[Correlation between hepatitis B virus infection and adverse pregnancy outcomes-a systematic review and meta-analysis].

Objective: To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes. Methods: We searched PubMed, Embase, Web of Science, and Cochrane databases. Two researchers independently screened the literature, extracted data, and evaluated the quality. Meta-analysis and cumulative meta-analysis were performed using R4.4.1 software. Fixed/random effects models were used to analyze heterogeneous and non-heterogeneous results. Heterogeneous modifiers were identified by subgroup analysis. Funnel plots and Peters' test were used to analyze potential publication bias. Results: A total of 48 studies involving 92 836 HBsAg-positive pregnant women and 7 123 292 HBsAg-negative pregnant women were included. In terms of adverse pregnancy outcomes, HBV infection was significantly correlated with the occurrence of gestational diabetes mellitus [odds ratio (OR)=1.34, 95% confidence interval (CI): 1.17-1.53] and intrahepatic cholestasis (OR=2.48, 95%CI: 1.88-3.29), with statistically significant differences. In terms of adverse neonatal outcomes, HBV infection was significantly correlated with the occurrence of neonatal asphyxia (OR=1.49, 95%CI: 1.20-1.86) and preterm birth (OR=1.22, 95%CI: 1.12-1.33), with statistically significant differences. In addition, the cumulative meta-analysis demonstrated that the risk of gestational diabetes mellitus and preterm birth both tended to be stable in pregnant women with HBV infection following 2009 and 2010, respectively. The supplementary questions answered for repeated studies had limited significance. Conclusion: Intrahepatic cholestasis, gestational diabetes mellitus, neonatal asphyxia, and preterm birth occurrence risk can be raised with HBV infection in pregnant women.

[Autosomal dominant hearing loss resulting from mutation in the GJB2 gene:nonsyndromic presentation in a Chinese family].

Objective:To investigate the genotype, phenotype and genetic features. The mutations in GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) were tested in a Chinese family with autosomal dominant nonsyndromic hearing loss. Method:Blood samples and clinical data of the proband and her partial family members were collected. DNA was extracted from the blood samples. The GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) mutations were analyzed by polymerase chain reaction(PCR) and direct sequencing. Result:Heterozygous mutation of GJB2 R75Q was identified in the proband and her mother. No mutation of other testing genes was detected. Conclusion:The R75Q mutation of the GJB2 gene cause autosomal dominant nonsyndromic deafness in the proband and her mother. Children can inherit the R75Q mutation from their parents, so the results of gene testing will be helpful for further guidance of procreation.

Astrocyte-derived estrogen enhances synapse formation and synaptic transmission between cultured neonatal rat cortical neurons.

Recent in vitro studies have found that astrocytes exert powerful control over the number of neuronal synapses, leading us to consider why glia can exert this control and what the underlying mechanism(s) may be. To understand the potential possibility, we studied the formation of synapses and synaptic function in primary rat cortical neurons. We found that primary cultured neonatal rat cortical astrocytes modulate synaptogenesis and synaptic function through producing and secreting estradiol into culture medium. The concentration of estradiol produced by pure cultured astrocytes increased in correspondence with the days of culture and the number of proliferating astrocytes, which peaked at 266+/-22 ng/l around day 14 of culture. When astrocyte-conditioned medium (ACM) was added into pure cultured cortical neurons, the number of synapses formed between cortical neurons increased by nearly sixfold. The mean frequency and the amplitude of mini-postsynaptic currents (mPSCs) increased from 13+/-4 events/min and 20.5+/-2 pA to 73+/-16 events/min and 29.1+/-3 pA, respectively. In the meantime, the level of estrogen receptor-alpha (ER-alpha) expressed on neonatal rat cortical neurons was significantly up-regulated. Moreover, the effect of ACM on synaptic formation and transmission was blocked by tamoxifen (estrogen receptor antagonist) in culture. After the treatment of tamoxifen, the number of synapses on neurons decreased from 79+/-9 to 32+/-3. The mean amplitude and frequency of mPSCs were also dropped to 24.5+/-2 pA and 35+/-10/min, respectively. Unexpectedly, exogenic estradiol can mimic the effect of ACM on synaptic formation and transmission. Finally, to understand whether astrocyte-derived estradiol regulates the synaptic transmission via presynapse, the release of presynaptic vesicle from neuron was monitored by FM 4-64 assay. The results showed that when ACM or exogenic estradiol was added into neurons, the kinetics of vesicle release speed are similar to that of neuronal cultured with astrocytes, which were faster than that of just pure neuronal cultures. These observations suggest that estrogen synthesized and secreted by astrocytes can regulate synapse formation and synaptic transmission.

The expression of ccn3 (nov) RNA and protein in the rat central nervous system is developmentally regulated.

AIMS: To establish the expression pattern of ccn3 (nov) in the central nervous system (CNS) of adult rats and to determine whether spatiotemporal variations in the expression of ccn3 (nov) are related to specific developmental stages and/or specific CNS functions. METHODS: The sites of ccn3 (nov) expression have been identified by in situ hybridisation using didoxigenin labelled cRNA and by the reverse transcription-polymerase chain reaction (RT-PCR). The rat CCN3 (NOV) protein was characterised by western blotting performed on brain extracts. The localisation of the CCN3 (NOV) protein in the brain was established by immunocytochemistry. RESULTS: Increased expression of ccn3 (nov) was detected in the developing brain of rats after birth, as shown by RT-PCR and immunocytochemistry analysis performed on a series of samples taken between day 5 (P5) and day 300 (P300), with a pronounced peak between P15 and P150, suggesting that CCN3 (NOV) might play a role in the maintenance or establishment of specific brain functions. The relatively high amounts of an N-terminal truncated CCN3 (NOV) related protein detected both in the brain tissues and cerebrospinal fluid suggested that post translational processing of CCN3 (NOV) might be particularly prevalent in the brain. Such processing might be of biological importance in the light of the previously reported growth stimulatory effects of N-terminal truncated CCN3 (NOV) isoforms. CONCLUSIONS: The postnatal differential expression of ccn3 (nov) in the brain of developing rats suggests that CCN3 (NOV) might be involved in the acquisition of specific functions. The rat species provides an as yet unequalled system for these studies. Because the CCN3 (NOV) protein is detected in restricted areas of the brain, it will be interesting to establish whether variations of ccn3 (nov) expression are associated with normal cognitive processes and whether ccn3 (nov) expression is affected by aging. In addition, because CCN3 (NOV) is found in the spinal cord and along the axonal processes, it will be of interest to determine the expression of the normal and truncated isoforms of CCN3 (NOV) in various pathological conditions, such as neurodegenerative diseases.

[A review of brain aromatase].

Aromatase catalyzes the conversion of androgen to estrogen. This enzyme has been primarily localized in the neurons of specific areas of limbic system and hypothalamus of the brain. Astrocytes may also express this enzyme. Studies show that the gene expression of aromatase is driven by multiple tissue-specific exons, and the effective concentration of brain estrogen depends on the expression of brain aromatase. The locally produced estrogen plays an important role in the regulation of synaptogenesis, density of dendritic spine and the expression of neurotrophic factors and/or their receptors. Estrogen can also protect brain cells from the damages of neurotoxins and can greatly improve the deficits of learning and memory resulted from neurodegenerative disorders such as Alzheimer's diseases.

[Relationships between learning and memory and expression of nov gene of rats].

During the establishment of learning and memory of adult rats with active avoidance reaction expression of nov gene, nov mRNA positive neurons and NOV protein immunoreactive neurons were found in hippocampus, cingulate cortex, globus pallidus, caudate putamen and hypothalamus. The strongest positive reaction of NOV protein was observed in high ability group of learning and memory (HALM). Basic expression was found in pseudoconditioning (PC) group. The expression of NOV protein was higher in low ability group of learning and memory (LALM) than in PC group. No significant difference was detected in nov mRNA positive reaction between the three groups. The results indicate that nov gene may play an important role in learning and memory of adult rats. This regulation occurs at the level of NOV protein translation.

Quantitative analysis of calcitonin gene-related peptide- and neuropeptide Y-immunoreactive nerve fibers in mesenteric blood vessels of rats irradiated with cobalt-60 gamma rays.

The effects of 60Co gamma rays on calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers and neuropeptide Y (NPY)-immunoreactive nerve fibers were examined in mesenteric blood vessels of rats. Using a free-floating immunostaining streptavidin-biotin peroxidase complex method combined with a nickel-enhancement technique, we found that the distribution pattern of these two peptidergic nerve fibers in superior mesenteric arteries and superior mesenteric veins did not change, while the densities of CGRP-immunoreactive nerve fibers and NPY-immunoreactive nerve fibers in superior mesenteric arteries and veins varied with the time after irradiation. The results suggested that CGRP and NPY may be important in the development and elimination of radiation-induced injury.

A developmental study of novH gene expression in human central nervous system.

The expression pattern of the human nephroblastoma overexpressed (novH) gene in the fetal human central nervous system was examined by in situ hybridization using digoxigenin-labeled novH-specific riboprobes. In the spinal cord, the nov-expressing neurons were first detected both in the ventral region at 16 weeks of gestation (G16W) and in the dorsal region at G38W. In the medulla, nov-expressing neurons were detected in the principal nucleus of the inferior olive, the hypoglossal nucleus and the dorsal motor nucleus of vagus at G16W. Nov-positive neurons were detected at G28W in the nucleus of the spinal tract of the trigeminal and cuneate nucleus, and at G38W in the abducens nucleus of pons, the red nucleus and the substantia nigra of the midbrain, the ventral posterolateral and the mediodorsal thalamic nucleus. A strong labeling was also detected in the striatum of the cerebrum and the cerebral cortex of the parietal lobe. These data established that novH is mainly expressed in somato-motor neurons in the lower central nervous system at early developmental stages and in the higher central nervous system at later stages, suggesting that nov may play an important role in neuronal differentiation.

[Somatostatin inhibited pain modulation action of substance P in spinal cord].

In the present study, the effect of somatostatin (SST) on pain modulation induced by substance P in spinal cord was studied. The results showed that intrthecal injection of SST increases pain threshold, prevented pain response and c-fos expression in spinal cord induced by SP. Injection of formalin in the hindpaw induced pain response and increased the SP-LI, which could be inhibited by injection of SST. It is suggested that the analgesic effect of SST may be resulted from the inhibition of the noxious response induced by SP.

A study of the ultrastructure of developing human umbilical vessels.

Electron microscopic techniques were used to examine the ultrastructure of developing human umbilical arteries and vein (8-12, 13-17 and 37-40 wk gestational age). These showed that with increasing age there is (1) an increase in the size of the lumen and the thickness of the media; (2) an increase in the ratio of contractile smooth muscle phenotypic cells; (3) an increase in the myofilament content of the smooth muscle cells and the number of Weibel-Palade bodies; (4) a decrease in the glycogen content; (5) an appearance of microvilli on the luminal surface of the endothelium. Lipid vesicles, nerves and vasa vasorum were not observed in any region of the umbilical vein or arteries.

Effect of 5-HT on pain modulation of substance P in spinal cord of rats.

AIM: To study the effect of serotonin (5-HT) on pain modulation of substance P (SP) in spinal cord of rats. METHODS: Using immunohisto-chemistry and measurement of pain threshold. RESULTS: The c-fos expression evoked by intrathecal injection (it) SP 10 micrograms and sc 5% formaldehyde (For) 150 microL in the hindpaw was densely distributed in the laminae I, II, V, and VI of spinal dorsal horn. The pain threshold in the SP group was decreased while the pain intensity rating measured by behavioral method in the For group was increased. The c-fos expression induced by it 5-HT 20 micrograms was mostly distributed in the spinal dorsal horn in laminae III-IV and the pain threshold was increased. SP and For induced c-fos expressions in the spinal cord and the pain responses were reduced by 5-HT and increased by 5-HT depletor fenclonine 300 mg.kg-1. CONCLUSION: SP mainly played an algogenesia in the spinal cord. 5-HT inhibited the c-fos expression in the spinal cord evoked by SP and participated in pain modulation of SP.

Colocalization of vasoactive substances in the endothelial cells of human umbilical vessels.

Human umbilical vessels are unique in lacking any innervation; thus endothelial cells may play the major role in local control and regulation of the blood flow. In the present study, we examined ultrathin sections of cultured human umbilical vein endothelial cells and tissue preparations of umbilical vein and artery, immunostained by the post-embedding colloidal gold double-labelling technique. We observed colocalization of atrial natriuretic peptide and neuropeptide Y, as well as colocalization of atrial natriuretic peptide and neuropeptide Y with other vasoactive substances, namely, vasoactive intestinal peptide, substance P, calcitonin gene-related peptide and arginine vasopressin. The functional significance of the colocalization of these vasoactive substances in the human umbilical vessel endothelial cells is discussed.

Endothelium of human umbilical blood vessels: ultrastructural immunolocalization of neuropeptides.

Endothelial cells of human umbilical vein and artery, both in situ and in culture, were examined ultrastructurally and at the light-microscope level using either the pre-embedding peroxidase-antiperoxidase or avidin-biotin peroxidase complex immunostaining techniques. Vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and arginine-vasopressin (AVP) immunoreactivity were localized in subpopulations of endothelial cells of the term umbilical vein and artery. The percentage of VIP-, SP-, CGRP- and AVP-immunoreactive cells in the umbilical vein was 12, 10, 11, and 7.5%, respectively, out of a total of 5,364 cells (from 15 umbilical cords) examined. The artery contained fewer VIP-, SP-, and CGRP-immunoreactive cells, but more AVP-immunoreactive cells, than the vein. In conclusion, subpopulations of endothelial cells in the human umbilical vein and artery contain the neuropeptides VIP, SP, CGRP and AVP, although their physiological roles are not yet known.

In situ hybridization of atrial natriuretic peptide mRNA in the endothelial cells of human umbilical vessels.

The localization of mRNA encoding preproatrial natriuretic peptide (ANP) was investigated in cultured human umbilical vein endothelial cells (HUVEC) and tissue preparations of umbilical vein and artery. The techniques used were in situ hybridization and in situ hybridization combined with immunocytochemistry, using 32P-radiolabelled and non-radioactive digoxigenin labelled complementary RNA probes. Human ANP mRNAs are mainly localized in the endothelial cells of the umbilical vein and, to a lesser extent, in the endothelial cells of the umbilical artery. The autoradiographic labelling and the intensity of digoxigenin staining were significantly reduced by treatment with RNase before in situ hybridization. This study provides unequivocal evidence for the expression of the ANP gene in the endothelial cells of human umbilical vessels, confirming that these endothelial cells have the ability to synthesize this peptide. The functional significance of the presence of the ANP mRNA in the endothelial cells of human umbilical vessels is discussed.

Localization of neuropeptide Y and atrial natriuretic peptide in the endothelial cells of human umbilical blood vessels.

The localization of neuropeptide Y (NPY) and atrial natriuretic peptide (ANP) in the endothelial cells of human umbilical blood vessels was studied using the pre-embedding peroxidase-antiperoxidase (PAP) technique for electron microscopy and avidin-biotin-complex (ABC) immunostaining for endothelial cells cultured from umbilical vein. Subpopulations of NPY- and ANP-immunoreactive endothelial cells were present in term umbilical vein and artery. The umbilical vein contained more positive cells than the artery. The percentage of NPY- and ANP-immunoreactive umbilical vein cells in culture was 32% and 44%, respectively, out of a total of 3013 cells examined. The possibility that these potent vasoactive substances located in the endothelial cells of the non-innervated umbilical vessels are involved in the local regulation of blood flow is discussed.

Structure and innervation of the musculature at the gastroduodenal junction of the guinea-pig.

The musculature of the pylorus of the guinea-pig consists of a conspicuous ring of circular musculature. On one side, this tissue is apposed to the circular muscle layer of the duodenum, a complete septum of connective tissue intervening between the two muscles. On the other side, it is in continuity with the circular musculature of the gastric antrum. Bundles of longitudinal muscle, running close to the submucosa of the antrum, form a loop and contribute to the circular musculature of the pylorus. The subserosal longitudinal muscle of the antrum continues into the pylorus and the duodenum. The density of innervation, i.e. number of bundles, number of axons and percentage of varicosities per unit sectional area or per number of muscle cell profiles (estimated on large photographic montages of transversely sectioned muscles) is higher in the pylorus than in the duodenum, and is lowest in the antrum. In the duodenum nerve bundles occur in both the circular and the longitudinal muscle layer; the majority of axons and varicosities are situated between the bulk of the circular muscle and a layer of special muscle cells adjacent to the submucosa.

Catecholamine-containing cells in the nerve plexus of the guinea pig gallbladder.

A population of catecholamine-containing cells, broadly belonging to the class of small intensely fluorescent (SIF) cells, was observed in the ganglionated plexus and around blood vessels of the guinea pig gallbladder. Their morphological features were studied by fluorescence and electron microscopy. Some cells were closely associated with ganglion neurons within the ganglionated plexus. Others were clustered into small groups located along blood vessels. Counts carried out on the whole gallbladder showed that these cells varied greatly in number between individuals and that they were most numerous shortly after birth (on average 230 cells). In the adult, their average number was about 30.