Three generations of matrilineal excess of birth defects in Irish families with neural tube defects

Background

Neural tube defects (NTDs) and birth defects overall are more likely to occur among maternal compared to paternal relatives in two generations (uncles/aunts and first cousins) of Irish families where an individual has been born with an NTD.

Aims

The aim of this study was to determine if the matrilineal excess persisted into the third generation.

Methods

First cousins were interviewed about their pregnancy outcomes and their offsprings’ health.

Results

Maternal first cousins once removed (FCOR) were more likely to have birth defects than paternal FCOR: 6.7 versus 3.5% (adjusted odds ratio 1.49, 95% CI 0.57, 3.89). No NTDs occurred. Folic acid supplementation significantly reduced the risk of birth defects (P = 0.04).

Conclusions

This study demonstrates an excess of birth defects among maternal relatives in three consecutive generations of NTD families, and supports the hypothesis that an underlying mechanism links distant maternal relatives in at least some NTD families.

     

An Ethical Evaluation Index System for Clinical Approval of Medical Technology in China: A Structural Equation Model Study

Objective

To construct a quantitative ethical evaluation index system for the clinical approval of medical technology in China.

Methods

Exploratory factor analysis (EFA) and first-order confirmatory factor analysis (CFA) based on a structure equation model (SEM), higher-order CFA and normalisation were used to establish an ethical evaluation index system for the clinical approval of medical technology. Data were processed in SPSS 13.0 and Lisre l5.3.

Results

There were 52 third class indices, 15 second class indices, and 3 first class indices in this ethical evaluation index system. The weight of each index was calculated by normalisation.

Conclusion

This study developed a three-level ethical evaluation index system, comprising 70 indices, for the clinical approval of medical technology.

     

Unravelling the genome: a review of molecular genetic research in schizophrenia

Background

Schizophrenia is a common and complex mental illness that affects approximately 1% of the population worldwide. Despite intensive research over the years, the aetiology and pathogenesis of schizophrenia is poorly understood. However, it has long been recognised that schizophrenia is highly familial suggesting a possible genetic aetiology.

Aim

To review recent molecular genetic research in schizophrenia.

Methods

Medline and Embase search.

Results

Over the past decade, with the completion of the Human Genome Project, molecular genetic research has now identified a number of genes that are very likely to predispose to schizophrenia.

Conclusion

This article discusses the methodologies that have been used to identify schizophrenia susceptibility genes and provides a review of recently identified genes thought to play a role in the pathogenesis of this illness.

     

Effect of Jiaotai Pill (交泰丸) on Intestinal Damage in Partially Sleep Deprived Rats

Objective: To explore the effect and mechanism of Jiaotai Pill(交泰丸, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation(PSD). Methods: Obesity resistant(OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide(LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin(Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes(Cry1 and Cry2) in the intestine were also determined. Results: The treatment of JTW significantly decreased LPS level in OR rats with PSD(P0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting(P0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. Conclusions: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.     

Pure Total Flavonoids from Citrus paradisi Macfad Induce Leukemia Cell Apoptosis In Vitro

Objective

To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel (PTFC) on the proliferation of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms.

Methods

PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay.

Results

Treatment with PTFC inhibited leukemia cell proliferation in a dose- and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis.

Conclusion

PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.

     

Effects of Banxia Xiexin Decoction (半夏泻心汤) on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells

Objective: To examinie the synergistic effects of Banxia Xiexin Decoction(半夏泻心汤,Known as Banhasasim-tang in Korean) extract(BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines. Methods: A549 cells were treated with varying concentrations(50–200 μg/m L) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. Results: The exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose-and time-dependently(P0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V+/propidium iodide-stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethylketone(z-VAD-FMK). Conclusions: BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.     

Construction-related eye injuries in Irish nationals and non-nationals: attitudes and strategies for prevention

Background

Construction-related ocular injuries are an important cause of vision loss but few studies on the incidence, epidemiology and nature of these injuries exist.

Aims

Due to the perceived increase in occupation-related eye injuries in non-nationals we aimed to investigate the nature of such injuries presenting to a single eye unit over a two-month period.

Methods

One hundred and fifty-five patients presenting to the accident and emergency department with construction related ocular injury were examined.

Results

Of 155 patients, 80 were Irish and 75 non-national, of whom 60, 21.3 and 6.7% were Polish, Lithuanian and Romanian, respectively. Common causative factors included hammering, grinding, drilling and splash injury. Average rate of eyewear protection usage was 35%, with attendance at safety courses highest in Irish nationals. A penetrating eye injury rate of 4.9% overall was observed, all in non-nationals.

Conclusion

Construction related ocular injury is a serious cause of visual loss in non-nationals. Greater adherence to safety regulations and training is required.

     

Chemical Composition, Anticancer, Anti-neuroinflammatory, and Antioxidant Activities of the Essential Oil of Patrinia scabiosaefolia

Objective: To study the chemical composition, anticancer, anti-neuroinflammatory, and antioxidant activities of the essential oil of Patrinia scabiosaefolia (EO-PS). Methods: Patrinia scabiosaefolia was analyzed by gas chromatography-mass spectrometry. Eight human carcinoma cell lines, including SGC-7901, AGS, HepG2, HT-29, HCT-8, 5-FU/HCT-8, HeLa, and MDA-MB-231, were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Anti-neuroinflammatory activity was assessed by production of interleukin (IL)-1β and IL-6 induced by lipopolysaccharide in BV-2 cells (microglia from mice). The antioxidant activity was evaluated with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. Results: Forty-four components, representing 83.919% of the total oil, were identified in the EO-PS. The major constituents were caryophyllene oxide (12.802%), caryophyllene (6.909%), α-caryophyllene (2.927%), β-damascenone (3.435%), calarene (5.621%), and phenol (3.044%). The MTT assay showed that the EO-PS exhibited significant dose-dependent growth inhibition in the 50–200 μg/mL dilution range. The EO-PS exhibited a dose-dependent scavenging activity against the DPPH radical, with an half of maximal inhibitory concentration 1.455 mg/mL. Conclusion: The EO-PS possesses a wide range of antitumor, anti-neuroinflammatory and antioxidant activities, suggesting that it may be a good candidate for further investigations of new bioactive substances.     

Clopidogrel and proton pump inhibitor (PPI) interaction: separate intake and a non-omeprazole PPI the solution?

Background

Dual therapy with aspirin and clopidogrel increases the risk of gastrointestinal bleeding. Therefore, co-therapy with a proton pump inhibitor (PPI) is recommended by most guidelines. However, there are warnings against combining PPIs with clopidogrel because of their interactions with cytochrome P450 isoenzyme 2C19 (CYP2C19).

Methods

The effects of the combined or separate intake of 20 mg of omeprazole and 75 mg of clopidogrel on the clopidogrel-induced inhibition of platelet aggregation were measured in four healthy subjects whose CYP2C19 exon sequences were determined. The effects of co-therapy with 10 mg of rabeprazole were also examined.

Results

Two subjects showed the wild-type CYP2C19 sequence. The concurrent intake of omeprazole had no effect on clopidogrel-induced platelet inhibition in these subjects. Two subjects were heterozygous for the *2 allele, with predicted reduced CYP2C19 activity. One of them was a clopidogrel non-responder. In the second heterozygous subject, omeprazole co-therapy reduced the clopidogrel anti-platelet effect when taken simultaneously or separately. However, the simultaneous intake of rabeprazole did not reduce the clopidogrel effect.

Conclusion

The clopidogrel-PPI interaction does not seem to be a PPI class effect. Rabeprazole did not affect the clopidogrel effect in a subject with a clear omeprazole-clopidogrel interaction. The separate intake of PPI and clopidogrel may not be sufficient to prevent their interaction.

     

Suppression of Oxidative Stress of Modified Gongjin-Dan (WSY-1075) in Detrusor Underactivity Rat Model Bladder Outlet Induced by Obstruction

Objective

To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model.

Methods

Rats were randomly allocated to three groups: shamoperated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders.

Results

Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05).

Conclusion

WSY-1075 had beneficial effect on prevention of BOO-DU.

     

Necrotizing fasciitis: microbiological characteristics and predictors of postoperative outcome

Objective

Necrotizing fasciitis is a life threatening soft-tissue infection with a high morbidity and mortality. Prompt treatment based on extensive surgical debridement and antibiotic therapies are the therapeutic principles.

Methods

The medical records of patients with necrotizing fasciitis (n = 26) from 1996 to 2005 were retrospectively analyzed.

Results

The localization of necrotizing fasciitis was most commonly the trunk (42.3%). Type I polymicrobial infection was the dominating infection. The involvement of anaerobic bacteria was associated with an increase in the number of surgical revisions (p = 0.005). Length of postoperative intensive care unit stay, duration of postoperative ventilation and mortality were significantly increased in the ASA IV-V group. Computed tomography displayed only a limited significance as diagnostic tool for initial diagnosis.

Conclusions

In severe cases the combination of necrotic skin and soft tissue gas facilitates the correct diagnosis, which should than be followed by immediate - and most often - repeated debridement. If anaerobes are isolated an early and aggressive second look is necessary.

     

Analysis of clinical features of ocular presentation in cranial venous sinus thrombosis

Background

To recognize ocular presentations in cranial venous sinus thrombosis (CVST) which were easy to be misdiagnosis.

Design

Retrospective study.

Methods

Review clinical informations including general informations, general performances, and ocular presentations of 118 inpatients with CVST in the general hospital of chinese people's liberation army during 2005-2009.

Main Outcome Measures

The ocular symptoms as the initial onset presentations or simultaneous phenomenon among different onset type patients were analyzed.

Results

Of all the CVST patients, 21.2% (25/118) presented with ocular symptom as the initial presentation, 30.5% (36/118) presented with ocular symptom as well as the other symptoms, and 48.3% (57/118) presented with non-ocular symptoms as the initial onset. The CVST patients were divided into 3 groups according to the onset type. There was no marked statistical significance among groups. The most common major complaints were blurring and degeneration of acute vision, accounting for 85.9% (61/71) of all abnormal ocular chief complaints. The most common objective sign in eyes was papilloedema, accounting for 48.3% (57/118) in this group of CVST patients. About 22.4% (13/58) showed acute vision deterioration at 1-year follow-up, due to optic atrophy.

Conclusions

As ophthalmologists, we should master the onset characteristics and clinical manifestations of CVST. Early diagnosis and treatment is very important for the prevention of vision deterioration, especially for patients with ocular syndrome as the initial onset syndrome. For isolated agnogenic intracranial hypertension, we should consider the possibility of CVST.

     

Qualitative Analysis of A Sulfur-fumigated Chinese Herbal Medicine by Comprehensive Two-Dimensional Gas Chromatography and High-Resolution Time of Flight Mass Spectrometry Using Colorized Fuzzy Difference Data Processing

Objective: To investigate the chemical transformation of volatile compounds in sulfur-fumigated Radix Angelicae Sinensis. Methods: A comprehensive two-dimensional gas chromatography(GC×GC) and high-resolution time-of-flight mass spectrometry(HR-TOF/MS) with colorized fuzzy difference(CFD) method was used to investigate the effect of sulfur-fumigation on the volatile components from Radix Angelicae Sinensis. Results: Twenty-five compounds that were found in sun-dried samples disappeared in sulfur-fumigated samples. Seventeen volatile components including two sulfur-containing compounds were newly generated for the first time in volatile oils of sulfur-fumigated Radix Angelicae Sinensis. Conclusion: The strategy can be successfully applied to rapidly and holistically discriminate sun-dried and sulfur-fumigated Radix Angelicae Sinensis. GC×GC-HR-TOF/MS based CFD is a powerful and feasible approach for the global quality evaluation of Radix Angelicae Sinensis as well as other herbal medicines.     

In Vivo and In Vitro Anti-inflammatory Effects of Ethanol Fraction from Periploca forrestii Schltr.

Objective: To determine the anti-inflammatory effects of an ethanol fraction of Periploca forrestii Schltr. (EFPF) and to investigate the potential mechanisms underlying in vivo and in vitro models. Methods: The anti-inflammatory effects of EFPF were evaluated using the xylene-induced mouse ear edema and carrageenan-induced rat paw edema models in vivo. In vitro, RAW264.7 cells were exposed to 0–800 μg/mL EFPF and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then cells were treated with different concentrations of EFPF (100–400 μg/mL) and stimulated with lipopolysaccharide (LPS, 1 μg/mL) for 24 h. The supernatant was analyzed for nitric oxide (NO) using the Griess reagent, and the levels of inflammatory mediators and cytokines were determined using enzyme-linked immunosorbent assays for prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin (IL) 6, and IL-10. The protein expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB), and mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK were examined by Western blot. Results: Compared with the control group, EFPF significantly reduced mouse ear edema and rat paw edema rate (P<0.05 or P<0.01). Compared with the LPS group, EFPF significantly inhibited the LPS-stimulated production of NO, PGE2, TNF-α and IL-6 (P<0.05 or P<0.01), and increased the IL-10 production (P<0.05). EFPF also significantly inhibited LPS-induced protein expressions of iNOS and COX-2, suppressed the phosphorylation and degradation of inhibitor of NF-κB-α, decreased p65 level, and inhibited the phosphorylation of p38, ERK1/2 and JNK (P<0.05 or P<0.01). Conclusion: EFPF exerted anti-inflammatory effect by reducing protein expressions of iNOS and COX-2 and the production of the inflammation factors, including TNF-α, IL-6, NO and PGE2, mainly through inhibition of LPS-mediated stimulation of NF-κB and MAPK signaling pathways.     

Acupuncture Treatment Modulates the Resting-State Functional Connectivity of Brain Regions in Migraine Patients without Aura

Objective: To investigate the modulatory effect of acupuncture treatment on the resting-state functional connectivity of brain regions in migraine without aura(MWo A) patients. Methods: Twelve MWo A patients were treated with standard acupuncture treatment for 4 weeks. All MWo A patients received resting-state functional magnetic resonance imaging(f MRI) scanning before and after acupuncture treatment. Another 12 normal subjects matched in age and gender were recruited to serve as healthy controls. The changes of restingstate functional connectivity in MWo A patients before and after the acupuncture treatment and those with the healthy controls were compared. Results: Before acupuncture treatment, the MWo A patients had significantly decreased functional connectivity in certain brain regions within the frontal and temporal lobe when compared with the healthy controls. After acupuncture treatment, brain regions showing decreased functional connectivity revealed significant reduction in MWo A patients compared with before acupuncture treatment. Conclusions: Acupuncture treatment could increase the functional connectivity of brain regions in the intrinsic decreased brain networks in MWo A patients. The results provided further insights into the interpretation of neural mechanisms of acupuncture treatment for migraine.     

Anti-fibrotic Effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 Cells Involved with Increased N-myc Downstream-Regulated Gene 2 Expression

Objective: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstream-regulated gene 2 (NDRG2, a tumor suppressor gene). Methods: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×104 cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 μL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot. Results: With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected. Conclusion: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.     

Relationship between Two Blood Stasis Syndromes and Inflammatory Factors in Patients with Acute Coronary Syndrome

Objective

To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).

Methods

Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).

Results

Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).

Conclusions

Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

     

Key Symptoms Selection for Two Major Syndromes Diagnosis of Chinese Medicine in Chronic Hepatitis B

Objective

To identify key symptoms of two major syndromes in chronic hepatitis B (CHB), which can be the clinical evidence for Chinese medicine (CM) doctors to make decisions.

Methods

Standardization scales on diagnosis for CHB in CM were designed including physical symptoms, tongue and pulse appearance. The total of 695 CHB cases with dampness-heat (DH) syndrome or Pi (Spleen) deficiency (SD) syndrome were collected for feature selection and modeling, another 275 CHB patients were collected in different locations for validation. Key symptoms were selected based on modified information gain (IG), and 5 classifiers were applied to assist with models training and validation. Classification accuracy and area under receiver operating characteristic curves (AUC) were evaluated.

Results

(1) Thirteen DH syndrome key symptoms and 13 SD syndrome key symptoms were selected from original 125 symptoms; (2) The key symptoms could achieve similar or better diagnostic accuracy than the original total symptoms; (3) In the validation phase, the key symptoms could identify syndromes effectively, especially in DH syndrome, which average prediction accuracy on 5 classifiers could achieve 0.864 with the average AUC 0.772.

Conclusion

The selected key symptoms could be simple DH and SD syndromes diagnostic elements applied in clinical directly. (Registration N0.: ChiCTR-DCC-10000759)

     

Effects of Hedan Tablet(荷丹片)on Lipid Profile,Proprotein Convertase Subtilisin/Kexin Type 9 and High-Density Lipoprotein Subfractions in Patients with Hyperlipidemia:A Primary Study

Objective: To investigate the effects of Hedan Tablet(荷丹片) on serum lipid profile, proprotein convertase subtilisin/kexin type 9(PSCK9) and high-density lipoprotein(HDL) subfractions in patients with hyperlipidemia. Methods: Thirty-seven patients with hyperlipidemia were randomized to treatment with Hedan Tablet 4.38 g/day as Hedan group(18 cases) or placebo(19 cases) as control group for 8 weeks. The lipid profile, PCSK9 and HDL subfractions were determined at day 0 and week 8 in both groups respectively. Results: Hedan treatment for 8 weeks mildly decreased serum low-density lipoprotein cholesterol(LDL-C) levels, while no changes were found in total cholesterol(TC), triglycerides(TG) and PCSK9 concentrations. Furthermore, Hedan treatment increased the concentration of large high-density lipoprotein cholesterol(HDL-C) and the percentage of large HDL subfraction, while decreased the concentration of small HDL-C and the percentage of small HDL subfraction without changing serum HDL-C levels in patients with hyperlipidemia. Conclusion: Hedan treatment of 4.38 g per day for 8 weeks could confer a favorable effects on serum LDL-C concentration as well as HDL subfractions.