[Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase â ¡ clinical trial study on plasma ATP, 4-HNE, and ACTH levels].

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

C3: Consensus Cancer Driver Gene Caller.

Next-generation sequencing has allowed identification of millions of somatic mutations in human cancer cells. A key challenge in interpreting cancer genomes is to distinguish drivers of cancer development among available genetic mutations. To address this issue, we present the first web-based application, consensus cancer driver gene caller (C3), to identify the consensus driver genes using six different complementary strategies, i.e., frequency-based, machine learning-based, functional bias-based, clustering-based, statistics model-based, and network-based strategies. This application allows users to specify customized operations when calling driver genes, and provides solid statistical evaluations and interpretable visualizations on the integration results. C3 is implemented in Python and is freely available for public use at http://drivergene.rwebox.com/c3.

Evaluation of the ability of cervical length and fetal fibronectin measurement to predict preterm delivery in asymptomatic women with risk factors.

OBJECTIVE: To evaluate the power of transvaginal ultrasound cervical length (CL) and fetal fibronectin (fFN) measurement for the prediction of preterm delivery (PTD) in asymptomatic women with risk factors. METHODS: Between January 2010 and October 2012, 218 women with singleton pregnancies and a high risk for PTD (i.e. prior history of PTD, cervical surgeries, late miscarriages, uterine abnormalities or premature rupture of the membranes) were selected. CL was measured by transvaginal ultrasonography between 14 and 22 weeks, and a CL<2.5 cm was considered to be short. The fFN was measured with a sterile speculum examination. The primary outcome was the spontaneous PTD rate at <34(+0) and <37(+0) weeks, and the PTD rate was analyzed by either of two methods alone or combined. RESULTS: There were 213 cases included in the analysis, and 47 women (22.1%) had positive fFN. The average CL of women with positive fFN (2.3 ± 0.9 cm) was significantly shorter than that of women with negative fFN (3.1 ± 0.8 cm; p=0.02). There were 25 (11.7%) and 38 (18.8%) cases with PTD at <34(+0) and <37(+0) weeks, respectively. By individual analyses, the highest PTD rate was 51.2% in women with positive fFN at <37(+0) weeks. The sensitivity and diagnostic efficiency values for PTD prediction by CL were low at <34(+0) and <37(+0) weeks. The values of diagnostic efficiency by fFN were >80% at <34(+0) and <37(+0) weeks. In the combined analysis, the highest PTD rate was 57.1% in women with CL ≤ 2.5 cm and positive fFN at <37(+0) weeks. The Kaplan-Meier curve indicated that there were significant differences among the four groups (χ(2)=54.261; p=0.000). CONCLUSIONS: These results indicate a significant correlation between fFN and PTD prediction. The PTD prediction could be enhanced by combined CL and fFN measurement.

Sorting out inherent features of head-to-head gene pairs by evolutionary conservation.

BACKGROUND: A 'head-to-head' (h2h) gene pair is defined as a genomic locus in which two adjacent genes are divergently transcribed from opposite strands of DNA. In our previous work, this gene organization was found to be ancient and conserved, which subjects functionally related genes to transcriptional co-regulation. However, some of the biological features of h2h pairs still need further clarification. RESULTS: In this work, we assorted human h2h pairs into four sequentially inclusive sets of gradually incremental conservation, and examined whether those previously asserted features were conserved or sharpened in the more conserved h2h pair sets in order to identify the inherent features of the h2h gene organization. The features of TSS distance, expression correlation within h2h pairs and among h2h genes, transcription factor association and functional similarities of h2h genes were examined. Our conservation-based analyses found that the bi-directional promoters of h2h gene pairs are most likely shorter than 100 bp; h2h gene pairs generally have only significant positive expression correlation but not negative correlation, and remarkably high positive expression correlations exist among h2h genes, as well as between h2h pairs observed in our previous study; h2h paired genes tend to share transcription factors. In addition, expression correlation of h2h pairs is positively related with the TF-sharing and functional coordination, while not related with TSS distance. CONCLUSIONS: Our findings remove the uncertainties of h2h genes about TSS distance, expression correlation and functional coordination, which provide insights into the study on the molecular mechanisms and functional consequences of the transcriptional regulation based on this special gene organization.

DBH2H: vertebrate head-to-head gene pairs annotated at genomic and post-genomic levels.

DBH2H collects head-to-head (h2h) gene pairs identified from human, mouse, rat, chicken and fugu genomes, and distinguishes the ortholog mapping relationship among them. The gene pairs in DBH2H are annotated with sequential features including single nucleotide polymorphisms, CpG islands and transcription factor binding sites, as well as functional terms and genetic disorders. In addition, the expression correlation information based on 117 microarray datasets is included. By providing user-friendly access to these data, DBH2H represents a valuable resource for further analyses of this important gene arrangement in terms of transcriptional regulation mechanisms, evolutionary conservation, disease relevance, etc.Database URL:http://lifecenter.sgst.cn/h2h/

[Clinical characteristics of 7 patients with gestational diabetes insipidus].

OBJECTIVE: To investigate the clinical feature, treatment and prognosis of both the mother and the fetus with gestational diabetes insipidus. METHODS: A total of 7 cases of gestational diabetes insipidus collected in the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Combination of Traditional Chinese Medicine with Western Medicine Hospital, and Zhejiang Taizhou Hospital from June 1993 to June 2006 were analyzed retrospectively. RESULTS: Seven cases symptoms all characterized by excessive thirst polydipsia and polyuria. The average 24 h urinary output was between 11 L to 13 L and manifested of hypobaricuria. After effective treatment (three cases were treated with 1-deamino-8-D-arginine vasopressin, another three patients were managed with hydrochlorothiazide, and the last one was cured with antisterone), seven patients with gestational diabetes insipidus did not have any severe consequences. Their symptoms of excessive thirst, polyuria, and polydypsia disappeared from 7 days to 3 months after parturition. Urinary volume returned to normal standard of 1000-2000 ml during 24 hours. Specific gravity of urine recovered normally between a range 1.015-1.025 and serum sodium recovered between 135-147 mmol/L. The average duration of illness was 52 days. Eight newborn infants survived. Two of them were sent to neonatal intensive care unit for treatment. One was because of premature delivery caused by antepartum eclampsia, and the other case was one of the twins who had hydronephrosis. The baby of the first case left hospital after 3 weeks' treatment. The latter one's symptom disappeared 2 weeks after delivery. No obvious symptom was discovered among all the babies through follow-up telephone calls 42 days after childbirth. CONCLUSION: Gestational diabetes insipidus is a rare endocrinopathy complicating pregnancy. This disorder is characterized by excessive thirst, polydypsia, polyuria, hypobaric urine and electrolyte disturbances usually manifesting in the third trimester of pregnancy or puerperium. This is a transient syndrome. The first treatment of choice in patients with gestational diabetes insipidus is 1-deamino-8-D-arginine vasopressin and the second-choice is hydrochlorothiazide. Early diagnosis and appropriate management of the disease may reduce the hazard for both the mother and the fetus during perinatal period.

[Effect of lipoxins on proliferation and secretion of peritoneal macrophages from patients with preeclampsia in vitro].

OBJECTIVE: To study the effect of lipoxins on the proliferation and secretion of peritoneal macrophages from patients with preeclampsia in vitro. METHODS: Peritoneal macrophages were obtained from 24 patients with preeclampsia (preeclampsia group) and 24 normal pregnant women (normal pregnant group) who were treated in the First Affiliated Hospital of Wenzhou Medical College from March to July 2007. Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of tumor necrosis factor-alpha (TNF-alpha) in the supernatant of macrophages which were pulsed with lipoxins at different concentrations (0, 10, 100 nmol/L) in both groups after 48 hours. Methyl thiazolyl tetrazolium (MMTT) assay was used to detect the inhibition rate of cell proliferation of macrophages which were pulsed with lipoxins at different concentrations (0, 10, 100 nmol/L) in both groups after 24 hours. RESULTS: (1) The concentration of TNF-alpha: the levels of TNF-alpha were (1867.5 +/- 47.3), (1836.9 +/- 4.5) and (1800.5 +/- 2.7) ng/L after treatment with different concentrations of lipoxins (0, 10, 100 nmol/L) in preeclampsia group vs normal pregnant group [(791.3 +/- 62.2), (789.4 +/- 2.3), (781.5 +/- 1.9) ng/L]. The levels of TNF-alpha in preeclampsia group were significantly higher than that in normal pregnant group (P < 0.05). Lipoxins significantly inhibited the concentration of TNF-alpha in a dose-dependent manner in preeclampsia group (P < 0.05), while it had no significant effect in normal pregnant group (P > 0.05). (2) Cell proliferation inhibition: Incubation with lipoxins produced a dose-dependent (0, 10, 100 nmol/L) inhibitory effect on proliferation in preeclampsia group, [ 14. +/-6. )% , (32. +/-3.6)%, ( 6. ++/-3. )% vs normal pregnant group [(16.8 +/- 6.9)%, (16.7 +/- 5.4)%, (15.9 +/- 2.1 )%]. The rate of cell proliferation in preeclampsia group was significantly higher than that in normal pregnant group. Lipoxins significantly inhibited this growth (P < 0.05) , while it had no significant effect in normal pregnant group (P > 0.05). CONCLUSION: Lipoxins can inhibit the proliferation of macrophage and secretion of TNF-alpha in preeclampsia in a dose-dependent manner. Lipoxins may be potentially useful in prevention and treatment of preeclampsia.

Study on the relationship between serum high density lipoprotein and Pi-deficiency syndrome in patients with coronary heart disease.

OBJECTIVE: To explore the relationship of Pi-deficiency syndrome in TCM with the change of serum high density lipoprotein (HDL) in blood lipid metabolic disorder. METHODS: Sixty-eight patients with confirmed coronary heart disease (CHD) were selected for TCM syndrome typing into Pi-deficiency (PD) group and non-Pi-deficiency (NPD) group. Routine blood lipids and serum lipoprotein electrophoretogram (SLPG) were determined in all patients to analyze the total content of HDL and its relative contents of sub-components HDL(1-5), as well as their relation with PD syndrome. Besides, a healthy control group (62 cases) was set up. RESULTS: The level of serum HDL-C was lowered, SLPG abnormality rate increased in the patients with CHD, with total HDL and the relative contents of subcomponent HDL(1) and HDL(3) significantly lower than those in the healthy control group (P<0.01). The total HDL, HDL(1) and HDL(3) in the PD group were also lower than those in the NPD group (P<0.05, P<0.01). CONCLUSION: Serum HDL and its sub-components showed a definite relation with TCM PD syndrome type, therefore, further exploring the granular specificity of HDL and its sub-components as well as their influence on reverse cholesterol transport (RCT) may hopefully provide clues for developing RCT regulatory Chinese new drugs and for CHD prevention and treatment.

[Some insights into clinical detection and analysis of serum lipoprotein for studies on integrated traditional Chinese and western medicine].

Dyslipoproteinemia is correlated with the occurrence and development of atherosclerosis and cardiocerebral vascular diseases. The metabolism of serum lipoprotein, however, is a complicated and ordered metabolic process. On one hand, every organ, tissue and even cell of the body participates in and affects the state of serum lipoprotein dynamic balance (SLDB) in different degrees. On the other hand, SLDB is a direct factor for maintaining the normality of whole vascular system, especially the vascular endothelium system. The serum lipoprotein dynamic imbalance, as an inducement or even etiological factor, can bring about various clinical diseases. Therefore, integrated analysis is needed to appropriately assess the state of SLDB. It is suggested that serum lipoprotein dynamic imbalance syndrome should be the key risk factor for those related diseases. Serum lipoprotein electrophoretogram can ideally express the state of SLDB and be taken as a new index for cognizing the serum lipid metabolism and the function of speen-qi to distribute Jing (Essonse) in the integrated traditional Chinese and western medicine. Practice has showed that concrete integration and bilateral development should be one of the main tasks in current researches of integrated traditional Chinese and western medicine.

[Analysis of pregnancy outcomes after in vitro fertilization-embryo transfer and intracytoplasmic sperm injection].

OBJECTIVE: To compare pregnancy and perinatal outcomes between in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). METHODS: A retrospective study was carried out to measure pre-clinical and clinical abortion, ectopic pregnancies, multiple gestations, birth weight, gestational age, congenital malformation and perinatal mortality in patients receiving either IVF-ET (n = 143, group 1) or ICSI (n = 173, group 2) from January 1999 to June 2001. The outcomes of singleton and twin were compared separately. RESULTS: The maternal age, infertility duration, parity and the number of transferred embryo were comparable between the two groups. There were no significant differences in abortion rate (16.1% vs 13.3%), birth rate (65.7% vs 74.6%) between IVF-ET and ICSI groups (P > 0.05). In singleton, the rates of low birth weight, small for gestational age and pre-term birth were 1.8%, 7.3%, 5.5% respectively in IVF-ET group and 6.8%, 8.1%, 14.9% respectively in ICSI group. In twin, the rates of low birth weight, small for gestational age and pre-term birth were 34.2%, 30.3%, 42.1% respectively in IVF-ET group and 42.6%, 38.0%, 46.3% respectively in ICSI group. There were no significant differences between the two groups (P > 0.05). But the rates of low birth weight, small for gestational age and pre-term birth were higher in twin than in singleton (P < 0.01). The incidence of congenital malformation was 2.2% and 1.6% in IVF-ET and ICSI group respectively (P > 0.05). CONCLUSIONS: The pregnancy and perinatal outcomes are similar between IVF-ET and ICSI groups. Twin is the main cause of low birth weight, small for gestational age and pre-term birth.

Features of serum beta-lipoprotein electrophoretogram in patients with coronary heart disease.

OBJECTIVE: To investigate the changes in serum beta-lipoprotein (beta Lp) electrophoretogram in the patients with coronary heart disease (CHD). METHODS: This study included 36 CHD patients, 28 non-CHD patients and 8 normal control subjects, from whom serum beta Lps (prestained with Sudan Black B) were isolated by means of the first double-gradient polyacrylamide gel electrophoresis (f-DGPAGE). The secondary DGPAGE was performed for isolating beta Lps into 4 subfractions (beta Lp1-4) in order to complete the quantitative analysis of beta Lp electrophoretogram. A parallel test to examine the serum concentration of low-density lipoprotein cholesterol (LDLc) was also carried out. RESULTS: The relative amount of beta Lp1 was significantly elevated in CHD patients (53.4+/-10.0%) as compared with normal subjects (39.3+/-6.7%) and non-CHD patients (42.8+/-6.8%, P < 0.05 for both comparisons) regardless of serum LDLc concentrations, and beta Lp1 content between the latter 2 groups showed no significant difference. CONCLUSION: Serum beta Lp subfraction imbalance evidenced by increased beta Lp1 level characterizes the patients with CHD.

[A new method for detecting serum beta-lipoprotein electrophoretogram].

OBJECTIVE: To establish a new method for isolating serum beta-lipoprotein (betaLp) subfractions using second double gradient polyacrylamide gel electrophoresis (s-DGPAGE). METHODS: After the betaLp subfractions were isolated by mechanisms of molecular sieving and isoelectric focusing due to density and pH grade in the non-linear density gradient polyacrylamide gel, the gels were acquired with a gel imaging system, the electrophoretograms were quantitatively analyzed with optical density scanner. The isolation of serum betaLp was completed through first DGPAGE. RESULTS: s-DGPAGE separated the serum betaLp into four subfractions, designated respectively as betaLp1, betaLp2, betaLp3 and betaLp4, and their amounts in the betaLp and in the whole lipoproteins could be quantified. CONCLUSION: s-DGPAGE is a simple and practical method to show the heterogeneity of serum betaLp and the quantitative variation of its subfractions.