Management of prolactinoma: a survey of endocrinologists in China

Objective: To assess the current management of prolactinoma among endocrinologists in China. Methods: An online survey of a large sample of endocrinologists was conducted in China. The questionnaire included 21 questions related to controversial issues about the management of prolactinomas. Doctors in the endocrinology department of a university-affiliated hospital or a comprehensive secondary hospital in 12 cities from East, West, South, North and Middle China were surveyed. Results: A total of 290 valid questionnaires were collected, and the response rate was 40%. When hyperprolactinemia occurred, 97% of the respondents would test thyroid-stimulating hormone routinely. 22% of the respondents considered that prolactin levels 250 ng/mL could occur in all the following situations as macroprolactinoma, mircoprolactinoma, macroprolactinemia and drug-induced hyperprolactinemia. Surgery was not recommended by 272 (94%) endocrinologists as the first choice for treating microprolactinomas. 58% and 92% of endocrinologists would start drug treatment for microprolactinomas and macroprolactinomas at diagnosis. 70% and 40% chose to withdraw treatment after 2–3 years of prolactin normalization in microprolactinomas and macroprolactinomas. In case of pregnancy, 57% of the respondents considered bromocriptine as choice for women patients. Drug discontinuation after pregnancy was advocated in 63% and 27% for microprolactinoma and macroprolactinoma. Moreover, 44% of endocrinologists believed that breastfeeding was allowable in both micro- and macroprolactinoma. Conclusion: This is the first study to investigate the management of prolactinomas among endocrinologists in China. We found that the current clinical treatment was not uniform. Therefore, it is necessary to strengthen the training of endocrinologists to improve clinical diagnosis and treatment practices

Precise and Rapid Validation of Candidate Gene by Allele Specific Knockout With CRISPR/Cas9 in Wild Mice

It is a tempting goal to identify causative genes underlying phenotypic differences among inbred strains of mice, which is a huge reservoir of genetic resources to understand mammalian pathophysiology. In particular, the wild-derived mouse strains harbor enormous genetic variations that have been acquired during evolutionary divergence over 100s of 1000s of years. However, validating the genetic variation in non-classical strains was extremely difficult, until the advent of CRISPR/Cas9 genome editing tools. In this study, we first describe a T cell phenotype in both wild-derived PWD/PhJ parental mice and F1 hybrids, from a cross to C57BL/6 (B6) mice, and we isolate a genetic locus on Chr2, using linkage mapping and chromosome substitution mice. Importantly, we validate the identification of the functional gene controlling this T cell phenotype, Cd44, by allele specific knockout of the PWD copy, leaving the B6 copy completely intact. Our experiments using F1 mice with a dominant phenotype, allowed rapid validation of candidate genes by designing sgRNA PAM sequences that only target the DNA of the PWD genome. We obtained 10 animals derived from B6 eggs fertilized with PWD sperm cells which were subjected to microinjection of CRISPR/Cas9 gene targeting machinery. In the newborns of F1 hybrids, 80% (n = 10) had allele specific knockout of the candidate gene Cd44 of PWD origin, and no mice showed mistargeting of the B6 copy. In the resultant allele-specific knockout F1 mice, we observe full recovery of T cell phenotype. Therefore, our study provided a precise and rapid approach to functionally validate genes that could facilitate gene discovery in classic mouse genetics. More importantly, as we succeeded in genetic manipulation of mice, allele specific knockout could provide the possibility to inactivate disease alleles while keeping the normal allele of the gene intact in human cells

Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation

Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions

Relationship between the Composition of Flavonoids and Flower Colors Variation in Tropical Water Lily (Nymphaea) Cultivars

Water lily, the member of the Nymphaeaceae family, is the symbol of Buddhism and Brahmanism in India. Despite its limited researches on flower color variations and formation mechanism, water lily has background of blue flowers and displays an exceptionally wide diversity of flower colors from purple, red, blue to yellow, in nature. In this study, 34 flavonoids were identified among 35 tropical cultivars by high-performance liquid chromatography (HPLC) with photodiode array detection (DAD) and electrospray ionization mass spectrometry (ESI-MS). Among them, four anthocyanins: delphinidin 3-O-rhamnosyl-5-O-galactoside (Dp3Rh5Ga), delphinidin 3-O-(2″-O-galloyl-6″-O-oxalyl-rhamnoside) (Dp3galloyl-oxalylRh), delphinidin 3-O-(6″-O-acetyl-β-glucopyranoside) (Dp3acetylG) and cyanidin 3- O-(2″-O-galloyl-galactopyranoside)-5-O-rhamnoside (Cy3galloylGa5Rh), one chalcone: chalcononaringenin 2′-O-galactoside (Chal2′Ga) and twelve flavonols: myricetin 7-O-rhamnosyl-(1→2)-rhamnoside (My7RhRh), quercetin 7-O-galactosyl-(1→2)-rhamnoside (Qu7GaRh), quercetin 7-O-galactoside (Qu7Ga), kaempferol 7-O-galactosyl-(1→2)-rhamnoside (Km7GaRh), myricetin 3-O-galactoside (My3Ga), kaempferol 7-O-galloylgalactosyl-(1→2)-rhamnoside (Km7galloylGaRh), myricetin 3-O-galloylrhamnoside (My3galloylRh), kaempferol 3-O-galactoside (Km3Ga), isorhamnetin 7-O-galactoside (Is7Ga), isorhamnetin 7-O-xyloside (Is7Xy), kaempferol 3-O-(3″-acetylrhamnoside) (Km3-3″acetylRh) and quercetin 3-O-acetylgalactoside (Qu3acetylGa) were identified in the petals of tropic water lily for the first time. Meanwhile a multivariate analysis was used to explore the relationship between pigments and flower color. By comparing, the cultivars which were detected delphinidin 3-galactoside (Dp3Ga) presented amaranth, and detected delphinidin 3′-galactoside (Dp3′Ga) presented blue. However, the derivatives of delphinidin and cyanidin were more complicated in red group. No anthocyanins were detected within white and yellow group. At the same time a possible flavonoid biosynthesis pathway of tropical water lily was presumed putatively. These studies will help to elucidate the evolution mechanism on the formation of flower colors and provide theoretical basis for outcross breeding and developing health care products from this plant

Opportunities, Challenges and Safeguard Measures for Sustainable Development of Fumian District, Yulin City

This paper first analyzes the main opportunities for sustainable development of Fumian District, Yulin City, and then discusses the challenges faced by Fumian District in its sustainable development. Finally, it proposes safeguard measures for sustainable development of Fumian District: (i) strengthening leadership and implementing responsibilities; (ii) enhancing cooperation and gathering forces; (iii) reinforcing supervision and ensuring implementation; (iv) increasing input and integrating resources; (v) strengthening publicity and creating an atmosphere

Strategies for Construction of Sustainable Development Experimental Zone in Fumian District, Yulin City

From strengthening the construction of an innovation system, adhering to the green development model of the industry, advancing the rural revitalization strategy, strengthening the protection and inheritance of cultural heritage, accelerating the development of social undertakings, and expanding the space for regional cooperation, this paper discusses the strategies for the construction of sustainable development experimental zone in Fumian District, Yulin City. It is intended to build Fumian District into a vibrant, economically prosperous, urban and rural integrated, characteristic cultural, safe and harmonious, inclusive and open district

Statistical Analysis for Identifying Differentially MicroRNA in Serum Exosomes of Lead Workers

Exosomes can transmit central nervous system (CNS) information to the peripheral circulatory system through the brain barrier, and exosomes in the blood can also enter the central nervous system likewise. The components of exosomal contents play a pivotal role in cell signal communication, and thus, the transmission of exosomal content components is considered as a newly discovered method of long-distance communication between cells. The current is aimed to explore the changes of the exosomal microRNA group in the serum of lead-exposed workers, which might be involved in the lead-induced neuroinflammation, especially the activation of microglia and the release of inflammatory factors. We proposed a method combining statistical analysis and experiment according to the different expression of exosomal microRNA. Firstly, we divided workers into two groups, lead-exposed group and control group, and then questionnaires were used to obtain their basic information, and medical testing methods were used to obtain their serum exosomes. Secondly, principal component analysis was used to construct a comprehensive index of neurobehavioral function. Furthermore, volcano map and heatmap were used to display the differential gene distribution and correlation analysis of expression levels, respectively. Finally, two software applications, TargetScan and miRanda, were used to predict the target genes of the significantly different microRNAs, respectively, and the target genes predicted by the two software applications are screened according to the scoring standards of each software. Our results showed that 73 microRNAs were changed in the serum exosomes of lead-exposed worker, among which 48 microRNAs are upregulated and 25 microRNAs are downregulated. Moreover, the miR-124 and miR-506 were identified, and they might be involved in the process of lead-induced neuroinflammation

Toxic response of antimony in the Comamonas testosteroni and its application in soil antimony bioremediation

Antimony (Sb) is toxic to ecosystems and potentially to public health via its accumulation in the food chain. Bioavailability and toxicity of Sb have been reduced using various methods for the remediation of Sb-contaminated soil in most studies. However, Sb-contaminated soil remediation by microbial agents has been rarely evaluated. In this study, we evaluated the potential for the use of Comamonas testosteroni JL40 in the bioremediation of Sb-contamination. Strain JL40 immobilized more than 30 % of the Sb(III) in solution and oxidized over 18 % to Sb(V) for detoxification. Meanwhile, strain JL40 responds to Sb toxicity through such as Sb efflux, intracellular accumulation, biofilm production, and scavenging of reactive oxygen species (ROS), etc. The results of the pot experiment showed the average Sb content of the brown rice was decreased by 59.1%, 38.8%, and 48.4%, for 1.8, 50, and 100 mg/kg Sb spiked soils, respectively. In addition, the results of plant, soil enzyme activity, and rice agronomic trait observations showed that the application of strain JL40 could maintain the health of plants and soil and improve rice production. The single-step and sequential extraction of Sb from rhizosphere soil showed that strain JL40 also plays a role in Sb immobilization and oxidation in the soil environment. During rice potted cultivation, bacterial community analysis and plate counting showed that the strain JL40 could still maintain 103 CFU/g after 30 days of inoculation. With phenotypic and differential proteomics analysis, strain JL40 conferred Sb(III) tolerance by a combination of immobilization, oxidation, efflux and scavenging of ROS, etc. Our study demonstrates the application of Sb-immobilizing and oxidizing bacteria to lower soil Sb and reduce accumulation of Sb in rice. Our results provide guidance for bacterial remediation of Sb-contaminated soil

Evaluation of the risk of human exposure to thiamethoxam by extrapolation from a toxicokinetic experiment in rats and literature data

Previous studies suggest that exposure to thiamethoxam (TMX) may cause adverse effects to human. However, the distribution of TMX in various organs of human body and the associated risk are little-known. This study aimed to explore the distribution of TMX in human organs by extrapolation from a toxicokinetic experiment in rats and to assess the associated risk based on literature data. The rat exposure experiment was performed using 6-week female SD rats. Five groups of rats were oral-exposed to 1 mg/kg TMX (water as solvent) and executed at 1 h, 2 h, 4 h, 8 h and 24 h after treatment, respectively. The concentrations of TMX and its metabolites in rat liver, kidney, blood, brain, muscle, uterus and urine were measured in different time points using LC-MS. Data on concentrations of TMX in food, human urine and blood as well as human cell-based in vitro toxicity of TMX were collected from the literature. After oral exposure, TMX and its metabolite clothianidin (CLO) were detected in all organs of the rats. The steady-state tissue-plasma partition coefficients of TMX for liver, kidney, brain, uterus and muscle were 0.96, 1.53, 0.47, 0.60 and 1.10, respectively. Based on literature analysis, the concentration of TMX in human urine and blood for general population were 0.06–0.5 ng/mL and 0.04–0.6 ng/mL, respectively. For some people, the concentration of TMX in human urine reached 222 ng/mL. By extraplation from rat experiment, the estimated concentrations of TMX in human liver, kidney, brain, uterus and muscle for general population were 0.038–0.58, 0.061–0.92, 0.019–0.28, 0.024–0.36 and 0.044–0.66 ng/g, respectively, well below the relevant concentrations for cytotoxic endpoints (HQs ≤ 0.012); however, for some people they could be up to 253.44, 403.92, 124.08, 158.40 and 290.40 ng/g, respectively, with very high developmental toxicity (HQ = 5.4). Therefore, the risk for highly exposed people should not be neglected