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.

     

Appraisal of the Quality and Contents of Clinical Practice Guidelines for Hypertension Management in Chinese Medicine: A Systematic Review

Objective: To evaluate the quality and consistency of recommendations in the clinical practice guidelines(CPGs) for hypertension in Chinese medicine(CM). Methods: CM CPGs were identified from 5 electronic databases and hand searches through related handbooks published from January 1990 to December 2013. Three reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation(AGREE Ⅱ) instrument, and compared the CPGs' recommendations on CM syndrome pattern classification and treatment. Results: Five CM CPGs for hypertension were included. The quality score of the evidence-based(EB) guideline was higher than those of the consensus-based with no explicit consideration of evidence-based(CB-EB) and the consensus-based(CB) guidelines. Three out of five patterns in the CPGs were recommended by the EB guideline. Tianma Gouteng Formula(天麻钩藤复方) in the EB guideline was recommended mostly for hypertension patients with pattern of ascendant hyperactivity of Gan(Liver)-yang and pattern of yin deficiency with yang hyperactivity in the CPGs. Acupuncture and massage were recommended for Grade Ⅰ and Grade Ⅱ hypertension with severe symptoms weakening the quality of life in the EB guideline. For Grade Ⅰ and Grade Ⅱ hypertension, CM could be used alone, while for Grade Ⅲ hypertension, they should be used in combination with Western medicines. Conclusion: The quality of EB guideline was higher than those of CB and CB-EB CPGs in CM for hypertension and CM should be prescribed alone or combined with Western medicines based on the grade of hypertension.     

Validation of the state version questionnaire on autonomic regulation (state-aR) for cancer patients

Objectives

Current quality of life inventories used in oncology mainly measure the effects of chemo- or radiotherapy alongside functional and role scales. A new approach is to measure the autonomic state of regulation with the trait-inventory of autonomic regulation (Trait-aR). Loss of Trait-aR has been shown in different medical conditions such as breast cancer (BC) but not in colorectal cancer patients (CRC). In this paper we report the validation of a new state autonomic regulation scale (State-aR) of the last week.

Methods

Study 1 included 114 participants: (41 women/16 men with cancer and 57 age- and gender-matched healthy people) to conduct a reliability-, factor- and validity-analysis. Concurrent and convergent validity was evaluated with Trait-aR, Fatigue-Numeri-cal-Scale, Hospital Anxiety and Depression Scale (HADS-D) and the self-regulation scale, 65 participants were retested. Study 2 completed 42 participants: 17 with BC and 25 with CRC receiving chemotherapy. The State-aR was administered prior, during and after chemotherapy for measuring responsiveness.

Results

The factor analysis loaded to four subscales of State-aR (rest-activity, orthostatic-circulatory, thermosweating and digestive regulation) with a: Cronbach-α r_α = 0.77-0.83 and a test-retest-reliability r_rt = 0.60-0.80. The sum- and sub scales correlated with their concurrent subscales in the Trait-aR (0.48-0.74) and with the sum-scale moderately with all convergent criteria (r = 0.41 --0.44; p < 0.001). During chemotherapy the State-aR-sum and rest-activity-scale decreased significantly compared to the change in the Trait-aR (p < 0.05).

Conclusions

These findings support that the state autonomic regulation scale has satisfactory to good reliability, good validity and acceptable responsiveness in the context of chemotherapy treatment.

     

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.

     

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)

     

Classifying Syndromes in Chinese Medicine Using Multi-label Learning Algorithm with Relevant Features for Each Label

Objective

To develop an effective Chinese Medicine (CM) diagnostic model of coronary heart disease (CHD) and to confifirm the scientifific validity of CM theoretical basis from an algorithmic viewpoint.

Methods

Four types of objective diagnostic data were collected from 835 CHD patients by using a self-developed CM inquiry scale for the diagnosis of heart problems, a tongue diagnosis instrument, a ZBOX-I pulse digital collection instrument, and the sound of an attending acquisition system. These diagnostic data was analyzed and a CM diagnostic model was established using a multi-label learning algorithm (REAL).

Results

REAL was employed to establish a Xin (Heart) qi defificiency, Xin yang defificiency, Xin yin defificiency, blood stasis, and phlegm fifive-card CM diagnostic model, which had recognition rates of 80.32%, 89.77%, 84.93%, 85.37%, and 69.90%, respectively.

Conclusions

The multi-label learning method established using four diagnostic models based on mutual information feature selection yielded good recognition results. The characteristic model parameters were selected by maximizing the mutual information for each card type. The four diagnostic methods used to obtain information in CM, i.e., observation, auscultation and olfaction, inquiry, and pulse diagnosis, can be characterized by these parameters, which is consistent with CM theory.

     

Efficacy and Safety of Qiaoshao Formula(翘芍方) on Patients with Lifelong Premature Ejaculation of Gan(Liver) Depression and Shen(Kidney) Deficiency Syndrome:A Randomized Controlled Trial

Objective: To observe the efficacy and safety of Qiaoshao Formula(翘芍方, QSF) on patients with lifelong premature ejaculation(LPE) of Gan(Liver) depression and Shen(Kidney) deficiency syndrome. Methods: A total of 60 LPE patients were randomly divided into treatment(QSF) and control(dapoxetine) groups. The treatment group received QSF twice a day and the control group received dapoxetine 1 to 2 h prior to planned sexual intercourse for 4 weeks. The outcomes included intra-vaginal ejaculation latency time(IELT), premature ejaculation diagnostic tool(PEDT), clinical global impression of change(CGIC), scores of Chinese medicine symptoms(CMSS), sex life satisfaction(SLS) and adverse events(AEs). Results: In the treatment group, the median IELT was 3 min vs. 1.5 min before and after treatment(P0.05). PEDT in the treatment group was reduced to 11.76±1.68 from 15.83±2.30 after treatment(P0.05). Besides, patient's SLS was improved from 1.30±0.05 to 6.30±0.04(P0.05), and spouse's SLS was increased from 1.30±0.08 to 6.10±0.06(P0.05); CMSS was decrease from 14.86±3.02 to 9.62±2.87(P0.05). In addition, no significant AE was observed in both groups. Conclusion: QSF may be effective and safe on LPE patients with Gan depression and Shen deficiency syndrome.     

Preliminary Research on Syndrome Types of Chinese Medicine in Children with Primary Nephrotic Syndrome

Objective

To provide an objective reference for the syndrome types of Chinese medicine (CM) associated with pediatric primary nephrotic syndrome (PNS).

Methods

A cross-sectional study was performed. Data on clinical symptoms, CM syndrome types, biochemical indices, and medications used were collected from 98 children with PNS. Then, the correlation between CM syndromes and biochemical indices, as well as medications used, was analyzed.

Results

The four most common symptoms in children with PNS were brown urine, red tongue, excessive sweating, and swelling of the face and limbs. The syndromes of qi deficiency of Fei (Lung) and Shen (Kidney) (FSQD) and yin deficiency of Gan (Liver) and Shen (GSYD) were the most common main CM syndrome types. FSQD syndrome score correlated significantly with the total cholesterol level, urine protein/creatinine ratio, and urine IgG and albumin levels (P<0.01 or P<0.05). The use of maintenance glucocorticoids combined with immunosuppressive agents correlated with FSQD syndrome, and the use of maintenance glucocorticoids alone correlated with GSYD syndrome (P<0.05).

Conclusion

Two of the most common CM syndrome types were FSQD and GSYD syndromes. FSQD syndrome may be caused by some factors related to lipid levels, protein loss, and the use of immunosuppressive agents. The use of maintenance glucocorticoids may cause GSYD syndrome

     

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.

     

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.     

Chinese Tuina Downregulates the Elevated Levels of Tissue Plasminogen Activator in Sciatic Nerve Injured Sprague-Dawley Rats

Objective

To elucidate the mechanism of Chinese tuina in treating sciatic nerve crush injury, and to detect the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), which is thought to play an important role in nerve regeneration.

Methods

Thirty-two adult male Sprague-Dawley rats were subjected to sciatic nerve crush injury and 16 rats (sham-operated group) went through a sham operation. Control group was given no treatment while tuina group received tuina therapy since day 7 post-surgery. Tuina treatment was performed once a day and lasted for 20 days. The sciatic functional index was examined every 5 days during the treatment session. The rats’ gastrocnemius muscles were evaluated for changes in mass and immunohistochemistry techniques were performed to detect the levels of tPA and PAI-1.

Results

Tuina therapy improved the motor function of sciatic nerve injured rats (P<0.05), however, it did not increase muscle volume (P<0.05). Tuina downregulated the levels of tPA and PAI-1 (P<0.05).

Conclusions

The present study implies that tuina treatment could accelerate rehabilitation of peripheral nerve injury.

     

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.

     

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.     

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.     

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.

     

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.