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Background MicroRNAs (miRs) have received extensive attention in osteoarthritis (OA) pathogenesis in recent years, and our previous study have confirmed that single intra-articular injection (IAJ) of miR-140-5p alleviates early-stage OA (EOA) progression in rats. This study aims to further investigate the effects of single IAJ of miR-140-5p on different stage OA and multiple IAJs of miR-140-5p on EOA, as well as the potential mechanisms. Methods Firstly, OA model was surgically induced in rats, 9 rats were treated with IAJ of Cy5-miR-140-5p at 1 week after surgery, and fluorescence distribution was measured. Then, 72 rats were treated with single IAJ of miR-140-5p at different time after surgery or multiple IAJs of miR-140-5p at 1 week after surgery, and OA progression were evaluated macroscopically and histologically. Finally, bioinformatics analyses were performed and the potential targets and molecular mechanisms of miR-140-5p were predicted. Results Strong fluorescence was observed in the chondrocytes and joint where Cy5-miR-140-5p was injected. Behavioural scores, chondrocyte numbers and cartilage thickness in cartilage were higher, while pathological scores were lower in the miR-140-5p group than in the control group. Specifically, the earlier a single IAJ of miR-140-5p, the better the therapeutic effect, and multiple IAJs exhibited better therapeutic effect than single IAJ on EOA. Bioinformatics analyses predicted 84 potential target genes of rno-miR-140-5p and revealed that these genes enrich in various biological processes and pathways. Conclusions IAJs of miR-140-5p effectively alleviate EOA progression by modulating various biological processes and pathways, and may be a promising therapeutics for EOA.

Two practical and simple synthetic methodologies towards various heterobenzyl halides were developed. A series of 2-halomethylquinolines were readily prepared by the one-pot reaction of 2-methylquinolines with CuX (X = I, Br, Cl) and TBHP in CH3CN. A large variety of heterobenzyl iodides, including 2-iodomethylquinolines, 2-iodomethylquinoxalines, 2-iodiomethylbenzooxazole, and 2-iodiomethylbenzothiazole, were efficiently synthesized by one-pot reaction of 2-methylheterocycles with iodine in the presence of CuSO4·5H2O in CH3CN.

Background Hydrogen sulfide (H2S) is a crucial signaling molecule with a wide range of physiological functions. Previously, we confirmed that stress-induced depression is accompanied with disturbance of H2S generation in hippocampus. The present work attempted to investigate the inhibitory effect of H2S on chronic unpredictable mild stress-induced depressive-like behaviors and the underlying mechanism. Methods We established the rat model of chronic unpredictable mild stress to simulate depression. Open field test, forced swim test, and tail suspension test were used to assess depressive-like behaviors. The expression of Sirt-1 and three marked proteins related to endoplasmic reticulum stress (GRP-78, CHOP, and cleaved caspase-12) were detected by western blot. Results We found that chronic unpredictable mild stress-exposed rats exhibit depression-like behavior responses, including significantly increased immobility time in the forced swim test and tail suspension test, and decreased climbing time and swimming time in the forced swim test. In parallel, chronic unpredictable mild stress-exposed rats showed elevated levels of hippocampal endoplasmic reticulum stress and reduced levels of Sirt-1. However, NaHS (a donor of H2S) not only alleviated chronic unpredictable mild stress-induced depressive-like behaviors and hippocampal endoplasmic reticulum stress, but it also increased the expression of hippocampal Sirt-1 in chronic unpredictable mild stress-exposed rats. Furthermore, Sirtinol, an inhibitor of Sirt-1, reversed the protective effects of H2S against chronic unpredictable mild stress-induced depression-like behaviors and hippocampal endoplasmic reticulum stress. Conclusion These results demonstrated that H2S has an antidepressant potential, and the underlying mechanism is involved in the inhibition of hippocampal endoplasmic reticulum stress by upregulation of Sirt-1 in hippocampus. These findings identify H2S as a novel therapeutic target for depression.

The present meta-analysis synthesized evidence from 10 articles encompassing 28 independent studies to verify the association between hypertension and osteoporotic fracture risk in women and men. Our results indicate that the risk of osteoporotic fracture among individuals with hypertension was higher than that among individuals without hypertension. Epidemiological studies have suggested that hypertension is related to osteoporotic fracture. However, discrepancies exist in the reported findings. In this study, a systematic review of relevant published articles was conducted to verify the association between hypertension and osteoporotic fracture risk in women and men. PubMed (1953_October 5th, 2016) and Embase (1974_October 5th, 2016) were systematically searched for relevant articles. Odds ratios (ORs) and confidence intervals (CIs) were derived using random effect models. Categorical, subgroup, heterogeneity, publication bias, and meta-regression analyses were conducted. We analyzed 10 articles encompassing 28 independent studies, 1,430,431 participants, and 148,048 osteoporotic fracture cases. The risk of osteoporotic fracture among individuals with hypertension was higher (pooled OR = 1.33, 95% CI 1.25–1.40; I 2 = 72.3%, P

Low birth weight (LBW) and preterm birth (PB) are associated with newborn mortality and diseases in adulthood. We explored factors related to LBW and PB by conducting a population-based case-control study from January 2011 to December 2013 in Wuhan, China. A total of 337 LBW newborn babies, 472 PB babies, and 708 babies with normal birth weights and born from term pregnancies were included in this study. Information of newborns and their parents was collected by trained investigators using questionnaires and referring to medical records. Univariate and logistic regression analyses with the stepwise selection method were used to determine the associations of related factors with LBW and PB. Results showed that maternal hypertension (OR=6.78, 95% CI: 2.27-20.29, P=0.001), maternal high-risk pregnancy (OR=1.53, 95% CI: 1.06-2.21, P=0.022), and maternal fruit intake ≥300 g per day during the first trimester (OR=1.70, 95% CI: 1.17-2.45, P=0.005) were associated with LBW. BMI ≥24 kg/m2 of mother prior to delivery (OR=0.48, 95% CI: 0.32-0.74, P=0.001) and gestation ≥37 weeks (OR=0.01, 95% CI: 0.00-0.02, P

Background Hydrogen sulfide (H2S) has therapeutic effects on Parkinson's disease (PD). Warburg effect, namely aerobic glycolysis, is benefit to PD. Leptin, a hormone secreted in adipose, plays an important role in the treatment of PD. Objective To determine whether the mechanism underlying protection of H2S against PD is involved in promoting Warburg effect via upregulation of leptin. Methods We set a PD model via unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in Sprague Dawley rat. PD-like behavior was analyzed by apomorphine-induced rotations, open field activity test, stepping test and cylinder test. Dopaminergic neurons were detected by immunohistochemistry. The expressions of Hexokinase-2, pyruvate kinase M-2, lactate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase, and leptin were measured by Western blot. Lactate dehydrogenase (LDHA) activity was monitored by ELISA. The lactate content was measured by lactate assay kit. Results We showed that NaHS (a donor of H2S) prevented 6-OHDA-induced PD-like behaviors as well as the loss of dopaminergic neurons. We also found that NaHS enhanced the Warburg effect and upregulated leptin expression in the substantia nigra of 6-OHDA-exposed rats. While, inhibited leptin signaling by OBR13-A reversed the protections of H2S against 6-OHDA-exerted PD-like behaviors and the loss of dopaminergic neurons in the substantia nigra, and abolished H2S-enhanced in the Warburg effect in the substantia nigra. Conclusion: These data indicated that leptin mediates the protection of H2S against PD, which involves enhancing the Warburg effect of the substantia nigra.

The present dose-response meta-analysis shows linearly decreased hip fracture (HF) risk and nonlinearly decreased osteoporotic fracture (OF) risk associated with increasing number of parity of up to five live births among postmenopausal women. Epidemiological reports suggest that parity is associated with reduced OF risk among women. However, these findings are controversial. Here, we present a meta-analysis of prospective studies of parity in relation to OF risk. We performed systematic searches using Medline and Embase from January 1, 1966, to December 31, 2014, with limits of language in English and prospective study design. Relative risks (RRs) and confidence intervals (CIs) were derived mainly using random-effects models. Categorical, dose-response, heterogeneity, publication bias, and subgroup analyses were conducted. We analyzed 10 articles of 19 independent reports from 1966 to 2014, comprising a total of 217,295 participants and 26,525 cases of OF. Compared to nulliparous women, the OF and HF risks of parous women with at least one live birth were reduced by 11 % (95 % confidence interval (CI) 3–19 %; I 2 = 77.1 %, p

To observe the expression of catechol-O-methyltransferase (COMT) in inferior colliculus and auditory cortex of guinea pigs with age-related hearing loss(AHL) induced by D-galactose, so as to explore the possible mechanism of electroacupuncture(EA) underlying preventing AHL.Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group(Compared with the control group, the latencies of ABR Ⅲ wave were significantly prolonged and the expressions of COMT in the inferior colliculus and auditory cortex were significantly decreased in the model group and the elderly group(EA at "Yifeng" (SJ 17) and "Tinggong" (SI 19) can improve the hearing of age-related deafness in guinea pigs, which may contribute to its effect in up-regulating the expression of COMT in the inferior colliculus and auditory cortex.

Pregnancy is a critical stimulator of bone mineral resorption. We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women. Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too. In this article, we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women. The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012. A total of 1000 participants, including 250 pregnant women in the first, second, and third trimesters and 250 non-pregnant women, were enrolled in the study. Finally, after excluding 27 participants unable to provide blood samples, 973 eligible participants (i.e., 234,249, and 248 pregnant women in the first, second, and third trimesters, respectively, and 242 non-pregnant women) were included in the research. The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers, with standardized coefficients of 0.086 (P

Lithium-doped zinc oxide(ZLO) thin films were deposited on glass substrates by sol-gel method.And then by controlling processing parameters such as the amount of doped lithium and stability, etc,Well-aligned ZLO nanorod arrays were successfully grown on substrates by hydrothermal method, where the substrates were spin-coated with seed layer.The experiments show the 5% Li-doped and diameter of about 50nm of ZLO thin films nanorod arrays has the best performance photoluminescence and surfactants can promote the growth of ZLO rod-like nano-structures and contribute to the formation of ZLO nanorod arrays with highly oriented.

Under the framework of soil-wheat system, the sampling area was selected in the Lingxian country of Shandong province, based on the DGPS localization data, a total of 849 sampling sites of Ji wheat 22 yield which was cultivated by Shandong Academy of Agricultural Science were involved in the study, combination with grid sampling and random sampling. the spatial estimation comparison study of wheat yield was developed on the precision scale, with the support of Kriging and Inverse Distance Weighted (IDW) method. The main objective of the study analyzed the spatial estimation on basis of sampling sites with the help of two methods. The results showed that IDW method is more accurate on basis of the sampling sites data than Kriging method, under less than 40m interval between sites for Ji wheat 22 yield, though the major advantage of kriging in comparison with IDW is estimating weights for locations based not only on the distance between separated locations but also on the global semivariogram model fitted to the collected data. The results also indicated that the estimation accuracy depended on the threshold of sampling numbers, if the numbers are less than the threshold, the sampling density is in contact with the spatial estimation accuracy, if the numbers are more than the threshold, the density of the sampling numbers is improved, but the estimation results are not proportional to the density.

To quantitatively assess the association between parity and all-cause mortality, we conducted a meta-analysis of cohort studies. Relevant reports were identified from PubMed and Embase databases. Cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) of all-cause mortality in three or more categories of parity were eligible. Eighteen articles with 2,813,418 participants were included. Results showed that participants with no live birth had higher risk of all-cause mortality (RR= 1.19, 95% CI = 1.03–1.38; I2 = 96.7%, P P for non-linearity

Few studies have focused on the accuracy of using the Integrated Exposure Uptake Biokinetic (IEUBK) model in Chinese children with site- and age-specific exposure data. This study aimed to validate the accuracy and sensitivity of the IEUBK model in lead risk assessment of Chinese children aged 61-84 months old. A total of 760 children were enrolled from two respective counties in Central China by using random cluster sampling method. Blood lead levels (BLLs) of all subjects were determined using graphite furnace atomic absorption spectrometry, as well as that in the environmental media, such as air, drinking water, soil, dust and food. Age- and site-specific time-activity patterns and water consumption were evaluated by using questionnaires for children. Exposure parameters including outdoor and indoor activity time, ventilation rate and water consumption in this study were different from the default values of the IEUBK model. Statistical analysis revealed no significant differences between the predicted and observed BLLs. Diet and soil/dust lead intake contributed approximately 83.39% (57.40%-93.84% range) and 15.18% (3.25%-41.60% range) of total lead intake, respectively. These findings showed that the IEUBK model is suitable for lead risk assessment of Chinese children aged 61-84 months old and diet acts as an important lead source.

BackgroundPregnancy is an important stimulus of bone lead release. Elevated blood lead levels (BLLs) may cause adverse pregnancy outcomes for mothers and harmful lead effects on fetuses. However, the reports about maternal BLL changes during pregnancy are conflicting to some extent. This article is to explore the variations in BLLs among pregnant women. The relationships of BLLs with methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms, which are associated with bone resorption, were also studied. A total of 973 women, including 234, 249, and 248 women in their first, second, and third trimesters, respectively, and 242 non-pregnant women, were recruited at the Wuhan Women and Children Medical Health Center.MethodsBLLs were determined using a graphite furnace atomic absorption spectrometer. Single-nucleotide polymorphisms of MTHFR were identified with the TaqMan probe method.ResultsThe geometric mean (geometric standard deviation) of BLLs was 16.2 (1.78) μg/L for all participants. All the studied MTHFR alleles were in Hardy-Weinberg equilibrium. Multiple-linear regression analysis revealed the following results. Among the pregnant women, those that carried MTHFR 677CC (i.e. wild-genotype homozygote) and 1298CC (i.e. mutant-genotype homozygote) exhibited higher BLLs than those that carried 677CT/TT (standardized β = 0.074, P = 0.042) and 1298AC/AA (standardized β = 0.077, P = 0.035) when other covariates (e.g., age, no. of children, education and income, etc.) were adjusted. The BLLs of pregnant women consistently decreased during the pregnancy and these levels positively correlated with BMI (standard β = 0.086-0.096, PConclusionsThe 1298CC mutant-type homozygote in the MTHFR gene is a risk factor for high BLLs among low-level environmental lead-exposed Chinese pregnant women, whose BLLs consistently decreased during gestation.

1) A set of period components corresponding well to those of Earth tides and barometric pressure can be separated from the hydro-spectra of deep well. The well-aquifer system responds to these components in some degree, which shows that groundwater regime is influenced by Earth tides and barometric pressure. However, in different frequency bands a well-aquifer system possesses different transfer ability for various inputs.

The Construction of the Meta-Synthetic of Army Material Facility System of Systems(MSOAMFSOS) is a complicated systems engineering, which relates to the classification & composition, architecture & organization, and operational application, etc. This paper discusses the ideal and theory based on meta-synthesis, and the meta-synthetic assessment process from qualitative hypothesis to quantitative validation, establish general path and technique route of its system analysis.

To investigate the distribution of human leukocyte antigen (HLA)-G and E on human first trimester placenta and its relationship with unexplained recurrent spontaneous abortion (RSA).Fifteen women with normal first trimester pregnancy and fifteen patients with RSA were included in this study. In situ hybridization and immunohistochemical staining were employed to detect the mRNA and protein of HLA-G, E in first trimester placenta.The HLA-G, E mRNA were detected in all trophoblasts, including syncytiotrophoblast, villous and extravillous cytotrophoblast. HLA-G protein was only found at extravillous trophoblast by mAb 4H84 specific to HLA-G. The same expression sites were observed for both HLA- E protein and its mRNA. The expression of HLA-G, E mRNA in the RSA group were much lower than those in the control group. The HLA-G, E protein were also expressed at low level in RSA group.The inconsistency of the distribution of HLA-G mRNA and protein was probably due to the monoclone antibody 4H84. There is strong correlation between lack of the mRNA and protein expression of HLA-G, E found in the trophoblasts at the fetal-maternal interface and RSA.

To study the relationship between CYP1A1 genetic polymorphism and intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China.MspI and Ile/Val genotypes of CYP1A1 gene were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification-PCR (ASA-PCR) in a case-control study, including 100 cases of ICP and 100 controls.There was no significant correlation between MspI polymorphism and ICP susceptibility (P0.05). However, the Ile/Val+Val/Val genotypes of CYP1A1 significantly increased the risk of ICP (P=0.047, OR=1.768).The Ile/Val polymorphism in exon 7 of CYP1A1 may be associated with the susceptibility of ICP in Chengdu. The MspI polymorphism of CYP1A1 is not associated with the risk of ICP in Chengdu.

To investigate the expression of human leucocyte antigen G (HLA-G) on human placenta and its gene polymorphism in relation to intrahepatic cholestasis of pregnancy (ICP).Immunohistochemistry was utilized to detect the HLA-G protein expression on third trimester placenta of fifteen normal pregnant women (control group 1), fifteen ICP patients treated with dexamethasone (ICP group with dexamethasone treatment) and ten ICP patients treated without dexamethasone (ICP group without dexamethasone treatment). We used polymerase chain reaction with sequence-specific primer (PCR-SSP) method to detect the 14 bp deletion polymorphism in exon 8 of HLA-G gene of thirty normal pregnant women and their babies (control group 2), thirty ICP patients and their babies (ICP group).(1) The positive expression of HLA-G on placenta extravillous cytotrophoblast and its mean optical density of ICP group without dexamethasone treatment 56 +/- 8 was significantly lower than those of normal control group 70 +/- 10 and ICP group with dexamethasone treatment 66 +/- 9 (P0.05). No significant differences were found between normal control group and ICP group with dexamethasone treatment (P0.05). (2) There were no statistical differences between the control group and the ICP group with regard to the allele and genotype of the 14 bp deletion polymorphism in exon 8 of HLA-G gene (P0.05).The reduced expression of HLA-G on placenta in ICP patients may alter the maternal-fetal immune response and thus be involved in the pathogenesis of this disorder. Dexamethasone can upregulate the expression of HLA-G on placenta. The 14 bp deletion polymorphism in exon 8 of HLA-G gene might not have a significant influence on the development of ICP.

To investigate the relationship between human leucocyte antigen (HLA)-G, E and intrahepatic cholestasis of pregnancy (ICP).In situ hybridization and immunohistochemistry methods were adopted in this study to detect the expression of HLA-G and HLA-E mRNA and protein in the placentae of three groups, namely normal control group, ICP group with dexamethasone (DEX) treatment, and ICP group without DEX treatment.No significant differences in respect to HLA-G, HLA-E mRNA expression on extrovillous cytotrophoblasts (EVCT ) of the placentae were found between the normal control group, the ICP group with DEX treatment and the ICP group without DEX treatment. However, the protein expression of HLA-G and HLA-E on the placental EVCT of ICP group without DEX treatment was significantly lower than that of the normal control group and the ICP group with DEX treatment.The decreased EVCT expression of HLA-G, HLA-E protein may cause the disturbance of the maternal-fetal immune tolerance of ICP patient and play a role in the pathogenesis of ICP. DEX can upregulate the EVCT expression of HLA-G, HLA-E protein; this may be one of the underlying mechanisms for its use in the treatment of ICP.

To investigate the expression of HIF-1alpha mRNA and HIF-2alpha mRNA in placentas of pregnant women with intrahepatic cholestasis of pregnancy(ICP).Twenty samples of placentas from pregnant women with ICP and 20 samples of normal term placentas were selected. The expression levels of HIF-1alpha mRNA and HIF-2alpha mRNA were measured by RT-PCR.There was no statistically significant difference in respect to the expression levels of HIF-1alpha mRNA and HIF-2alpha mRNA between the two groups of samples (P0.05).Under hypoxic conditions, HIF-1alpha and HIF-2alpha proteins are not transcriptionally regulated at the mRNA level but are probably regulated at the post-mRNA level.

To study the clinical features and diagnosis of intrahepatic cholestasis of pregnancy (ICP).During the last 10 years 1241 cases of ICP stayed in our hospital. Their clinical data were retrospectively reviewed.5.2% of all the maternity patients had ICP. It occurred more in winter and 3.5% of ICP occurred in multiple pregnancies. The recurrence rate of ICP was 30.2%. On the average, it occurred at gestational week 32.6. Skin pruritus was the characteristic manifestation and the presenting symptom in 1201 patients (96.8%). The other presenting features included elevated serum ALT and AST (2.3%), jaundice (8 patients), diarrhea (3 patients), deep yellow urine (2 patients) and right upper abdominal pain (1 patient). The serum transaminases levels were elevated, of which 60% were between 50-200 IU/L. Serum total bile acid (TBA) levels were elevated in 82.4% of the patients and bilirubin levels in 33.4%. The elevated bilirubin levels were 30 to 90 micromol/L in 85% of those patients with this condition, and it was never higher than 170 micromol/L.The basic diagnostic points of ICP are pruritus and abnormal liver function characterized by increased transaminases and TBA. Therefore paying attention to typical pruritus and other atypical features such as elevated serum transaminases, jaundice, diarrhea, deep yellow urine and right upper abdominal pain during antenatal care is important for an early diagnosis of ICP.

Intrahepatic cholestasis of pregnancy (ICP) is a disease happening during pregnancy and does a great harm to the fetus. The etiology and pathogenesis of ICP are not clear. It is very important to investigate the relationship between ICP cord blood lymphocytes (CBLs) apoptosis and its clinical significance.The CBLs were isolated from 20 patients with ICP and 20 normal pregnant women. Flow cytometry (FCM) was used to detect the apoptosis cells in the CBLs. The apoptosis regulatory molecules (Fas/FasL, Bcl-2) of CBLs were detected by immunohistochemical technique.The percentage of apoptotic CBLs in ICP patients were significantly lower than that in the normal pregnant women (P0.05). The FasL protein expression of CBLs in ICP patients was significantly higher than that in normal pregnant women (P0.05), but Fas and Bcl-2 protein expression were normal.The abnormal apoptosis of CBLs may influence the immune reaction of ICP patients, which does something in the pathogenesis of ICP.

To investigate the expression of corticotropin-releasing hormone and its receptor type-1 in human placental tissues during caesarian operations.IHC-SP staining and ISH methods were adopted to identify the expression patterns of CRH and its receptor CRH-R1 in the placenta taken from the women who had uncomplicated pregnancies. The placental tissues were collected after caesarian operations on the women with threatened labor.Positive expressions of both CRH and CRH-R1 messenger ribonucleic acid and peptide were found in the placental tissues, but the later was stronger (P0.05).The elevated level of placental CRH may be a trigger of the transcription of its own receptor CRH-R1 during caesarian operations. This positive feedback of CRH on its own receptor may represent a functional adaptation of human utero-plcental-fetal unit in responding to stress.

Owing to the molecular mechanisms unexplored yet to fetal hypoxia signaling in the intrahepatic cholestasis of pregnancy (ICP), and therefore we intend to investigate the significant expression of the hypoxia-inducible transcription factor-1alpha (HIF-1alpha) in placenta of pregnant women with ICP during hypoxia.The villous placenta tissues were in vitro cultured under hypoxia condition. The immuno-histochemistry technique was applied to probe the HIF-1alpha and P53 expressions in placentas of pregnant women and patient with ICP.Under the condition of normal concentration oxygen, P53 was highly expressed in the placenta of pregnant women with ICP (P0.01), however the HIF-1alpha expression was not up to higher than in normal control. Under the condition of lower concentration oxygen (2% O2), the HIF-1alpha and P53 expressions were detected from the placental villous tissues cultured for 4 h of normal control and patient with ICP, and with HIF-1alpha and P53 proteins increased in the placenta of pregnant women with ICP (P0.05 and P0.001 respectively). Whatever was hypoxia condition, P53 protein got always a high expression, and had a positive correlation with HIF-1alpha expression in ICP (P0.01).Under hypoxic conditions, high increase of HIF-1alpha may influence the increase of P53 directly, which may be one of the hypoxia pathogenesis factors in ICP. The fetal hypoxia and stillbirth may be the results of unbalance of HIF-1alpha and P53 which induced apoptosis under hypoxia condition.

To explore effect of fetal lymphocyte on pathogenesis of intrahepatic cholestasis of pregnancy (ICP).Twenty pregnant women with ICP and 20 normal pregnant women were enrolled in the study. The single mixed lymphocyte culture/reaction (MLC/MLR) was conducted using inactive lymphocyte obtained from maternal peripheral blood and lymphocyte of cord blood from fetus. Antigen-induced-lymphocyte-proliferation-reaction was used for dermic soluble antigen and decidual soluble antigen obtained from maternal blood and cord blood from fetus. The intense of proliferation was calculated and compared between normal and ICP-complicated pregnancies.(1) The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group 2.75 +/- 0.36 than those of normal control group 1.45 +/- 0.19 in single mixed lymphocyte culture (P0.05). (2) The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group 1.45 +/- 0.19 than those of normal control group 0.67 +/- 0.24 in decidual soluble antigen induced lymphocyte proliferation reaction (P0.05). (3) The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group (1.22 +/- 0.44) than those of normal control group (0.66 +/- 0.27) in dermic soluble antigen induced lymphocyte proliferation reaction.(1) The fetal lymphocyte may be one of the effector cells in pathogenesis of ICP. (2) The disturbance of fatal-maternal immune-tolerance is one of the important mechanisms underlying ICP.

To investigate the kinds of ERa, ERbeta mRNA and the localization of ERa, ERbeta on normal human placenta.The expression and localization of ERa,ERbeta on normal human placenta were detected by reverse transcription-ploymerase chain reaction (RT-PCR) and immunhistochemistry (SP-assay).There was mRNA expression of ERalpha and ERbeta on human term placenta, and ERbeta was identified with ERbeta5. The ERa immunoreactivity on human term placenta was in villous cytotrophoblastic nucleus, and that of ERbeta was in syncytiotrophoblastic cytoplasm.The findings indicate that ERbeta5 is the kind of ERbeta on placenta. It is localizated in the cytoplasm of syncytiotrophoblast and is probably connected with the production of estrogen.

To explore the relationship between human leukocyte antigen-DQA1 (HLA-DQA1) allele gene polymorphism and intrahepatic cholestasis of pregnancy (ICP).Forty-five patients with ICP, eighteen ICP families, forty-five normal pregnant women and eighteen normal control families were tested for HLA-DQA1 allele gene polymorphism by polymerase chain reaction with sequence-specific primer (PCR-SSP) method.The frequency of HLA-DQA1*0301 in normal pregnant women was markedly higher than that in the ICP group (P0.05). No significant differences were observed between the frequencies of other detected HLA-DQA1 alleles in both groups. The analysis of feto-maternal or couples sharing of the HLA-DQA1 alleles showed that no significant differences were observed between the two groups.The above findings suggest that there is no significant association between the genetic polymorphisms in HLA-DQA1 and ICP in Chengdu district; HLA-DQA1*0301 may be a protective gene against ICP. It may prevent the development of ICP.

investigate whether polymorphisms in estrogen-metabolizing genes, CYP17 and CYP3A4, are associated with intrahepatic cholestasis of pregnancy (ICP) in Chengdu China.The -1931T/C polymorphism in the 5'-untranslated region of CYP17 gene and the -290A/G polymorphism in the 5'-regulatory region of CYP3A4 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 pregnant women with ICP (ICP group) and 100 normal pregnant women (control group) in Chengdu.The T/C polymorphism of the CYP17 gene was shown clearly in ICP and control groups, but the genotype distributions (TT, TC and CC) and allele frequencies (T and C) of CYP17 polymorphism were of no significant difference between the two groups (P0.05). No CYP3A4-V (CTP3A4 * 1B) allele was found in the 200 individuals studied. The genotype of CYP3A4 was wt/wt in all the pregnant women.The T/C polymorphism of CYP17 gene is not associated with the risk of ICP in Chengdu. There are not -290A/G polymorphism of CYP3A4 gene among pregnunt women in Chengdu.

To investigate the relation ship of estrogen receptor 2 gene (ESR2) polymorphism associated with intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China.By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the Rsa I polymorphism in exon 5 and the Alu I polymorphism in exon 8 of ESR2 were detected in 100 pregnant women with ICP (ICP group) and 100 normal pregnant women (control group) in Chengdu.(1) The frequency of the allele A of Alu I polymorphism in exon 8 was significantly higher in ICP group than in control group (P=0.031, OR=1.975), so did the frequency of the Aa+AA genotypes (P=0.028, OR=2.144). (2) The genotype distributions (rr, Rr and RR) and allele frequencies (r and R) of Rsa I polymorphism in exon 5 were not significantly different between the two groups (P0.05).The Alu I polymorphism in exon 8 of ESR2 may be associated with the susceptibility of ICP in Chengdu. The Aa+AA genotype significantly elevated the risk suffering from the ICP. The Rsa I polymorphism in exon 5 of ESR2 is not associated with the risk getting the ICP in Chengdu.

To investigate the expression pattern of vascular cell adhesion molecule-1(VCAM-1) and endothelial selectin (E-selectin) in the placental bed extravillous cytotrophoblast (EVCT) as well as its relationship with preeclampsia.Placentas from severe preeclampsia (n=20) and gestional age-matched normal pregnancies (n=20) were studied. The staining intensity and the Mean Optical Density (MOD) of VCAM-1 and E-selectin in EVCT of placental bed deciduas were measured by immunohistochemistry.The staining intensity and MOD of VCAM-1 and E-selectin on placental bed EVCT in severe preeclampsia were significantly lower than those in the control group respectively (P0.05, P0.01).The decreased EVCT expression of vascular adhesion phenotype VCAM-1 and E-selectin may account for the shallow trophoblast invasion in preeclampsia, which is the major pathological change of this disease.

To study the perinatal outcomes of intrahepatic cholestasis of pregnancy (ICP).The clinical data of 1210 cases of ICP in recent ten years were retrospectively analyzed.The incidence rates of perinatal outcomes of ICP were as follows: 19.0% (230/1210) for threatened premature labor, 24.0% (290/1210) for premature delivery; 23.2% (281/1210) for meconium stained amniotic fluid, 7.1% (86/1210) for neonatal asphyxia, 22.5 per thousand (27/1210) for perinatal mortality, 85.9% (1039/1210) for cesarean section, 0.9% (11/1210) for fetal growth restriction (FGR), 1.4% (17/1210) for postpartum hemorrhage, and 8.1% (101/1210) for preeclampsia. Threatened premature labor occurred beyond the gestation gestation period of 32 weeks in 88.7% (204/230) of the patients, and the fetal death rate in threatened premature labor was 46.7% (7/15). Premature delivery occurred after 34 weeks of gestation in 96.2% of the patients (279/290) 89.7% (260/290) of which were caused by cesarean section because of abnormal fetal monitoring. 41.3% of the cases with meconium stained amniotic fluid (116/281) occurred before the onset of labor. Fetal death accounted for 56% (15/27) of perinatal death, 80% (12/15) of which happened after the gestation week of 35 (36.5 +/- 1.2) with normal fetal heart rate monitoring. 95% (19/20) of the fetal death and stillbirth occurred after threatened premature labor and occasional uterine contractions, or at the early stage of labor.The rates of FGR, postpartum hemorrhage, and preeclampsia in ICP are almost the same as those of the normal pregnancy. Routine fetal heart rate monitoring methods cannot predict fetal death. The important measures to decrease the perinatal mortality include paying attention to fetal monitoring when threatened premature labor, occasional uterine contractions and prenatal meconium occur, and at the early stage of labor, and management of threatened premature labor and timely intervention of pregnancy (at the gestation period of 34 - 37 weeks).

To study the expression of corticotropin-releasing hormone(CRH) and its receptor type-1 in the placental cotyledon vessels at term.IHC-SP staining and ISH methods were used to investigate the expression patterns of CRH and its receptor CRH-R1 in the placental cotyledon vessels at term from women who had undergone uncomplicated pregnancies. Placental tissues were collected after cesarian section before threatened labor.This study revealed for the first time that endothelial cells and even smooth muscle cells of the cotyledon vessel expressed CRH messenger ribonucleic acid and peptide as well as the CRH-R1.The novel findings disclosed that the CRH derived from endothelial cells and even smooth muscle cells of the cotyledon vessel may represent the main source of CRH levels in fetal plasma, thus indicating the capability of mobilizing the compensation mechanism for adapting to the acute stress.

To investigate the influence of transforming growth factor-beta2 (TGF-beta2) on production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) from placenta of patients with intrahepatic cholestasis of pregnancy (ICP).Villous explants from 10 ICP patients (ICP group) and 10 normal gravidae (control group) were cultured in vitro. The concentrations of TNF-alpha and IFN-gamma in the culture medium were determined by enzyme linked immunoadsorbent assay (ELISA) after incubation with different concentrations of TGF-beta2 for 1, 24 and 48 hours.(1) After cultured for 1, 24 and 48 hours, TNF-alpha level in ICP group was (771 +/- 187) pg/g, (2 490 +/- 575) pg/g, and (3339 +/- 1106) pg/g, respectively, while IFN-gamma level was (931 +/- 148) pg/g, (1888 +/- 545) pg/g, and (3027 +/- 667) pg/g, respectively. All were significantly higher than those in the normal group (P0.001). (2) TGF-beta2 could inhibit the release of above cytokines in a time- and dose-dependent manner: TNF-alpha level was (2490 +/- 575) pg/g, (1806 +/- 502) pg/g, and (1231 +/- 238) pg/g after 24 h, (3339 +/- 1106) pg/g, (2168 +/- 794) pg/g, and (1047 +/- 183) pg/g after 48 h, respectively; IFN-gamma level was (1888 +/- 545) pg/g, (1 347 +/- 405) pg/g, and (913 +/- 303) pg/g after 24 h, and (3027 +/- 667) pg/g, (2062 +/- 795) pg/g, and (1001 +/- 301) pg/g after 48 h, respectively.(1) The excessive production of TH1 type cytokines TNF-alpha and IFN-gamma may involve in the pathogenesis of ICP; (2) TGF-beta2 may exert immunoprotection effect through inhibiting the production of TNF-alpha and IFN-gamma.

To investigate the clinical characteristics of intrahepatic cholestasis of pregnancy (ICP).Totally 1241 cases of ICP during the 10 years from Jan 1991 to Dec 2000 in our hospital were retrospectively reviewed.Forty-four (3.5%) patients were multiple gestation. One hundred and one (8.1%) patients had pregnancy induced hypertension. ICP recurred in 30.2% multipara (38/126). On average, it occurred at gestational week of 32.6. Pruritus was the first symptom in 1201 (96.8%) patients while 8 (0.6%) patients had jaundice and 28 (2.3%) patients had abnormal liver function at the onset. Serum total bile acid (TBA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were usually mild or moderately elevated, while some patients had normal TBA (17.7%), ALT (15.6%), or AST (17.1%) level. The albumin/globulin ratio was reversed in 35 (3.2%) patients.ICP tends to recur in subsequent pregnancy. It is more likely to develop in multiple gestation. Pruritus is the most common and prominent manifestation. Elevated TBA and ALT or AST level is helpful for diagnosis. It should be noted that the above manifestations might not be typical in some patients.