A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia.

Background: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. Methods: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. Results: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis. Conclusions: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.

[Effect of electrothermal acupuncture on moderate to severe cancer pain with yin-cold stagnation: a randomized controlled trial].

OBJECTIVE: To observe the effectiveness and safety of electrothermal acupuncture therapy for patients of moderate to severe cancer pain with yin-cold stagnation. METHODS: A total of 60 patients of moderate to severe cancer pain with yin-cold stagnation were randomized into an observation group and a control group, 30 cases in each one. In the control group, opioid painkillers (oxycodone hydrochloride prolonged-release tablet or morphine sulfate sustained-release tablet) were taken. On the basis of the control group, electrothermal acupuncture was applied at Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Hegu (LI 4), Sanyinjiao (SP 6) in the observation group, 30 min each treatment, once a day for 5 days. Before and after treatment, the scores of pain numerical rating scale (NRS) and Karnofsky performance scale (KPS) were observed in the two groups. The pain remission rate, reduction of opioid painkillers and safety were compared. RESULTS: The variation of NRS scores in the observation group were larger than the control group 3, 5 days into treatment (P<0.01, P<0.05). The variation of KPS score in the observation group was larger than the control group after treatment (P<0.05). The pain remission rate was 100.0% (30/30) in the observation group, higher than 86.7% (26/30) in the control group (P<0.05). The reduction of opioid painkillers in the observation group was larger than the control group (P<0.01). There was no adverse reaction during the treatment in the two groups. CONCLUSION: On the basis of the conventional western medication for analgesia, electrothermal acupuncture could relieve pain, reduce the dose of opioid painkillers and improve the quality of life in patients of moderate to severe cancer pain with yin-cold stagnation, has a better safety.

L-Arginine Supplementation Improves Vascular Endothelial Dysfunction Induced by High-Fat Diet in Rats Exposed to Hypoxia.

INTRODUCTION: Our previous study showed that high-fat diet inhibited the increase in nitric oxide and endothelial nitric oxide synthase expression in the aortic endothelium of rats exposed to hypoxia, and hypoxia plus a high-fat diet led to earlier and more severe vascular endothelial dysfunction (VED) than hypoxia alone. The purpose of the present study was to investigate the effects of L-arginine on high-fat diet-induced VED of rats in hypoxia. METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups and treated with hypoxia (H group), hypoxia plus high-fat diet (H+HFD group), hypoxia plus L-arginine (H+L-Arg group), and hypoxia plus high-fat diet and L-arginine (H+HFD+L-Arg group) for 1 wk. Hypoxia was simulated in a hypobaric chamber with an altitude of 5000 m. Aortic morphology and endothelium-dependent vasorelaxation were used to assess VED. RESULTS: High-fat diet impaired vascular remodeling and reduced endothelium-dependent vasodilator response to acetylcholine in rats exposed to hypoxia, secondary to dysregulation of the nitric oxide pathway. L-arginine supplementation significantly increased plasma nitrates and nitrites and endothelial nitric oxide synthase mRNA levels and improved ultrastructural changes in aortic endothelium and endothelium-dependent vasodilator response. CONCLUSIONS: L-arginine prevents aortic ultrastructural changes and reverses VED induced by high-fat diet in rats exposed to hypoxia, which may have implications for VED induced by high-fat diet in high altitude dwellers.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with ß-Thalassemia Major: A Meta-Analysis.

BACKGROUND: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. METHODS: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

Effects of Yishengukang decoction on expression of bone-specific alkaline phosphatase, carboxyterminal propeptide of type â procollagen, and carboxyterminal cross-linked telepeptide of type â collagen in malignant tumor patients with bone metastasis.

OBJECTIVE: To investigate the effect of Yishengukang decoction on the expression of the metabolic bone markers, bone-specific alkaline phosphatase (BAP), carboxyterminal propeptide of type Ⅰ procollagen (PICP), and arboxyterminal cross-linked telepeptide of type Ⅰ collagen (ICTP), in cancer patients with bone metastasis. METHODS: Patients (n = 180) were divided into three groups: (a) bone metastasis patients treated with Yishengukang and pamidronate disodium injection (treatment group, n = 60); (b) bone metastasis patients treated with pamidronate disodium injection alone (control group, n = 60); (c) cancer patients without metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the metabolic markers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent assay pre- and post-therapy. RESULTS: A significant decrease in serum BAP level was observed in the treatment group compared with the control group. However there were no significant differences in serum levels of PICP and ICTP before or after treatment compared with the control group. CONCLUSION: Yishengukang decoction combined with pamidronate disodium injection reduced serum BAP level to a greater extent that pamidronate disodium injection alone. Furthermore, the combined therapy was more beneficial in regulating imbalanced bone metabolism after bone metastasis, and may represent the molecular mechanism underpinning the effects of Yishengukang decoction.

Emodin inhibits angiogenesis in pancreatic cancer by regulating the transforming growth factor-ß/drosophila mothers against decapentaplegic pathway and angiogenesis-associated microRNAs.

Emodin is a traditional Chinese medicine, which has been demonstrated to inhibit the growth of pancreatic cancer cells. However, the underlying molecular mechanisms remain to be elucidated. The present study investigated whether emodin suppresses angiogenesis in pancreatic cancer. A nude mouse pancreatic cancer xenograft model was established using SW1990 human pancreatic cancer cells by surgical orthotopic implantation. Different doses of emodin were injected into the abdominal cavities of the tumor­bearing mouse models and controls three times each week for 2 weeks. The tumors were measured and weighed, the expression of cluster of differentiation 34 was detected using immunochemistry, and microvessel densities were calculated. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blotting were performed to determine the mRNA and protein expression levels of transforming growth factor (TGF)­ß and drosophila mothers against decapentaplegic (Smad) homologs. The angiogenesis­associated microRNAs (miR), miR­20, miR­155 and miR­210 were assessed by RT­qPCR. A negative dose­dependent association was revealed between treatment with emodin and the volume and weight of tumors and microvessel density. Emodin was associated with lower mRNA and protein expression levels of TGF­ß1 and its downstream target, angiopoietin­like 4, and higher mRNA and protein expression levels of TGF­ß receptor (TßR)I, TßRII and Smad4. Notably, treatment with emodin was associated with lower expression levels of miR­155 and miR­210 and higher expression levels of miR­20b. The present study suggested that treatment with emodin may repress angiogenesis in pancreatic cancer by altering the activities of the TGF-ß/Smad pathway and angiogenesis-associated miR-20b, miR-155, and miR-210.

Effects of the aqueous extract of a Tibetan herb, Rhodiola algida var. tangutica on proliferation and HIF-1α, HIF-2α expression in MCF-7 cells under hypoxic condition in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola algida var. tangutica is a traditional Tibetan herb. Its root and rhizome have been successfully used as an effective clinical remedy for the prevention and treatment of cancer and high-altitude sickness. This study aimed to investigate the effect of Rhodiola algida var. tangutica on hypoxic MCF-7 breast cancer cells and the underlying mechanisms. MATERIALS AND METHODS: The antiproliferative effects of R. algida on MCF-7 breast cancer cells were compared in vitro under hypoxic and normal conditions by using MTT analysis. The influence of R. algida on cancer cell apoptosis was determined by flow cytometry. The expression levels of hypoxia-inducible factor (HIF)-1α and HIF-2α were evaluated by western blot analysis. RESULTS: R. algida inhibited the proliferation of MCF-7 breast cancer cells in a dose- and time-dependent manner. The results of flow cytometry indicated that the antiproliferative effect of R. algida was mediated by apoptosis induction. Pretreatment with R. algida significantly suppressed the hypoxia-induced proliferation and expression of HIF-1α and HIF-2α in MCF-7 breast cancer cells. CONCLUSIONS: R. algida might exert an anti-carcinogenic effect on MCF-7 breast cancer cells by decreasing the protein levels of HIF-1α and HIF-2α, which are overexpressed under hypoxic conditions. This effect might be elicited by inhibiting the hypoxia-induced proliferation of MCF-7 breast cancer cells.

Antiangiogenic effects of oxymatrine on pancreatic cancer by inhibition of the NF-κB-mediated VEGF signaling pathway.

Oxymatrine, the main alkaloid component in the traditional Chinese herbal medicine Sophora japonica (Sophora flavescens Ait), has been reported to have antitumor properties. However, the mechanisms of action in human pancreatic cancer are not well established to date. In the present study, we investigated the antiangiogenic effects of oxymatrine on human pancreatic cancer as well as the possible mechanisms involved. The results of the cell viability assay showed that treatment of PANC-1 pancreatic cancer cells with oxymatrine resulted in cell growth inhibition in a dose- and time-dependent manner. To investigate the possible mechanisms involved in these events, we performed western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The results revealed that oxymatrine decreased the expression of angiogenesis-associated factors, including nuclear factor κB (NF-κB) and vascular endothelial growth factor (VEGF). Finally, the antiproliferative and antiangiogenic effects of oxymatrine on human pancreatic cancer were further confirmed in pancreatic cancer xenograft tumors in nude mice. In conclusion, our studies for the first time suggest that oxymatrine has potential antitumor effects on pancreatic cancer via suppression of angiogenesis, probably through regulation of the expression of the NF-κB-mediated VEGF signaling pathway.

[Dynamic changes in functional genes for nitrogen bioremediation of petroleum-contaminated soil cycle during].

Microorganisms in nitrogen cycle serve as an important part of the ecological function of soil. The aim of this research was to monitor the abundance of nitrogen-fixing, denitrifying and nitrifying bacteria during bioaugmentation of petroleum-contaminated soil using real-time polymerase chain reaction (real-time PCR) of nifH, narG and amoA genes which encode the key enzymes in nitrogen fixation, nitrification and ammoniation respectively. Three different kinds of soils, which are petroleum-contaminated soil, normal soil, and remediated soil, were monitored. It was shown that the amounts of functional microorganisms in petroleum-contaminated soil were far less than those in normal soil, while the amounts in remediated soil and normal soil were comparable. Results of this experiment demonstrate that nitrogen circular functional bacteria are inhibited in petroleum-contaminated soil and can be recovered through bioremediation. Furthermore, copies of the three functional genes as well as total petroleum hydrocarbons (TPH) for soils with six different treatments were monitored. Among all treatments, the one, into which both E. cloacae as an inoculant and wheat straw as an additive were added, obtained the maximum copies of 2.68 x 10(6), 1.71 x 10(6) and 8.54 x 10(4) per gram dry soil for nifH, narG and amoA genes respectively, companying with the highest degradation rate (48% in 40 days) of TPH. The recovery of functional genes and removal of TPH were better in soil inoculated with E cloacae and C echinulata collectively than soil inoculated with E cloacae only. All above results suggest that the nitrogen circular functional genes could be applied to monitor and assess the bioremediation of petroleum-contaminated soil.

Clinical research of compound zhebei granules for increasing the therapeutic effect of chemotherapy in refractory acute leukemia patients.

OBJECTIVE: To observe the effects of Compound Zhebei Granules (CZG) in chemotherapy for refractory acute leukemia. METHOD: Using a randomized, double-blind and multi-central concurrent control clinical research project, the patients conformed with the diagnostic criteria, according to the drug randomized method, were divided into a CZG group and a control group. The patients of the two groups respectively took the observation drug or a placebo 3 days before chemotherapy, and the therapeutic effects were evaluated after one course of chemotherapy. According to the clinical research project, 137 patients were enrolled, including 71 cases in the CZG group and 66 cases in the control group. RESULTS: The clinical complete remission (CR) rate was 42.3% in the CZG group with a total effective rate of 73.2%, and it was 25.8% in the control group with a total effective rate of 53.0%, showing a statistically significant difference between the two groups (P < 0.05). CONCLUSION: CZG can increase the clinical remission rate for refractory acute leukemia during chemotherapy.