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.

     

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.

     

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.

     

Effects of Electro-acupuncture at Tongli (HT 5) and Xuanzhong (GB 39) Acupoints from Functional Magnetic Resonance Imaging Evidence

Objective

To explore the specifificity of Tongli (HT 5) and Xuanzhong (GB 39) paired acupionts in aspects of Deqi sensation and brain activation patterns during electroacupuncture.

Methods

In this study, 15 healthy subjects were enrolled. All participants suffered two kinds of functional magnetic resonance imaging (fMRI) examinations randomly: Examination A received electro-acupuncture (EA) at the bilateral Tongli (HT5) and Xuanzhong (GB 39) acupoints (ACU), and examination B received EA at bilateral non-acupoints (NAP). The subjects reported the feeling of Deqi at each examination later respectively. A multi-voxel pattern analysis method and Statistical Program for Social Sciences were used to analyze the data.

Results

The ACU group (Exam A) reported fullness, heaviness, numbness, soreness and throbbing of signifificantly greater intensity than the NAP group (Exam B). In addition, there was no statistical signifificance between two groups in aching, tingling, deep pressure, sharp pain, dull pain, warmness and cold. Meanwhile, fMRI data revealed differences between two groups in discriminating accuracy of brain somatosensory cortex and language-related cortices.

Conclusions

Needling HT 5 and GB 39 may modulate language function through a complex brain network, suggesting that it may be benefificial to the recovery of language function in patients with aphasia.

     

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.

     

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.

     

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.     

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.     

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.

     

Bromelain and Cardiovascular Risk Factors in Diabetes: An Exploratory Randomized, Placebo Controlled, Double Blind Clinical Trial

Objective: To assess whether the dietary supplement(bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease(CVD) risk factors in patients with diabetes. Methods: This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain(1,050 mg/day) on plasma fibrinogen. This randomized controlled trial(RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years(standard deviation(SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg(3×350 mg) of either bromelain or starch-filled placebo capsules, two to be taken(2×350 mg) after breakfast and another(350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks. Results: The change in the fibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L(standard deviation(SD) 0.86g/L) compared with the mean reduction of 0.36 g/L(SD 0.96 g/L) for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups(mean difference=0.23g/L(SD 0.22 g/L), P=0.291). Similarly, the difference in mean change in other CVD risk factors(blood lipids, blood pressure), blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study. Conclusion: This RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain.     

Development, Reliability and Validity of Traditional Chinese Medicine Health Self-Evaluation Scale (TCM-50)

Objective: To develop a health-evaluating scale from a Chinese medicine(CM) perspective and reflecting CM conception of health. Methods: The Traditional Chinese Medicine Health Self-Evaluation Scale(TCM-50) was developed by verification of dimensions, formation of item pool, verification of scoring methodology, and pilot test of scale and item analysis. Results: TCM-50 composed of 50 items that could be classified into 4 dimensions including physiology and health, psychology and health, nature and health, and society and health. An examination of reliability and validity of TCM-50 yielded Cronbach's α coefficient of 0.927, and half coefficient of r was 0.876. The intraclass correlation coefficient of total score was 0.912. After using SF-36 questionnaire to evaluate the criterion validity, the Pearson r of the score of the two scales from the same participant was 0.740. Conclusions: TCM-50 has good reliability and validity, and can yield similar levels of efficacy as SF-36 in terms of evaluating people's overall health level. As a scale based on CM theory, TCM-50 is suitable for self-measuring the general health of Chinese patients.     

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.     

Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

Objective: To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction(茵陈术附汤, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus(HBV-ACLF) with cold pattern in Chinese medicine(CM). Methods: This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine(WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM(integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease(MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results: The mortality was decreased 14.28% in the integrative treatment group compared with WM group(χ2=6.156, P=0.013). The integrative treatment was found to significantly improve the MELD score(t=2.353, P=0.020). There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups(P0.05 or P0.01). The complications of ascites(χ2=9.033, P=0.003) and spontaneous bacteria peritonitis(χ2=4.194, P=0.041) were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions: The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy.(Trial registration No. Chi CTR-TRC-10000766)     

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.

     

Diagnostic Indicators for Blood Stasis Syndrome Patients with Gynaecological Diseases

Objective

To investigate the important diagnostic indicators for blood stasis syndrome (BSS) in patients of childbearing age with gynaecological diseases.

Methods

A partial least squared-discriminant analysis (PLS-DA) were applied to BSS symptoms data of patients with gynaecological diseases, and the diagnostic indicators used by doctors of Korean medicine (DKMs) among BSS patients with gynaecological diseases were also investigated.

Results

A total of 103 patients of childbearing age with gynaecological diseases and 40 healthy controls were enrolled. Among the 103 patients, 63 (61.7%) and 40 (38.8%) were diagnosed with BSS and non-BSS, respectively, and BSS patients exhibited a more severe extent of disease. A score plot of PLS-DA showed clearly different patterns among the 3 groups. Based on the variable importance on projection of PLS-DA model, menstrual pains, dark lumps in the menstrual blood, ileocoecal tenderness and resistance, sharp pains, and sublingual varicosities were selected as the top five most important indicators. Moreover, more than 75% of DKMs chose dark lumps in menstrual blood, menstrual pain, and dark menstrual blood as the diagnostic indicators of BSS in patients with gynaecological diseases, and more than 49% of them also considered sharp pains, dark red tongue, sublingual varicosities, and tendency to bruise easily as diagnostic indicators of BSS.

Conclusion

DKMs focused on menstrual symptoms and certain gynaecological symptoms to diagnose BSS patients of childbearing age with female diseases.

     

Text Mining of Rheumatoid Arthritis and Diabetes Mellitus to Understand the Mechanisms of Chinese Medicine in Different Diseases with Same Treatment

Objective

To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment.

Methods

A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention.

Results

Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM.

Conclusion

Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.

     

Current Situation of International Organization for Standardization/Technical Committee 249 International Standards of Traditional Chinese Medicine

Objective

To review the current situation and progress of traditional Chinese medicine (TCM) international standards, standard projects and proposals in International Organization for Standardization (ISO)/ technical committee (TC) 249.

Methods

ISO/TC 249 standards and standard projects on the ISO website were searched and new standard proposals information were collected from ISO/TC 249 National Mirror Committee in China. Then all the available data were summarized in 5 closely related items, including proposed time, proposed country, assigned working group (WG), current stage and classifification.

Results

In ISO/TC 249, there were 2 international standards, 18 standard projects and 24 new standard proposals proposed in 2014. These 44 standard subjects increased year by year since 2011. Twenty-nine of them were proposed by China, 15 were assigned to WG 4, 36 were in preliminary and preparatory stage and 8 were categorized into 4 fifields, 7 groups and sub-groups based on International Classifification Standards.

Conclusion

A rapid and steady development of international standardization in TCM can be observed in ISO/TC 249.

     

Electroacupuncture Stimulation of Language-Implicated Acupoint Tongli (HT 5) in Healthy Subjects: An fMRI Evaluation Study

Objective

To explore brain activations associated with electroacupuncture simulation at Tongli (HT 5) and its comparison with brain activations during picture-naming task.

Methods

Twenty healthy subjects were enrolled in this study. Half of them received electroacupuncture stimulation at HT 5 (ACUP group) and the other half of them received stimulation at a nonmeridian sham acupoint (SHAM group). All subjects performed picture-naming task. Each subject finished two runs of functional magnetic resonance imaging examinations in one session and picture-naming task was performed before electroacupuncture stimulation. Subjective brain activations were obtained using generalized linear model and inter-group analyses were performed after that.

Results

The electroacupuncture stimulation at HT 5 induced significant brain activations in both the anterior and posterior language regions, including the left inferior frontal gyrus, which was in consistent with activations induced during picture-naming task. Group analysis showed a tendency of increased activation of ACUP group in left inferior frontal gyrus compared with SHAM group (P<0.05 FDR corrected).

Conclusions

Electroacupuncture treatment at the acupoint HT 5 has modulation effect on typical language-implicated brain regions in healthy subjects, which provides supporting evidence for beneficial effects of needling at HT 5 for recovery of language function in aphasia.