GSK-3β) and cleaved caspase-3 were detected in heart tissue by western blotting. The mRNA expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using reverse transcription-polymerase chain reaction. At the end of the experiment, the hearts were removed and perfused in an isolated perfusion heart apparatus with Evans blue (1%) in order to determine the non-ischemic areas. The risk and infarct areas of the heart were not dyed. As expected, I/R induced myocardial infarction, as determined by the increased serum levels of cTnI, CK-MB and MDA, and the decreased levels of SOD. Post-ischemic treatment with DEX increased the expression levels of p-Akt and p-GSK-3β, whereas caspase-3 expression was reduced following DEX treatment compared with in the I/R group. Compared with the I/R group, the ratio of Bcl-2/Bax at the mRNA level was elevated in the DEX and ischemic post-conditioning groups, whereas the expression levels of Bax were decreased. Conversely, the effects of DEX were attenuated by Wort. These results indicated that, similar to post-ischemic conditioning, post-ischemic treatment with DEX protects the heart against I/R via the PI3K/Akt-dependent signaling pathway, possibly by activating GSK-3β.

ObjectiveMetabolic syndrome (MetS) is a notable risk factor of coronary heart disease (CHD). However, there are differences in the methods used to define MetS. The purpose of this study was to determine which MetS definition most fully reflects the 10-year probability of CHD based on the Framingham risk algorithm.DesignCross-sectional study.SettingData were obtained from the China Health and Nutrition Survey and the Influencing Factors of Chronic Diseases Survey conducted among residents of Nanshan District in Shenzhen, China.ParticipantsIn total, 1721 participants aged 20–80 years were included in this study.MethodsMetS was diagnosed according to the criteria of the National Cholesterol Education Program’s Adult Treatment Panel (revised NCEP-ATP III), the International Diabetes Federation (IDF) and the Chinese Diabetes Society (CDS). The NCEP-ATP III algorithm was used to calculate the Framingham risk score, and the Framingham risk score was used to define the probability of developing CHD within 10 years either as low (20%). Chi-square tests with or without the Bonferroni correction were used to compare the differences in the distribution of the 10-year estimated risk of developing CHD among the three definitions.ResultsCompared with the other definitions, the revised NCEP-ATP III criteria identified more participants (30.96%, 95% CI 28.8% to 33.2%) as having MetS, while the CDS criteria showed the highest 10-year probability of developing CHD. The 10-year probability of developing CHD in the participants with MetS was significantly higher than that in the participants without MetS (CDS: χ2=157.65, revised ATP III: χ2=45.17, IDF: χ2=306.15, all p2=72.83; IDF: χ2=63.60; CDS: χ2=23.84; all pConclusionsThis study demonstrates the differences in the prevalence and distribution of the 10-year estimated risk of developing CHD based on the definition of MetS. A significant finding of this study is that the MetS definitions have better performance for men than for women. Further studies in China, especially longitudinal studies, are needed to determine which definition of MetS is best suited for predicting CHD risk.

Based on the recently explored regulatory fit effect in social contexts, the present research is the first to investigate the interaction between interviewer's regulatory focus and interviewee's impression management (IM) tactics. We hypothesized that assertive and defensive IM tactics would fit with interviewer's promotion and prevention focus, respectively, and that interviewer's experience of this regulatory fit would lead to enhanced interview evaluation. We conducted four studies in which the participants were asked to rate an interviewee after reading a list of the interviewee's IM-related behaviours or watching a videotaped interview. Additionally, the participant's regulatory focus was operationalized as both an induced situational state and a measured chronic trait. The results supported our hypotheses by showing a significant interaction of the interviewer's regulatory focus and the IM tactics on interview evaluation: the promotion-assertive and the prevention-defensive ratings were more positive than the prevention-assertive and the promotion-defensive ratings. Moreover, mediation analysis revealed that the interaction exerts its effects on interview evaluation by providing interviewers with an intrapersonal regulatory fit experience.

This study aimed to investigate the role of different types and frequencies of physical exercise in biomarkers of oxidative stress among middle-aged and elderly community residents with essential hypertension in China. A community-based cross-sectional survey was undertaken in 7 subdistricts. Individuals, 45-79 years old, with essential hypertension (n=402) and without cardiovascular disease (n=1047) were included. Superoxide dismutase (SOD) activities and plasma levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were determined. Multilevel linear regression was used to estimate the associations between various types of physical exercise and oxidative stress biomarker levels. Participants engaged in high frequency walking/square dancing or taiji/yoga demonstrated decreased systolic blood pressure in both groups; however, diastolic blood pressure decreased only among individuals with hypertension participating in walking/square dancing. In individuals with hypertension, MDA levels decreased in those participating in walking/square dancing, SOD activity increased in those participating in walking/square dancing, and 4-HNE levels decreased in those involved in taiji/yoga. In individuals without cardiovascular disease, MDA levels decreased in those involved in walking/square dancing or taiji/yoga, SOD activity increased in those performing walking/square dancing, and 4-HNE levels decreased in those involved in taiji/yoga. Oxidative stress marker levels also improved in those involved in walking/square dancing or taiji/yoga groups as the exercise frequency increased. Thus, frequent participation in walking/square dancing or taiji/yoga effectively decreases hypertension-related oxidative stress biomarker levels.

To investigate the effects of hydrogen sulfide (H2S) on nitric oxide (NO) content and inducible nitric oxide syn-thase (iNOS) activity in diaphragm from type 1 diabetic rats.Thirty-two male SD rats were randomly divided into four groups:nor-mal control group (NC), diabetes mellitus group (DM), DM treatment group (DM + NaHS) and NaHS control group (NaHS) (Compared with the NC group, there was no significant difference in the various indexes in the NaHS group. While FBG was increased significantly, DW/BW was decreased obviously in the DM group. HE staining revealed obvious changes in diaphragmatic tissues. The activity of iNOS and the content of NO were increased. The levels of iNOS mRNA and protein were in-creased significantly. Compared with the DM group, DW/BW and pathological damages were improved in the DM + NaHS group. The activity of iNOS and NO content were decreased significantly. The levels of iNOS mRNA and protein were decreased obviously.Exoge-nous H2S can suppress iNOS activity and expression to decrease the content of NO, which improving the capacity of diaphragm in type 1 diabet-ic rats.

To observe the protective effect of irbesartan on myocardial fibrosis in diabetic rats, and analyze the role of extracellular signal-regulated kinase (ERK) pathway in this protection.Thirty two male SD rats were randomly divided into two groups:normal control group (CON,Compared with CON group, in diabetic rats, the levels of FBG, H/B and LVWI were increased while BW was decreased. The contents of col I and col Ⅲ were increased as well as the protein expression of p-ERK1/2 and the ratio of p-ERK1/2/ERK1/2(Diabetes can induce the happening of myocardial fibrosis, and irbesartan can induce the damage of myocardial fibrosis through inhibitting the activation of ERK.

To explore the protective effects of hydrogen sulfide (HThirty-two male SD rats were randomly divided into four groups:normal control (NC) group, diabetes mellitus (DM) group, DM treatment (NaHS+DM) group and NaHS control (NaHS) group. The rats from DM group and NaHS+DM group were injected intraperitoneally with Streptozotocin 55 mg/kg to induce type 1 diabetes mellitus (There was no significant difference in the respective measured indexes in rats between NC group and NaHS group. However, in DM group, the levels of 24 h urinary protein, FBG, BUN, Scr and renal index were increased significantly; HE staining showed that the basement membrane was thickened and the amount of glomerular mesangial matrix was increased; MDA content, Caspase-3 activity and Bax expression levels were increased, while SOD activity and Bcl-2 expression were decreased. Compared with those in DM group, the morphological changes of renal tissue and its function were improved; MDA content, Caspase-3 activity and Bax expression were decreased significantly, while SOD activity and Bcl-2 expression were increased obviously in NaHS+DM group.H

Waardenburg syndrome type 2 (WS2) is a rare genetic disorder, characterized by bright blue eyes, moderate to profound hearing loss and pigmental abnormalities of the hair and skin. Between 10 and 20 mutations in the SRY‑box 10 (SOX10) gene were previously identified to be associated with WS2. The present study aimed to identify the genetic causes of WS2 in a Chinese family. Clinical and molecular analyses were performed to genetically characterize a Chinese family with two cases of WS2. The clinical data of the proband were collected using a questionnaire. The genomic DNA was extracted from peripheral blood samples of each individual in the family, and 168 candidate genes associated with hearing loss were sequenced using the Illumina HiSeq 2000 and confirmed by Sanger sequencing. A heterozygous nonsense mutation [substitution; position 127; cytosine to thymine (c.127C>T)] was identified in exon 2 of SOX10 (transcript ID: NM_006941.3) in the proband and the mother; however, not in other family members or healthy controls. The novel nonsense heterozygous mutation may cause the replacement of codon 43 [arginine (Arg)] with a stop codon (Arg43stop), leading to premature termination of protein translation. The novel nonsense heterozygous mutation c.127C>T in the SOX10 gene was considered to be the cause of WS2 in the family. This mutation has not been identified in any databases, to the best of the authors' knowledge, including The Single Nucleotide Polymorphism Database, The Human Gene Mutation Database, 1000 Genomes Project and ClinVar and Exome Sequencing Project v. 6500.

Coumarin osthole is a dominant bioactive ingredient of the natural Cnidium monnieri plant commonly used for traditional Chinese herbal medicines for therapies and treatments including antipruritus and antidermatitis. However, the molecular mechanism underlying the action of osthole remains unclear. In this study, we report that osthole exerts an antipruritic effect through selective inhibition of Ca2+-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) cation channels that are primarily expressed in the keratinocytes of the skin. Coumarin osthole was identified as an inhibitor of TRPV3 channels transiently expressed in HEK293 cells in a calcium fluorescent assay. Inhibition of the TRPV3 current by osthole and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV3-expressing HEK293 cells and mouse primary cultured keratinocytes. Behavioral evaluation demonstrated that inhibition of TRPV3 by osthole or silencing by knockout of the TRPV3 gene significantly reduced the scratching induced by either acetone-ether-water or histamine in localized rostral neck skin in mice. Taken together, our findings provide a molecular basis for use of natural coumarin osthole from the C. monnieri plant in antipruritic or skin care therapy, thus establishing a significant role of the TRPV3 channel in chronic itch signaling or acute histamine-dependent itch sensation.

PURPOSE To determine the cumulative five-year incidence and progression of myopic maculopathy in a rural Chinese adult population. METHODS The Handan Eye Study was a population-based longitudinal study. In 2006, 6830 subjects aged 30+ years participated in this study (baseline). Five years later, 5394 subjects (follow-up rate: 85.3%) took part in the follow-up study. Participants had a detailed eye examination, including visual acuity, standardized refraction and fundus photography according to a similar protocol at both baseline and follow-up. Myopic maculopathy was defined as any of the following signs: diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, lacquer cracks and myopic choroidal neovascularization at the posterior pole. Parapapillary atrophy was assessed separately. RESULTS Of 5394 participants, 5078 (10 021 eyes) had gradable fundus photographs. Over the five years, four participants (five eyes) developed new myopic maculopathy, with an eye-specific incidence of 0.05% (95% CI, 0.02-0.10%). Among the 51 eyes with myopic maculopathy at baseline, the progression occurred in 18 eyes (35.3%), with new signs of patchy chorioretinal atrophy in 11 eyes (21.6%), diffuse chorioretinal atrophy in seven eyes (13.7%), lacquer cracks in three eyes (6.9%), macular atrophy in three eyes (6.9%) and myopic choroidal neovascularization in two eyes (3.9%). By multivariable analysis, female gender (OR, 9.14; p = 0.004) and higher educational level (OR, 8.24; p = 0.004) were associated with a higher risk of progression of myopic maculopathy, whereas lower myopia at baseline (OR, 0.79; p

Near-infrared (NIR) laser induced phototherapy has been considered as a noninvasive option for cancer therapy. Herein, we report plasmonic PEGylated molybdenum oxide nanoparticles (PEG-MoO

Objective. The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. Methods. A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assigned to five groups: diabetic sham-operated group (DM-S), diabetic I/R group (DM-I/R), diabetic DEX group (DM-D), diabetic DEX + Wort group (DM-DW), and diabetic Wort group (DM-W). Another 12 age-matched male normal SD rats were randomly divided into two groups: sham-operated group (S) and I/R group (I/R). All rats were subjected to 30 min myocardial ischemia followed by 120 min reperfusion except sham groups. Plasmas were collected to measure the malondialdehyde (MDA), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH) levels and superoxide dismutase (SOD) activity at the end of reperfusion. Pathologic changes in myocardial tissues were observed by H-E staining. The total and phosphorylated form of Akt and GSK-3β protein expressions were measured by western blot. The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results. DEX significantly reduced plasma CK-MB, MDA concentration, and LDH level and increased SOD activity caused by I/R. The phosphorylation of Akt and GSK-3β was increased, Bcl-2 mRNA and the Bcl-2/Bax ratio was increased, and Bax mRNA was decreased in the DEX group as compared to the I/R group, while posttreatment with Wort attenuated the effects induced by DEX. Conclusion. The results of this study suggest that DEX postconditioning may increase the phosphorylation of GSK-3β by activating the PI3K/Akt signaling pathway and may inhibit apoptosis and oxidative stress of the myocardium, thus exerting protective effects in diabetic rat hearts suffering from I/R injury.

Computer-based procedures (CBPs) are expected to improve operator performance in nuclear power plants (NPPs), but they may reduce the openness of interaction between team members and harm teamwork consequently. To support teamwork in the main control room of an NPP, this study proposed a team-level integrated CBP that presents team members' operation status and execution histories to one another. Through a laboratory experiment, we compared the new integrated design and the existing individual CBP design. Sixty participants, randomly divided into twenty teams of three people each, were assigned to the two conditions to perform simulated emergency operating procedures. The results showed that compared with the existing CBP design, the integrated CBP reduced the effort of team communication and improved team transparency. The results suggest that this novel design is effective to optim team process, but its impact on the behavioural outcomes may be moderated by more factors, such as task duration.The study proposed and evaluated a team-level integrated computer-based procedure, which present team members' operation status and execution history to one another. The experimental results show that compared with the traditional procedure design, the integrated design reduces the effort of team communication and improves team transparency.

Hypertriglyceridemic waist (HW) phenotype was associated with an atherogenic lipid profile in adolescents. But unlike adults, the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use. The present study tested the hypothesis that simple variables, such as waist-to-height ratio (WHtR) and serum triacylglycerol (TG) concentrations, could be used as screening tools for the identification of adolescents characterized by atherogenic lipid profile. In 2006, anthropometric and biochemical measurements were assessed in a cross-sectional population-based study of 3136 Han adolescents, aged 13-17 years. The hypertriglyceridemic waist-to-height ratio (HWHtR) phenotype was defined as serum TG concentrations ≥1.47 mmol/L and WHtR ≥0.48 for boys and ≥0.46 for girls. Hypercholesterolemia (total cholesterol ≥5.18 mmol/L), high low-density lipoprotein cholesterol (LDL-C ≥3.37 mmol/L), low high-density lipoprotein cholesterol (HDL-C1.03 mmol/L), and high non-HDL-C (≥3.76 mmol/L) were considered as atherogenic lipid profiles. After control for age and sex, adolescents with the HWHtR phenotype were more likely to have hypercholesterolemia (odds ratio (OR) = 7.8, 95 % confidence interval (CI) = 3.5-17.3, P 0.001), high LDL-C (OR = 9.4, 95 % CI = 2.8-31.2, P 0.001), low HDL-C (OR = 10.8, 95 % CI = 6.9-17.0, P 0.001), and high non-HDL-C (OR = 22.9, 95 % CI = 10.0-52.2, P 0.001) than those adolescents with normal WHtR and normal serum TG concentrations.The present study demonstrates that HWHtR phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with HW phenotype, HWHtR phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents.• The hypertriglyceridemic waist phenotype is represented by the simultaneous presence of elevated serum triacylglycerol and increased waist circumference. Hypertriglyceridemic waist phenotype can identify adolescents with metabolic syndrome. But the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use.• The present study demonstrates that hypertriglyceridemic waist-to-height ratio phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with hypertriglyceridemic waist phenotype, hypertriglyceridemic waist-to-height ratio phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents.

Objective *These authors contributed equally to this work. To study the relationship between tumour angiogenesis and expression of cyclo-oxygenase ( COX)-2 and vascular endothelial growth factor ( VEGF)-A in human renal cell carcinoma. Methods Archival samples of primary human renal cell carcinoma tissue and surrounding normal renal tissue (control samples) obtained from patients diagnosed with renal cell carcinoma were analysed for COX-2 and VEGF-A expression by immunohistochemistry using specific monoclonal antibodies. Tumour microvasculature was examined using factor VIII-related antigen antibody staining. Results A total of 33 renal cell carcinoma and 12 control renal tissue specimens were included. COX-2 and VEGF-A genes were overexpressed in tumour specimens compared with normal epithelia. A significant correlation was found between COX-2 and VEGF-A expression. Microvessel density was found to be increased in tumour tissues that expressed COX-2 and VEGF-A. Conclusion Microvessel density was increased in tumour tissues that expressed COX-2 and VEGF-A, suggesting that COX-2 and VEGF-A are related to tumour angiogenesis in human renal cell carcinoma.

OBJECTIVE: To investigate the effect of dexmedetomidine postconditioning in alleviating myocardial ischemiareperfusion (IR) injury and inflammation in diabetic mellitus rats. METHODS: Thirty normal male Sprauge Dawley (SD) rats were randomly allocated into 3 groups (n=10), namely the sham-operated group, IR group, and dexmedetomidine postconditioning (DP) group. Similarly, another thirty diabetic SD rats were also randomly allocated into diabetic sham (DM-S) group, diabetic IR (DM-IR) group and diabetic dexmedetomidine postconditioning (DM-DP) group. The mean arterial pressure (MAP), heart rate (HR) and the rate pressure product (RPP) were recorded at baseline, after 30 min of ischemia, and at 30 and 120 min during reperfusion. Myocardial infarct size was analyzed by TTC double staining method, and plasma levels of CTnI, TNF-a, IL-6, IL-10 and IL-1β were measured at 120 min of reperfusion. RESULTS: Compared with those in the sham-operated group, normal and diabetic rats in IR and DP groups showed significantly lowered MAP, HR, and RPP and increased levels of plasma CTnI, TNF-a, IL-6, IL-10 and IL-1β levels after 30 min of ischemia and at 30 min and 120 min of reperfusion (P < 0.05). Compared with those in the IR group, the normal rats in DP group showed decreased MAP, HR, and RPP at 30 min of ischemia and at 30 min of reperfusion, which increased at 120 min of reperfusion (P < 0.05); the infarct size and plasma CTnI, TNF-a, IL-6 and IL-1β levels were decreased while IL-10 was increased in DP group (P < 0.05). Compared with those in DP group, the rats in DM-DP group showed similar MAP, HR and RPP (P > 0.05) but significantly increased infarct size and plasma CTnI, TNF-a, IL-6 and IL-1β levels (P < 0.05). CONCLUSION: Dexmedetomidine postconditioning may produce a cardioprotective effect against myocardial IR injury in normal rats by alleviating inflammation, but can not reduce the release of inflammatory mediators in diabetic rats to improve myocardial infarction.

Photodynamic therapy (PDT) is a process that combines a photosensitizing drug and light and promotes phototoxic responses in target cells, mainly via oxidative damage. Antifungal photodynamic therapy has been successfully employed against Candida species, dermatophytes, and deep mycoses. We present a case of a cutaneous granuloma caused by C. albicans treated with 5-aminolevulinic acid (ALA)-PDT. A 64-year-old man presented with two plaques on his right hand and wrist for 2 years. The diagnosis was made based on histopathology, mycology, and molecular identification of paraffin-embedded tissues. The patient was treated with itraconazole for 1 month and two sessions of ALA-PDT. After 2 months of follow-up, the patient was cured and has not experienced any recurrence to date. ALA-PDT was well tolerated in this patient with little pain. In general, application of PDT in mycoses is safe and effective in most cases. ALA-PDT is a good choice for inactivation of C. albicans.

DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4

Objective To observe the changes of mitochondria fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1) in the cardioprotection of fasudil, and analyze the significance. Methods Hearts isolated from male Sprague-Dawley rats were subjected to ischemia for 30 minutes (occlusion of left anterior descending artery), and continuously perfusion for 120 minutes to establish myocardial ischemia/reperfusion (I/R) injury model. The rats were divided into 3 groups: sham group, I/R group and fasudil group. The left ventricular hemodynamics were continuously recorded; lactate dehydrogenase (LDH) content was measured during reperfusion; myocardial ultrastructure was observed by electron microscopy; the protein expression of phosphorylated protein phosphatase 1 regulatory subunit 12A (p-PPP1R12A/p-MYPT1) was detected by immunohistochemistry; and the protein expressions of Mfn2, Drp1 and cleaved caspase-3 (c-caspase-3) were detected by Western blot analysis. Results Compared with the sham group, the left ventricular systolic and diastolic function was weakened, and LDH release was promoted in the other two groups during reperfusion. Compared with the I/R group, fasudil improved left ventricular systolic and diastolic function and reduced LDH release. Electron microscopy and immunohistochemical results showed that myofibril and mitochondria were damaged obviously, and p-MYPT1 protein expression was enhanced in the I/R group. Compared with the I/R group, fasudil attenuated the damage of myofibril and mitochondria, and decreased p-MYPT1 protein expression. Western blotting showed that, compared with the sham group, Mfn2 protein expression decreased, Drp1 and c-caspase-3 protein expressions increased in the I/R group. Compared with I/R group, there was no obvious change in Mfn2 protein expression, while Drp1 and c-caspase 3 protein expressions decreased in the fasudil group. Conclusion Fasudil can protect against myocardial I/R damage through inhibiting Rho kinase, which has no clear correlation with Mfn2 protein expression, but may be related with decreasing Drp1 protein expression and reducing mitochondrial injury, thereby inhibiting apoptosis.

Purpose: To assess changes in visual field (VF) values after gene therapy for Leber’s hereditary optic neuropathy (LHON). Methods: VF recovery, VF indices, and mean deviation in injected and uninjected eyes, before and after gene therapy, were examined in 2 groups of patients according to disease duration (≤2 years and > 2 years). Nine patients with LHON were treated by monocular intravitreal injection of AAV2-ND4. Finally, 7 patients were considered for subsequent comparisons; the first and second eyes were treated separately. Results: There were no significant differences in VF indices and mean deviation between injected and uninjected eyes (p = 0.910 and p = 0.929, respectively). However, there was a significant difference before and after injection (p = 0.016 and p = 0.015, respectively). There was no significant difference in VF improvement between patients with ≤2 years’ disease duration and those with a longer disease duration. Conclusion: There was a statistically significant VF improvement after gene therapy. This suggests that monocular intravitreal injection of AAV2-ND4 can improve binocular VF values. This study also suggests that gene therapy can be effective in patients with a disease duration of > 2 years.

The development of poorly water-soluble drugs faces the risk of low bioavailability and therapeutic efficacy. The co-amorphous drug delivery system has recently gained considerable interest because it offers an alternative approach to modify properties of poorly water-soluble drugs. Herein, we developed a co-amorphous system of atenolol (ATE) and poorly water-soluble hydrochlorothiazide (HCT) by means of cryogenic milling. The co-administration of ATE and HCT has been reported to show therapeutic advantages for patients with uncomplicated hypertension. The co-amorphous ATE-HCT sample with 1:1 molar ratio showed excellent physical stability, which could be attributed to the formation of strong molecular interactions between ATE and HCT as evidenced by FT-IR spectra. Compared to the pure crystalline form, amorphous form and physical mixture, HCT in the co-amorphous form exhibited the significantly increased intrinsic dissolution rate, as well as the enhanced bioavailability in the pharmacokinetic study. It was found that the enhanced bioavailability of HCT in the co-amorphous formulation was achieved by the synergistic effect of amorphized HCT and the water-soluble coformer ATE. The present study provides an improved approach to implement the combination therapy of ATE and HCT for potential clinical treatments.