FPR1 Antagonist (BOC-MLF) Inhibits Amniotic Epithelial-mesenchymal Transition.

OBJECTIVE: Premature rupture of membranes (PROM) is a common pregnancy disorder that is closely associated with structural weakening of fetal membranes. Studies have found that formyl peptide receptor 1 (FPR1) activates inflammatory pathways and amniotic epithelialmesenchymal transition (EMT), stimulates collagen degradation, and leads to membrane weakening and membrane rupture. The purpose of this study was to investigate the anti-inflammatory and EMT inhibitory effects of FPR1 antagonist (BOC-MLF) to provide a basis for clinical prevention of PROM. METHODS: The relationship between PROM, FPR1, and EMT was analyzed in human fetal membrane tissue and plasma samples using Western blotting, PCR, Masson staining, and ELISA assays. Lipopolysaccharide (LPS) was used to establish a fetal membrane inflammation model in pregnant rats, and BOC-MLF was used to treat the LPS rat model. We detected interleukin (IL)-6 in blood from the rat hearts to determine whether the inflammatory model was successful and whether the anti-inflammatory treatment was effective. We used electron microscopy to analyze the structure and collagen expression of rat fetal membrane. RESULTS: Western blotting, PCR and Masson staining indicated that the expression of FPR1 was significantly increased, the expression of collagen was decreased, and EMT appeared in PROM. The rat model indicated that LPS caused the collapse of fetal membrane epithelial cells, increased intercellular gaps, and decreased collagen. BOC-MLF promoted an increase in fetal membrane collagen, inhibited EMT, and reduced the weakening of fetal membranes. CONCLUSION: The expression of FPR1 in the fetal membrane of PROM was significantly increased, and EMT of the amniotic membrane was obvious. BOC-MLF can treat inflammation and inhibit amniotic EMT.

The association of social support and hope with self-stigma and perceived recovery among people with schizophrenia: The serial mediation effect.

BACKGROUND: It is essential to assist individuals with a mental illness who have achieved clinical recovery in their personal recovery. Understanding the relationship between self-stigma and social support and the effects on perceived recovery can be valuable for clinical professionals in helping patients lead meaningful lives. AIM: To examine the serial mediating roles of social support and perceived hope in self-stigma and the effects on perceived recovery. DESIGN: A cross-sectional study. METHODS: The study was conducted from September 2019 to June 2020. One hundred and fifty-seven patients with schizophrenia in seven chronic rehabilitation wards were enrolled. Each patient had a Positive and Negative Syndrome Scale score ≤ 60 points, and they regularly participated in occupational rehabilitation. Research tools included demographic data, the Internalized Stigma of Mental Illness Scale (ISMIS), Multidimensional Scale of Perceived Social Support (MSPSS), Herth Hope Index (HHI), and Perceived Recovery Inventory (PRI). IBM SPSS 24.0 was used to analyse the data. Pearson correlation was used to analyse the relationships between variables, and models 4 and 6 of PROCESS macro V3.4 for SPSS were used to examine the mediation model. RESULTS: The results indicated that self-stigma and perceived recovery in patients with schizophrenia are negatively correlated, that peer support and perceived hope mediate the relationship between them, and that peer support and perceived hope also have a statistically significant serial mediating effect. CONCLUSION: The serial mediation effect of peer support and perceived hope on the relationship between self-stigma and perceived recovery was statistically significant in this study. IMPACT: This research delves into strategies to assist psychiatric patients in reducing self-stigma and achieving recovery. The findings underscore the heightened significance of peer support for patients in rehabilitative wards and offer valuable insights for medical staff. REPORTING METHOD: STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

LRP6-mediated phosphorylation of connexin43 in myocardial infarction.

Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gαs) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gαs which played a role in VT of AMI.

Prognostic and clinical significance of subcellular CDC27 for patients with rectal adenocarcinoma treated with adjuvant chemotherapy.

Rectal adenocarcinoma (READ) constitutes one-third of newly diagnosed colorectal cancer cases. Surgery, chemotherapy and concurrent chemoradiotherapy are the main treatments to improve patient outcomes for READ. However, patients with READ receiving these treatments eventually relapse, leading to a poor survival outcome. The present study collected surgical specimens from patients with READ and determined that cytoplasmic cell division cycle 27 (CDC27) expression was associated with the risk of lymph node metastasis and distant metastasis. Nuclear CDC27 expression was negatively associated with 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Multivariate Cox proportional regression analysis showed that nuclear CDC27 was an independent prognostic factor in the patients with READ, especially in those treated with adjuvant chemotherapy. High nuclear CDC27 expression was significantly associated with poorer 5-year DFS (HR, 2.106; 95% CI, 1.275-3.570; P=0.003) and 5-year OS (HR, 2.369; 95% CI, 1.270-4.6810; P=0.005) rates. The data indicated that cytoplasmic CDC27 expression could affect tumor progression and that it plays an important role in metastasis. Nuclear CDC27 expression was markedly associated with poorer survival outcomes and was an independent prognostic factor in patients with postoperative adjuvant chemotherapy-treated READ. Thus, CDC27 expression serves as a potential prognostic marker for rectal tumor progression and chemotherapy treatment.

Relationship between chromatin configuration and in vitro maturation ability in guinea pig oocytes.

BACKGROUND: Germinal vesicle (GV) chromatin configurations of oocytes are proposed to be related to oocyte competence and may reflect the quality of oocyte. Currently, a limited number of published studies investigated the GV chromatin configurations of guinea pig oocytes. OBJECTIVE: In this study on the in vitro maturation (IVM) of guinea pig oocytes, we examined the changes in their GV chromatin configurations during meiotic progression. METHODS: Based on the degree of chromatin compaction, the GV chromatin configurations of guinea pig oocytes could be divided into three categories depending on whether the nucleolus-like body (NLB) was surrounded or partly surrounded by compacted chromatin, namely the uncondensed (NSN), the intermediate type (SN-1) and the compacted type (SN-2). RESULTS: The percentage of cells displaying the SN-2 configuration increased with the growth of guinea pig oocytes, suggesting that this configuration presents the potential for maturation in oocytes. Oocytes derived from larger follicle exhibited increased meiotic potential. Serum starvation affected the GV chromatin configurations of guinea pig oocytes. CONCLUSIONS: Collectively, these results suggest that the SN-2 type might be a more mature form of configuration in guinea pig oocyte, whose proportion was associated with the follicle size and susceptible to the environment (e.g. serum concentration).

Differences in Immune Responses between Children and Adults with COVID-19.

Over 85 590 000 individuals have been infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although there have been an increasing number of reports on coronavirus disease 2019 (COVID-19), it is unclear why infected children show milder symptoms than adults. A retrospective case study was performed at two designated hospitals for COVID-19. Patients (56 children and 63 adults) with confirmed SARS-CoV-2 infection and mild pneumonia were randomly enrolled in this study. The median age of the children was 7.0 years, and 51.79% of them were boys. The median age of the adults was 57 years, and 47.62% were men. The most common symptoms were fever, cough, sputum and diarrhoea. There were no significant differences in symptoms between children and adult patients. In terms of immunological indices on admission, adult patients displayed typical leukopenia and markedly higher levels of IL-2, IL-4, and IL-6 than child patients. The elevation of IL-2, IL-4 and IL-6 in adults induced more extensive lung injury. The effective and non-aggressive immune response successfully resisted SARS-CoV-2 invasion and maintained mild symptoms in child patients. The correlation of higher IL-2, IL-4, and IL-6 with the lung injury might be evidence that preventing excessive cytokine production can avoid further lung damage in these patients.

Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1.

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

H63D CG genotype of HFE is associated with increased risk of sporadic amyotrophic lateral sclerosis in a single population.

This paper describes the genetic etiology of sporadic amyotrophic lateral sclerosis in a single population. Polymerase chain reaction-restriction fragment length polymorphism and DNA sample sequencing of 3 common HFE gene variants (C282Y and H63D and S65C) were performed on 10 randomly selected samples of H63D gene variant (124 patients with sporadic amyotrophic lateral sclerosis) and 10 wild types of H63D samples (210 controls). The C282Y and S65C gene variant were absent. There were 24 cases (7.18%) with H63D heterozygous variants, including 16 cases (13%) in the sporadic amyotrophic lateral sclerosis group and 8 cases (4%) in the healthy control group. The polymorphism frequency of the H63D gene variant in the sporadic amyotrophic lateral sclerosis group was significantly different than that in the control group (p < 0.05), and the difference at allele level, which is still more significant (p < 0.05). H63D gene variant could be a risk factor for sporadic amyotrophic lateral sclerosis in a single population. The results showed HFE gene variants play a role in the occurrence of sporadic amyotrophic lateral sclerosis, but its effect should be carefully estimated.

[Screening, identification and antagonistic effect evaluation of biocontrol strains to Asarum leaf blight].

Leaf blight is the main disease of Asarum. At present, chemical treatment is main measure for disease control, and there is no report on biological control. In order to achieve the biological control of Asarum leaf blight, the biocontrol strains with antagonistic effect on Asarum leaf blight were screened. The rhizosphere bacteria of healthy Asarum plants were isolated by soil dilution method, and the isolated strains were screened by the methods of antagonistic antifungal and fermentation liquid antifungal, then the strains were identified and the control effect in vivo was determined. Abiocontrol bacterial strains S2-31 which with high antagonism to leaf blight was obtained from more than 100 isolated strains. The inhibitory rates of antagonistic antifungal and fermentation liquid antifungal reached 92.47% and 60.56%, respectively. It was identified by morphology and 16 S rDNA sequence analysis, and the strain was identified as Brevibacillus laterosporus. The results of indoor potted experiment showed that the control effect was 79.87%, 71.44% and 66.82% on the 3 rd, 5 th and 7 th day after inoculation, respectively, which indicated that S2-31 could reduce the disease index and control the development of Asarum leaf blight.

Early Intratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Meta-analysis.

There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67; 95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.94) and 0.64 (95% CI: 0.41-0.99) respectively. Moreover, the percentage of infants using PS more than one time was lower in ICS group than in the placebo control group, with the RR and 95% CI being 0.55 (95% CI: 0.45-0.67), and that in ICS intratracheal instillation subgroup lower than in ICS inhalation subgroup (RR: 0.56; 95% CI: 0.45-0.69, and RR: 0.35; 95% CI: 0.08-1.52 respectively). There was no significant difference in the incidence of infection or retinopathy of prematurity and neuro-motor system impairment between ICS group and placebo control group, with the corresponding RR being 0.95 (95% CI: 0.59-1.52), 0.92 (95% CI: 0.62-1.38) and 1.13 (95% CI: 0.92-1.39), respectively. It was concluded that early administration of ICS and PS is an effective and safe option for preterm infants with NRDS in preventing BPD and reducing mortality, decreasing the additional PS usage, especially for the ICS intratracheal instillation subgroup. Furthermore, the appropriate dose and duration of ICS, combined use of inhalation or instillation of ICS with PS and the long-term safety of airway administration of corticosteroids need to be assessed in large trials.

Photoelectrochemical aptamer-based sensing of the vascular endothelial growth factor by adjusting the light harvesting efficiency of g-C3N4 via porous carbon spheres.

A "signal-off" sensor is described for sensitive photoelectrochemical (PEC) determination of the vascular endothelial growth factor (VEGF165). Graphitic carbon nitride (g-C3N4) is used as the signalling material, and porous carbon spheres as efficient quenchers of the photocurrent. The quenching efficiency of carbon spheres is the result of two effects, viz. (a) the competitive light absorption and (b) competitive electron donor activity which decreases the number of light-generated electrons and holes and also reduces the charge separation efficiency. This new mechanism differs from the previous quenching mechanisms which usually are based on the suppression of electron transport or steric hindrance. A glassy carbon electrode was modified with an aptamer against VEGF165. On binding of analyte (VEGF165), the reduction of current is measured (at a typical potential of 0 V) using H2O2 as the electrochemical probe. The sensor has a linear response in the 10-5 nM to 102 nM VEGF165 concentration range, and the detection limit is 3 fM. Graphical abstract Schematic presentation of the quenching mechanism of carbon spheres: the competitive light absorption and competitive electron donor reduce the number of light-generated electrons in the conduction band (CB) and holes in the valence band (VB) and also reduce the charge separation efficiency.

Rhododendron oldhamii leaf extract improves fatty liver syndrome by increasing lipid oxidation and decreasing the lipogenesis pathway in mice.

Some members of Rhododendron genus are traditionally used as medicinal plants for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases. To the best of our knowledge, there is no report on the protective effects of R. oldhamii leaf extract on non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. In this study, the effects of R. oldhamii leaf extract on inhibiting the free fatty acid (FFA)-induced accumulation of fat in HepG2 cells and on improving fatty liver syndrome in mice with high fat diet (HFD)-induced NAFLD were investigated. For the in vitro assay, HepG2 cells were treated with FFAs (oleate/palmitate = 2:1) with or without treatment with R. oldhamii leaf ethyl acetate (EtOAc) fraction to observe lipid accumulation using Nile red and oil red O stains. For the in vivo assay, C57BL/6 mice were randomly assigned to three groups (n = 5), including the normal diet group, the HFD group and the HFD+EtOAc group. After 11 weeks, body weight, serum biochemical indices and the mRNA expressions of the liver tissue, as well as the outward appearance, weight and histopathological analysis of liver and adipose tissues were evaluated. Among the fractions derived from R. oldhamii leaf, the EtOAc fraction exhibited a strong fat-accumulation inhibitory activity. Following reverse-phase high-performance liquid chromatography (HPLC), four specific phytochemicals, including (2R, 3R)-astilbin (AS), hyposide (HY), guaijaverin (GU) and quercitrin (QU), were isolated and identified from the EtOAc fraction of R. oldhamii leaf extract. Among them, AS and HY showed excellent fat-accumulation inhibitory activity. Thus, the EtOAc fraction of R. oldhamii leaf and its derived phytochemicals have great potential in preventing FFA-induced fat accumulation. In addition, the EtOAc fraction of R. oldhamii leaf significantly improved fatty liver syndrome and reduced total cholesterol (TC) and triglyceride (TG) in HFD-induced NAFLD mice at a dosage of 200 mg/kg BW. These results demonstrated that the methanolic extracts from R. oldhamii leaf have excellent inhibitory activities against fat accumulation and anti-NAFLD activities and thus have great potential as a natural health product.

[Difference of Liver Enzymes in Different Metabolism States of Chronic Hepatitis B].

OBJECTIVE: To analyze the difference of liver enzymes in different metabolism state groups of chronic hepatitis B (CHB). METHODS: We use prospective cross-sectional study to analyze the difference of liver enzymes in different metabolism state groups in 110 cases of CHB, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutamyl transferase (GGT). RESULTS: Regardless of the presence or absence of fatty liver, the levels of ALP and GGT were increased along with the deterioration of glucose metabolism (P<0.05).The levels of ALP and GGT in the presence of fatty liver group were higher than those in the absence of fatty liver group (P<0.05). The levels of AST, ALP and GGT showed the trend of increasing along with the increase of HOMA-IR and the decrease of HOMA-ß. There was no difference of liver enzymes among the groups with or without other metabolism disorder (P>0.05). CONCLUSION: In CHB, abnormal glucose metabolism and fatty liver can lead to the increase of ALP and GGT. The increase of HOMA-IR and the decrease of HOMA-ß may lead to the increase of AST, ALP and GGT. Other metabolism disorder did not show any effect on the level of liver enzymes.

Expression of aromatase and estrogen receptors in lumbar motoneurons of mice.

Estrogen exerts protective roles in amyotrophic lateral sclerosis (ALS). However, the expression of aromatase (ARO) and estrogen receptors (ERs) in the motoneurons of spinal cord, has not yet been elucidated. By immunohistochemistry, we found that ARO and ERs were present in the ventral horn of adult mice lumbar spinal cord, and colocalized with SMI-32, a motoneuron specific marker. Within motoneurons, we observed that ARO is detected primarily in the cytoplasm, with fewer ARO in the nucleus; ERα and ERß mainly localized in the nucleus with less in the cytoplasm; while GPR30 is located in soma and processes. In conclusion, we found that ERs and ARO are expressed in the motoneurons of lumbar spinal cord in adult mice. These findings suggest that estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in ALS.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Short-term effects of air pollution on acute myocardial infarctions in Shanghai, China, 2013-2014.

BACKGROUND: Although particulate matter, with diameters < 2.5 µm (PM2.5) and < 10 µm (PM10), and other pollutants have been associated with cardiovascular morbidity and mortality, the effect of pollutants on acute myocardial infarctions (AMIs) has rarely been investigated in Asia, especially in Shanghai, China. METHODS: Between 1 November 2013 and 27 April 2014, 972 patients from the Pudong District, Shanghai City, were assessed by the Emergency Medical Service. A case-crossover design was used to analyze exposure to air pollution and the AMI risk. Exposures to PM2.5, PM10, nitrogen dioxide (NO2), sulphurdioxide (SO2), and carbon monoxide (CO) were based on the mean urban background levels. The associations among AMI admissions, the included pollutants, temperature, and relative humidity were analyzed using correlation and logistic regression. RESULTS: The urban background levels of PM2.5, PM10 and CO were associated with an increased risk of AMI, unlike NO2 and SO2 levels. The OR (95% CI) for AMI were 1.16 (1.03-1.29), 1.05 (1.01-1.16), 0.82 (0.75-1.02), 0.87 (0.63-1.95), and 1.08 (1.02-1.21) for PM2.5, PM10, NO2, SO2, and CO, respectively. Increases in the air quality index (AQI) were associated with more AMI occurrences. There was no correlation between fluctuations in temperature and relative humidity with AMI hospital admissions. CONCLUSIONS: Short-term exposure to moderate-serious pollution levels is associated with increased risk of AMI. Increased PM2.5, PM10 and CO levels are related to increased AMI admissions.

Antioxidative phytochemicals from Rhododendron oldhamii Maxim. leaf extracts reduce serum uric acid levels in potassium oxonate-induced hyperuricemic mice.

BACKGROUND: Some of the genus Rhododendron was used in traditional medicine for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases and many species of the genus Rhododendron contain a large number of phenolic compounds and antioxidant properties that could be developed into pharmaceutical products. METHODS: In this study, the antioxidative phytochemicals of Rhododendron oldhamii Maxim. leaves were detected by an online HPLC-DPPH method. In addition, the anti-hyperuricemic effect of the active phytochemicals from R. oldhamii leaf extracts was investigated using potassium oxonate (PO)-induced acute hyperuricemia. RESULTS: Six phytochemicals, including (2R, 3R)-epicatechin (1), (2R, 3R)-taxifolin (2), (2R, 3R)-astilbin (3), hyposide (4), guaijaverin (5), and quercitrin (6), were isolated using the developed screening method. Of these, compounds 3, 4, 5, and 6 were found to be major bioactive phytochemicals, and their contents were determined to be 130.8 ± 10.9, 105.5 ± 8.5, 104.1 ± 4.7, and 108.6 ± 4.0 mg per gram of EtOAc fraction, respectively. In addition, the four major bioactive phytochemicals at the same dosage (100 mmol/kg) were administered to the abdominal cavity of potassium oxonate (PO)-induced hyperuricemic mice, and the serum uric acid level was measured after 3 h of administration. H&E staining showed that PO-induced kidney injury caused renal tubular epithelium nuclear condensation in the cortex areas or the appearance of numerous hyaline casts in the medulla areas; treatment with 100 mmol/kg of EtOAc fraction, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin significantly reduced kidney injury. In addition, the serum uric acid level was significantly suppressed by 54.1, 35.1, 56.3, 56.3, and 53.2 %, respectively, by the administrations of 100 mmol/kg EtOAc fraction and the derived major phytochemicals, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin, compared to the PO group. The administration of 10 mg/kg benzbromarone, a well-known uricosuric agent, significantly reduced the serum uric acid level by 45.5 % compared to the PO group. CONCLUSION: The in vivo decrease in uric acid was consistent with free radical scavenging activity, indicating that the major phytochemicals of R. oldhamii leave extracts and the derived phytochemicals possess potent hypouricemic effects, and they could be potential candidates for new hypouricemic agents.

Function and mechanism of neurotensin (NTS) and its receptor 1 (NTSR1) in occurrence and development of tumors.

As a neuropeptide, neurotensin (NTS) is widely expressed in central and peripheral nervous system, which is mainly mediated byneurotensin receptor1 (NTSR1) to activate the related downstream signaling pathways. After summarized the function and mechanism of NTS/NTSR1 in various malignant tumors, we found that NTS/NTSR1 played essential roles during tumor initiation and development. NTS/NTSR1 regulates tumor initiation, proliferation, apoptosis, metastasis and differentiation mainly through three pathways, including IP3/Ca2+ /PKC/MAPKs pathway, MMPs/EGFR/MAPKs (PI3K/Akt) pathway, or Rho-GTPsaes and non-receptor tyrosine kinase pathway. Besides, NTS/NTSR1 is also regulated by some upstream pathways and some traditional Chinese medicine preparations and traditional Chinese medicine therapies. In this article, we summarized the function of NTS/NTSR1 and its mechanisms, and discussed the prospective in its application to clinical diagnosis and drugs targeting.

Scattered radiation doses absorbed by technicians at different distances from X-ray exposure: Experiments on prosthesis.

UNLABELLED: This work aimed to investigate the spatial distribution of scattered radiation doses induced by exposure to the portable X-ray, the C-arm machine, and to simulate the radiologist without a shield of lead clothing, radiation doses absorbed by medical staff at 2 m from the central exposure point. MATERIAL AND METHOD: With the adoption of the Rando Phantom, several frequently X-rayed body parts were exposed to X-ray radiation, and the scattered radiation doses were measured by ionization chamber dosimeters at various angles from the patient. Assuming that the central point of the X-ray was located at the belly button, five detection points were distributed in the operation room at 1 m above the ground and 1-2 m from the central point horizontally. RESULTS: The radiation dose measured at point B was the lowest, and the scattered radiation dose absorbed by the prosthesis from the X-ray's vertical projection was 0.07 ±0.03 µGy, which was less than the background radiation levels. The Fluke biomedical model 660-5DE (400 cc) and 660-3DE (4 cc) ion chambers were used to detect air dose at a distance of approximately two meters from the central point. The AP projection radiation doses at point B was the lowest (0.07±0.03 µGy) and the radiation doses at point D was the highest (0.26±0.08 µGy) .Only taking the vertical projection into account, the radiation doses at point B was the lowest (0.52 µGy), and the radiation doses at point E was the highest (4 µGy).The PA projection radiation at point B was the lowest (0.36 µGy) and the radiation doses at point E was the highest(2.77 µGy), occupying 10-32% of the maximum doses. The maximum dose in five directions was nine times to the minimum dose. When the PX and the C-arm machine were used, the radiation doses at a distance of 2 m were attenuated to the background radiation level. The radiologist without a lead shield should stand at point B of patient's feet. Accordingly, teaching materials on radiation safety for radiological interns and clinical technicians were formulated.