[Research progress of transcriptomics and proteomics in schizophrenia].

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.

Energy transfer rate and electron-phonon coupling properties in Eu3+ -doped nanophosphors.

A series of controllable emissions SrWO4 :Eu3+ and charge-compensated SrWO4 : Eum3+ (m = 0.01 or 0.20) phosphors was successfully prepared via a simple co-precipitation method. The energy transfer mechanism was studied based on the Huang's theory. A low magnitude of Huang-Rhys factor (10-2 ) was calculated using phonon sideband spectra. The Judd-Ofelt parameters Ωλ (λ = 2, 4 and 6) of Eu3+ -activated SrWO4 doped with charge compensation were obtained. The calculated Commission Internationale de l'Eclairage chromaticity coordinates were found to be about (0.67, 0.33) for SrWO4 : Eu0.203+ and charge-compensated SrWO4 : Eu0.203+ phosphors, which coincided with the National Television Standard Committee system standard values for red. A white light emission was obtained under 362 nm excitation. The correlated color temperature was computed by a simple equation to characterize light sources. Thus, warm white light-emitting diodes with higher Ra can be constructed by combining as-prepared high efficiency, low correlated color temperature and high color purity phosphor.

Clinical utility of tumour marker velocity of cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) in breast cancer surveillance.

BACKGROUND: Serum tumour markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) are not routinely recommended for detecting breast cancer recurrence and monitoring treatment. In this study, we aim to evaluate the diagnostic accuracy of absolute CA 15-3 and CEA levels and report on the clinical utility of tumour marker velocity in breast cancer surveillance. METHODS: 67 consecutive patients over a 15-year period (1998-2012) with available serial serum CA 15-3 and CEA measurements at recurrence were matched to a control group of patients. Tumour marker velocity was derived from the average change in consecutive tumour marker values over time, expressed in unit/year. Logistic regression analysis was performed to investigate the association between tumour characteristics, tumour marker velocity and disease recurrence. RESULTS: Using the Youden index values, the optimal cut-off values for absolute CA 15-3 and CEA corresponded to the normal assay reference range while tumour marker velocity values were derived to be 2.5U/mL/year and 1.2ng/mL/year respectively. CA 15-3 velocity > 2.5U/mL/year had the highest AUROC value of 0.85 than CEA velocity alone. When either tumour marker velocity exceeded threshold values, the sensitivity, specificity, negative predictive value and positive predictive value were 94.0%, 73.1%, 92.5%, and 77.8% respectively. In the multivariate logistic regression analysis, having both CA 15-3 and CEA velocity exceeding the cut-off values was shown to be a significant predictor for disease recurrence (p = 0.01). CONCLUSION: These findings highlighted the clinical utility of serial tumour markers measurements and its velocity in breast cancer surveillance.

Anti-Voltage-gated Potassium Channel Limbic Encephalitis with Psychiatric Features: a Case Report.

We report a case of anti-voltage-gated potassium channel (VGKC) limbic encephalitis in a 47-year-old man presenting with a 2-year history of psychiatric features. The patient had cognitive impairment, slurred speech, and a mildly unsteady gait but no other neurological deficits or seizures. Results of blood, urine, and cerebrospinal fluid tests and magnetic resonance imaging of the brain were normal. However, electroencephalography showed an epileptogenic focus in the bilateral temporal regions with mild to moderate diffuse encephalopathy. Autoimmune panel results confirmed the diagnosis of anti-VGKC limbic encephalitis, with a serum VGKC concentration of 6730 pmol/L. The patient was treated with Keppra and pulsed intravenous methylprednisolone for 3 days, and his behaviour improved.

Network meta-analysis of novel and conventional sentinel lymph node biopsy techniques in breast cancer.

Background: The aim of this network meta-analysis was to compare the performance of blue dye alone or in combination with radioisotope (technetium-99m, Tc) with three novel techniques for sentinel lymph node detection in breast cancer: indocyanine green fluorescence (ICG), superparamagnetic iron oxide (SPIO) nanoparticles and contrast-enhanced ultrasound imaging (CEUS). Methods: PubMed, Embase, the Cochrane Library, China Knowledge Research Integrated Database, ClinicalTrials.gov and OpenGrey databases were searched up to 31 November 2017, without language restriction. Studies that compared the detection performance of at least one of the novel methods (ICG, SPIO and CEUS) with that of traditional methods (blue dye and/or radioisotope) were included in network meta-analysis. Results: Thirty-five studies were included. Pooled risk ratios (RRs) for Tc (1·09, 95 per cent c.i. 1·04 to 1·15), ICG (1·12, 1·07 to 1·16) and SPIO (1·09, 1·01 to 1·18) showed statistically better performance in detecting sentinel lymph nodes than blue dye alone. ICG had the lowest false-negative rate, with a RR of 0·29 (0·16 to 0·54), followed by Tc (RR 0·44, 0·20 to 0·96) and SPIO (RR 0·45, 0·14 to 1·45), with blue dye alone as the reference group. Conclusion: SPIO or ICG alone are superior to blue dye alone and comparable to the standard dual-modality technique of blue dye with Tc.

Improving B mode ultrasound evaluation of breast lesions with real-time ultrasound elastography--a clinical approach.

Ultrasound elastography using the extended combined auto-correlation method of tissue elasticity allows for real-time strain image visualisation using a free-hand probe with concurrent conventional B mode imaging. Four hundred and fifteen consecutive women with 550 breast lesions confirmed on B mode ultrasound were assessed with elastography using the elasticity score. There were 119 malignant and 431 benign lesions. The elastography sensitivity was 78.0%, specificity was 98.5% and overall accuracy was 93.8%. The median score for malignancy was 5 and that for benign lesions was 2. There was good correlation with B mode BIRADS category. 98.6% of lesions with an elasticity score of 2 or below (95%CI=96.8-99.4) were benign. BIRADS 3 lesions with an elasticity score of 2 or below may be re-classified as BIRADS 2 lesions. We found that 15.3% of BIRADS 2 and 3 lesions with an elasticity score of 3 were malignant. Real-time ultrasound elastography is user-friendly with a high accuracy rate, thereby improving B mode ultrasound assessment.

Audit of Mental Capacity Assessment by Primary Care Physicians Versus Consultation-liaison Psychiatrists.

OBJECTIVE: To review the mental capacity assessment of in-patients referred to consultation-liaison psychiatrists and to compare the assessment first made by primary care physicians. METHODS: Medical records of in-patients who were referred to consultation-liaison psychiatrists for mental capacity assessment between May and October 2015 were retrospectively reviewed. Assessment was first made by a primary care physician; complex cases were referred to a consultation-liaison psychiatrist. Audit of each case note was conducted independently by at least two of the authors. RESULTS: Medical records of 37 female and 26 male in-patients aged 24 to 91 (mean, 68.2) years were audited. Only 33.3% of these patients had no psychiatric diagnosis. Overall, assessments by primary care physicians were suboptimal. Assessments by consultation-liaison psychiatrists were more detailed, with documentation of mental capacity (93.7%) and psychiatric diagnosis (88.9%). Nonetheless, patient wishes and beliefs were poorly documented (19.0%), as were whether the patient had a lasting power of attorney or a court-appointed deputy (6.3%) and whether the patient had made advance care planning (0%). CONCLUSION: Overall, mental capacity assessment was inadequately performed by primary care physicians and consultation-liaison psychiatrists. More work needs to be done to engage, educate, and empower all stakeholders involved.

Adoptive immunotherapy of HCMV infection.

Human cytomegalovirus (HCMV) infection or reactivation is a frequent cause of morbidity and mortality in immunocompromised individuals such as transplant recipients. Primary HCMV infection or reactivation of HCMV from latency is mostly asymptomatic in immunocompetent individuals and is controlled by the host's cell-mediated immune response. Healthy HCMV seropositive individuals develop high frequencies of HCMV-specific cytotoxic T lymphocytes (CTL) in the peripheral blood. Furthermore, a direct correlation between the recovery of HCMV-specific CTL responses and an improved outcome of HCMV disease could be demonstrated in immunocompromised patients. Deriving from these observations, the strategy of an adoptive transfer of HCMV-specific T cells has been developed. Protective immunity can be transferred successfully by the infusion of donor-derived HCMV-specific CD8+ cytotoxic T-cell clones or cell lines. In addition, several studies have supported the importance of antiviral effector functions of Th cells in maintaining CTL responses after adoptive transfer and their capacity to produce antiviral cytokines. Until today, a broad variety of clinical protocols for HCMV-specific immunotherapy has been published. These protocols vary regarding the isolation procedure, composition of cellular product, number of transferred cells and thus treatment efficacy. In this review, we aim to provide a comprehensive synopsis of the current standard of knowledge concerning cellular HCMV-specific immunotherapeutic approaches.

How relevant is breast cancer screening in the Asia/Pacific region?

Nationwide breast cancer screening with mammography is well-established in many western countries. Many studies have shown its benefit in mortality reduction. However, breast cancer screening in Asia has been slow to implement, as it was perceived that the breast cancer incidence was low and the parenchyma of Asian women was difficult to assess mammographically. With changing disease patterns, breast cancer is now one of the most common cancers amongst women in Asia. Breast cancer screening has become an important and relevant health problem. However, apart from biological differences between western and Asian women, cultural and economic considerations need to be addressed. This paper looks at the various issues pertaining to the feasibility and relevance of population-based screening in the Asia/Pacific region.

miR-200 promotes the mesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes.

The miR-200 family promotes the epithelial state by suppressing the Zeb1/Zeb2 epithelial gene transcriptional repressors. To identify other miR-200-regulated genes, we isolated mRNAs bound to transfected biotinylated miR-200c in mouse breast cancer cells. In all, 520 mRNAs were significantly enriched in miR-200c binding at least twofold. Putative miR-200-regulated genes included Zeb2, enriched 3.5-fold in the pull down. However, Zeb2 knockdown does not fully recapitulate miR-200c overexpression, suggesting that regulating other miR-200 targets contributes to miR-200's enhancement of epithelial gene expression. Candidate genes were highly enriched for miR-200c seed pairing in their 3'UTR and coding sequence and for genes that were downregulated by miR-200c overexpression. Epidermal growth factor receptor and downstream MAPK signaling pathways were the most enriched pathways. Genes whose products mediate transforming growth factor (TGF)-ß signaling were also significantly overrepresented, and miR-200 counteracted the suppressive effects of TGF-ß and bone morphogenic protein 2 (BMP-2) on epithelial gene expression. miR-200c regulated the 3'UTRs of 12 of 14 putative miR-200c-binding mRNAs tested. The extent of mRNA binding to miR-200c strongly correlated with gene suppression. Twelve targets of miR-200c (Crtap, Fhod1, Smad2, Map3k1, Tob1, Ywhag/14-3-3γ, Ywhab/14-3-3ß, Smad5, Zfp36, Xbp1, Mapk12, Snail1) were experimentally validated by identifying their 3'UTR miR-200 recognition elements. Smad2 and Smad5 form a complex with Zeb2 and Ywhab/14-3-3ß and Ywhag/14-3-3γ form a complex with Snail1. These complexes that repress transcription assemble on epithelial gene promoters. miR-200 overexpression induced RNA polymerase II localization and reduced Zeb2 and Snail1 binding to epithelial gene promoters. Expression of miR-200-resistant Smad5 modestly, but significantly, reduced epithelial gene induction by miR-200. miR-200 expression and Zeb2 knockdown are known to inhibit cell invasion in in vitro assays. Knockdown of each of three novel miR-200 target genes identified here, Smad5, Ywhag and Crtap, also profoundly suppressed cell invasion. Thus, miR-200 suppresses TGF-ß/BMP signaling, promotes epithelial gene expression and suppresses cell invasion by regulating a network of genes.

The effect of a clinical posting in psychiatry on the attitudes of medical students towards psychiatry and mental illness in a Malaysian medical school.

INTRODUCTION: The stigma attached to mental illness and the mentally ill is a universal phenomenon and a major barrier to the provision of mental health services. Stigmatising attitudes among doctors themselves can result in compromised patient care. The aim of this research project is to study the impact of a clinical posting in psychiatry on the attitudes of medical students to mental illness and to psychiatry. This paper reports the results of the first phase of a longitudinal study. MATERIALS AND METHODS: A total of 122 year 4 medical students responded to this study. The Attitudes Towards Mental Illness (AMI) and Attitudes Towards Psychiatry (ATP) questionnaires were administered before and after an 8-week attachment in psychiatry. RESULTS: We found that students had somewhat favourable attitudes towards psychiatry and mental illness at the start of their attachment, with a mean score of 108.34 on ATP (neutral score, 90) and 68.24 on AMI (neutral score, 60). There was a significant increase in the mean scores of both scales following the psychiatric attachment for female students (ATP: P = 0.003; AMI: P <0.0005), but not male students (ATP: P = 0.435; AMI: P = 0.283). CONCLUSIONS: An 8-week clinical posting of fourth-year medical students in psychiatry was associated with an increase in positive attitudes to mental illness and to psychiatry among female students but not among male students.

Does clinical exposure to patients in medical school affect trainee doctors' attitudes towards mental disorders and patients?--A pilot study.

Stigmatising attitudes towards mental illness may improve with clinical exposure during medical school training. Attitudes of 48 fourth year medical students in Universiti Kebangsaan Malaysia were assessed before and after their compulsory attachment in Psychiatry, using the Attitude Towards Psychiatry-30 (ATP) and the Attitude towards Mental Illness (AMI) questionnaires. ATP scores improved significantly with training (104.8 and 114.4, pre- and post-attachment respectively) as did AMI scores (63.4 and 68.1 respectively). Both improvements were statistically significant. (ATP: z = 4.55, p < 0.0005) (AMI: z = 3.75, p < 0.0005). Attitudes towards mental illness appeared to have become more favourable with clinical training in psychiatry.

Late-intervention study with ebselen in an experimental model of type 1 diabetic nephropathy.

BACKGROUND AND AIM: Previous studies have shown that preventive treatment with the antioxidant, ebselen, in experimental models of type 1 diabetic nephropathy resulted in an attenuation of structural and functional damage in the kidney. However, evidence for the effectiveness of ebselen in late-intervention studies is lacking. Thus, we aimed to investigate the effects of ebselen in attenuating established renal injury in type 1 diabetic nephropathy using the Akita mouse model. METHODS: Baseline blood glucose and albumin-to-creatinine ratio (ACR) were measured in wild-type (WT) and heterozygous Akita mice at 9 weeks of age. At 10 weeks of age, WT and Akita mice were randomized to receive either vehicle (5% carboxymethyl cellulose) or ebselen by oral gavage at 10mg/kg twice daily. Kidney and urine were collected after 16 weeks of treatment with ebselen for histological and functional analyses. RESULTS: At 9 weeks of age, Akita mice displayed well-established renal dysfunction with significant increases in ACR and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels when compared with WT controls. After 16 weeks of treatment with ebselen, oxidative stress, as measured by nitrotyrosine immunostaining and urinary 8-OHdG levels, was significantly reduced in the Akita mice. Furthermore, gene expression of the major reactive oxygen species-producing nicotinamide adenine dinucleotide phosphate enzyme, Nox4, was also reduced by ebselen. However, ebselen had no effect on ACR and glomerulosclerosis. CONCLUSION: Chronic treatment with ebselen significantly reduced oxidative stress in the Akita mice. However, ebselen failed to attenuate functional or structural kidney damage in this late-intervention study using the Akita mouse model.

Defining the repeating elements in the cysteine-rich region (CRR) of the CD18 integrin beta 2 subunit.

The cysteine-rich region (CRR) of the integrin beta subunits is organised into four repeating elements. By expression of a panel of truncated beta 2 subunits, and CRR segments fused to the C-terminal end of a CD4 soluble fragment, the segment required for the expression of two monoclonal antibody conformational epitopes was determined. This segment, E482-Q574, contains 16 cysteines representing two repeating units. We have thus defined the CRR unit motif of 'xC---C---C---CxCxxCxC---Cx', where 'x' represents a single residue, and '---' represents a stretch of four to 14 residues.

Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy.

We report the medium-term (median follow-up=52 months) results of a prospective randomised trial of multimodal therapy (neoadjuvant chemotherapy, Patey mastectomy, postoperative radiotherapy and adjuvant hormone therapy) (n=56) versus initial hormone therapy (n=52) for locally advanced primary breast cancer. Compared with multimodal therapy, initial hormone therapy was associated with reduced number of therapies for disease control (mean=3.6 versus 4.9) and mastectomy rate (31%). Multimodal therapy conferred better initial locoregional control and a longer disease-free interval. Nevertheless, there was no statistically significant differences in the rates of survival, metastasis and uncontrolled locoregional disease, as well as in the time to metastasis between the two therapy groups. Regardless of the therapy groups, oestrogen receptor positivity conferred a lower metastasis rate, better survival and locoregional control. Thus, initial hormone therapy may be a reasonable option for managing locally advanced primary breast cancer, especially for oestrogen receptor-positive tumours.

Purification and binding properties of a human ficolin-like protein.

Ficolin was initially identified from porcine uterus as a TGF-beta 1 binding protein and is considered to have an overall structure similar to that of the complement protein C1q and the collectins. Recent studies have shown that human ficolin is synthesized mainly by monocytes in peripheral blood and that it could potentially bind to sugar structures on microorganisms. The aim of the present investigations was to isolate ficolin from human plasma by affinity chromatography on immobilized sugars. A human serum protein was identified in the GlcNAc eluate from GlcNAc-Sepharose which migrated as a polypeptide of approx. 40 kDa on SDS-PAGE under reducing conditions and was, after further purification by FPLC on a mono-Q column, shown to have an identical N-terminal sequence, over the first 14 residues, to P35, a plasma protein having similar sequence and domain organisation to ficolin. This protein, named the ficolin-like protein, was shown to be sensitive to collagenase and similar to P35 in that it was also disulphide-linked into an oligomer of approx. 320 kDa. However, unlike P35, its binding to GlcNAc was independent of Ca2+. Gel-filtration studies showed that this ficolin-like protein also had a molecular weight of approx. 320 kDa under non-dissociating conditions. During the course of this study this ficolin-like protein was found to simply bind to CNBr-activated Sepharose which had been inactivated with Tris, and from which it could be eluted with GlcNAc. This ficolin-like protein was also shown to bind to GlcNAc, but not to mannose and maltose. The functional significance of the unusual binding property of this ficolin-like protein is not clear, but it has facilitated the development of a simple method for its purification.

Chimeras of the integrin beta subunit mid-region reveal regions required for heterodimer formation and for activation.

A central region of the beta2 integrin subunit, RN (residues D300 to C459), was replaced by the equivalent sequences from beta1 and beta7 to give the chimeras beta2RN1 and beta2RN7. Whilst the former construct failed to form heterodimer at the cell surface with alphaL, the later of these could be expressed together with the alphaL subunit to form a variant LFA-1. Based on recent modelling work, the RN region consists of two parts, one is the C-terminal end of the putative A-domain (RB, residues D300 to A359), and the other the mid-region (BN, residues Y360 to C459). Chimeras exchanging the two component regions were made. Of the four resultant chimeras, only the beta2RB1 chimera failed to support LFA-1 expression. Thus the beta1 specific residues of this region affect the interaction with the alphaL subunit. Whereas the alphaL/beta2RB7 LFA-1 variant is wildtype like with respect to ICAM-1 adhesion, the alphaLbeta2BN1 and alphaLbeta2BN7, as well as the alphaLbeta2RN7, variants are more adhesive than the wildtype. These results suggest that an authentic beta2 mid-region is, in part, required for maintaining the LFA-1 in a resting state.

A retrospective study comparing the individual modalities of triple assessment in the pre-operative diagnosis of invasive lobular breast carcinoma.

AIMS: Early invasive lobular breast carcinoma (ILC) is associated with few symptoms and signs. The individual sensitivity of clinical examination, mammography, ultrasonography, cytology and core biopsy have each been reported to be of limited value. The aim of this study was to evaluate the accuracy of triple assessment in the pre-operative detection of patients identified to have ILC from their surgical pathology. METHODS: Pure ILC was defined as tumours containing at least 90% lobular features. The triple assessment of 273 patients diagnosed primarily at our institution were reviewed. RESULTS: 87.5% of women were symptomatic and 12.5% were screen detected. The mean patient age was 59 (range 30-81) years and the median tumour size was 26 (range 5-110) mm. The main mammographic abnormalities were a spiculated lesion (33.3%), an ill-defined mass (33.3%) or architectural distortion (23.5%). The sensitivities for detecting ILC of each modality were: clinical examination (76.6%), mammography (79.8%), ultrasound examination (93.9%), fine-needle aspiration cytology (FNAC) (60.5%) and core biopsy (90.8%). Combining the three modalities of clinical examination, imaging and cyto/pathology increased the pre-operative detection rate of ILC. CONCLUSION: Triple assessment is useful in the diagnosis of ILC. As the features of ILC may be subtle, a high index of suspicion is required to facilitate early diagnosis.

Ureteroscopic lithoclast lithotripsy: a cost-effective option.

Seventy-four consecutive cases of ureteral stones listed for ureteroscopic lithotripsy were studied prospectively. In all cases, the Wolf 7.5F or 9F ureteroscope was used in conjunction with the Swiss Lithoclast system. Dormia baskets were employed on four occasions to prevent forward propulsion of fragments. Ureteroscopic access to the stones was successful in 70 patients (95%). Lithoclast lithotripsy was successfully applied in 68 patients (92%), with complete fragmentation noted in 62 patients (91%), one requiring two sessions. The 6-week stone-free rate was 96% for these patients. Five patients with partial fragmentation had successful adjuvant SWL. The overall successful fragmentation rate was thus 84% (62 of 74) and 91% (67 of 74) in combination with adjuvant SWL. Cost analysis indicated a three-fold advantage for the Lithoclast over Candela lasertripsy. Ureteroscopic Lithoclast lithotripsy is a cost-effective treatment modality for ureteral stones.

Diffusion resonances in action space for an atom optics kicked rotor with decoherence.

We numerically investigate momentum diffusion rates for the pulse kicked rotor across the quantum to classical transition as the dynamics are made more macroscopic by increasing the total system action. For initial and late time rates we observe an enhanced diffusion peak which shifts and scales with changing kick strength, and we also observe distinctive peaks around quantum resonances. Our investigations take place in the context of a system of ultracold atoms which is coupled to its environment via spontaneous emission decoherence, and the effects should be realizable in ongoing experiments.