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Histone post-translational modifications play important roles in transcriptional regulation. It is known that multiple histone modifications can act in a combinatorial manner. In this study, we investigated the effects of multiple histone modifications on expression levels of five gene categories (four kinds of pattern genes and non-pattern genes) in coding regions. The combinatorial patterns of modifications for the five gene categories were also studied in the regions. Our results indicated that the differences in the expression levels between any two gene categories were significant. There were some corresponding differences in multiple histone modification levels among the five gene categories. Multiple histone modifications jointly impacted expression levels of every gene category. Four mutual combinations of histone modifications were found and analyzed.

We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy. Osteopenic-osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16-1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03-0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.

The spongy body of the penis metastasis from other primary sites is a rare clinical entity. It is frequently associated with widespread metastatic disease and poor prognosis clinically. We report a case of a 61-year-old man with a previous history of cystectomy due to infiltrating urothelial carcinoma of the bladder 12 months ago and presented with penile shaft swelling pain and hematuria for 3 months. The restaging F-FDG PET/CT scan demonstrated a hypermetabolic mass at his penile shaft. This lesion was confirmed on phallectomy to be infiltrating urothelial carcinoma metastasis from the known primary bladder tumor.

Biomechanical tests are widely used in animal studies on osteoporotic fracture healing. However, the biomechanical recovery process is still unknown, leading to difficulty in choosing time points for biomechanical tests and in correctly assessing osteoporotic fracture healing. To determine the biomechanical recovery process during osteoporotic fracture healing, studies on osteoporotic femur fracture healing with biomechanical tests in ovariectomized rat (OVX) models were collected from PUBMED, EMBASE, and Chinese databases. Quadratic curves of fracture healing time and maximum load were fitted with data from the analyzed studies. In the fitted curve for normal fractures, the predicted maximum load was 145.56 N, and the fracture healing time was 88.0 d. In the fitted curve for osteoporotic fractures, the predicted maximum load was 122.30 N, and the fracture healing time was 95.2 d. The maximum load of fractured femurs in OVX rats was also lower than that in sham rats at day 84 post-fracture (D84 PF). The fracture healing time was prolonged and maximum load at D84 PF decreased in OVX rats with closed fractures. The maximum load of Wister rats was higher than that of Sprague-Dawley (SD) rats, but the fracture healing time of SD and Wister rats was similar. Osteoporotic fracture healing was delayed in rats that were < = 12 weeks old when ovariectomized, and at D84 PF, the maximum load of rats < = 12 weeks old at ovariectomy was lower than that of rats >12 weeks old at ovariectomy. There was no significant difference in maximum load at D84 PF between rats with an osteoporosis modeling time <12 weeks and > = 12 weeks. In conclusion, fracture healing was delayed and biomechanical property decreased by osteoporosis. Time points around D95.2 PF should be considered for biomechanical tests of osteoporotic femur fracture healing in OVX rat models. Osteoporotic fracture healing in OVX rats was affected by the fracture type but not by the strain of the rat.

Myofibroma of the muscle is extremely rare. This report describes a 46-year-old man with myofibroma of the left supraspinous muscle on 18F-FDG PET/CT and includes MRI and 18F-FDG PET/CT findings. Whole-body 18F-FDG PET/CT showed abnormal tracer uptakes in the left supraspinous muscle, which was subsequently confirmed as myofibroma by histopathology.

Metastatic malignant fibrous histiocytoma (MFH) in the stomach is extremely rare. We report a 73-year-old man with MFH in the left popliteal fossa that metastasized to the stomach. Whole-body F-FDG PET/CT showed abnormal tracer uptakes in the stomach, which was subsequently confirmed as metastatic MFH.

Spinal cord injury (SCI) leads to loss of function below the lesion and affects individuals worldwide. An increasing number of experimental studies support the effectiveness of melatonin (MT) for SCI. Our objectives were to investigate neurological recovery and anti-oxidant effects of MT in animal models of SCI, and to explore the appropriate dose. Published MT studies in SCI animal models described in six databases were searched. Two practiced investigators selected the studies, extracted the data, and independently evaluated the quality of the included studies. A meta-analysis evaluated the effect of MT in SCI and a network meta-analysis was performed to explore the appropriate MT dose for SCI models. Thirteen studies were analyzed, of which three were high quality. The results of the meta-analysis manifested that the behavioral evaluation (Basso, Beattie, and Bresnahan scales, n = 90, p = 0.003; motor function scores, n = 92, p = 0.004; Tarlov's criteria, n = 150, p = 0.002; inclined plane test, n = 150, p = 0.001) and biochemical outcomes (malondialdehyde, n = 121, p = 0.0010; glutathione levels, n = 64, p < 0.0001; and myeloperoxidase activity, n = 32, p < 0.00001) were improved, compared with the control group, after MT administration. A dose of 12.5 mg/kg was most effective in SCI rat models. Studies indicated that MT administration significantly improved neurological recuperation and anti-oxidant effects in rat models of SCI. The appropriate dose of MT was 12.5 mg/kg for SCI rat models. The majority of included studies were low quality; however, optimal MT treatment in SCI still requires high quality studies.

Some genes tend to cluster and be co-expressed. Multiple factors affect gene co-expression. In this study, we investigated the relationships between multiple factors and the correlations of expression levels of neighboring genes, which were divided into four kinds of pattern genes and one type of non-pattern gene. Our results indicate that the correlation between expression levels of neighboring non-pattern genes is related to multiple factors with the exception of transcriptional orientations of neighboring genes. The correlation between expression levels of neighboring specific genes or neighboring repressed genes is likely to be dependent on the co-functions of neighboring genes. The correlation between expression levels of neighboring housekeeping genes is associated with histone modifications in intergenic regions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To assess the characteristics of 18F-FDG uptake in elastofibroma dorsi (EFD)., Methods: Seventeen patients with EFD were retrospectively studied., Results: The mean±S.D. of SUV was 2.29±0.60 (range, 1.2-4.3), and the uptake were Grade 0 in 6, Grade 1 in 12, Grade 2 in 7, and Grade 3 in 1. There is no correlation between lesion volume, SUVmax, and computer tomography value. All EFD lesions showed soft tissue density with low or moderate diffused and homogeneous uptake of 18F-FDG., Conclusions: Mild and moderate uptake of 18F-FDG is frequently observed in EFD, which should be known to avoid making wrong diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Pulmonary alveolar proteinosis is a rare lung disease caused by diffuse, abnormal intra-alveolar surfactant accumulation. Here, we report a case of autoimmune pulmonary alveolar proteinosis with heterogeneous accumulation of F-FDG in both lungs shown on the combined F-FDG PET/CT.

Objective: To evaluate the efficacy and safety of the combination therapy of Xipayimaizipizi Capsules and Tamsulo- sin in the treatment of benign prostatic hyperplasia (BPH)., Methods: We randomly assigned 60 BPH patients to a control and a combination group of equal number, the former aged 62.03 ± 10.19 years with a disease course of 3.24 ± 2.18 years and the latter aged 64.77 ± 10.33 years with a disease course of 4.09 ± 2.63 years. We treated the patients in the control group with Tamsulosin at 0.2 mg qd and those in the combination group with Tamsulosin at 0.2 mg qd plus Xipayimaizipizi at 0.5 g tid, respectively, both for 4 weeks. Then, we obtained the mean frequency of nocturnal urination, maximal urinary flow rate (Qmax), residual urine volume, International Prostate Symptom Score (IPSS) , and quality of life scores (QOL) of the patients, and recorded their adverse reactions., Results: Before treatment, the nocturnal urination frequency, Qmax, IPSS, and QOL were 3.60 ± 1.81, (10.40 ± 3.53) ml/min, 22.47 ± 8.58, and 4.43 ± 1.50 in the control group, as compared with 3.43 ± 1.61, (10.14 ± 3.43) ml/min, 21.93 ± 8.79, and 4.73 ± 1.31 in the combination group. After 4 weeks of medication, the combination group showed more significant improvement than the control in the nocturnal urination frequency (1.30 ± 1.18 vs 2.27 ± 1.60), Qmax ([13.85 ± 3.15] vs [14.36 ± 3.03] ml/min), IPSS (13.00 ± 1.53 vs 17.20 ± 8.43), and QOL (2.57 ± 1.61 vs 2.93 ± 1.68), all significantly better than the baseline (P < 0.05). The combination therapy achieved remarkable improvement as compared with the control in the nocturnal urination frequency (- [2.13 ± 1.11] vs -[1.73 ± 1.07]), IPSS (- [8.93 ?6.01] vs -[4.80 ± 3.87]), and QOL (- [2.17 ± 1.12] vs -[1.50 ± 1.01]) (P < 0.05), but exhibited no significant differences from the latter in Qmax ([3.72 ± 2.281 vs [3.95 ± 2.53] ml/min) and residual urine volume (- [34.30 ± 37.43] vs - [26.43 ± 30.49] ml) (P > 0.05). Adverse reactions were found in 5 cases in the combination group (16.67%) and 3 cases in the control (10%) , with no remarkable differences between the two groups (P > 0.05)., Conclusion: The combination therapy of Xipayimaizipizi Capsules and Tamsulosin can improve the symptoms of BPH and the patients quality of life of.

Background: Hip osteoarthritis (HOA) is one of the major causes of disability in seniors and is costly to society. Manual therapy is one therapeutic approach to treating HOA., Objectives: To assess the effect of manual therapy compared to the placebo or wait-list/no treatment or a minimal intervention control for HOA at post-treatment and short-, intermediate- and long-term follow-ups., Study Design: A systematic review and meta-analysis of randomized controlled trials (RCTs)., Setting: Hospital outpatient clinic in China., Methods: We searched PubMed, EMBASE, the Cochrane Library, CINAHL, ISI web of knowledge, and Chinese databases from the inception to October 2014 without language restrictions. References of systematic reviews and other related reviews, files in our department, and conference proceedings as grey literature were also screened by hand. RCTs compared manual therapy to the placebo, wait-list/no treatment or a minimal intervention control with an appropriate and precise description of randomization. Two reviewers independently conducted the search results identification, data extraction, and methodological quality assessment. We calculated the risk difference (RD) for dichotomous data and the mean difference (MD) or standardized mean difference (SMD) for continuous data in a fixed or random effect model., Outcome Measures: The primary outcomes were self-reported pain in the past week and physical function. The secondary outcomes were the quality of life, global perceived effect, patients' satisfaction, cost, and adverse events., Results: Six studies involving 515 HOA patients were included. Five of the 6 studies ranked as high quality in the methodological assessment. Immediately post-treatment, there was low-quality evidence that manual therapy could not statistically significantly relieve pain (SMD: -0.07 [95%CI -0.38 to 0.24]); for physical function, a moderate quality of evidence showed that manual therapy could not improve the physical function significantly (SMD: 0.14 [95%CI -0.08 to 0.37]). We still found low-quality evidence that manual therapy did not benefit the patients in the global perceived effect (RD: 0.12 [95%CI -0.12 to 0.36]), and in terms of quality of life. In addition, the risks of patients in the manual therapy group was 0.13 times higher than that in the controls (RD: 0.13 [95%CI -0.05 to 0.31]) in the low-quality evidence studies. We could not find any evidence that manual therapy benefits the patients at short-, intermediate- or long-term follow-up. There were no studies reporting patients' satisfaction or cost., Limitations: The limitations of this systematic review include the paucity of literature and inevitable heterogeneity between included studies., Conclusion: This review did not suggest there was enough evidence for manual therapy for the management of HOA. However, we are not confident in making such a conclusion due to the limitations listed above.

In order to examine how implanted bone marrow stromal cells (BMSCs) encourage peripheral nerve regeneration, the present study investigated the interaction of BMSCs and Schwann cells (SCs) using an indirect in vitro co‑culture model. SCs and BMSCs were obtained from adult Sprague‑Dawley rats. The passaged BMSCs were CD29‑ and CD44‑positive but CD45‑negative and were co‑cultured with the primary SCs using a Millicell system, which allows BMSCs and SCs to grow in the same culture medium but without direct contact. Expression of the typical SC markers S‑100 and glial fibrillary acidic protein (GFAP) of the treated BMSCs as well as the proliferation capacity of the co‑cultured SCs was evaluated by immunocytochemical staining on the 3rd and 5th day of co‑culture. Immunocytochemical staining showed that >75% of the BMSCs in the indirect co‑culture model were GFAP‑ and S‑100‑positive on the 3rd and 5th day after co‑culture, as opposed to <5% of the BMSCs in the control group. On the 3rd day after co‑culture, only a few co‑cultured BMSCs showed the typical SC‑like morphology, while most BMSCs still kept their native appearance. By contrast, on the 5th day after co‑culture, almost all of the co‑cultured BMSCs appeared with the typical SC‑like morphology. Furthermore, 70.71% of the SCs in the indirect co‑culture model were S‑100‑positive on the 5th day of co‑culture, as opposed to >30.43% of the SCs in the control group. These results indicated that BMSCs may interact synergistically with SCs with regard to promoting peripheral nerve regeneration.

Background: Chromosome 1 open reading frame 63 (C1orf63) is located on the distal short arm of chromosome 1, whose allelic loss has been observed in several human cancers. C1orf63 has been reported to be up-regulated in IL-2-starved T lymphocytes, which suggests it might be involved in cell cycle control, a common mechanism for carcinogenesis. Here we investigated the expression and clinical implication of C1orf63 in breast cancer., Methods: Paraffin-embedded specimens, clinicopathological features and follow-up data of the breast cancer patients were collected. Publicly available microarray and RNA-seq datasets used in this study were downloaded from ArrayExpress of EBI and GEO of NCBI. KM plotter tool was also adopted. The expression of C1orf63 and CDK10, one known cell cycle-dependent tumor suppressor in breast cancer, was assessed by immunohistochemistry. Western blotting was performed to detect C1orf63 protein in human breast cancer cell lines, purchased from the Culture Collection of the Chinese Academy of Sciences, Shanghai., Results: In a group of 12 human breast tumors and their matched adjacent non-cancerous tissues, C1orf63 expression was observed in 7 of the 12 breast tumors, but not in the 12 adjacent non-cancerous tissues (P < 0.001). Similar results were observed of C1orf63 mRNA expression both in breast cancer and several other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma. In another group of 182 breast cancer patients, C1orf63 expression in tumors was not correlated with any clinicopathological features collected in this study. Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (-) group (P = 0.145). However, the analyses of KM plotter displayed a valid relationship between C1orf63 and RFS (relapse free survival)/OS (P < 0.001; P = 0.007). Notablely, in breast cancers with advanced TNM stages (III ~ IV) among these 182 patients, C1orf63 expression was an independent prognostic factor predicting better clinical outcome (HR: 0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001)., Conclusions: Compared to adjacent non-cancerous tissues, C1orf63 expression was elevated in tumor tissues. However, C1orf63 predicts better prognosis for breast cancers with advanced TNM stage, and the underlying mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle related gene, CDK10.

Vertically aligned ZnO/MgO coaxial nanowire (NW) arrays were prepared on sapphire substrates by metal-organic chemical vapor deposition combined with a sputtering system. We present a comparative investigation of the morphological and optical properties of the produced heterostructures with different MgO layer thicknesses. Photoluminescence measurements showed that the optical performances of ZnO/MgO coaxial NWs were strongly dependent on the MgO layer thickness. The intensity of deep-level emission (DLE) decreased monotonously with the increase of MgO thickness, while the enhancement of ultraviolet (UV) emission showed a critical thickness of 15 nm, achieving a maximum intensity ratio (∼226) of IUV/IDLE at the same time. The significantly improved exciton emission efficiency of the coaxial NW structures allows us to study the surface passivation effect, photogenerated carrier confinement and transfer in terms of energy band theory. More importantly, we achieved an ultralow threshold (4.5 mA, 0.58 A cm(-2)) electrically driven UV lasing action based on the ZnO/MgO NW structures by constructing an Au/MgO/ZnO metal/insulator/semiconductor diode, and the continuous-current-driven diode shows a good temperature tolerance. The results obtained on the unique optical properties of ZnO/MgO coaxial NWs shed light on the design and development of ZnO-based UV laser diodes assembled with nanoscale building blocks.

Study Design: Systematic review of cross-cultural adaptation., Objective: To perform a systematic review of cross-cultural adaptations of the Neck Disability Index (NDI) and to give a critical assessment to improve its translation., Summary of Background Data: The NDI is used to assess functional capacity and physical activity in patients with neck pain, but the quality of its cross-cultural adaptations has not been systematically reviewed., Methods: PubMed, Cochrane Library, and EMBASE were searched up through 2013 to identify studies of cross-cultural NDI adaptations. Search terms were "Neck Disability Index" or "NDI" and "cross-cultur*" or "cultur*" or "valid*" or "equivalence" or "transl*." Data were extracted and study quality was assessed., Results: Twenty-four different NDI versions were identified from 14 different languages/cultures. Most reported forward and back translation and pretesting, but sample size was a problem for most studies. The Cronbach α was generally acceptable, and 13 versions met the criterion of reliability by reporting an intraclass correlation coefficient of 0.70 or more, although some versions did not reach the minimal intraclass correlation coefficient. Eleven versions tested ceiling and floor effects, but only 1 Japanese version reported a floor effect. No study reported interpretability, and none provided the minimal important change or minimal important difference., Conclusion: The Arabic, Italian, and Thai versions were of higher quality than the other versions according to the overall assessment of the 3 checklists. The Catalan, Chinese, Japanese, Korean, Thai, and Turkish versions need more research according to the Quality Criteria for Psychometric Properties of Health Status Questionnaire. Pretest sample size was not large enough in most cases., Level of Evidence: 1.

Mutations in the basal core promoter (BCP) and precore (PC) regions of the hepatitis B virus (HBV) are more common in genotypes B and C than in genotype A, suggesting that these mutations might affect replication competency depending on genotype. The purpose of the study was to investigate the influence of these mutations on the capacity of HBV for replication and antiviral drug susceptibility according to genotype. Genotypes A, B, and C of HBV strains with a BCP mutation, PC mutation, or BCP + PC mutation were made by site-directed mutagenesis. Replication competency of each construct and susceptibility to nucleos(t) ide analogues were tested in an Huh7 cell line. In genotype A, the BCP and BCP + PC mutations increased the viral replication around 6.5 times compared with the wild type, and the PC mutation alone similarly increased the viral replication around three times. In genotypes B and C, all three mutant types increased viral replication to a similar extent, regardless of mutation pattern. Interestingly, the BCP mutation appeared to have a greater effect on viral replication in genotype A than in genotypes B and C. This finding was unexpected because the BCP mutation is more common in HBV genotypes B and C. Moreover, the BCP, PC, and BCP + PC mutations decreased the sensitivity of HBV to antiviral agents to various degrees (2- to 10-fold) regardless of genotype. In conclusion, BCP and PC mutations increased viral replication regardless of HBV genotype and decreased in vitro antiviral susceptibility to the nucleos(t) ide analogues., (© 2015 Wiley Periodicals, Inc.)

Spinal cord injury (SCI) is a devastating condition affecting young, healthy individuals worldwide. Existing agents have inadequate therapeutic efficacy, and some are associated with side effects. Our objective is to summarize and critically assess the neurological recovery and antioxidant effects of curcumin for treatment of SCI in rat models. PubMed, Embase, and Chinese databases were searched from their inception date to February 2014. Two reviewers independently selected animal studies that evaluated neurological recovery and antioxidant effects of curcumin, compared to placebo, in rats with SCI, extracted data, and assessed the methodological quality. A pair-wise analysis and a network meta-analysis were performed. Eight studies with adequate randomization were selected and included in the systematic review. Two studies had a higher methodological quality. Overall, curcumin appears to significantly improve neurological function, as assessed using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale (four studies, n=132; pooled mean difference [MD]=3.09; 95% confidence interval [CI], 3.40-4.45; p=0.04), in a random-effects model and decrease malondialdehyde (MDA) using a fixed-effects model (four studies, n=56; pooled MD=-1.00; 95% CI=-1.59 to -0.42; p=0.00008). Effect size, assessed using the BBB scale, increased gradually with increasing curcumin dosage. The difference between low- and high-dose curcumin using the BBB scale was statistically significant. Neurological recovery and antioxidant effects of curcumin were observed in rats with SCI despite poor study methodological quality.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and posttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 (HIF-1), p53, nitric oxide (NO), and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications (PTMs) occurring in GAPDH in cancer cells result in new activities unrelated to the original glycolytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described.

Background: High incidences of neck pain morbidity are challenging in various situations for populations based on their demographic, physiological and pathological characteristics. Chinese proprietary herbal medicines, as Complementary and Alternative Medicine (CAM) products, are usually developed from well-established and long-standing recipes formulated as tablets or capsules. However, good quantification and strict standardization are still needed for implementation of individualized therapies. The Qishe pill was developed and has been used clinically since 2009. The Qishe pill's personalized medicine should be documented and administered to various patients according to the ancient TCM system, a classification of personalized constitution types, established to determine predisposition and prognosis to diseases as well as therapy and life-style administration. Therefore, we describe the population pharmacokinetic profile of the Qishe pill and compare its metabolic rate in the three major constitution types (Qi-Deficiency, Yin-Deficiency and Blood-Stasis) to address major challenges to individualized standardized TCM., Methods/design: Healthy subjects (N = 108) selected based on constitutional types will be assessed, and standardized pharmacokinetic protocol will be used for assessing demographic, physiological, and pathological data. Laboratory biomarkers will be evaluated and blood samples collected for pharmacokinetics(PK) analysis and second-generation gene sequencing. In single-dose administrations, subjects in each constitutional type cohort (N = 36) will be randomly divided into three groups to receive different Qishe pill doses (3.75, 7.5 and 15 grams). Multiomics, including next generation sequencing, metabolomics, and proteomics, will complement the Qishe pill's multilevel assessment, with cytochrome P450 genes as targets. In a comparison with the general population, a systematic population pharmacokinetic (PopPK) model for the Qishe pill will be established and verified., Trial Registration: This study is registered at ClinicalTrials.gov, NCT02294448 .15 November 2014.

Objective. The objective of this study was to conduct a systematic review to assess the effectiveness and safety of traditional Chinese herb combined with surgery for male varicocele infertility compared to surgery. Methods. Randomized controlled trials (RCTs) data of traditional Chinese herbs combined with surgery for male varicocele fertility versus surgery were collected by searching the Cochrane Library, Embase, PubMed, and Chinese databases. The risk of bias was assessed using Cochrane Handbook. Study outcomes were presented as risk ratios (RRs) for dichotomous data. Results. Seventeen of 72 potentially relevant trials met the inclusion criteria. The methodological qualities of the RCTs were low. Compared with the surgery group, the traditional Chinese herb combined with surgery group had superiority in pregnancy rate at 3-month (RR = 1.76, and P = 0.008), 6-month (RR = 1.58, and P = 0.0005), and 2-year (RR = 1.58, and P = 0.0005) follow-ups. No RCT was found to describe the side effects. Conclusion. On considering the low methodological quality of RCTs, there was no enough evidence on traditional Chinese herb with surgery for male varicocele infertility, and more high-quality RCTs of large sample sizes are required.

Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8 % (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC.

Background: Adefovir (ADV) resistance is more frequent in lamivudine (LMV)-resistant chronic hepatitis B (CHB) patients than in nucleos(t)ide analogue-naïve patients. The majority of LMV-resistant mutants harbor the rtM204V/I mutation, while a minor fraction harbor the rtA181V/T mutation. We aimed to elucidate the mechanism of the high rate of ADV resistance in LMV-resistant patients during ADV therapy., Methods: We performed a clonal analysis of HBV reverse transcriptase in treatment-naïve (n = 3) and LMV-resistant patients before ADV therapy (n = 14). Dynamic changes in the viral population (n = 9) during ADV therapy were also analyzed., Results: Before ADV therapy, rtA181V/T was observed in 30 of 680 clones (4.4%) from 7 patients with LMV resistance under dominant rt204V/I mutation and in one of 150 clones in treatment-naïve patients. The rtA181V/T mutation was more frequently found in clones from LMV-resistant patients than in treatment-naïve patients (p = 0.029). The rtN236T mutation was not observed in any clone. During ADV therapy, most rtM204V/I mutants were replaced by wild type in all 3 patients without the rtA181V/T mutation and in one patient with the rtA181V/T mutation. Subsequently, wild type was replaced by the rtN236T and/or rtA181V/T mutant. In patients with the rtA181V/T mutation (n = 6), the rtA181V/T mutant overtook the rtM204V/I mutant in 3 of 4 patients with ADV resistance. In 2 patients without ADV resistance, most of the viral population was replaced by wild type by the last follow-up., Conclusion: The high rate of ADV resistance in patients with LMV-resistance might be attributable to preexisting rtA181V/T mutant virus., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Maize architecture is a major contributing factor to their high level of productivity. Maize varieties with an erect-leaf-angle (LA) phenotype, which increases light harvesting for photosynthesis and grain-filling, have elevated grain yields. Although a large body of information is available on the map positions of quantitative trait loci (QTL) for LA, little is known about the molecular mechanism of these QTL. In this study, the ZmCLA4 gene, which is responsible for the qLA4-1 QTL associated with LA, was identified and isolated by fine mapping and positional cloning. The ZmCLA4 gene is an orthologue of LAZY1 in rice and Arabidopsis. Sequence analysis revealed two SNPs and two indel sites in ZmCLA4 between the D132 and D132-NIL inbred maize lines. Association analysis showed that C/T/mutation667 and CA/indel965 were strongly associated with LA. Subcellular localization verified the functions of a predicted transmembrane domain and a nuclear localization signal in ZmCLA4. Transgenic maize plants with a down-regulated ZmCLA4 RNAi construct and transgenic rice plants over-expressing ZmCLA4 confirmed that the ZmCLA4 gene located in the qLA4 QTL regulated LA. The allelic variants of ZmCLA4 in the D132 and D132-NIL lines exhibited significant differences in leaf angle. ZmCLA4 transcript accumulation was higher in D132-NIL than in D132 during all the developmental stages and was negatively correlated with LA. The gravitropic response was increased and cell shape and number at the leaf and stem junctions were altered in D132-NIL relative to D132. These findings suggest that ZmCLA4 plays a negative role in the control of maize LA through the alteration of mRNA accumulation, leading to altered shoot gravitropism and cell development. The cloning of the gene responsible for the qLA4-1 QTL provides information on the molecular mechanisms of LA in maize and an opportunity for the improvement of plant architecture with regard to LA through maize breeding., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To evaluate value of a new method in detecting bladder lesion with (18)F-FDG PET/CT., Methods: Routine and delayed scans of 14 patients were retrospectively studied. All these bladder lesions were confirmed by pathology. By increasing display threshold of SUVmax, routine images were analyzed for the second time., Results: Of 12 (18)F-FDG-avid cases, 10 cases were confirmed to be primary bladder carcinoma, 2 false-positive cases were inflammation. There were 25% positive cases on routine display and 50% on display with increased SUVmax threshold., Conclusion: The method can effectively increase the sensitivity and accuracy in detecting bladder cancer with (18)F-FDG PET/CT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of extracorporeal shockwave therapy (ESWT) and provide clinicians with an evidence base for their clinical decision making., Data Sources: PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Evidence-Based Medicine Reviews., Study Selection: All randomized or quasi-randomized controlled trials of ESWT for chronic recalcitrant plantar fasciitis were searched. Searching identified 108 potentially relevant articles; of these, 7 studies with 550 participants met inclusion criteria., Data Extraction: Number of patients, population, body mass index, duration of symptoms, adverse effects, blinding method, and details of shockwave therapy were extracted., Data Synthesis: For intervention success rate, ESWT of low intensity was more effective than control treatment of low intensity. For pain relief, the pooled data showed a significant difference between the ESWT and control groups. For function, only low-intensity ESWT was significantly superior over the control treatment., Conclusions: The efficacy of low-intensity ESWT is worthy of recognition. The short-term pain relief and functional outcomes of this treatment are satisfactory. However, owing to the lack of a long-term follow-up, its long-term efficacy remains unknown., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects., Methods: Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot., Results: Treatment with α-mangostin (3-10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells., Conclusion: The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.

Background: Skin and soft-tissue infections (SSTIs) are common infections of the epidermis, dermis or subcutaneous tissue. SSTIs range in severity from minor, self-limiting, superficial infections to deep, aggressive, gangrenous, life-threatening infections. Some classifications divide SSTIs into 'complicated' and 'uncomplicated' infections based on clinical severity. Treatments of SSTIs involves antibiotic therapy, surgical debridement or drainage, and resuscitation if required. Sometimes these treatments are limited by high treatment costs, bacterial resistance to antibiotics and side effects, therefore, many people with SSTIs are turning to Chinese herbal medicines to treat this problem.Chinese herbal medicines are natural substances that have been used for centuries in China where they are generally considered to be effective for SSTIs. Some Chinese herbal medicines have been shown to have antibacterial and anti-inflammatory properties, although a few herbal medicines have been reported to have side effects. Therefore there is a need to review the current clinical evidence systematically to inform current practice and guide future studies on Chinese herbal medicines for SSTIs., Objectives: To evaluate the benefits and harms of Chinese herbal medicines for treating skin and soft-tissue infections (SSTIs)., Search Methods: Searches were not restricted by date, language or publication status. In July 2014 we searched the following electronic databases: the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; Ovid AMED (Allied and Complementary Medicine); and EBSCO CINAHL., Selection Criteria: All randomised controlled trials (RCTs) in people with SSTIs that compared Chinese herbal medicines with another intervention or control., Data Collection and Analysis: Two review authors screened the literature search results independently; there were no disagreements., Main Results: We identified no RCTs that met the inclusion criteria., Authors' Conclusions: There is currently no information available from RCTs to support or refute the use of Chinese herbal medicines in treating people with SSTIs.

Xanthogranulomatous osteomyelitis is a rare inflammatory process characterized histologically by collection of foamy macrophages admixed with mononuclear cells. We describe 2 cases with chest and back pain; radiography and CT scan identified expansile osteolytic rib destructive lesions with soft tissue mass. F-FDG PET/CT revealed accumulation of F-FDG similar to malignancy. Xanthogranulomatous osteomyelitis was histologically confirmed with numerous foamy histiocytes admixed with inflammatory infiltrate.

Newcastle disease virus (NDV) of paramyxovirus and Marek's disease virus (MDV) of herpesvirus, two of the most serious threats to the poultry industry, can give rise to complex co-infections that hinder diagnosis and prevention. In the current study, two different peptides, derived from the MDV gH (gHH2L) and gB (gBH3), respectively, exhibit antiviral activity against NDV in vitro. The potent inhibitory effect of heptad repeat 2 from fusion glycoprotein of the NDV on MDV infection also has been demonstrated. Plaque formation and embryo infectivity assays confirmed these antiviral results. Furthermore, each tandem peptide consisting of two motifs from different viruses exhibits more potent antiviral activity than the constituent peptides. The current work provides a new strategy for developing novel peptides and vaccines against virus infection and co-infections., (Copyright © 2013 Elsevier B.V. All rights reserved.)

It is an usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. Therefore, the construction of a bifunctional chimeric protein for the treatment of cancer, complicated with thrombosis, is of great significance. Utilizing the superantigenic activity of staphylococcal enterotoxin C2 (SEC2) and the thrombolytic activity of staphylokinase (Sak), Sak-linker-SEC2 and SEC2-linker-Sak were constructed which had good anti-tumor and thrombolytic activities at the same time. Due to the intrinsic emetic activity of SEC2 and high molecular weight (MW) of chimeric proteins (44 kDa), their clinical applications will be restricted. In this study, novel chimeric proteins including ΔSEC2-ΔSak and ΔSak-ΔSEC2 were constructed through the truncation of SEC2 and Sak without 9-Ala linker and His-tag. Compared with the former, both the truncated proteins preserved nearly the same anti-tumor and thrombolytic activities. In addition, their MWs were only 29 kDa and their immunoreactivities were slightly lower than that of Sak-linker-SEC2 and SEC2-linker-Sak, respectively. Therefore, the novel chimeric proteins possessed merits and characteristics, such as low MS, low immunogenicity, and difunctionality which the former had not. It will be of great interest if the above-mentioned proteins can be used to cure Trousseau syndrome in clinic.

Objectives: The aim of this study was to analyze the association between aspirin intake and its effect for chemoprevention of pancreatic cancer incidence by using a meta-analysis method., Methods: The databases of MEDLINE, EMBASE, and Wangfang (Chinese database) were retrieved to identify eligible studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model., Results: A total of 10 studies (4 case-control studies, 5 prospective cohort studies, and 1 randomized controlled trial) with 7,252 cases of pancreatic cancer and more than 120,0000 healthy control subjects were enrolled in the studies. Pooled analyses showed that high-dose aspirin intake was marginally associated with decreased risk for pancreatic cancer for overall analysis (OR, 0.88; 95% CI, 0.76-1.01) as well as for both cohort and case-control studies (OR, 0.70; 95% CI, 0.54-1.16, for the cohort studies; OR, 0.82; 95% CI, 0.62-1.02, for the case-control studies), without between-study heterogeneity. Stratified analysis for Americans showed a similar result (OR, 0.82; 95% CI, 0.65-1.02). In contrast, our study inferred that low-dose aspirin intake was not associated with risk for pancreatic cancer for the total and subgroup analyses., Conclusions: In summary, our study indicated that high-dose aspirin, rather than low-dose aspirin, might be associated with decreased risk for pancreatic cancer, especially for Americans.

Objective: To evaluate the CT characteristics of primary abdominopelvic desmoplastic small round cell tumor (DSCRT) and investigate the relation between radiologic features and corresponding clinicopathologic features., Patients and Methods: A cohort study was performed on 12 abdominopelvic DSCRT patients, the preoperative computed tomography (CT) and contrast enhancement CT scan were performed in all cases. Tumor dimension, location, calcification, organs involvement, metastasis and enhancement characteristics were retrospectively evaluated and catalogued. Histopathology and serial immunological histological chemistry (IHC) studies were as diagnostic reference standard, all clinicopathological and radiological data were analyzed with emphasis on the corresponding imaging findings., Results: Abdominopelvic DSRCT mainly affects young males (male to female was 2:1), Predominantly, two individualized CT subtype patterns were noted according to its characteristic features and the most common imaging findings are extensively disseminated masses in the peritoneal cavity and/or mesentery with slight enhancement after administration of contrast (subtype 1, 9/12; 75%), the type was in correlated with the histopathologic findings of a large stromal component and scare of vessels or tumor cells. In subtype 2 (3/12; 25%), the tumor was solitary and bulky soft-tissue mass localized in retroperitoneum or retrovesical space, it manifested as heterogeneous enhancement which correlated well with the presence of abundance of microvessels and tumor cells., Conclusions: Radiologically, abdomino-pelvic DSRCT is lack of pathognomonic CT character, the most common CT finding is multiple soft tissue masses or solitary bulky lesion inclined to extensively peritoneal and mesenteric spread with heterogeneous enhancement. These radiological findings are related to different histological compositions, awareness of these radiological features may facilitate the CT diagnosis.

Background: Neck pain is a common symptom in most patients suffering from cervical radiculopathy. However, some conservative treatments are limited by their modest effectiveness. On the other hand, surgical intervention for cervical disc disorders is indicated when symptoms are refractory to conservative treatments and neurological symptoms are progressive. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. The purpose of the present study is to examine the efficacy and safety of Qishe Pill, a compound traditional Chinese herbal medicine, for neck pain in patients with cervical radiculopathy., Methods/design: A multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of the Qishe Pill is proposed. The study will include 240 patients from five sites across China and diagnosed with cervical radiculopathy, according to the following inclusion criteria: age 18 to 65 with pain or stiffness in the neck for at least 2 weeks (neck disability index score 25 or more) and accompanying arm pain that radiates distally from the elbow. Qualified participants will be randomly allocated into two groups: Qishe Pill group and placebo group. The prescription of the trial medications (Qishe Pill/placebo) are 3.75 g each twice a day for 28 consecutive days. The primary outcome is pain severity. Secondary outcomes are functional status, patient satisfaction, and adverse events as reported in the trial., Discussion: Qishe Pill is composed of processed Radix Astragali, Muscone, Szechuan Lovage Rhizome, Radix Stephaniae Tetrandrae, Ovientvine, and Calculus Bovis Artifactus. According to modern research and preparation standards, Qishe Pill is developed to improve on the various symptoms of cervical radiculopathy, especially for neck pain. As it has a potential benefit in treating patients with neck pain, we designed a double-blind, prospective, randomized-controlled trial and would like to publish the results and conclusions later. If Qishe Pill can alleviate neck pain without adverse effects, it may be a unique strategy for the treatment of cervical radiculopathy., Trial Registration: This study is registered at ClinicalTrials.gov, NCT01274936.

The aim of the present study was to investigate the efficacy of colorectal cancer (CRC) screening with a three-tier fecal occult blood test (FOBT) in the Chinese population. The study was performed between 1987 and 2008 at the Beijing Military General Hospital, in a cohort of army service males and females aged >50 years. Between 1987 and 2005, a three-tier screening program, comprising guaiac-based FOBTs (gFOBTs), followed by immunochemical FOBTs for positive guaiac test samples and then colonoscopy for positive immunochemical test subjects, was performed annually. The cohort was followed up until 2008. The cohort included 5,104 subjects, of which, 3,863 subjects participated in screening (screening group) and 1,241 did not (non-screening group). The two groups did not differ in age, gender or other major risk factors for colon cancer. Overall, 36 CRCs occurred in the screening group and 21 in the non-screening group. Compared with the non-screening group, the relative risk for the incidence and mortality of CRC was 0.51 [95% confidence interval (CI), 0.30-0.87] and 0.36 (95% CI, 0.18-0.71), respectively, in the screening group. The general sensitivity of this three-tier FOBT was 80.6% (95% CI, 65.3-91.1). Thus, annual screening using the three-tier FOBT program may reduce the CRC incidence and mortality rate.

Meridian essence has been investigated through anatomy, electrophysiology, biophysics, and biochemistry. Various hypotheses of meridian essence exist, but no hypothesis can truly reflect the internal character of Chinese medicine (CM). The research of meridian essence requires a holistic viewpoint and innovative awareness. Initially, any hypothesis regarding meridian essence should begin with observation of the human body. Secondly, the research should arise from the meridians' physical functions and pathological changes, so as to maintain the fundamental nature of the meridians themselves. Thirdly, the research should be based upon the theory of CM, yet coupled with the integration of modern techniques to deepen our understanding of the scientific contents of meridians. Fourthly, theoretical research should be combined closely with clinical practice, in order to test the achievements in actual conditions. Lastly, more attention should be given to negative results in studies to more accurately discover the real essence of meridians.

The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (-1.41 cm 95% CI [-1.61, -1.21]), SF-MPQ at the 3-month followup (WMD -2.33, 95% CI [-4.11, -0.54]) and 6-month followup (WMD -4.67, 95% CI [-7.30, -2.04]), and MDQ at the 3-month followup (WMD -2.31, 95% CI [-3.74, -0.87]) and 6-month followup (WMD -4.67, 95% CI [-7.30, -2.04]). All trials did not report adverse events. These results were limited by the methodological flaws of trials.

Background. Osteoporosis is a major health problem for the elderly population. Chinese herb may be beneficial to osteoporosis due to its capability. Objectives. This study was designed to evaluate the effectiveness of Chinese medicine treatment on the patients with osteoporosis. Search Methods. Randomized controlled trials were retrieved from different 9 databases. Results. This meta analysis included 12 RCTs involving 1816 patients to compare Chinese herbs with placebo or standard anti-osteoporotic therapy in the treatment of bone loss. The pooled data showed that the percent change of increased BMD in the spine is higher with Chinese herb compared to placebo (lumber spine: WMD = 0.07, 95% CI: 0.01-0.04). In the femoral, Chinese herb showed significantly higher increments of BMD compared to placebo (femoral neck: WMD = 0.06, 95% CI: -0.02-0.13). Compared to the other standard anti-osteoporotic drugs, Chinese herbs also show advantage in BMD change (lumber spine: WMD = 0.03, 95% CI: -0.01-0.08; femoral: WMD = 0.01, 95% CI: -0.01-0.02). Conclusions. Our results demonstrated that Chinese herb significantly increased lumbar spine BMD as compared to the placebo or other standard anti-osteoporotic drugs.

The association between transforming growth factor β1 (TGF-β1)-509 C>T and risk of digestive tract cancer (DTC) remained uncertain as previous studies reported conflicting results. The aim of this study was to assess the association by using a meta-analysis. The databases of MEDLINE, EMBASE and WANGFANG (Chinese database) were retrieved, and latest update was on 2nd February, 2012. Pooled odds ratio and 95% confidence interval (OR and 95% CI) were calculated by using a fixed- or random-effect model. Ultimately, twenty nine case-control studies with 8664 cases and 12,532 controls were included in this meta-analysis. Overall, there was no association between TGF-β1-509 C>T and risk of DTC in all genetic comparison models (OR and 95% CI: 0.96 and 0.81-1.15 for TT vs. CC, 0.98 and 0.91-1.05 for T carriers vs. C carriers). When subgroup analyses were conducted according to ethnicity, types of cancer and sample size, T allele was significantly associated with decreased risk of DTC for Caucasians and for large sample-sized studies, and was associated with decreased risk of colorectal cancer (OR and 95% CI for TT vs. CC: 0.82 and 0.70-0.97 for Caucasians, 0.80 and 0.68-0.98 for large sample-sized studies, 0.78 and 0.62-0.97 for colorectal cancer). This study indicated that TGF-β1-509 C>T polymorphism was probably associated with risk of DTC, especially for Caucasians. Because of modest limitation, our findings should be confirmed by future studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Fifteen derivatives of 8-oxocoptisine were prepared based on that 8-oxocoptisine showed potent reversing effect against human cancer cells charactering multidrug resistance (MDR). The derivatives were evaluated for their growth inhibition and effects on reversing P-gp-mediated MDR against MCF-7/AMD cells. 12, 13-dinitro-8-oxocoptisine (6c), the most potential candidate with weak growth inhibition, significantly increased the sensitivity of adriamycin (ADM) against MCF-7/ADM cells by 213-fold at 10 μM that was comparable to the reference compound verapamil. The preliminary structure-activity relationships (SARs) of these derivatives were discussed on the basis of the in vitro MDR reversal activities.

This study evaluates 23 (9 Chinese and 14 non-Chinese) randomized controlled trials for efficacy and side effects of Chinese herbal medicine on menopausal symptoms. Menopause was diagnosed according to western medicine criteria in all studies while seven Chinese studies and one non-Chinese study further stratified the participants using traditional Chinese medical diagnosis "Zheng differentiation." Efficacy was reported by all 9 Chinese and 9/14 non-Chinese papers. Side effects and adverse events were generally mild and infrequent. Only ten severe adverse events were reported, two with possible association with the therapy. CHM did not increase the endometrial thickness, a common side effect of hormone therapy. None of the studies investigated long-term side effects. Critical analysis revealed that (1) high-quality studies on efficacy of Chinese herbal medicine for menopausal syndrome are rare and have the drawback of lacking traditional Chinese medicine diagnosis (Zheng-differentiation). (2) Chinese herbal medicine may be effective for at least some menopausal symptoms while side effects are likely less than hormone therapy. (3) All these findings need to be confirmed in further well-designed comprehensive studies meeting the standard of evidence-based medicine and including Zheng-differentiation of traditional Chinese medicine.

Histone modification is an important subject of epigenetics that plays an intrinsic role in transcriptional regulation. It has been suggested that multiple histone modifications act in a combinatorial fashion to form a 'histone code'. In this study, the combinatorial patterns of histone modifications were studied by using a Bayesian network at the level of individual nucleosomes in S. cerevisiae. Our results indicated that there were 23 combinatorial patterns for 12 histone modifications investigated when a general Bayesian network was constructed. Meanwhile, different networks were also constructed for the genes with high transcript levels (H-network) and low transcript levels (L-network), respectively. Comparison among the general network, H-network and L-network illustrated four conserved combinations: H2BK16Ac → H3K4me3; H3K14Ac → H3K4me3; H2AK7Ac → H3K14Ac; and H4K12Ac → H3K18Ac. The detailed analysis for some combinations demonstrated that the combinations were ascribed to some histone-modifying enzymes., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Osteoporosis is a growing worldwide problem, with the greatest burden resulting from fractures. Nevertheless, the majority of fractures in adults occur in those with "osteopenia" (bone mineral density (BMD) only moderately lower than young normal individuals). Since long-term drug therapy is an expensive option with uncertain consequences and side effects, natural herbal therapy offers an attractive alternative. The purpose of this study is to evaluate the effect on BMD and safety of the Classic Yin and Yang Tonic Formula for treatment of osteopenia and to investigate the mechanism by which this efficacy is achieved., Methods/design: We propose a multicenter double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of the Classic Yin and Yang Tonic Formula for the treatment of osteopenia. Participants aged 55 to 75 with low bone mineral density (T-score between -1 and -2.5) and kidney deficiency in TCM will be included and randomly allocated into two groups: treatment group and control group. Participants in the treatment group will be treated with Classic Yin and Yang Tonic Granule, while the controlled group will receive placebo. Primary outcome measure will be BMD of the lumbar spine and proximal femur using dual-energy X-ray absorptiometry. Secondary outcomes will include pain intensity measured with visual analogue scales, quality of life, serum markers of bone metabolism, indices of Neuro-endocrino-immune network and safety., Discussion: If the Classic Yin and Yang Tonic Formula can increase bone mass without adverse effects, it may be a novel strategy for the treatment of osteoporosis. Furthermore, the mechanism of the Chinese medical formula for osteoporosis will be partially elucidated., Trial Registration: This study is registered at ClinicalTrials.gov, NCT01271647.

The poor survival and differentiation of the donor cells in the infarcted myocardium has hampered the therapeutic efficacy of cell transplantation. A self-assembling polypeptide RAD16-II (Ac-RARADADARARADADA-CONH₂) spontaneously assembles into stable nanofiber scaffolds, which mimic natural extracellular matrix at 0.1-1% peptide concentrations in the myocardium. We isolated mesenchymal stem cells from the bone marrow of adult male rats that express both c-kit and Nkx2.5, a cardiac transcription factor, yielding selected mesenchymal stem cells (SMSCs). We initially confirmed that the self-assembling polypeptide scaffolds are conducive to growth, survival and differentiation of SMSCs in vitro. Subsequently, SMSCs mixed with the self-assembling polypeptide were injected into the infarcted area at 30 min after the establishment of myocardial infarction in female rats. The donor cells were tracked with Y chromosome in the myocardium. The changes of cardiac function, myocardial structure and capillary density were detected at 4 weeks after cell transplantation. The hearts transplanted with SMSCs incorporated into the nanofiber scaffolds showed smaller infarction size (19.55 ± 2.1%) than the hearts injected with SMSCs (27.37 ± 4.8%). Importantly, the systolic function indices, left ventricle ejection fraction and left ventricle fractional shortening, were significantly improved in the animals transplanted with SMSCs mixed with the nanofiber scaffolds (59.31 ± 4.9% and 31.91 ± 8.1%), compared to those with SMSCs alone (48.31 ± 9.2% and 23.58 ± 8.5%). In conclusion, transplantation of SMSCs mixed with the self-assembling polypeptide RAD16-II is more effective to promote myocardial regeneration and attenuate cardiac injury in a rat model of myocardial infarction.

Study Design: Several senescence biomarkers were observed to investigate cell senescence in degenerative intervertebral lumbar discs of foreleg-amputated rats., Objective: To determine if cell senescence is accelerated in degenerative intervertebral lumbar disc cells in an upright-rat model., Summary of Background Data: Cellular senescence was accelerated in human and sand rat degenerative intervertebral disc (IVD) cells. Repeated use of upright posture by rats contributed to degenerative disc changes. No convincing evidence of cell senescence was observed in the lumbar disc of the foreleg amputated rat., Methods: The forelimbs of 20 rats were amputated at 1 month of age such that they maintained an upright stance; rats were housed in custom-made cages. Nonamputated rats, also 1 month of age, were kept in regular cages and served as a control group. The lumbar IVDs were harvested from rats in 2 groups, at 5 or 9 months following amputation. Senescence-associated-β-galactosidase-positive staining was used to detect cell senescence. p16INK4a and p27KIP were assessed by immunohistochemistry analysis. Total RNA isolated from these samples was used to measure the gene expression of p16INK4a, RB, cyclin D1, CDK4, PTEN, p27KIP, p19ARF, p21, TERT, and RAGE by real-time polymerase chain reaction assay., Results: The highest levels of SA-β-GAL activity were detected in 9-month amputated rats. Quantitative immunohistochemical analysis showed that there were highest rates of p16INK4a and p27KIP protein expression in the cartilage endplate and anulus fibrosus of 9-month amputated rats. The mRNA levels of p16INK4a, RB, PTEN, p27KIP, p19ARF, and RAGE were upregulated. The increased cyclin D1 mRNA level was statistically significant only at the ninth month following amputation; CDK4 and TERT mRNA levels were downregulated to a similar extent at both points compared with nonamputated controls. mRNA expression of p21 was significantly downregulated., Conclusion: Accelerated cell senescence was associated with forelimb amputation that causes abnormal loading in rat lumbar IVDs.

Objective: To investigate the effects of a Chinese herb Cordyceps sinensis (C. sinensis) extract on hypoxia-induced proliferation and the underlying mechanisms involved., Methods: This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells (PASMCs) was measured using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen (PCNA), c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry., Results: We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs., Conclusion: Our results indicated that C. sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle (S+G2/M) phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension.

A new ordered mesoporous carbon (OMC) composite modified electrode was fabricated for the first time. Binuclear cobalt phthalocyaninehexasulfonate sodium salt (bi-CoPc) can be adsorbed onto didodecyldimethylammonium bromide (DDAB)/OMC film by ion exchange. UV-vis spectroscopy, scanning electron microscopy (SEM) and electrochemical methods were used to characterize the composite film. The cyclic voltammograms demonstrate that the charge transfer of bi-CoPc is promoted by the presence of OMC. Further study indicated that bi-CoPc/DDAB/OMC film is the excellent electrocatalyst for the electrochemical reduction of oxygen in a neutral aqueous solution and hemoglobin (Hb) at lower concentrations. Additionally, as an amperometric 2-mercaptoethanol (2-ME) sensor, this modified electrode shows a wider linear range (2.5 x 10(-6) to 1.4 x 10(-4) M), high sensitivity (16.5 microA mM(-1)) and low detection limit of 0.6 microM (S/N=3). All these confirm the fact that the new composite film may have wide potential applications in biofuel cells, biological and environmental sensors., (Copyright 2010 Elsevier B.V. All rights reserved.)

It has been hypothesized that naturally occurring mutations in HBV may play a role in the pathogenesis of HBV-related disease. We determined the molecular characteristics of naturally occurring HBV isolates and performed a functional analysis of full-length hepatitis B virus quasispecies from a patient with chronic hepatitis B. The 10 HBV clones isolated were identified as HBV genotype B4 and subtype adw. In most clones, amino acid substitutions and nucleotide changes occurred in a specific region of the core protein, X protein and in the core promoter. In the core protein, cI3L, cL60M, and cI97L were detected in 8 of 10 clones and cP130T was detected in all 10 clones. In the X protein, xI127M was detected in 5 clones. In the basal core promoter, the A1762T/G1764A mutation was found only in 1 clone. An 11-bp nucleotide insertion between nucleotides 1772 and 1773, was found in 2 clones. Six clones that were replication-competent exhibited variation in the level of replicating capacity in vitro even though the average genetic distance between the HBV clones was only 0.5% (range: 0.3-0.7%). Among the replication-competent 6 clones, 5 clones showed higher replication competency compared with clone B9 (reference clone used in this study) in Huh7 cells. However, 4 clones showed lower replication competency compared with clone B9 in HepG2 cells. In conclusion, the HBV virus exhibits genetic variation in the form of quasispecies with different mutation patterns, and these quasispecies may be recognized by distinct viral replication patterns even in patients with subtle genetic mutation., ((c) 2010 Elsevier B.V. All rights reserved.)