Adolescent ; Adult ; Aged ; Child ; Cholinesterase Reactivators ; therapeutic use ; Female ; Hemoperfusion ; Humans ; Insecticides ; poisoning ; Male ; Middle Aged ; Organophosphate Poisoning ; Poisoning ; therapy

The chemical constituents of Poria cocos were studied by means of silica gel, ODS column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from this plant. By analysis of the ESI-MS and NMR data, the structures of these compounds were determined as tumulosic acid (1), dehydrotumulosic acid (2), 3beta, 5alpha-dihydroxy-ergosta-7, 22-dien-6-one (3), 3beta, 5alpha, 9alpha-trihydroxy-ergosta-7, 22-diene -6-one (4), ergosta-7, 22-diene-3-one (5), 6, 9-epoxy-ergosta-7,22-diene-3-ol (6), ergosta-4,22-diene-3-one (7), 3beta, 5alpha, 6beta-trihydroxyl-ergosta-7,22-diene (8), ergosta-5, 6-epoxy-7,22-dien-3-ol (9), beta-sitosterol (10), ribitol (11), mannitol (12), and oleanic acid 3-O-acetate (13), respectively. Compounds 3-13 were isolated from the P. cocos for the first time.
Drugs, Chinese Herbal ; chemistry ; Organic Chemicals ; analysis ; Poria ; chemistry

BACKGROUNDPDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart.

METHODSWe employed Cre/loxP system to generate PDK1(flox/flox): α-MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting.

RESULTSPDK1(flox/flox): α-MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) -MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts.

CONCLUSIONOur results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease.

3-Phosphoinositide-Dependent Protein Kinases ; Adult ; Animals ; Female ; Glycogen Synthase Kinase 3 ; physiology ; Heart ; physiology ; Heart Failure ; enzymology ; etiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Myosin Heavy Chains ; physiology ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; Tamoxifen ; pharmacology

OBJECTIVETo study the effect and potential mechanism of Modified Cangfu Daotan Decoction (MCDD) on endometrial receptivity in infertility patients with polycystic ovarian syndrome (PCOS).

METHODSTotally 298 women having normal ovulation who underwent artificial insemination were recruited as the control group, and they received no drug therapy. Another 355 infertility patients with PCOS who received ovarian stimulation therapy were recruited as the treatment group. Then they were further assigned to the treatment group I (195 cases) and the treatment group II (160 cases) according to random digit table. Patients in the treatment group I received clomiphene (CC) + human menopause gonadotropin (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II received CC + HMG + HCG and additionally took modified MCDD. The therapeutic course for all was three menstrual cycles. The pregnancy ratio, the endometrial thickness, and spiral artery pulsatility index (PI), resistance index (RI), and homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot.

RESULTSCompared with the control group, the endometrial thickness decreased and PI and RI increased in the treatment group I (all P < 0.05). Compared with the treatment group I , the endometrial thickness increased and PI and RI decreased in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR levels were significantly decreased in the treatment group II after treatment (P < 0.05). Compared with the control group before treatment, the HOMA-IR level increased in the treatment group I and the treatment group II before treatment (P < 0.05). Compared with the control group after treatment, the HOMA-IR level increased in the treatment group I (P < 0.05). But there was no statistical difference in the post-treatment HOMA-IR level between the control group and the treatment group II (P < 0.05). Compared with the control group, the post-treatment UCP2 level was increased in the treatment group II (P < 0.05). After one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group, 23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment group II. Compared with the control group, the pregnancy rate was significantly increased in the treatment group II (P < 0.05).

CONCLUSIONMCDD was found to be capable of increasing the pregnancy rate of infertility patients with PCOS, which might be associated with improving endometrial blood flow and insulin resistance, increasing the UCP2 expression, and finally improving the endometrial receptivity.

Chorionic Gonadotropin ; Clomiphene ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gonadotropins ; Humans ; Infertility ; Infertility, Female ; Insulin Resistance ; Ovulation ; Ovulation Induction ; methods ; Polycystic Ovary Syndrome ; drug therapy ; Pregnancy ; Pregnancy Rate

Objective To investigate the abnormalities of gray matter volume in obsessive-compulsive disorder (OCD) patients relative to controls using the method of voxel-based morphometry (VBM), and to analyze the extent of change relative to clinical symptom. Methods Using VBM to compare the MRI images of 31 adult OCD patients with 31 healthy controls. Correlation analyses were conducted between the structural abnormalities of gray matter volume in each brain area among patients relative to their clinical scores. Results Compared with the healthy controls, the OCD patients showed reductions of gray matter volume in left putamen, insula, premotor area, superior parietal and right angular gyrus (P<0.01, Alphasim corrected). The gray matter volumes of left putamen and insular in the OCD patients showed a negative correlation with the Beck anxiety inventory (BAI) scores. Conclusion The changes in gray matter volumes of left putamen, insula, premotor area, superior parietal lobule and right angular gyrus may be related to the pathogenesis of OCD. The declines of left putamen and insula are related to the abnormal anxiety in the OCD patients.

Objective:To observe the effect of isopimpinellin on primary hippocampal neuron cells γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and receptor genes expressions, in order to explore its hypnotic mechanism. Method:The primary hippocampal neurons of neonatal Sprague-Dawley rats were cultured in vitro. And subsequent experiments were conducted in the optimal state of cell growth, and the purity was identified by immunohistochemistry of neuron-specific enolase. Hippocampal neurons were randomly divided into five groups, namely blank control group, diazepam group (25 mg·L^-1), and low-dose (5 mg·L^-1), moderate-dose (10 mg·L^-1) and high-dose (20 mg·L^-1) isopimpinellin groups. Early apoptosis of hippocampus neuron cells were detected using flow cytometry technique after 24 h administration, and the changes in the levels of GABA and 5-HT were detected using enzyme-linked immunosorbent. The changes in mRNA expressions of receptor genes relating to gamma-aminobutyric acid type A receptor(GABAA) genes GABRA₁,GABRA₅,GABBR₁, gamma-aminobutyric acid type B receptor genes (GABAB) GABRB₂, 5-hydroxytryptamine 1A receptor (5-HT1_A)5-HT1_A(A),5-HT1_A(B),5-HT1_A(C) were detected by real-time quantitative PCR(Real-time PCR). Result:On the 7^th day, the hippocampal neurons grew in a good condition, and the purity was above 90%. Apoptosis rates of hippocampal neurons in the low-dose and moderate-dose groups were significantly lower than that in the blank control group (P<0.01). The level of GABA secreted by hippocampal neurons in the high-dose isopimpinellin group were significantly higher than that in the blank control group (P<0.01). The mRNA expression levels of GABRA₁,GABRA₅,5-HT1_A(A),5-HT1_A(C) in the moderate-dose and high-dose isopimpinellin groups were significantly higher than those in the blank control group (P<0.05, P<0.01). The mRNA expression levels of GABBR₁,5-HT1_A(B) in the low-dose, moderate-dose and high-dose isopimpinellin groups were significantly higher than those in the blank control group (P<0.05, P<0.01). Conclusion:The hypnotic mechanism of isopimpinellin may be related to the inhibition of hippocampal neuron apoptosis, the increase of the content of inhibitory neurotransmitter GABA, and the up-regulation of GABA and 5-HT-related receptor genes.

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation ( CONCLUSIONS A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.
Birth Weight ; Bone Diseases, Metabolic/etiology* ; China/epidemiology* ; Female ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats.

METHODSPaclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0.

RESULTSThe pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC, from 4 820±197 to 4 205±186 ng·mL·) and AUC(from 5 237±280 to 4 514±210 ng·mL·) significantly decreased in response to the 14-day pretreatment with SGD. The values of V(L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t(h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUCand AUCvalues decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel.

CONCLUSIONSSGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.

Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Injections, Intravenous ; Male ; Paclitaxel ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Rats, Sprague-Dawley ; Reference Standards ; Time Factors

OBJECTIVE: To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis. METHODS: 365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123 RESULTS: The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123 CONCLUSION CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.
Humans ; Interleukin-3 Receptor alpha Subunit ; Karyotype ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Patients ; Prognosis ; Retrospective Studies

OBJECTIVE: To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by Pollen Typhae total flavone (PTF). METHODS: Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), a shRNA group (transducted with PERK shRNA lentiviral particles), a scramble shRNA group (transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability, and the level of apoptosis was monitored by flow cytometry. RESULTS: The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and shRNA groups. Moreover, the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK, eIF2α, ATF4 and CHOP, which were attenuated in PTF treatment groups and shRNA groups. CONCLUSIONS The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway, which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.