Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

The allostery and modification of hGHRH molecules and specific dimer produced significant fertility effect by proliferating and activating in-situ ovarian mesenchymal stem cells.

The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.

Magnetic resonance imaging of knees: a novel approach to predict recombinant human growth hormone therapy response in short-stature children in late puberty.

BACKGROUND: There is no appropriate tool to predict recombinant human growth hormone (rhGH) response before therapy initiation in short-stature children in late puberty. The current study aimed to explore the associations between magnetic resonance imaging (MRI) stages of the knee growth plates and rhGH response in short-stature children in late puberty. METHODS: In this prospective cohort study, short-stature children in late puberty were treated with rhGH and followed up for 6 months. We proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups: unclosed growth plate group, marginally closed growth plate group, and nearly closed growth plate group. The primary outcomes were height gain and growth velocity (GV), which were assessed three months later. RESULTS: Fifty participants were enrolled, including 23 boys and 27 girls. GV and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion, especially when grouped by proximal tibias (GV1-3 mon from 9.38 to 6.08 to 4.56 cm/year, GV4-6 mon from 6.75 to 4.92 to 3.25 cm/year, and height gain from 4.03 to 2.75 to 1.95 cm, all P < 0.001). Moreover, the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy, especially when grouped by proximal tibias (all P < 0.01). CONCLUSION: The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty.

Blood Lipid Disorders in Post-Operative Craniopharyngioma Children and Adolescents and the Improvement with Recombinant Human Growth Hormone Replacement.

Context: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients. Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement. Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy. Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (-0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement. Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.

Insights into the release of triclosan from microplastics in aquatic environment assessed with diffusive gradient in thin-films.

Organic chemicals associated with microplastics (MPs) can be released and thus pose potential risks during weathering processes. However, the thermodynamics and kinetics of their release processes still need to be better understood. Herein, the adsorption and desorption kinetics of triclosan on polystyrene (PS) and polyvinyl chloride (PVC) were investigated by using both batch experiments and diffusive gradients in thin-films (DGT) technique. The pseudo-second-order model fitted the data best, implying that both intraparticle diffusion and external liquid film diffusion influence the adsorption and desorption processes. DGT continuously accumulated triclosan from MP suspensions but slower than theoretical values, indicating some restrictions to desorption. The DGT-induced fluxes in Soils/Sediment (DIFS) model, employed to interpret DGT data, gave distribution coefficients for labile species (Kdl) of 5000 mL g-1 (PS) and 1000 mL g-1 (PVC) and the corresponding response times (Tc) were 10 s and 1000 s, respectively. Higher Kdl but smaller Tc for PS than PVC showed that more triclosan adsorbed on PS could be rapidly released, while there were some kinetic limitations for triclosan on PVC. A novel finding was that pH and ionic strength individually and interactively affected the supply of triclosan to DGT. This is the first study to quantify interactions of organics with MPs by using DGT, aiding our understanding of MPs' adsorption/desorption behavior in the aquatic environment.

A high-performance SNP panel developed by machine-learning approaches for characterizing genetic differences of Southern and Northern Han Chinese, Korean, and Japanese individuals.

Population stratification analyses targeting genetically closely related East Asians have revealed that distinguishable differentiation exists between Han Chinese, Korean, and Japanese individuals, as well as between southern (S-) and northern (N-) Han Chinese. Previous studies offer a number of choices for ancestry informative single nucleotide polymorphisms (AISNPs) to discriminate East-Asian populations. In this study, we collected and examined the efficiency of 1185 AISNPs using frequency and genotype data from various publicly available databases. With the aim to perform fine-scale classification of S-Han, N-Han, Korean, and Japanese subjects, machine-learning methods (Softmax and Random Forest) were used to screen a panel of highly informative AISNPs and to develop a superior classification model. Stepwise classification was implemented to increase and balance the discrimination in the process of AISNP selection, first discriminating Han, Korean, and Japanese individuals, and then characterizing stratification between S-Han and N-Han. The final 272-AISNP panel is an alternative optimization of various previous works, which promises reliable and >90% accuracy in classification of the four East-Asian groups. This AISNP panel and the machine-learning model could be a useful and superior choice in medical genome-wide association studies and in forensic investigations for unknown suspect identity.

49AISNP: a study on the ancestry inference of the three ethnic groups in the north of East Asia.

The ancestry inference of unknown samples plays an important role in forensic investigations. An ideal panel is a set of few markers with high ancestry inference accuracy. We collected 428 AISNP (ancestry informative SNP) that can distinguish the three ethnic groups in north of East Asia, including northern Han, Japanese and Korean. The genotypes of 428 AISNP in 307 samples from these three ethnic groups were obtained. Based on the information of Fst value and clustering by allele frequency, the panel was further refined into 49AISNP smart panel. Inference accuracy of the 49AISNP was verified by the leave-one-out method with 307 samples, and the results showed that its accuracy was higher than 99% in the northern Han, Japanese and Korean ethnic groups. This panel can also be helpful to further distinguish the ethnic sub-groups in East Asia.

Polyphenol oxidase dominates the conversions of flavonol glycosides in tea leaves.

Flavonol glycosides are associated with astringency and bitterness of teas. To clarify the dominant enzymatic reaction of flavonol glycosides in tea leaves, the catalytic effects of polyphenol oxidase (PPO), peroxidase (POD) and ß-glucosidase were studied, with the maintaining rates of total flavonol glycosides (TFG) being 73.0%, 99.8% and 94.3%. PPO was selected for further investigations, including the effects of pH value (3.5 ~ 6.5), temperature (25 °C ~ 55 °C) and dosage (39 ~ 72 U/mL PPO and 36 U/mL PPO, 3 ~ 36 U/mL POD). The oxidation of flavonol glycosides were intensified at pH 6.5, with 51.8% and 15.4% of TFG maintained after PPO and PPO + POD treatments, suggesting an enhancement from POD. The sensitivity ranking to PPO was: myricetin glycosides > quercetin glycosides > kaempferol glycosides. The inhibitor treatment testified the leading role of PPO in catalyzing flavonol glycosides in tea leaves. Sugar moiety enhanced the docking affinity of flavonol glycosides for PPO. PPO shows the potential of modifying flavonol glycoside composition.

Effectiveness of Tolvaptan in the Treatment for Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-analysis.

AIMS AND OBJECTIVE: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. MATERIALS AND METHODS: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. RESULTS: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. CONCLUSION: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Involvement of Salicylic Acid in Anthracnose Infection in Tea Plants Revealed by Transcriptome Profiling.

Anthracnose is a major leaf disease in tea plant induced by Colletotrichum, which has led to substantial losses in yield and quality of tea. The molecular mechanism with regards to responses or resistance to anthracnose in tea remains unclear. A de novo transcriptome assembly dataset was generated from healthy and anthracnose-infected leaves on tea cultivars "Longjing-43" (LJ43) and "Zhenong-139" (ZN139), with 381.52 million pair-end reads, encompassing 47.78 billion bases. The unigenes were annotated versus Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), National Center for Biotechnology Information (NCBI) non-redundant protein sequences (Nr), evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) and Swiss-prot. The number of differential expression genes (DEGs) detected between healthy and infected leaves was 1621 in LJ43 and 3089 in ZN139. The GO and KEGG enrichment analysis revealed that the DEGs were highly enriched in catalytic activity, oxidation-reduction, cell-wall reinforcement, plant hormone signal transduction and plant-pathogen interaction. Further studies by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography (HPLC) showed that expression of genes involved in endogenous salicylic acid biosynthesis and also accumulation of foliar salicylic acid are involved in the response of tea plant to anthracnose infection. This study firstly provided novel insight in salicylic acid acting as a key compound in the responses of tea plant to anthracnose disease. The transcriptome dataset in this study will facilitate to profile gene expression and metabolic networks associated with tea plant immunity against anthracnose.

Erratum to: The treatment effect of novel hGHRH homodimer to male infertility hamster.

[This corrects the article on p. 637 in vol. 22, PMID: 30402024.].

The treatment effect of novel hGHRH homodimer to male infertility hamster.

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

Novel hGHRH homodimer promotes fertility of female infertile hamster by up-regulating ovarian GHRH receptor without triggering GH secretion.

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in infertility. The female infertility models were formed by intraperitoneally injecting cyclophosphamide in 5-week-old Chinese hamster once in a week for 5 weeks. All the models mated with healthy male hamster in the ratio of 1:1 in the experimental 6-8th week and the couples were separated to breed in the 9-10th week. 20 mg/kg of cyclophosphamide induced temporary interference of reproduction and did not cause significant difference in the weight of body, bilateral ovaries, or liver. By intramuscularly injecting twice in a week during the experimental 4-10th week, 2, 4, 8 mg/kg of Grin induced 30, 42.9, 60% of total pregnancy rates in a dose-dependent manner whereas 200 U/kg of hMG induced 50% of total pregnancy rates. The single cyclophosphamide dose caused strongly eosinophilic ovarian cells, scattered early follicles, many atretic follicles, and no corpora luteum was observed. The hMG group individually presents many follicles at all levels, especially secondary ones in the ovarian cortex and medulla. Much of loose connective tissue, vacuoles, and sparse interstitial cells distribute in the medulla. Grin induced many follicles at all dose levels and corpora lutea in the cortex, and the compactly aligned interstitial cells occurred in the whole ovarian tissue. The less TUNEL staining and higher expression of ki67 showed the proliferation and protection effect of Grin on ovarian cells. Grin obviously promotes fertility by up-regulating ovarian GHRH receptor and strengthening the development and maturation of follicles without triggering central and ovarian GH secretion.

Evaluation of educational program on osteoporosis awareness and prevention among nurse students in China.

This study assessed a targeted continuing osteoporosis educational program and investigated awareness and prevention of osteoporosis in Chinese female pre-internship nurse students. A quasi-experimental study was conducted. The program was presented to 256 nurse students. The baseline knowledge score of the nurse students was low (9.78 ± 3.13). They had inadequate osteoporosis health beliefs, self-efficacy and related behaviors. The educational program significantly augmented osteoporosis knowledge (Student's paired t = -13.42, P < 0.001), total osteoporosis health beliefs (Student's paired t = -4.46, P < 0.001), and the subscale (P < 0.001) except for the perceived barriers to exercising and calcium intake. Participants showed a significant increase in self-efficacy (Student's paired t = -6.45, P < 0.001) post intervention. Those who completed the program were better prepared to prevent and manage osteoporosis. Additionally, nurse students became more concerned about bone health of family members, subjects and themselves because of attending the program. Results of this study reinforce the need for osteoporosis-related continuing education in nurse students before clinical internship.