Abstract:Prostate cancer (PCa) is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the survival of PCa patients. Current PCa biomarkers lack sufficient sensitivity and specificity to cancer. Metabolite biomarkers are evolving as a new diagnostic tool. This review is aimed to evaluate the potential of metabolite biomarkers for early detection, risk assessment, and monitoring of PCa. Of the 154 identified publications, 27 and 38 were original papers on urine and serum metabolomics, respectively. Nuclear magnetic resonance (NMR) is a promising method for measuring concentrations of metabolites in complex samples with good reproducibility, high sensitivity, and simple sample processing. Especially urine-based NMR metabolomics has the potential to be a cost-efficient method for the early detection of PCa, risk stratification, and monitoring treatment efficacy.
Keywords:Prostate cancer;Metabolomics;Nuclear magnetic resonance (NMR);Biomarker
Abstract:Heart failure has become one of the biggest threats to human health. Transplantation remains the most effective therapy for heart failure, but because of the shortage of donors, it cannot meet the demand. Ventricular assist devices (VADs) were developed to treat heart failure, and have now been clinically applied worldwide. As the country with the largest population, China is also facing the threat of heart failure. However, the development of VADs in China is very slow and is seldom discussed. This paper first talks about the background for VAD development in China. Then several home-developed VADs in China are introduced. The current clinical application status of VADs in China is also presented. Finally the challenge and opportunity for VAD development in China are discussed.
Abstract:Background and objective:Rivaroxaban is a new oral anticoagulant for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), which has less drug–food interaction than warfarin. We conducted this prospective randomized study to evaluate the metabolic benefits as well as the safety and efficacy with rivaroxaban versus warfarin in patients with NVAF following radiofrequency catheter ablation (RFCA).Methods:From April to July 2014, 60 patients with NVAF undergoing RFCA were prospectively enrolled in our study. Following RFCA, all patients were randomly assigned to receive rivaroxaban (Group R, n=30) or warfarin (Group W, n=30). Metabolic indices including serum total protein, albumin, globulin, and high-density lipoprotein (HDL) as well as bleeding, stroke, and systemic thromboembolism events were evaluated and compared during follow-up after 15, 30, 60, and 90 d of RFCA procedure. Results:Serum total protein, albumin, globulin, and HDL levels were all significantly elevated at each follow-up stage in Group R when compared to the baseline (P<0.05 respectively). In Group W, the metabolic indices decreased at first and then had an increasing trend. There were no deaths or thromboembolic complications in each group. The prevalence of total bleeding complications was similar between Group R and Group W (11/30, 36.7% vs. 10/30, 33.3%, P=0.79). Conclusions:Patients with NVAF receiving rivaroxaban after RFCA procedures appear to benefit from a metabolic perspective compared with warfarin, providing practical clinical reference for the choice of the anticoagulant. Rivaroxaban seems to be as safe and effective in preventing thromboembolic events as warfarin for these patients.
Abstract:Objective:Fentanyl-induced cough (FIC) is a common complication with a reported incidence from 18.0% to 74.4% during general anesthesia induction. FIC increases the intrathoracic pressure and risks of postoperative nausea and vomiting, yet available treatments are limited. This study was designed to investigate whether administering fentanyl via a slow intravenous fluid line can effectively alleviate FIC during induction of total intravenous general anesthesia.Methods:A total number of 1200 patients, aged 18–64 years, were enrolled, all of whom were American Society of Anesthesiologists (ASA) grade I or II undergoing scheduled surgeries. All patients received total intravenous general anesthesia, which was induced sequentially by midazolam, fentanyl, propofol, and cisatracurium injection. Patients were randomly assigned to receive fentanyl 3.5 μg/kg via direct injection (control group) or via a slow intravenous fluid line. FIC incidence and the severity grades were analyzed with the Mann-Whitney test. Other adverse reactions, such as hypotension, hypertension, bradycardia, tachycardia, hypoxemia, vomiting, and aspiration, during induction were also observed. The online clinical registration number of this study was ChiCTR-IOR-16009025.Results:Compared with the control group, the incidence of FIC was significantly lower in the slow intravenous fluid line group during induction (9.1%, 95% confidence interval (CI): 6.7%–11.4% vs. 55.9%, 95% CI: 51.8%–60.0%, P=0.000), as were the severity grades (P=0.000). There were no statistical differences between the two groups with regard to other adverse reactions (P>0.05).Conclusions:The administration of fentanyl via a slow intravenous fluid line can alleviate FIC and its severity during induction for total intravenous general anesthesia. This method is simple, safe, and reliable, and deserves clinical expansion.
Abstract:Objective:A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated.Methods:A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits.Results:After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2–8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA.Conclusions:The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.
Abstract:Objective:The aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment.Methods:Artesunate was loaded with poly(D,L-lactic-co-glycolic acid) (PLGA) by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calorimetry analyses. In vivo antimalarial studies at 4 mg/kg were performed on Swiss male albino mice infected with Plasmodium berghei. Hematological and hepatic toxicity assays were performed. In vitro cytotoxicity of free and encapsulated artesunate (Art-PLGA) to cell line RAW 264.7 was determined at concentrations of 7.8–1000 µg/ml.Results:The particle size of the formulated drug was (329.3±21.7) nm and the entrapment efficiency was (38.4±10.1)%. Art-PLGA nanoparticles showed higher parasite suppression (62.6%) compared to free artesunate (58.2%, P<0.05). Platelet counts were significantly higher in controls (305 000.00±148 492.40) than in mice treated with free artesunate (139 500.00±20 506.10) or Art-PLGA (163 500.00±3535.53) (P<0.05). There was no sign of hepatic toxicity following use of the tested drugs. The half maximal inhibitory concentration (IC50) of Art-PLGA (468.0 µg/ml) was significantly higher (P<0.05) than that of free artesunate (7.3 µg/ml) in the in vitro cytotoxicity assay.Conclusions:A simple treatment of PLGA-entrapped artesunate nanoparticles with dual advantages of low toxicity and better antiplasmodial efficacy has been developed.
Abstract:Prolonged farrowing remains one of the critical challenges in intensive pig farming. This study aims to explore the effects and mechanism of Yimu San (YMS), a Chinese veterinary medicine micro mist, on delivery ability with mouse models. Thirty-two pregnant mice were randomly divided into a control group and low-YMS, med-YMS, and high-YMS groups. The labor process time and stillbirth rate were recorded, the levels of serum oxytocin and prostaglandin E2 (PGE2) were measured with enzyme-linked immunosorbent assay (ELISA). Contractility measurements of the isolated uterus and the expression of connexin 43 (Cx43) in uterine smooth muscle were evaluated. The results showed that compared with the control group, the birth process time and stillbirth rate in the med-YMS and high-YMS groups were remarkably lower. The in vitro uterine contractions, levels of oxytocin, PGE2, and Cx43 in the med-YMS and high-YMS groups were significantly higher than those in the control group. The differences of the above measurements between the low-YMS group and the control group were not obvious. It can be speculated that YMS could significantly promote labor in pregnant mice by enhancing the levels of oxytocin, Cx43, and PGE2.
Abstract:Accumulating evidence indicates that endostatin inhibits fibrosis. However, the mechanism is yet to be clarified. The aim of this study is to evaluate the effect of endostatin on platelet-derived growth factor-BB (PDGF-BB)-or transforming growth factor β1 (TGF-β1)-induced fibrosis in cultured human skin fibroblasts, and to further examine the molecular mechanisms involved. Human dermal fibroblasts were cultured in Dulbecco’s modified Eagle’s medium (DMEM) and serum-starved for 48 h before treatment. Cells were grouped as follows: “PDGF-BB”, “PDGF-BB+endostatin”, “TGF-β1”, “TGF-β1+endostatin”, “endostatin”, and “blank control”. The fibroblasts were stimulated with either TGF-β1 or PDGF-BB for 72 h in order to set up the fibrosis model in vitro. The cells were co-cultured with either TGF-β1 or PDGF-BB and endostatin and were used to check the inhibiting effect of endostatin. A blank control group and an endostatin group were used as negative control groups. The biomarkers of fibrosis, including the expression of collagen I, hydroxyproline, and α-smooth muscle actin (α-SMA), were evaluated using an enzyme-linked immunosorbent assay (ELISA) and Western blot. The expression of phosphorylated PDGF receptor β (p-PDGFRβ), PDGFRβ, phosphorylated extracellular signal-regulated kinase (p-ERK), and ERK was detected using Western blot and immunofluorescent staining was used to explore the mechanisms. Both PDGF-BB and TGF-β1 significantly up-regulated the expression of collagen I, hydroxyproline, and α-SMA. Endostatin significantly attenuated both the PDGF-BB-and TGF-β1-induced over-expression of collagen I, hydroxyproline, and α-SMA. PDGF-BB and TGF-β1 both promoted the expression of PDGFR, ERK, and p-ERK. Endostatin inhibited the expression of PDGFR and p-ERK but did not affect the expression of total ERK. Endostatin inhibited hypertrophic scar by modulating the PDGFRβ/ERK pathway. Endostatin could be a promising multi-target drug in future fibrosis therapy.
Abstract:Lycium ruthenicum is a perennial shrub species that has attracted considerable interest in recent years owing to its nutritional value and ability to thrive in a harsh environment. However, only extremely limited transcriptomic and genomic data related to this species can be found in public databases, thereby limiting breeding research and molecular function analysis. In this study, we characterized the physiological and biochemical responses to saline-alkaline mixed stress by measuring photochemical efficiency, chlorophyll content, and protective enzyme activity. We performed global transcriptomic profiling analysis using the Illumina platform. After optimizing the assembly, a total of 68 063 unique transcript sequences with an average length of 877 bp were obtained. Among these sequences, 4096 unigenes were upregulated and 4381 unigenes were down-regulated after saline-alkaline mixed treatment. The most abundant transcripts and over-represented items were assigned to gene ontology (GO) terms or Kyoto Encyclopedia of Genes and the Genomes (KEGG) categories for overall unigenes, and differentially expressed unigenes were analyzed in detail. Based on this set of RNA-sequencing data, a total of 9216 perfect potential simple sequence repeats (SSRs) were identified within 7940 unigenes with a frequency of 1/6.48 kb. A total of 77 primer pairs were synthesized and examined in wet-laboratory experiments, of which 68 loci (88.3%) were successfully amplified with specific products. Eleven pairs of polymorphic primers were verified in 225 individuals from nine populations. The inbreeding coefficient and the polymorphism information content value ranged from 0.011 to 0.179 and from 0.1112 to 0.6750, respectively. The observed and expected heterozygosities ranged from 0.064 to 0.840 and from 0.115 to 0.726, respectively. Nine populations were clustered into three groups based on a genetic diversity study using these novel markers. Our data will be useful for functional genomic investigations of L. ruthenicum and could be used as a basis for further research on the genetic diversity, genetic differentiation, and gene flow of L. ruthenicum and other closely related species.
Abstract:This study aimed to evaluate fertility and oncologic outcomes in women with complex hyperplasia (CH) or complex atypical hyperplasia (CAH) who received fertility-sparing therapy and in vitro fertilization (IVF). Endometrial carcinoma is the most common carcinoma of the female genital tract, and is associated with endometrial hyperplasia (EH) resulting from long-term unopposed estrogenic stimulation of the endometrium. EH is characterized by non-physiological proliferation of endometrium that results in glands with irregular shapes and varying sizes. The World Health Organization (WHO) classified it into four types: simple or complex hyperplasia with or without atypia. CH is characterized by glands with irregular outlines that demonstrate marked structural complexity and back-to-back crowding. Atypical hyperplasia designates a proliferation of glands exhibiting cytologic atypia, in which varying degrees of nuclear atypia and loss of polarity are present. It has been reported that high-dose progestin is safe and efficient for CAH or early-stage low-grade carcinoma for young women who desire fertility-preserving treatment. However, few studies have reported the differences of pregnancy outcomes between patients with CAH and CH, while those patients take a great proportion in people suffered from infertility. More studies about the outcome of IVF are needed. Our aim is to evaluate fertility and oncological outcomes in women with CH or CAH who received fertility-sparing therapy.
Abstract:Metastatic breast involvement from extra-mammary neoplasms is unusual with a low incidence of 0.5% to 1.2% in clinical practice, 2.7% in cytological series, and 1.7% to 6.6% in autopsy series of all breast malignancies. Nearly 500 cases have been reported in small series and case reports. Gastric carcinoma rarely metastasizes to the breast. There are only 38 cases reported in PubMed. In this study, we present a case report of a 49-year-old woman who was diagnosed with right breast metastasis from a gastric carcinoma and undertake a literature review to pay attention to the diagnosis, treatment, and the prognosis of the disease.