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Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis and showed osteoprotective effect in ovariectomized rodent animals and regulatory action on calcium transporters. This study aimed to determine if GSK could ameliorate aged osteoporosis by modulating serum level of calciotropic hormones and improving calcium balance. 18-month-old male mice were orally administered with either GSK (0.38 g/kg body weight) or calcitriol (1 μ g/kg body weight) combined with high calcium diet (HCD, 1.2% Ca) for 60 days. The aged mice fed with normal calcium diet (NCD, 0.6% Ca) were a negative control. Trabecular bone and cortical bone properties as well as calcium balance were determined. Treatment with GSK significantly increased 25(OH)D and 1,25-(OH)2D levels in serum, moreover, it markedly attenuated trabecular bone micro-architectural deteriorations and elevated trabecular bone mass as well as strengthened cortical bone mechanical properties shown by the increase in maximal bending load and elastic modulus. Calcium balance, including urinary Ca excretion, fecal Ca level and net calcium retention, was remarkably improved by GSK, which up-regulated TRPV6 expression in duodenum and TRPV5 expression in kidney and down-regulated claudin-14 expression in duodenum and kidney. Additionally, 1-OHase and 24-OHase expression was significantly decreased (vs. NCD group) and increased (vs. HCD group), respectively, in kidney of GSK- and calcitriol-treated mice. Taken together, this study demonstrated the ameliorative effects of Gushukang on aged osteoporosis by effectively stimulating vitamin D production and improving calcium balance of aged mice with high dietary calcium supplement. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. Methods: In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. Results: At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601–0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. Conclusions: Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination therapy much more decrease pro-inflammatory factors associated than those without metformin therapy. [ABSTRACT FROM AUTHOR]

Background: ETS2 is a downstream effector of the RAS/RAF/ERK pathway, which plays a critical role in the development of malignant tumor. However, the clinical impact of ETS2 expression in AML remains unknown.Methods: In this study, we evaluated the prognostic significance of ETS2 expression using two relatively large cohorts of AML patients.Results: In the first cohort, compared to low expression of ETS2 (ETS2 low), high expression of ETS2 (ETS2 high) showed significant shorter OS, EFS and RFS in the current treatments including the allogeneic HCT group (n = 72) and the chemotherapy group (n = 100). Notably, among ETS2 high patients, those received allogeneic HCT had longer OS, EFS and RFS than those with chemotherapy alone (allogeneic HCT, n = 39 vs. chemotherapy, n = 47), but treatment modules play insignificant role in the survival of ETS2 low patients (allogeneic HCT, n = 33 vs. chemotherapy, n = 53). Moreover, gene/microRNA expression data provides insights into the biological changes associated with varying ETS2 expression levels in AML. The prognostic value of ETS2 was further validated in the second AML cohort (n = 329).Conclusions: Our results indicate that ETS2 high is a poor prognostic factor in AML and may guide treatment decisions towards allogeneic HCT. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocytes (CTLs) are important for the recognition of the hepatitis B virus (HBV), mediating immunoprotective mechanisms and determining the clinical outcome following HBV infection. CTLs recognize the invading virus via the T cell receptor (TCR). The aim of the current study was to investigate the variability of TCR in lymphocytes from patients with chronic hepatitis B and whether TCR genomic recombination is regulated by the current treatment strategies. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with chronic hepatitis B and high-throughput sequencing was performed to analyze the gene expression diversity of β chain complementarity determining region. High-throughput sequencing produced ~380,000 reads. The sequences of V and J family mRNAs of the β chain V area were analyzed and databases were created for all 30 V family and J family genes. Using the Basic Local Alignment Search Tool, 15 genes were identified to be upregulated in the samples following treatment. Among them, the expression of T cell receptor β variable 28 (TRBV28)_T cell receptor β joining 1-5 (TRBJ1.5) and TRBV6_TRBJ2.10 were significantly different in the treated samples compared with samples taken prior to treatment. Genomic recombination patterns of TRBV and TRBJ of the β chain V area were observed to be different in the samples following treatment. The data of the current study demonstrated that the genomic rearrangement of the V and J segments of TCR β chain V area may be associated with the chronic progression of HBV and impact on treatment efficacy. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the 24-hour ocular dimensional profile in normal-tension glaucoma (NTG) patients on medical treatment. Methods: Consecutive, medically treated NTG subjects were recruited from a university eye center. Subjects were on a mean of 1.7±0.7 types of antiglaucoma medications and 56.6% were on a prostaglandin analog. A contact lens-based sensor device was worn in one eye of NTG patients to record the intraocular pressure (IOP)-related profile for 24 hours, recording the following: variability from mean over 24 hours, nocturnally and diurnally, as well as the number of peaks and troughs diurnally and nocturnally. Results: In 18 NTG subjects, the nocturnal variability around the mean contact lens-based sensor device signal was 48.9% less than the diurnal variability around the mean. The number of peaks was 54.7% less during the nocturnal period than during the diurnal period. The rate of increase in the ocular dimensional profile when going to sleep was significantly greater than the rate of decrease upon waking (P<0.001). Conclusion: In medically treated NTG subjects, there was more variability in the IOP-related pattern during the daytime and there were fewer peaks during sleep. [ABSTRACT FROM AUTHOR]

Abstract: Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded a library of brominated polyunsaturated lipids including eight new compounds, named xestonarienes A–H (3–10) and thirteen known analogues (11–23). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by comparison with literature data. The isolated lipids were evaluated for their inhibitory activity against pancreatic lipase (PL), an essential enzyme for efficient fat digestion and the major metabolite, 14, exhibited a marked inhibitory activity (IC50 = 3.11 μM), similar to that of the positive control Orlistat (IC50 = 0.78 μM). The preliminary structure–activity relationships on the series of compounds clearly evidenced that a terminal (E)-enyne functionality, a diyne within the chain, and methyl ester group are all key functional groups for the activity of this class of PL inhibitors. Further biological investigation on compound 14 revealed a significant decrease in the plasma triglyceride level following an oral lipid challenge in C57BLKS/J male mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to 1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity for brominated polyunsaturated lipids and the obtained results qualify compound 14 as a potent and bioavailable drug candidate for a mild and safe treatment to prevent and reduce obesity. [Copyright &y& Elsevier]

Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway. [ABSTRACT FROM AUTHOR]

Aims A systematic literature review comparing the efficacy of ephedrine and phenylephrine for the management of spinal anesthesia-induced hypotension during Cesarean sections ( C-sections) was published in 2002. A number of well-designed trials with controversial results have been published afterward. Therefore, an updated meta-analysis was necessary. Methods The MEDLINE, EMBASE, and the Cochrane Library databases were searched (last search performed on September 26, 2011). Pooled risk ratio ( RR) or standard mean difference ( SMD) and their 95% confidence intervals (95% CI) were calculated for the incidence of intra-operative hypotension or umbilical blood p H values. Results A total number of 15 trials and 742 parturients under elective C-sections were analyzed. When used to prevent hypotension, patients receiving ephedrine and phenylephrine did not differ significantly in the incidence of hypotension ( RR = 1.22; 95% CI, 0.83-1.80), umbilical arterial p H values ( SMD = −0.38; 95% CI, −1.67 to 0.92) or venous p H values ( SMD = −0.18; 95% CI, −0.44 to 0.07). And administration routes did not affect the incidence of hypotension and umbilical blood p H values. When used to treat hypotension, patients given ephedrine and phenylephrine had comparable incidence of intra-operative hypotension ( RR = 0.79; 95% CI, 0.40-1.56), while parturients receiving phenylephrine had neonates with higher umbilical arterial pH values ( SMD = −1.32; 95% CI, −2.35 to −0.30) and venous p H values ( SMD = −0.79; 95% CI, −1.09 to −0.49) than those given ephedrine. Conclusion Prophylactic use of ephedrine and phenylephrine were both effective in preventing maternal hypotension during C-section under spinal anesthesia; phenylephrine was superior to ephedrine in treating hypotension, evidenced by higher umbilical blood p H values. [ABSTRACT FROM AUTHOR]

Rosai–Dorfman disease (RDD) is a rare non-neoplastic histioproliferative disorder characterised by painless lymphadenopathy, low fever, high erythrocyte sedimentation rate, leucocytosis and hypergammaglobulinaemia. Overactivity of nuclear factor κB (NF-κB) is linked with inflammatory, cancerous and autoimmune diseases. The first case is described of an unusual life-threatening RDD of the trachea with no lymphadenopathy at risk of suffocation in a 39-year-old Chinese woman. A diagnosis of RDD was made following CT scans, thoracotomy and histological examination. Gel shift assay revealed an essential role for NF-κB overactivity in RDD. The patient remains well with no evidence of progression without treatment. Histological confirmation should be sought in all cases as the clinical manifestation of RDD is similar to asthma or lung carcinoma. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the risk of injuries associated with adults with attention-deficit hyperactivity disorder (ADHD), even though several studies have suggested a higher risk of injury in children and adolescents with ADHD.Aims: To investigate the risk of injury in adults with ADHD.Methods and Procedures: We included 665 adults with ADHD from January 1, to December 31, 2000, and 1995 sex-, age- and index day-matched controls without ADHD from the Longitudinal Health Insurance Database (LHID) subset of the National Health Insurance Research Database in Taiwan. The Cox proportional hazard models were used to analyze the associations between the relevant demographics, and the psychiatric comorbidities and the risk of injury.Outcomes and Results: The patients with ADHD had a 143% increased risk of overall injuries than the controls after considering all the confounding factors. In addition, the use of methylphenidate was associated with a 22.6% decrease in the risk of injuries in the patients with ADHD.Conclusions and Implications: Our findings strongly support that adults with ADHD are at an increased risk of injury, and imply that methylphenidate therapy may attenuate this risk. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the potential benefits of N -acetylcysteine (NAC) on the risk of chronic kidney disease (CKD) progression to dialysis-requiring end-stage renal disease (ESRDd). Methods In a population-based cohort study of 145,062 individuals, 123,608 CKD patients who were followed up for 10 years were included, and CKD patients treated with NAC (ICD-9-CM) were compared with those who were not treated. Using propensity score matching, we analyzed the predictors of CKD progression to ESRDd by Cox proportional hazards regression with adjustments for sex, age, and comorbidities, and evaluated the effect of NAC using cumulative defined daily dose (cDDD). Results NAC use was associated with a reduced risk for progression to ESRDd [hazard ratio (HR), 0.819; 95% confidence interval (CI), 0.781–0.965; P = 0.017]. Risk reduction was proportional to cDDD in NAC users compared with that in NAC non users (HR, 0.835, 0.811, and 0.799 for cDDD 91–180, 181–360, and > 360, respectively; P for trend = 0.018). Risk reduction was apparent in women (P = 0.001) and in younger-aged patients of 18–29 years (P = 0.021) and 30–39 years (P = 0.033), in the presence of hypertension (P = 0.003), and in the absence of diabetes mellitus (P = 0.042) and congestive heart failure (P = 0.036). Conclusion NAC use was associated with a reduced risk for progression to ESRDd. These results, obtained from retrospective data, indicate that a prospective study is warranted. [ABSTRACT FROM AUTHOR]