Objective To explore the associations of the genetic polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with early-onset severe pre-eclampsia and the efficacy of labetalol therapy. Methods Totally 105 gravidas diagnosed with early-onset severe pre-eclampsia (experimental group) and 103 healthy gravidas (control group) were recruited from Beijing Obstetrics and Gynecology Hospital between August 2013 and July 2016. Labetalol was given to control blood pressures in gravidas with early-onset severe pre-eclampsia. If labetalol administration alone did not exceed the mean dose (100 mg, one dose per eight hours) and effectively controlled the blood pressures, it would be considered to be valid (n=75), otherwise it would be viewed as an invalid treatment. Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686 and rs3892097) in the gravidas were analyzed by TaqMan probe polymerase chain reaction. Differences in the genotype and allele frequencies were compared between the experimental and control groups, and the valid and invalid labetalol treatment groups. Chi-square test, analysis of variance and LSD test were used as statistical methods. Results The gravidas in both experimental and control groups were AA genotype in CYP2C9 gene rs1057910, TT genotype in CYP2D6 gene rs35742686 and CC genotype in CYP2D6 gene rs3892097. Frequencies of CC and CT genotypes in CYP2D6 gene rs28371725 in the experimental group were higher than those in the control group [18.1% (19/105) vs 14.6% (15/103);56.2% (59/105) vs 42.7% (44/103); χ2=6.707], and higher C allele frequency in CYP2D6 gene rs28371725 was also observed in the experimental group [46.2% (97/210) vs 35.9% (74/206), χ2=4.529] (all P<0.05). No statistical differences in maternal age, diastolic pressure, body mass index before pregnancy, serum triglyceride, creatinine and neonatal birth weight were observed among women with CC, CT or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P>0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5±2.1) vs (29.5±1.8) and (29.8±2.2) weeks] and higher plasma albumin [(27.2±9.3) vs (20.3±10.4) and (22.5±7.4) g/L], but lower systolic pressure and 24 hours urine protein (LSD test, all P<0.05). The G allele frequency in CYP2D6 gene rs1065852 in invalid labetalol treatment group was higher than that in valid labetalol treatment group [93.3% (56/60) vs 76.0% (114/150), χ2=8.351, P=0.004]. Conclusions The polymorphism of CYP2D6 gene rs28371725 may be associated with early-onset severe pre-eclampsia, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of early-onset severe pre-eclampsia.

Water cultured propagation technology of Polygonum multiflorum was investigated with Rooting Powder No. 2 (ABT 2) comparison experiments, and the dynamic changes of endogenous hormones including indole acetic acid (IAA), abscisic acid (ABA), zeatin riboside (ZRs) contents and activities of indoleacetic acid oxidase (IAAO), polyphenol oxidase (PPO) were analyzed during rooting period. The results showed that rooting percentage of softwood cutting with 50 mg x L(-1) ABT2 and 10 mg x L(-1) ABT2 + 0.2% Urea + 0.2% KH2PO4 treatments was 94%, rooting percentage of softwood cuttings of control was 46% only. The adventitious rooting displayed three distinct phases i. e. root-inducing, root formation and root-elongating phases. The dynamic changes of contents of endogenous plant hormones (IAA, ABA, ZRs) and activities of IAAO, PPO tested were tightly related to the rooting process of soft-wood cuttings in P. multiflorum. During root-inducing phase the contents of IAA, ABA and ZRs decreased sharply, whereas ZRs content and IAAO activity kept higher level. IAA content reached the peak and PPO activity increased obviously during root formation phase, while IAAO activities and ABA, ZRs contents declined to minimum. During root-elongating phase PPO, IAAO activities were higher and IAA, ABA, ZRs contents kept steady. During rooting ABT2 (50 mg x L(-1)) treatment increased the content of IAA and PPO activity in cuttings, while the opposite result occurred in contents of ZRs, ABA and IAAO activity.
Catechol Oxidase ; metabolism ; Culture Techniques ; Kinetics ; Peroxidases ; metabolism ; Plant Growth Regulators ; metabolism ; pharmacology ; Plant Roots ; drug effects ; growth & development ; metabolism ; Polygonum ; drug effects ; growth & development ; metabolism

Objective To explore the clinical application value of left atrial function with feature tracking cardiac magnetic resonance imaging (FT-CMR) by evaluating preliminarily left atrial strain and strain rate in patients with atrial fibrillation. Methods Thirty patients with paroxysmal atrial fibrillation, thirty patients with persistent atrial fibrillation and twenty-two healthy subjects were enrolled. All the subjects underwent cardiac magnetic resonance imaging with the real steady-state free precession(SSFP) sequence. FT-CMR parameters included left atrial strain and strain rate parameters, left atrial volume and function parameters were detected by using offline cardiovascular analysis software, respectively. Left atrial strain and strain rate parameters included left atrial total strain(Εs), passive strain(Εe), active strain(Εa), peak positive strain rate(SRs), peak early negative strain rate(SRe)and peak late negative strain rate(SRa). Volume and function parameters included maximum of left atrial volume(LAVmax), minimum of left atrial volume(LAVmin), total left atrial emptying fraction(LATEF), passive left atrial emptying fraction(LAPEF)and active left atrial emptying fraction(LAAEF). The differences in the general data among the paroxysmal atrial fibrillation group, the persistent atrial fibrillation group and the control group were compared by usingχ2 test or ANOVA analysis. The differences in all parameters between the atrial fibrillation group and the control group, the paroxysmal atrial fibrillation group and the persistent atrial fibrillation group were compared by using independent t test. Left atrial strain and strain rate parameters on an intra-observer and inter-observer were determined by intraclass correlation coefficient(ICC)analyses. Results Compared to control group, LAVmax and LAVmin in atrial fibrillation group were significantly increased(t=9.737,7.889,P<0.001);The LATEF and LAPEF had no significant difference, the LAAEF in two groups had statistically significant difference(t=-4.762,P<0.001).The absolute value of Es, Ee, Ea, SRs, SRe, SRa in atrial fibrillation group were significantly reduced than in control group(t=-7.732,-6.610,-6.493,-7.546, 6.864, 5.917,P<0.001). Compared with paroxysmal atrial fibrillation group, LAVmax and LAVmin in persistent atrial fibrillation group were increased obviously, LATEF and LAPEF were significantly decreased, and the differences were statistically significant(t=-4.575,-5.524, 4.002, 4.028,P<0.001).The LAAEF in two groups had no statistically significant difference. Compared with strain and strain rate in two groups, absolute value of Es, Ee, Ea, SRs, SRe, SRa in persistent atrial fibrillation group significantly decreased than in paroxysmal atrial fibrillation(t=4.310, 3.128, 4.465, 5.496,-3.290,-3.863,P<0.001). The intra-group and inter-group had well correlation coefficients between the observers in the left atrial strain and strain rate parameters of the subjects(ICC=0.85—0.94,0.81—0.90). Conclusions FT-CMR technique can be used to assess the left atrial strain and strain rate in patients with atrial fibrillation;Left atrial reservoir, conduit and booster-pump functions in patients with atrial fibrillation were impaired. Patients with persistent atrial fibrillation had worse left atrial function throughout the entire cardiac cycle compared with those with paroxysmal atrial fibrillation.

We reported a female fetus diagnosed with X-linked dominant chondrodysplasia punctata 2 with severe phenotype. The fetus was found with abnormal short limbs, thick metaphysis on the right lower limb and a narrow and small thorax by prenatal ultrasound at 24+5 weeks of gestation. Non-invasive prenatal test indicated the risks of trisomies 21, 18 and 13 were low. The pregnancy was terminated at 27 weeks of gestation and postnatal X-ray imaging showed that the fetus had short femur and humerus, a narrow and small thorax, thickened metaphysis with a "splashed paint spot" pattern, and asymmetric shortened lower limbs. Whole-exome analysis showed that the fetus carried a heterozygous pathogenic mutation c.440G>A (p.Arg147His) in the EBP gene. The mutation was confirmed to be a de novo mutation as neither of her parents carried the same mutation. Thus, the patient was diagnosed as having X-linked dominant chondrodysplasia punctata 2. The severe phenotype of this case migh be related to random X chromosome inactivation.

Background:Based on the effect of seasonal changes on human visceral function,this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippo-campal-receptor in rats,aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods:Vernal equinox,summer solstice,autumn equinox,and winter solstice were selected as four experimental time points,and rats were randomly divided into normal control group,sham operation group,and pinealectomized group.The seasonal changes in corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone,hypothalamic melatonin receptor(MTR),and hippocampal corticosterone receptor(CORTR)were examined by enzyme-linked immunosorbent assay.Results:Comparing the same group between different seasons,we showed that in the normal control group,CRH,ACTH,corticosterone,and MTR were higher,while CORTR was lower in autumn and winter than in spring(all P＜.05).Compared with the normal control group,the pinealectomized group showed higher levels of corticosterone(P=.01),MTR(P=.01),and CORTR(P=.03)during spring;reduced levels of MTR and CORTR(both P＜.001)during summer;higher levels of ACTH(P=.001)and MTR(P＜.001),and lower levels of CRH(P=.001),corticosterone(P＜.001),and CORTR(P=.003)during autumn;and lower levels of CRH(P＜.001)and MTR(P=.004),and higher level of ACTH(P＜.001)in winter.Conclusions:Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin,resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor,which may be the pathophysiological basis for the onset of seasonal affective disorder.

Objective:To explore the heterogeneity of behavioral problems and cognitive function of three subtypes of attention deficit hyperactivity disorder(ADHD), and to analyze the related factors of cognitive function.Methods:The outpatients with ADHD were evaluated by Wechsler children′s intelligence test (C-WISC), SNAP-Ⅳ parental rating scale (SNAP-Ⅳ), Conners parental symptom questionnaire (PSQ) and 12 online cognitive function tests. The differences of behavioral problems and cognitive function of children with different subtypes of ADHD, and the correlation between their intelligence level, PSQ, SNAP-Ⅳ and cognitive function were compared by SPSS 22.0 software.Results:The results of PSQ questionnaire showed that ADHD-C ((1.11±0.59), (1.59±0.58), (1.62±0.50)) had higher behavior problems, impulse-hyperactivity and hyperactivity index than ADHD-I ((0.64±0.27), (1.01±0.54), (1.09±0.32)) and ADHD-HI ((0.75±0.35), (1.22±0.58), (1.05±0.38)) ( F=9.374, F=7.644, F=15.176, P<0.05), while ADHD-C (2.01±0.55) had higher learning problems than ADHD-I (1.66±0.58) and ADHD-HI (1.16±0.43) ( F=11.709, P<0.05). In terms of cognitive function, there were differences in language understanding ability, digital reasoning ability, sequence relationship and short-term memory ability ( χ2=6.734, 7.192, 7.822, 8.646, all P<0.05) among the three groups of ADHD children. ADHD-HI (4.00(4.00, 5.00), 5.00(4.25, 6.00), 5.00(4.00, 7.00)) had better language understanding ability, digital reasoning ability and sequence relationship than ADHD-I (3.00(2.00, 5.00), 3.00(2.50, 6.00), 4.00(3.00, 5.50)). The short-term memory ability of ADHD-HI (5.00(4.00, 6.00)) and ADHD-C (5.00(4.00, 6.00)) were better than that of ADHD-I (4.00(3.00, 5.00)). The intellectual structure of ADHD children was positively correlated with spatial cognitive ability, sequential relationship, Raven reasoning test, short term memory span and Wisconsin card sorting test ( r=0.25-0.57, all P<0.05). Children′s learning problems and psychosomatic problems were negatively correlated with their digital comprehension ability ( r=-0.26, -0.25, both P<0.05). Conclusion:The behavioral problems and cognitive function of children with different subtypes of ADHD are different and have a certain correlation.

Background: Based on the theory of"five Zang-organs corresponding to the seasons"in traditional Chinese medicine (TCM), physiological functions including emotions vary with the seasons. We aimed to investigate the seasonal photoperiod effects of melatonin (MT) released from the pineal gland on the MT receptor (MTR)-Gs/Gi-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in the hippocampus.Methods: Rats were divided into three groups: control, operation (surgery with pineal gland removal), and pseudo-operation groups (same surgery as operation group but without removing pineal gland), and fed at specific time across the four seasons. The levels of MTR, adenylate cyclase (AC), cAMP, PKA, and CREB in the hippocampus were analyzed using ELISA. The concentrations of Gs and Gi were analyzed using Western blot. The expression of CREB mRNA was detected by PCR. Results: For intragroup comparisons, compared with spring, the levels of Gs/Gi in the control group were higher in summer, autumn, and winter (P=.009 in summer;P<.001 in autumn and winter);the levels of MTR, cAMP, PKA, and CREB in the control group were significantly higher in autumn and winter than in spring (all P<.001). The levels of MTR, cAMP, PKA, and CREB in each season were significantly lower in the operation group than in the control group (all P < .05). Significant differences were noted in Gs/Gi levels between the operation group and control group in spring, autumn, and winter (all P<.05). Conclusion: Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions. It can support the prevention and treatment of the seasonal onset of mental dis-orders, and enrich the theory of"five Zang-organs corresponding to the seasons".

OBJECTIVE To investigate the multi-target mechanism of action of Poecilobdella manillensis lyophilized powder(SZ) against hyperuricemia(HUA) based on network pharmacology and transcriptomics approaches, combined with animal experiments. METHODS Utilizing Symmap, SwissTargetPrediction, and Pharmmapper databases, the potential active components and corresponding targets of SZ were obtained. Through the Gene Cards and OMIM databases, HUA-related targets were obtained. By taking the intersection mapping, the common targets of SZ and HUA were identified. Cytoscape 3.9.0 software was used to construct a drug component-disease target interaction network, and in combination with the STRING database, a protein interaction network was built and core targets were screened. The DAVID database was used to perform GO biological function annotation and KEGG pathway enrichment analysis on the intersecting targets. A mouse model of HUA was constructed using potassium oxyzate combined with high purine diet, and the effects of SZ on these mice were examined using ELISA and biochemical index detection. qRT-PCR was used to validate the results of RNA-Seq and network pharmacology enrichment analysis. RESULTS Network pharmacological analysis identified 11 major bioactive substances in SZ and 72 potential targets involved in the treatment of hyperuricemia, involving multiple biological processes and different signaling pathways. It was shown that SZ significantly reduced serum uric acid, creatinine and urea nitrogen levels in hyperuricemic mice by inhibiting xanthineoxidase activity. SZ also reduced the levels of URAT1 while increasing the levels of ABCG2. RNA sequencing analysis revealed that there were 112, 536 and 107 differentially expressed genes in the model group vs treated group, control group vs model group and control group vs treated group, respectively. qRT-PCR results indicated that SZ downregulated the expression of genes related to Th17 cell differentiation as well as mRNA of genes on IL-17 and PI3K/Akt signaling pathways. CONCLUSION SZ has therapeutic effects on hyperuricemia. The mechanism of action maybe related to the inhibition of hepatic xanthineoxidase activity, down-regulation of URAT1 levels, up-regulation of ABCG2 levels, affecting the differentiation of Th17 cells and thus the IL-17 signaling pathway, thereby reducing the inflammatory response.

This paper systematically analyzed the understanding of qi from the perspectives of matter， energy， information and relationship reality， introduced the original holistic principle of systematic traditional Chinese medicine （TCM）， and considered the latest research results of qi （three-layer material theory）， trying to optimize the structure framework of the qi theoretical system and exhibit the occurrence and development rules of original qi. It emphasizes the hierarchical order of qi transformation following the original holistic principle， and takes this to guide the clinical understanding of “qi diseases”， helping doctors grasp the basic pathogenesis of the disease， that is abnormal qi movement， and helping them establish the awareness of providing systematic TCM treatment to patients by taking qi regulation as the key. At the same time， it discusses people within the structure of time and space， and points out that the treatment of diseases must comply with the principle of “the harmony of heaven， earth， and human beings”.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.