Hydrogen Sulfide Inhibits Chronic Unpredictable Mild Stress-Induced Depressive-Like Behavior by Upregulation of Sirt-1: Involvement in Suppression of Hippocampal Endoplasmic Reticulum Stress.

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.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Cerebral venous sinus thrombosis in pregnancy: A case report.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare but life-threatening disease in pregnant women. Anticoagulation is the first-line therapy for CVT management. However, some patients have poor outcomes despite anticoagulation. Currently, the endovascular treatment of CVT in pregnant women remains controversial. We report a rare case of CVT in a pregnant woman who was successfully treated with two stent retriever devices. CASE SUMMARY: The patient was a 29-year-old pregnant woman. She was first diagnosed with hyperemesis gravidarum due to severe nausea and vomiting for one week. As the disease progressed, she developed acute left hemiplegia. Imaging confirmed the diagnosis of superior sagittal sinus, right transverse sinus and sinus sigmoideus thrombosis. As anticoagulant therapy was ineffective, she underwent thrombectomy. After the mechanical thrombectomy, her headache diminished. Three weeks later, the patient was completely independent. At a 3-mo follow-up, no relapse of symptoms was observed. CONCLUSION: Mechanical thrombectomy may be an effective alternative therapy for CVT in pregnant women if anticoagulation therapy fails.

Leptin mediates protection of hydrogen sulfide against 6-hydroxydopamine-induced Parkinson's disease: Involving enhancement in Warburg effect.

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.

Different protein expression patterns in rat spinal nerves during Wallerian degeneration assessed using isobaric tags for relative and absolute quantitation proteomics profiling.

Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a labeling technique termed isobaric tags for relative and absolute quantitation to investigate the protein profiles of spinal nerve tissues from Sprague-Dawley rats. In response to Wallerian degeneration, a total of 626 proteins were screened in sensory nerves, of which 368 were upregulated and 258 were downregulated. In addition, 637 proteins were screened in motor nerves, of which 372 were upregulated and 265 were downregulated. All identified proteins were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of bioinformatics, and the presence of several key proteins closely related to Wallerian degeneration were tested and verified using quantitative real-time polymerase chain reaction analyses. The differentially expressed proteins only identified in the sensory nerves were mainly relevant to various biological processes that included cell-cell adhesion, carbohydrate metabolic processes and cell adhesion, whereas differentially expressed proteins only identified in the motor nerves were mainly relevant to biological processes associated with the glycolytic process, cell redox homeostasis, and protein folding. In the aspect of the cellular component, the differentially expressed proteins in the sensory and motor nerves were commonly related to extracellular exosomes, the myelin sheath, and focal adhesion. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways. In conclusion, the present study screened differentially expressed proteins to reveal more about the di?erences and similarities between sensory and motor nerves during Wallerian degeneration. The present findings could provide a reference point for a future investigation into the differences between sensory and motor nerves in Wallerian degeneration and the characteristics of peripheral nerve regeneration. The study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. 2016-x9-07) in September 2016.

[Association between CYP1A1 gene polymorphism and intrahepatic cholestasis of pregnancy].

OBJECTIVE: To study the relationship between CYP1A1 genetic polymorphism and intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China. METHODS: 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. RESULTS: There was no significant correlation between MspI polymorphism and ICP susceptibility (P>0.05). However, the Ile/Val+Val/Val genotypes of CYP1A1 significantly increased the risk of ICP (P=0.047, OR=1.768). CONCLUSION: 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.

[The expression of human leukocyte antigen G and E on human first trimester placenta and its relationship with recurrent spontaneous abortion].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association of Bone Turnover Levels with MTHFR Gene Polymorphisms among Pregnant Women in Wuhan, China.

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<0.05) and 0.104 (P<0.01) of all the participants and the pregnant women, respectively. The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels (standardized ß=0.091,P<0.01) than the 1793GG/GA carriers among all the subjects. Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 (P<0.01) and 0.179 (P<0.01), respectively. Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 (P<0.05) and 0.125 (P<0.01), respectively. In conclusion, homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women. The MTHFR gene A1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.

[Expression of human leucocyte antigen G on human placenta and its gene polymorphism in relation to intrahepatic cholestasis of pregnancy].

OBJECTIVE: 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). METHODS: 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). RESULTS: (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 (P < 0.05). No significant differences were found between normal control group and ICP group with dexamethasone treatment (P > 0.05). (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 (P > 0.05). CONCLUSIONS: 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.

[A clinical analysis of intrahepatic cholestasis of pregnancy in 1241 cases].

OBJECTIVE: To study the clinical features and diagnosis of intrahepatic cholestasis of pregnancy (ICP). METHODS: During the last 10 years 1241 cases of ICP stayed in our hospital. Their clinical data were retrospectively reviewed. RESULTS: 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. CONCLUSION: 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.

[Expression of HIF-1alpha mRNA and HIF-2alpha mRNA in placentas of pregnant women with intrahepatic cholestasis of pregnancy].

OBJECTIVE: To investigate the expression of HIF-1alpha mRNA and HIF-2alpha mRNA in placentas of pregnant women with intrahepatic cholestasis of pregnancy(ICP). METHODS: 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. RESULTS: 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 (P > 0.05). CONCLUSION: 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.

[Action of corticotropin-releasing hormone on its own receptor type-1 in human placenta].

OBJECTIVE: To investigate the expression of corticotropin-releasing hormone and its receptor type-1 in human placental tissues during caesarian operations. METHODS: 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. RESULTS: Positive expressions of both CRH and CRH-R1 messenger ribonucleic acid and peptide were found in the placental tissues, but the later was stronger (P<0.05). CONCLUSION: 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.

[The preliminary study on cord blood lymphocytes apoptosis in patients with intrahepatic cholestasis of pregnancy].

OBJECTIVE: 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. METHODS: 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. RESULTS: The percentage of apoptotic CBLs in ICP patients were significantly lower than that in the normal pregnant women (P < 0.05). The FasL protein expression of CBLs in ICP patients was significantly higher than that in normal pregnant women (P < 0.05), but Fas and Bcl-2 protein expression were normal. CONCLUSION: The abnormal apoptosis of CBLs may influence the immune reaction of ICP patients, which does something in the pathogenesis of ICP.

[Relationship of human leucocyte antigen G, E with intrahepatic cholestasis of pregnancy].

OBJECTIVE: To investigate the relationship between human leucocyte antigen (HLA)-G, E and intrahepatic cholestasis of pregnancy (ICP). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea Pigs].

OBJECTIVE: 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. METHODS: Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group(n=10 in each group), and ten 18-month-old guinea pigs were allocated as elderly group. The AHL model was established by subcutaneous injection of D-galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for 15 min in the EA group while modeling, once daily for 6 weeks. After treatment, the latency of auditory brainstem response(ABR) Ⅲ wave was measured by a brain-stem evoked potentiometer. The expressions of COMT in the inferior colliculus and auditory cortex were detected by Western blot. RESULTS: 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(P<0.05). After the treatment, the latency of ABR Ⅲ wave was significantly shortened and the expressions of COMT in the inferior colliculus and auditory cortex were significantly increased in the EA group in comparison with the model group (P<0.05). CONCLUSIONS: 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.

Risk factors for low birth weight and preterm birth: A population-based case-control study in Wuhan, China.

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<0.034) were protective factors for LBW. Maternal hypertension (OR=3.36, 95% CI: 1.26-8.98, P=0.016), maternal high-risk pregnancy (OR=4.38, 95% CI: 3.26-5.88, P<0.001), maternal meal intake of only twice per day (OR=1.88, 95% CI: 1.10-3.20, P=0.021), and mother liking food with lots of aginomoto and salt (OR=1.60, 95% CI: 1.02-2.51, P=0.040) were risk factors for PB. BMI ≥24 kg/m2 of mother prior to delivery (OR=0.66, 95% CI: 0.47-0.93, P=0.018), distance of house from road ≥36 meters (OR=0.72, 95% CI: 0.53-0.97, P=0.028), and living in rural area (OR= 0.60, 95% CI: 0.37-0.99, P=0.047) were protective factors for PB. Our study demonstrated some risk factors and protective factors for LBW and PB, and provided valuable information for the prevention of the conditions among newborns.

[Association of genetic polymorphisms in human leukocyte antigen-DQA1 with intrahepatic cholestasis of pregnancy in Chengdu district].

OBJECTIVE: To explore the relationship between human leukocyte antigen-DQA1 (HLA-DQA1) allele gene polymorphism and intrahepatic cholestasis of pregnancy (ICP). METHODS: 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. RESULTS: The frequency of HLA-DQA1*0301 in normal pregnant women was markedly higher than that in the ICP group (P>0.05). 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. CONCLUSION: 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.

[An associated analysis of estrogen receptor 2 gene polymorphism linked with intrahepatic cholestasis of pregnancy].

OBJECTIVE: To investigate the relation ship of estrogen receptor 2 gene (ESR2) polymorphism associated with intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China. METHODS: 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. RESULTS: (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 (P>0.05). CONCLUSION: 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.

[Perinatal outcomes of intrahepatic cholestasis of pregnancy: analysis of 1210 cases].

OBJECTIVE: To study the perinatal outcomes of intrahepatic cholestasis of pregnancy (ICP). METHODS: The clinical data of 1210 cases of ICP in recent ten years were retrospectively analyzed. RESULTS: 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. CONCLUSION: 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).

[Study of fetal lymphocyte of intrahepatic cholestasis of pregnancy].

OBJECTIVE: To explore effect of fetal lymphocyte on pathogenesis of intrahepatic cholestasis of pregnancy (ICP). METHODS: 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. RESULTS: (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 (P < 0.05). (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 (P < 0.05). (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. CONCLUSIONS: (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.