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Background and aims: Several articles demonstrated that non-steroidal anti-inflammation drugs (NSAIDs) were effective in reducing the incidence of pancreatitis after endoscopic retrograde c...

Acid rain is a serious environmental problem in China, caused by the urbanization and industrialization. We used recent acid rain and urban pollutant emissions data from the eastern coastal Jiangsu province to analyze the spatial distribution of acid rain. Further, we analyzed the regional air pollution data of the commission discharge atmospheric research database (EDGAR) regional air pollution data and developed a back-trajectory model for the cluster analysis of the air mass transfer characteristics of acid rain. The results show that from 2007 to 2013 the precipitation pH were high in northern and low in southern parts of Jiangsu Province. The average precipitation pH in the northwest and northeast parts were higher than 5.6; the frequency of acid rain in the area south of the Huaihe River accounted for more than 50% of total rainfall samples. Precipitation conductive in the northwest and southwest was greater than 60 μs/cm. The SO2, NOX, and PM10 were lower in the northern part and higher in the southern part. The northern part has higher pH and lower emission of precursors. One likely source for high ammonium and calcium concentration is local soil. From the northwest air mass, the acid rain appeared to have the highest average pH and the air mass from the southwest had the highest percentage of acid rain. The local emission (SO2, NOX, and Dust) reduction from 2005 led the haze and the acid rain problems mitigated to a good trend. The haze day increase and acid rain decrease due to the NH4+, and Ca2+ increase, and the long-distance transmission and the alkaline pollutant played an important role in Jiangsu' acid rain problem and haze since 2009.

Enhancer of zeste homolog 2 (EZH2) is a highly conserved histone methyltransferase, which is overexpressed in different types of cancers such as breast and prostate cancer. It is reported that EZH2 can directly down-regulate RUNX3 by increasing histone H3 methylation. However, the role of EZH2 in the development and progression of laryngeal carcinoma has not yet been investigated, and the relationship between EZH2 and RUNX3 in laryngeal carcinoma is rarely reported. The current study aims to determine the role of EZH2 in the progression of laryngeal carcinoma, and investigate the interaction between EZH2 and the tumor suppressor RUNX3. Our study found that EZH2 is overexpressed in laryngeal carcinoma patients, and silencing EZH2 by EZH2 siRNA significantly inhibited the proliferation of laryngeal carcinoma cells. Besides, we also found that RUNX3 is repressed in laryngeal carcinoma patients. Moreover, RUNX3 as a downstream target protein of EZH2 is up-regulated by EZH2 siRNA accompanied by a decrease in the trimethylation modification pattern of H3K27. RUNX3 siRNA inhibits the decreased proliferation induced by EZH2 siRNA. Furthermore, β-catenin protein expression is down-regulated by EZH2 siRNA and up-regulated by RUNX3 siRNA, and RUNX3 siRNA inhibits the down-regulation effect of EZH2 siRNA on β-catenin protein expression. Additionally, the Wnt/β-catenin activator BIO reverses the inhibitory effect of EZH2 siRNA on Hep-2 cell proliferation. Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/β-catenin signaling pathway in laryngeal carcinoma.

Maternal genes play an important role in the early embryonic development of the silkworm. Early embryonic development without new transcription depends on maternal components stored in the egg during oocyte maturation. The maternal-to-zygotic transition (MZT) is a tightly regulated process that includes maternal mRNAs elimination and zygotic transcription initiation. This process has been extensively studied within model species. Each model organism has a unique pattern of maternal transcriptional clearance classes in MZT. In this study, we identified 66 maternal genes through bioinformatics analysis and expression analysis in the eggs of silkworm virgin moths (Bombyx mori). All 66 maternal genes were expressed in vitellogenesis in day eight female pupae. During MZT, the degradation of maternal gene mRNAs could be divided into three clusters. We found that eight maternal genes of cluster 1 remained stable from 0 to 3.0 h, 17 maternal genes of cluster 2 were significantly decayed from 0.5 to 1.0 h and 41 maternal genes of cluster 3 were significantly decayed after 1.5 h. Therefore, the initial time-point of degradation of cluster 2 was earlier than that of cluster 3. The maternal gene mRNAs decay of clusters 2 and 3 is first initiated by maternal degradation activity. Our study expands upon the identification of silkworm maternal genes and provides a perspective for further research of the embryo development in Bombyx mori.

Preeclampsia (PE) exerts a more intense systemic inflammatory response than normal pregnancy. Recently, the role of the cholinergic anti-inflammatory pathway (CAP) in regulating inflammation has been extensively studied. The aim of this study was to investigate the effect of nicotine, a selective cholinergic agonist, on lipopolysaccharide (LPS)-induced preeclampsia-like symptoms in pregnant rats and to determine the molecular mechanism underlying it.Rats were administered LPS (1.0 μg/kg) via tail vein injection on gestational day 14 to induce preeclampsia-like symptoms. Nicotine (1.0 mg/kg/d) and α-bungarotoxin (1.0 μg/kg/d) were injected subcutaneously into the rats from gestational day 14-19. Clinical symptoms were recorded. Serum and placentas were collected to determine cytokine levels using Luminex. The mRNA and protein expression levels of α7 nicotinic acetylcholine receptor (α7nAChR) were determined using Real time-PCR and Western blot analysis. Immunohistochemistry was performed to determine the level of activation of nuclear factor-κB (NF-κB) in placentas.Nicotine significantly ameliorated LPS-induced preeclampsia-like symptoms in pregnant rats (P 0.05). Nicotine treatment decreased the levels of LPS-induced pro-inflammatory cytokines in the serum (P 0.05) and placenta (P 0.05). Nicotine significantly increased the expression of α7nAChR (P 0.01) and attenuated the activation of NF-κB p65 in the placenta in LPS-induced preeclampsia (P 0.01). Meanwhile, these protective effects of nicotine were abolished by the administration of the cholinergic antagonist α-bungarotoxin in preeclampsia rats.Our findings suggest that the activation of α7nAChR by nicotine attenuates preeclampsia-like symptoms, and this protective effect is likely the result of the inhibition of inflammation via the NF-κB p65 pathway.

High transparent and biocompatible hydrogel dressing with bioactivity is attractive for clinical skin repair. Here we report a high optically transparent interpenetrating network (IPN) hydrogel that was fabricated by sericin and polyacrylamide. The hydrogels possess pH-dependent degradation as well as high porosity and porous structures with different sized diameters and distribution. Moreover, the swelling behaviors, degradation dynamics, and mechanical strength can be flexibly regulated by adjusting the content of sericin. In addition, the hydrogel system is compatible with hosting cells owing to its excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival. Together, our study demonstrates that the sericin-polyacrylamide interpenetrating network hydrogel may serve as a visualized dressing material for real-time monitoring of wounds.

Rationale: Because of the lack of an antidote or effective treatment, patients with severe acute diquat and glyphosate poisoning always died within a few hours. Extracorporeal membrane pulmonary oxygenation (ECMO), as an artificial heart-lung supporting system, can be applied to support lung that is expected to recover from reversible pathological damage. However, to our knowledge, the application of ECMO for patients with diquat and glyphosate poisoning has not been reported. Patient concerns: A 40-year-old man ingested in 100 ml of diquat (20 g/100 ml) and 400 ml glyphosate (41 g/100 ml) was admitted to the intensive care unit (ICU), immediately complicated by the development of ventricular fibrillation, respiratory failure, renal failure, and multi-organ failure. Diagnosis: Diquat and glyphosate poisoning were diagnosed by stated ingestion history, and the diagnostic criteria for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction syndrome were also met. Interventions: He was treated with veno-venous ECMO. Outcomes: He was successfully transferred out of the ICU on day 46 and discharged on day 67. The computed tomography scan showed no obvious pulmonary fibrosis 2 months after poisoning. Lessons: ECMO may be effective in the treatment of patients with severe ARDS caused by diquat and glyphosate poisoning when conventional management does not work.

Probiotic supplementation in early life may be effective in preventing atopic dermatitis (AD); however, results regarding efficacy have been controversial. The aim of our study was to investigate the effect of probiotic supplementation on the risk of AD. We systematically searched PubMed, EBSCO, Embase and Web of Science databases up to 8 March 2018 for potentially relevant studies regarding probiotic supplementation and AD. Included infants and children were those with probiotic exposure in utero and/or after birth who were not previously diagnosed with AD. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) and used the Jadad and Newcastle–Ottawa scales to assess methodologic quality. A total of 28 studies met the inclusion criteria. Compared with controls, probiotic treatment was associated with a reduced risk of AD (OR 0.69; 95% CI 0.58–0.82, P

Objective: Head and neck squamous cell carcinoma (HNSCC) represents as a common malignancy with increasing incidence in the worldwide. The fact of its poor survival rate urgently requires developing efficient predictive biomarkers for clinical use. MicroRNAs (miRNAs) recently represent as a novel direction for early diagnosis and prognosis prediction in HNSCC therapy. In this study, we comprehensively investigated the function and putative target of miRNA-451 in vitro. Methods: The expression of miRNA-451 was detected in HNSCC tissues and cell lines by real-time PCR. Forced expression or inhibition of miRNA-451 was done by transient transfection of mimics or inhibitor of miRNA-451 into indicated cells, respectively. Cell proliferation was evaluated by cell counting and crystal staining. Afterwards, we perform western blot to verify the expression of the miRNA-451 predicted target, c-myc, after miRNA-451 was overexpressed. Results: We showed that miRNA-451 was downregulated in paired HNSCC tissues as well as in cell lines. And overexpression of miRNA-451 in cells with low endogenous expression of miRNA-451 accelerated proliferation. To the contrast, knockdown of miRNA-451 in cells with high levels of miRNA-451 significantly reduced cell growth rate. Furthermore, we used bioinformatics and cellular methods to predict and prove that c-myc was targeted by miRNA-451, since forced expression of miRNA-451 leaded to decreased c-myc protein expression in HNSCC cells. Conclusion: Our findings identify miRNA-451 as a potential biomarker and suggest a key role of miRNA-451-c-myc pathway in HNSCC cell transformation, which could represent a novel therapeutic strategy in HNSCC treatment.

Background & Aims Recent several studies suggested that nonsteroidal anti-inflammation drugs (NSAIDs) could prevent the pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the routes of administration, the dosages of NSAIDs and the potential efficacy in reducing the severity of pancreatitis remain controversial. The aim of this meta-analysis was to evaluate the efficacy of NSAIDs for post-ERCP pancreatitis (PEP) prophylaxis. Methods We systematically searched PubMed, Embase, EBSCO, elsevier and web of science databases up to October 1, 2016 for relevant studies. Results A total of 24 studies were met the inclusion criteria. Compared to the controls, the risk of pancreatitis was much lower in the NSAIDs group (OR= 0.57, 95%CI: 0.48-0.67, P< 0.0001). However, NSAIDs were not effective in reducing the risk of moderate to severe pancreatitis compared with placebo (OR=0.75, 95%CI: 0.57-1.00). In the subanalyses, rectal administration was the only effective route (OR=0.51, 95%CI: 0.42-0.62), and the risk of PEP was reduced in both randomized controlled trials (RCTs) (OR=0.63, 95%CI: 0.52-0.76) and case-control articles (C-Cs) (OR=0.40, 95%CI: 0.28-0.58). Conclusions Prophylactic administration of NSAIDs reduced the incidence of PEP in both RCTs and C-Cs, especially when rectally administered, but was not effective in reducing the risk of moderate to severe pancreatitis. This article is protected by copyright. All rights reserved.

Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of preeclampsia and a leading cause of maternal and fetal mortality worldwide. Presently, magnesium sulfate (MgSO4) is the most effective treatment, but the mechanism by which MgSO4 prevents eclampsia has yet to be fully elucidated. We previously showed that systemic inflammation decreases the seizure threshold in a rat eclampsia-like model, and MgSO4 treatment can decrease systemic inflammation. Here, we hypothesized that MgSO4 plays a neuroprotective role in eclampsia by reducing neuroinflammation and brain edema. Pregnant Sprague-Dawley rats were given an intraperitoneal injection of pentylenetetrazol following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. Seizure activity was assessed by behavioral testing. Neuronal loss in the hippocampal CA1 region (CA1) was detected by Nissl staining. Cerebrospinal fluid levels of S100-B and ferritin, indicators of neuroinflammation, were detected by enzyme-linked immunosorbent assay, and ionized calcium binder adapter molecule 1 (Iba-1, a marker for microglia) and glial fibrillary acid protein (GFAP, a marker for astrocytes) expression in the CA1 area was determined by immunofluorescence staining. Brain edema was measured. Our results revealed that MgSO4 effectively attenuated seizure severity and CA1 neuronal loss. In addition, MgSO4 significantly reduced cerebrospinal fluid levels of S100-B and ferritin, Iba-1 and GFAP activation in the CA1 area, and brain edema. Our results indicate that MgSO4 plays a neuroprotective role against eclampsia-like seizure by reducing neuroinflammation and brain edema.

To investigate the effect of patient-controlled epidural analgesia (PCEA) on uterine electromyography (EMG) activity in term pregnant women during labor.Nulliparous pregnant women in spontaneous term labor (N = 30) were enrolled (PCEA group, n = 20 and control group, n = 10). Five time periods (30 minutes each) were defined for noninvasive abdominal recordings and analysis of uterine EMG activity, that is, period I: before PCEA treatment with 2-cm cervical dilation; periods II to IV: each period successively at 30, 60, and 120 minutes after PCEA; and period V: second stage of labor with cervix at 10 cm dilation. Control patients without PCEA were monitored during the same times. The number of bursts/30 min, power density spectrum peak frequency, mean amplitude, and duration of uterine EMG bursts were measured to assess uterine EMG activity. Maternal, fetal, and labor characteristics were also recorded. Data were analyzed by analysis of variance followed by other tests.Electromyography parameters are significantly lower (P.001) after PCEA (periods II to IV) compared to controls but similar between groups by period V (P.05). Also, patients with PCEA have a slower rate of cervical dilation (P.003, period IV only) and longer labor in both stage 1 and stage 2 (P.05). All patients have similar (P.05) positive labor outcomes.Patient-controlled epidural analgesia initially suppresses uterine EMG and slows cervical dilation thereby prolonging labor. However, the EMG activity recovers with labor progress with no effects on delivery outcomes.

Cranial fixation should be safe, reliable, ideally degradable, and produce no hazardous residues and no artifacts on neuroimaging. Protein-based fixation devices offer an exciting opportunity for this application. Here, the preclinical development and in vivo efficacy verification of a silk cranial fixation system in functional models are reported by addressing key challenges toward clinical use. A comprehensive study on this fixation system in rodent and canine animal models for up to 12 months is carried out. The silk fixation system shows a superb performance on the long-term stability of the internal structural support for cranial flap fixation and bone reconnection and has good magnetic resonance imaging compatibility, and tolerability to high dose radiotherapy, underscoring the favorable clinical application of this system for neurosurgery compared to the current gold standard.

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

BACKGROUND: Despite the tight correlation between T-type Ca2+ channels and a great variety of tumors, the roles of alpha1G subunit of T-type Ca2+ channels in laryngeal squamous cell carcinoma (LSCC) have not yet been investigated. METHODS: In the present study, we examined the expression of alpha1G subunit of T-type Ca2+ channel in human LSCC tissues and cell lines. One human laryngeal squamous cell carcinoma cell line, Hep-2, was also examined for T-type channels using voltage-clamp recordings. Cell proliferation assays were performed in the presence or absence of T-type channel blocker mibefradil and alpha1G subunit sepcific siRNA. The cell cycle was determined by flow cytometry. RESULTS: Our results indicated that the a1G subunit of T-type Ca2+ channel is highly expressed in human laryngeal squamous cell carcinoma tissues and cell lines. alpha1G siRNA significantly down-regulated the protein expression of the alpha1G subunit. Both alpha1G siRNA and mibefradil inhibited Hep-2 cell proliferation and arrested cell cycle progression. CONCLUSIONS: Together, these findings suggest a functional role of T-type channels in certain laryngeal carcinomas, and that inhibition of T-type channels reduces cell proliferation via cell cycle arrest, suggesting that the alpha1G subunit of T-type Ca2+ channel may be used as a therapeutic target for treating LSCC.

Introduction Pre-eclampsia (PE) exerts more intense systemic inflammatory response than normal pregnancy. We have demonstrated that the cholinergic anti-inflammatory pathway may contribute to the relief of Pre-eclampsia through α 7 nicotinic acetylcholine receptor ( α 7 nAChR). Furthermore, choline, an essential nutrient that is meanwhile a selective α 7 nAChR agonist, has been proved to prevent LPS-induced preeclampsia symptoms in rats. Objectives The objective of the study was to examine the effects of choline, an essential nutrient that is meanwhile a selective α 7 nAChR agonist, on the prevention of symptoms and inflammatory responses of preeclampsia in rats. Methods Preeclampsia model was induced by lipopolysaccharide (1.0 μ g/kg) via tail vein injection on gestational day (GD) 14. Pregnant SD rats were placed on a supplemented (5.0 g/kg diet) or normal (1.1 g/kg diet) choline diet throughout gestation. All the rats were divided into 4 groups (P = normal pregnant +1.1 g/kg choline diet; P-CHOLINE = normal pregnant +5.0 g/kg choline diet; PE = LPS +1.1 g/kg choline diet; PE-CHOLINE = LPS +5.0 g/kg choline diet). Maternal blood and placentas were collected on GD20 and assayed for pro-inflammatory cytokines (TNF- α , IL-1 β , IL-6, IL-2, IL-17, IFN- γ , GM-CSF) and anti-inflammatory cytokines (IL-4, IL-10). Results LPS treatment significantly elevates maternal blood levels of TNF- α , IL-1 β , IL-6, IL-17, IFN- γ , GM-CSF and reduced the levels of IL-4. The blood levels of IL-2 and IL-10 show no significant differences between the P and PE group. Of interest, choline supplementation during pregnancy significantly inhibited LPS-induced release of TNF-a, IL-1 β , IL-6, IL-17, IFN- γ , except for GM-CSF , and increased the level of IL-4. Correspondingly, in placenta, the levels of TNF- α , IL-1 β , IL-6, IL-17, GM-CSF and IL-2 were significantly increased after LPS administration, while the level of IL-4 was significantly decreased. The placenta levels of IFN- γ and IL-10 show no significant differences between the P and PE group. Similarly, choline supplementation during pregnancy significantly attenuated LPS-induced TNF- α , IL-1 β , IL-6 and IL-17 concentrations, except for IL-2, meanwhile, increased the level of IL-4. Conclusions Choline supplementation during pregnancy prevents the LPS-induced symptoms and inflammatory responses of preeclampsia in rats. These observations have important implications for prevention of inflammatory responses in preeclampsia.

Introduction Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ⩾20 weeks of gestation. Our previous study demonstrated that the cholinergic anti-inflammatory pathway may contribute to the relief of Pre-eclampsia through α7 nicotinic acetylcholine receptor (α7 nAChR). Choline, a selective α7 nAChR agonist, has recently been established as a promising treatment for inflammation. Objectives In order to examine the effects of gestational choline supplementation on LPS-induced pre-eclampsia symptoms in rats. Methods Pre-eclampsia model was induced by lipopolysaccharide (1.0 μ g/kg) via tail vein injection on gestational day (GD) 14. Pregnant SD rats were placed on a supplemented (5.0 g/kg diet) or normal (1.1 g/kg diet) choline diet throughout gestation. All the rats were divided into 4 groups (P = normal pregnant + 1.1 g/kg choline diet; P-CHOLINE = normal pregnant + 5.0 g/kg choline diet; LPS = LPS + 1.1 g/kg choline diet; LPS-CHOLINE = LPS +5.0 g/kg choline diet). Systolic blood pressure (SBP) was measured on GD 6,11,14,16 and 18. On GD 7, 12, 17, and 19, urine is collected for 24 h urinary albumin excretion measurements. On GD 20, dams were all sacrificed. Pups were then removed, counted and weighed. Percent of resorbed and malformation fetuses were also counted. Placental weights were measured. Results An injection with LPS on GD 14 resulted in higher blood pressure (GD 14 = 105 ± 1.5 mmHg VS GD 16 = 127 ± 0.9 mmHg; GD 18 = 130 ± 1.1 mmHg, P Conclusions Thus, choline supplementation during pregnancy protects against LPS-induced pre-eclampsia. This may provide a new potential prevention strategy for pre-eclampsia.

Introduction A considerable number of studies have demonstrated that nicotine, a α 7-nicotinic acetylcholine receptor ( α 7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. Objectives In the present study, possible anti-inflammation and neuro-protective effects of nicotine via α 7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. Methods Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14–19. Then, clinical symptoms were detected. Seizure severity was recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. Results Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF- α , IL-1 β , IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), dramatically increased Th1 cytokine (IL-4) and eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with α -bungarotoxin, a selective α 7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. Conclusion Our findings indicate that the administration of nicotine may increase eclampsia-like seizure threshold and attenuate microglial activity in rat hippocampus through the α 7 nicotinic receptor.

Background Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4. Methods A total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function. Results Of the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability. Conclusion An overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.

Objectives Eclampsia is defined as the development of seizure during pregnancy or postpartum in patients with signs and symptoms of preeclampsia. In general, the hypothesis that inflammation contributes to seizures is supported by some studies. In this study we will observe the effects of Cyclosporin A (CsA) in an eclampsia-like rat model. Methods Rats were administered lipopolysaccharide (1.0 mg/kg) by tail vein injection on gestational day 14 to establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal-pregnant, P) were injected intraperitoneally with PTZ (40 mg/kg) to induce seizures. CsA (5 mg/kg) was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures. Results PTZ successfully induced seizure activity in all groups. Latency to seizure was significantly ( P P P α and IL-17 in the PE-PTZ groups, and decreased ( P Conclusions Cyclosporin A may act as immune-modulators and anti-inflammatory therapies to attenuate seizure on an eclampsia-like rat model. Disclosures B. Hu: None. H. Liu: None. Y. Liu: None. J. Bao: None. J. Yang: None. G. Zhang: None. S.P. Brennecke: None.

Background Thirty thousand infants are born every year with congenital hearing impairment in mainland China. Racial and regional factors are important in clinical diagnosis of genetic deafness. However, molecular etiology of hearing impairment in the Tibetan Chinese population living in the Tibetan Plateau has not been investigated. To provide appropriate genetic testing and counseling to Tibetan families, we investigated molecular etiology of nonsyndromic deafness in this population. Methods A total of 114 unrelated deaf Tibetan children from the Tibet Autonomous Region were enrolled. Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT. A total of 106 Tibetan hearing normal individuals were included as genetic controls. For radiological comparison, 120 patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed by temporal CT. Results None of the Tibetan patients carried diallelic GJB2 or SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear malformation was made in 20.18% of the Tibetan patients and 21.67% of the Han deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity, was not found in theTibetan patients, but was seen in 18.33% of the Han patients. Common molecular etiologies, GJB2 and SLC26A4 mutations, were rare in the Tibetan Chinese deaf population. Conclusion The mutation spectrum of hearing loss differs significantly between Chinese Tibetan patients and Han patients. The incidence of inner ear malformation in Tibetans is almost as high as that in Han deaf patients, but the types of malformation vary greatly. Hypoxia and special environment in plateau may be one cause of developmental inner ear deformity in this population.

BackgroundCoat protein complex I (COPI) vesicles, coated by seven coatomer subunits, are mainly responsible for Golgi-to-ER transport. Silkworm posterior silkgland (PSG), a highly differentiated secretory tissue, secretes fibroin for silk production, but many physiological processes in the PSG cells await further investigation.Methodology/principal findingsHere, to investigate the role of silkworm COPI, we cloned six silkworm COPI subunits (α, β, β', δ, ε, and ζ-COP), determined their peak expression in day 2 in fifth-instar PSG, and visualized the localization of COPI, as a coat complex, with cis-Golgi. By dsRNA injection into silkworm larvae, we suppressed the expression of α-, β'- and γ-COP, and demonstrated that COPI subunits were required for PSG tube expansion. Knockdown of α-COP disrupted the integrity of Golgi apparatus and led to a narrower glandular lumen of the PSG, suggesting that silkworm COPI is essential for PSG tube expansion.Conclusions/significanceThe initial characterization reveals the essential roles of silkworm COPI in PSG. Although silkworm COPI resembles the previously characterized coatomers in other organisms, some surprising findings require further investigation. Therefore, our results suggest the silkworm as a model for studying intracellular transport, and would facilitate the establishment of silkworm PSG as an efficient bioreactor.

Objectives To investigate the clinical significance of TFPI-I and other coagulation factor (FII:C, FV:C, FVII:C, FVIII:C, FIX:C, FX:C, FXI:C, FXII:C) in women with placental abruption. Methods We used ELISA and clotting assays to examine the changes of TFPI-I and coagulation factors (FII:C, FV:C, FVII:C, FVIII:C, FIX:C, FX:C, FXI:C, FXII:C) in 5 women with placental abruption compared to 5 age-matched, healthy controls with normal vaginal deliveries. Results The levels of TFPI-1 (18.37 ± 2.61 ng/ml), FV:C (126.63 ± 36.27) and FX:C (117.11 ± 38.75) in placental abruption group were significantly lower than those in the control group (34.63 ± 2.09 ng/ml) (246.41 ± 93.02) (191.73 ± 47.36) ( P Conclusions Reduced activities of TFPI-1, FV:C, and FX:C in placental abruption may play an important role in the coagulation dysfunction of placental abruption. Disclosures J. Yang: None. Y. Gao: None. Y. Jiang: None. G. Zhang: None. H. Liu: None.

Objectives The aim of this study was to establish the physiologic changes of coagulation factors (FII:C, FV:C, FVII:C, FVIII:C, FIX:C, FX:C, FXI:C, FXII:C) during pregnancy and delivery period. Methods We investigated the blood samples of 100 pregnant women during each trimester of pregnancy and different delivery periods (before placental separation, during placental separation, 2 h after placental separation, and 24 h after placental separation). We measured serum concentrations of factors FII:C, FV:C, FVII:C, FVIII:C, FIX:C, FX:C, FXI:C and FXII:C. Results The FVII:C and FIX:C showed downward trends in the early stages of pregnancy ( P P P P P P Conclusions The marked change of FVII:C during and after placental separation is essential for the rapid hemostasis during delivery, which supports the coagulation factor FVII:C as an effective agent for intractable postpartum hemorrhage. Disclosures Y. Gao: None. J. Yang: None. G. Zhang: None. Y. Jiang: None. H. Liu: None.

Objectives Eclampsia is an acute and life threatening multisystem disorder, which may predisposes the brain to edema formation and increase the electric activity of neurons. Aquaporin 4 (AQP4) can function as water-channels and aquaporin 9 (AQP9) as neutral channel. We hypothesized that these AQPs in brain are associated with the pathogenesis of preeclampsia and eclampsia. Methods To test this hypothesis, we used our previous eclampsia-like model and compared localization (immunohistochemistry, IHC), mRNA (QRT-PCR), and protein levels (Western analysis) of AQP4 and AQP9 in hippocampus from Sprague Dawley rats that were non-pregnant (NP), normal pregnant rats (P); preeclampsia rats (PE) and eclampsia-like rats (E). Results IHC confirmed the presence of these proteins in the hippocampus. Western analysis revealed that the major AQP4 band at 32 kDa and AQP9 band at 33 kDa. AQPs were significantly elevated in PE and E group compared with NP and P rats. Both AQP4 and AQP9 mRNA were detected in the tissue of all the animals. AQPs mRNA increased in PE rats and got even higher after seizure. Conclusions This study suggests that the higher levels of AQPs in the brain during preeclampsia may predispose the brain to edema formation and increase the electric activity of neurons. These changes during preeclampsia may result in eclampsia. The AQPs expression is higher in preeclampsia rats and further increasing in eclampsia model, suggesting that AQPs may play a role in the pathological of preeclamsia. Disclosures Q. Huang: None. H. Liu: None. J. Bao: None. G. Zhang: None. B. Hu: None. S.P. Brennecke: None.

AIM: To analyze risk factors for refractoriness to proton pump inhibitors (PPIs) in patients with non-erosive reflux disease (NERD). METHODS: A total of 256 NERD patients treated with the PPI esomeprazole were enrolled. They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia (QolRad) scale. All subjects completed questionnaires on psychological status (self-rating anxiety scale; self-rating depression scale) and quality of life scale (Short Form 36). Multivariate analysis was used to determine the predictive factors for PPI responses. RESULTS: According to QolRad, 97 patients were confirmed to have residual reflux symptoms, and the remaining 159 patients were considered symptom free. There were no significant differences between the two groups in lifestyle factors (smoking and alcohol consumption), age, Helicobacter pylori infection, and hiatal hernia. There were significant differences between the two groups in relation to sex, psychological distress including anxiety and depression, body mass index (BMI), and irritable bowel syndrome (IBS) (P < 0.05). Logistic regression analysis found that BMI < 23, comorbid IBS, anxiety, and depression were major risk factors for PPI resistance. Symptomatic patients had a lower quality of life compared with symptom-free patients. CONCLUSION: Some NERD patients are refractory to PPIs and have lower quality of life. Residual symptoms are associated with psychological distress, intestinal disorders, and low BMI.