Quantitative assessment of the effect of pre-gestational diabetes and risk of adverse maternal, perinatal and neonatal outcomes.

Pregnancies complicated by pre-gestational diabetes (PGD) are associated with a higher rate of adverse outcomes, including an increased rage of preterm delivery, pregnancy-induced hypertension, pre-eclampsia, caesarean section, perinatal mortality, stillbirth, shoulder dystocia, macrosomia, small for gestational age, large for gestational age, low birth weight, neonatal hypoglycemia, neonatal death, low Apgar score, NICU admission, jaundice and respiratory distress. In the past two decades, numerous reports have been published regarding associations between PGD and risk of adverse outcomes. However, study results are inconsistent. To provide a synopsis of the current understanding of PGD for risk of adverse pregnancy outcomes, a random-effects meta-analysis over 40 million subjects from 100 studies was performed to calculate the pooled ORs. Potential sources of heterogeneity were systematically explored by multiple strata analyses and meta-regression. Overall, PGD were significantly associated with increased risk of preterm delivery (OR=3.48), LGA (OR=3.90), perinatal mortality (OR=3.39), stillbirth (OR=3.52), pre-eclampsia (OR=3.48), caesarean section (OR=3.52), NICU admission (OR=3.92), and neonatal hypoglycemia (OR=26.62). Significant results were also observed for 7 adverse outcomes with OR range from 1.54 to 2.82, while no association was found for SGA and respiratory distress after Bonferroni correction. We found that women with T1DM had higher risks for most of adverse pregnancy outcomes compared with women with T2DM. When stratified by study design, sample size, type of diabetes, geographic region, and study quality, significant associations remains. Our findings demonstrated that PGD is a strong risk-conferring factor for adverse maternal, perinatal and neonatal outcomes.

Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals.

Hetrombopag olamine (hetrombopag) is a novel small-molecule, orally bioavailable, non-peptide thrombopoietin (TPO) receptor agonist that is being developed as the treatment for thrombocytopenia. Two randomized, placebo-controlled phase I studies were conducted in 72 healthy individuals to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of hetrombopag. Hetrombopag was orally administered with a single dose in five dose cohorts (5 mg, 10 mg, 20 mg, 30 mg or 40 mg) in the first study, and given once daily for 10 days in three dose cohorts (2.5 mg, 5.0 mg or 7.5 mg) in the second study, respectively. Hetrombopag was well tolerated, and the majority of adverse events associated with medicine were platelet elevations significantly above the normal range in healthy individuals. The single dose-escalation study revealed a Tmax of approximate 8 hr, and a t1/2 of 11.9 hr to 40.1 hr in a dose-prolonged manner. A dose-proportional increase in maximum concentration (Cmax ) of hetrombopag was observed, with area under the curve (AUC) increasing in a greater than dose-proportional manner. The plasma concentration of hetrombopag reached the steady-state after 7 days. The steady-state AUC0-24 hr and Cmax were dose-proportionally elevated from the 5.0 mg to 7.5 mg dose level. The potent pharmacological effect of the hetrombopag-induced platelet elevation was observed in a time- and dose-dependent manner. Furthermore, the thrombopoietic response was significantly (p < 0.0001) correlated to the plasma exposure level of hetrombopag in single and multiple administration studies. Taken together, results of this study support further clinical development of hetrombopag in patients with thrombocytopenia.

[Features of anovulatory infertility patients of gan-yin deficiency syndrome: a primary exploration].

OBJECTIVE: To explore the laws of anovulatory infertility patients of Gan-yin deficiency syndrome (GYDS), and to analyze the correlation between GYDS and partial sex hormones and metabolic parameters. METHODS: Recruited were 103 anovulatory infertility patients, including 48 of GYDS and 55 of non-GYDS. At the same time, 20 healthy pluripara at the child-bearing period were recruited as the control group. The body mass index (BMI) and waist to hip ratio (WHR) were measured. Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2), sex hormone binding globulin (SHBG), fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and leptin were detected. The inter-group difference of the above indices was compared between the two groups. RESULTS: Levels of BMI, FINS, HOMA-IRI, leptin, TC, TG, LDL-C, T, PRL, and LH were higher in the GYDS group and the non-GDS group than in the control group (P < 0.01, P < 0.05), while SHBG was lower in the GYDS group and the non-GYDS group than in the control group (P < 0.01). Only the PRL level was higher in the GYDS group than in the non-GYDS group (P < 0.01). CONCLUSIONS: Gan-yin deficiency is a predominant manifestation in anovulatory infertility patients. Partial disorder of some sex hormones and metabolic derangement might be common pathological factors for anovulatory infertility, while increased PRL levels was dominant in GYDS.

[Effect of electroacupuncture intervention on ERK 1/2 signaling and TNF-α and IL-1ß protein levels in the substantia Nigra in rats with Parkinson's Disease].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on phosphalized extracellular regulated protein kinases(p-ERK) 1/2 signaling pathway and tumor necrosis factor (TNF)-α and IL-1ß protein levels in the substantia nigra (SN) in rats with Parkinson's disease (PD), so as to explore its mechanism underlying improvement of PD. METHODS: 32 male SD rats were randomly and averagely divided into normal control group, sham-operation group, model group and EA group. PD model was established by intra-dermal-injection of rotenone(1 mg/kg, dissolved in DMSO and saline, concentration: 0. 25 mg/mL) at the nape, once daily for 14 days. EA (2 Hz, 2 mA) was applied to "Fengfu"(GV 16)and "Taichong"(LR 3) for 20 min, once daily for 14 days. For sham-operation group, subcutaneous injection of the same dose of DMSO and saline was given in the same way. The expression levels of tyrosine hydroxylase (TH), p-ERK 1/2, inflammatory cytokines TNF-α and IL-1P proteins of the SN tissue were detected using Western blot. The rat's horizontal and vertical movement ability was assessed using open-field tests. RESULTS: The horizontal and vertical movement scores were significantly lower in the model group than in the normal control group, and markedly higher in the EA group than in the model group (P<0. 05). Compared with the normal control group, the expression level of TH protein in the SN was significantly reduced in the model group( P<0. 05 ),while the expression levels of p-ERK 1/2, TNF-α and IL-1ß proteins were significantly increased in the model group(P<0. 05). After EA intervention, the expression level of TH protein was significantly increased(P<0.05),and those of p-ERK 1/2, TNF-α and IL-1ß proteins were significantly down-regulated(P<0. 05) in the EA group compared to the model group. CONCLUSION: EA therapy may improve PD rats' movement ability, which may be associated with its effects in down-regulating the expression levels of p-ERK 1/2, TNF-α and IL-1ß proteins and up-regulating the expression of TH protein in the SN.

[Influence of electroacupuncture on p38-mitogen activated protein kinase in substantia nigra cells of rats with Parkinson disease model].

OBJECTIVE: To explore the role of inflammatory reaction mediated by p38-mitogen activated protein kinase (p38-MAPK) signal path on prevention and treatment of Parkinson disease (PD) model rats by electroacupuncture (EA). METHODS: Thirty-two healthy male SD rats were randomly divided into a normal group, a sham operation group, a model group and an EA group, eight rats in each one. The PD model was established in the model group and EA group by subcutaneous injection of rotenone in skin-back area (2 mg/kg, dissolved in sunflower oil, 2 mg/mL in density), while the injection of sunflower oil emulsion without rotenone at the same point and quantity as the model group was applied in the sham operation group. The normal group was not given any intervention. The EA treatment (continuous wave, 2 Hz in frequency, 1 mA in intensity, 20 min) was applied at "Fengfu" (GV 16) and "Taichong" (LR 3) in the EA group, once a day for continuously 14 days. No treatment was given in the other groups. The expression of tyrosine hydroxylase (TH), phosphorylated p38-MAPK, cyclooxygenase-2 (COX-2) in the substantia nigra were detected with immunohistochemical method. RESULTS: There was typical PD ethology change in the model group. Compared with the normal group and sham operation group, the expression of TH positive neuron in the substantia nigra in the model group was significantly decreased, while the expression of phosphorylated p38-MAPK and COX-2 were significantly increased (all P < 0.01). Compared with the model group, the expression of TH positive neuron in the EA group was apparently increased, while the expression of phosphorylated p38-MAPK and COX-2 were significantly decreased (all P < 0.01). CONCLUSION: The EA therapy could obviously reduce the expression of inflammation mediator COX-2, inhibit the phosphorylation of p38-MAPK, reduce the damage of dopaminergic neurons in the rats with PD, and this effect may be related with the impact of p38-MAPK signal path

[Study on the correlation between different Chinese medicine syndrome types and endocrine metabolism of polycystic ovarian syndrome].

OBJECTIVE: To explore the correlation between different Chinese medicine syndrome types and endocrine metabolism of polycystic ovarian syndrome (PCOS). METHODS: 223 PCOS patients were recruited. Of tem, 109 patients were classified as Pi deficiency type (PDT), 56 as Gan deficiency type (GDT), and 58 as Shen deficiency type (SDT). And twenty healthy females of the same age ranges were enrolled as the control group. The body mass index (BMI) and waist hip ratio (WHR) were measured. Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), prolactin (PRL), sex hormone binding globulin (SHBG), fasting blood sugar (FBG), fasting insulin (FINS), lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)], and leptin were detected. The intergroup difference of each index was compared. RESULTS: Higher results of leptin, FINS, HOMA-IRI, T, LH/FSH ratio were obtained in the three PCOS groups than in the control group, while the level of SHBG was lower in the three PCOS groups than in the control group (P<0.05, P<0.01). There was no statistical difference in the leptin level among the three PCOS groups. Higher levels of FINS and HOMA-IRI were shown in the PDT group than in the SDT group and the GDT group (P<0.05, P<0.01). Higher T and LH/FSH were shown in the SDT group than in the PDT group and the GDT group (P<0.05). Higher PRL levels were obtained in the GDT group than in the PDT group and the SDT group (P<0.01). CONCLUSION: Disorders of serum leptin and SHBG were the common pathological manifestations in different syndrome types of PCOS, while different syndrome types had specific endocrine metabolic features.