Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Novel non-synonymous mutations of PAX8 in a cohort of Chinese with congenital hypothyroidism.

BACKGROUND: The transcription factor paired box 8 (PAX8) was associated with type 2 congenital non-goitrous hypothyroidism (CHNG2), a clinical phenotype of congenital hypothyroidism (CH). Though studied in a few regions with different ethnicities, the incidence of PAX8 mutations varied, even among Chinese cohorts in different regions. This study aimed to identify and characterize PAX8 mutations and explore the prevalence of its mutations in another cohort of CH. METHODS: The 105 unrelated Chinese patients with CH were collected from four major hospitals. Exomes of the 105 samples were sequenced by Hiseq 2000 platform to identify mutations of PAX8 on genomic DNAs extracted from peripheral blood samples. Luciferase reporter assays were used to assess the effects of mutations on the transcription of thyroid peroxidase (TPO). RESULTS: Three PAX8 mutations in four subjects were identified in 105 samples. One variant, rs189229644, was detected in two subjects, and categorized as uncertain significance. The other two missense mutations (275T>C/Ile92Thr and 398G>A/Arg133Gln) were not detected in three large-scale genotyping projects, namely 1000 Genome Project, Exome Aggregation Consortium and GO Exome Sequencing Project. Functional studies for the two mutations revealed that they could impair the transcription ability of PAX8 on one of its target genes, TPO. Therefore, the two mutations were causative for the pathogenesis of CHNG2. After combining the studies of PAX8 mutations, an average frequency of 1.74% (21/1209) could be obtained in Chinese patients with CH. CONCLUSION: The study specifically demonstrates the role of two mutations in impairing the transcription ability of PAX8, which should be considered as pathogenic variants for CH.

Uterine Leiomyomas: Safety and Efficacy of US-guided Suprapubic Transvaginal Radiofrequency Ablation at 1-year Follow-up.

Purpose To assess the safety and efficacy of ultrasonography (US)-guided suprapubic transvaginal (ST) radiofrequency ablation (RFA) in the treatment of symptomatic uterine leiomyomas at 1-year follow-up. Materials and Methods The institutional review board approved this prospective study, and all patients provided informed consent. ST RFA was performed as an outpatient procedure 3 days after menstruation in 51 women (age range, 32-52 years; mean age, 42.2 years) with 62 leiomyomas. The leiomyomas were assessed with conventional and contrast material-enhanced US before and after ST RFA for leiomyoma size, location, and blood flow. All patients were evaluated for postoperative complications, including abdominal pain, injury to surrounding tissues and organs, vaginal bleeding, increased vaginal discharge, fever, dyspnea, and menorrhagia, after ST RFA and at follow-up visits. The leiomyoma volumes, improvement in leiomyoma-related symptoms, effect on quality of life (QOL), and patient satisfaction were assessed and compared before and after ST RFA and at follow-up visits by using statistical analyses. Results Sixty-two leiomyomas were successfully treated with ST RFA until 90% of the leiomyoma was echogenic. At 1-month follow-up, 46 (74%) leiomyomas had no contrast enhancement, five (8%) had peripheral enhancement, eight (13%) had focal enhancement, and three (5%) had scattered enhancement at contrast-enhanced US. At 6-month follow-up, the number of leiomyomas that had no enhancement, peripheral enhancement, focal enhancement, or scattered enhancement was 43 (69%), seven (11%), nine (15%), and three (5%), respectively. The leiomyoma volumes were significantly (P < .05) reduced at 1-, 3-, 6-, and 12-month follow-up (from 33.0 cm(3) ± 25.1 [standard deviation] before treatment to 6.8 cm(3) ± 7.7 at 12-month follow-up). The mean percentage volume reduction at 1-, 3-, 6-, and 12-month follow-up was 28%, 57%, 63%, and 78%, respectively. The scores for symptoms and QOL were all significantly improved (P < .05) at follow-up, going from 45 ± 14 and 65 ± 41, respectively, before treatment to 0 and 100, respectively, at 12-month follow-up. No complications were reported during the periprocedural period or throughout follow-up. Most patients (41 of 45) were satisfied. Conclusion ST RFA may be an effective and safe alternative in the treatment of uterine leiomyomas. (©) RSNA, 2015 Online supplemental material is available for this article.

The role of cystatin C in vascular remodeling of balloon-injured abdominal aorta of rabbits.

This study aimed to evaluate the role of cystatin C (CysC) in the vascular remodeling of balloon-injured abdominal aorta of rabbits. Forty-eight New Zealand white rabbits were randomly divided into three groups: the balloon-injured injury group (n = 16), the CysC monoclonal antibody group (n = 16), and the sham-operative group (n = 16). Serum CysC levels were detected by enzyme linked immunosorbent assay. Changes in adventitial area, adventitial thickness, lumen area (LA), neointimal area (IA), internal elastic lamina area (IELA), external elastic lamina area (EELA), vascular remodeling index (VRI) and residual stenosis (RS) were measured by the Leica image analysis system. Immunohistochemical analysis of α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were performed. Serum CysC levels of rabbits in the balloon-injured injury group were significantly higher than those in the CysC monoclonal antibody group and the sham-operative group (both P < 0.05). At 6 weeks after balloon injury, the adventitial area and thickness, LA, IA, IELA and EELA in the balloon-injured injury group were also higher than those in the CysC monoclonal antibody and sham-operative groups (all P < 0.05). In addition, the balloon-injured injury group showed higher VRI and RS than those of the CysC monoclonal antibody group (both P < 0.05). The positive expression of α-SMA in the vascular adventitia and media in the balloon-injured group were higher than that of the CysC monoclonal antibody and sham-operative groups. The balloon-injured group also showed a stronger expression of α-SMA in the neointima than that of the CysC monoclonal antibody group. There was a strong positive expression of PCNA in the vascular adventitia and neointima in the balloon-injured and CysC monoclonal antibody groups. However, the number of PCNA-positive cells in the balloon-injured group was higher than that of the CysC monoclonal antibody group (25.45 ± 4.21 vs. 6.75 ± 1.11, P = 0.003). Our findings provide empirical evidence that serum CysC levels may play an important role in the vascular remodeling of balloon-injured abdominal aorta of rabbits.

Correlations of SELE genetic polymorphisms with risk of coronary heart disease and myocardial infarction: a meta-analysis.

This meta-analysis of case-control studies was conducted to determine whether SELE genetic polymorphisms contribute to the pathogenesis of coronary heart disease (CHD) and myocardial infarction (MI). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Twenty case-control studies met the inclusion criteria, with a total of 2,292 CHD patients, 901 MI patients and 3,233 healthy controls. Six common polymorphisms in the SELE gene were evaluated, including 554L/F, 98G/T, 128S/R, 2692G/A, 1901C/T, and 1856A/G. The results of our meta-analysis suggest that SELE genetic polymorphisms might be strongly correlated with an increased risk of CHD (allele model: OR 2.08, 95% CI 1.67-2.58, P<0.001; dominant model: OR 2.12, 95% CI 1.68-2.68, P<0.001; respectively), especially the SELE 554L/F, 98G/T and 128S/R polymorphisms. Furthermore, our findings indicated that SELE genetic polymorphisms were closely linked to the risk of CHD in Asians but not Caucasians. However, our findings reveal no positive correlations between SELE genetic polymorphisms and MI risk (allele model: OR 1.39, 95% CI 1.00-1.94, P=0.054; dominant model: OR 1.40, 95% CI 0.96-2.04, P=0.081; respectively). The current meta-analysis suggests that SELE genetic polymorphisms may contribute to an increased risk of CHD, especially the SELE 554L/F, 98G/T and 128S/R polymorphisms in Asians. However, SELE genetic polymorphisms may not be important determinants of susceptibility to MI.

Tracking control and synchronization of four-dimensional hyperchaotic Rossler system.

In this paper we study the problem of the four-dimensional hyperchaotic Rossler system tracking control. A controller based on the reference signal is designed. It is theoretically proved that the controller can make the error converge to zero exponentially. Numerical results have verified the validity of the controller. The Rossler system cannot only track any reference signal fast, but can synchronize with identical or different chaotic systems.