The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis.

The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.

Association between dopamine D2 receptor gene polymorphisms and the risk of heroin dependence.

Heroin dependence is a chronic relapsing brain disease. Researchers have reported that the dopamine D2 receptor (DRD2) is involved in the development of opiate dependence. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin dependence and six polymorphisms of the DRD2 gene using the MassARRAY system. Three hundred and thirty-four patients with heroin dependence and 299 healthy controls participated in the research. Compared with the healthy controls, heroin-dependent patients had a significantly lower frequency of the AA genotype of rs6275 (P = 0.038), and a significantly higher frequency of the C allele of rs1125394 (P = 0.030). Statistically significant differences were observed in the genotypic and allelic frequencies of rs17115583 (P = 0.005 and P = 0.001, respectively) and rs1079597 (P = 0.03 and P = 0.02, respectively). Haplotype analysis revealed that the T-G-A (block 1) haplotype of the DRD2 gene conferred a protective effect (P = 0.020). These findings point to a role for DRD2 polymorphism in heroin dependence in the Chinese Han population, and may be informative for future genetic or neurobiological studies on heroin dependence.

[Efficacy of interventional therapy on paravalvular leakage after mitral valve replacement].

OBJECTIVE: To evaluate the efficacy of transcatheter intervention of paravalvular leakage (PVL) after mitral valve replacement. METHODS: Present respective study included 15 patients (8 males and mean age (53.5±11.7) years) with mitral PVL who underwent interventional therapy in our hospital from April 2014 to May 2015. There were 9 cases with NYHA heart function Ⅲ, 6 cases with NYHA heart function Ⅳ. Left ventricular ejection fraction was (46.8±8.2)%, and mitral regurgitation volume was 12.0 (10.0, 15.0)ml before the intervention. Transcatheter intervention was carried out in the catheterization laboratory or the hybrid operation room with initial local anesthesia. By puncturing femoral artery and implantation of different congenital heart disease devices, the mitral PVL were occluded interventionally. To some complicated cases, the occluder was implanted by puncturing apex and atrial septum. Follow-up evaluation included peri-operational mortality, complications and postoperative residual shunt. RESULTS: The median time between transcatheter intervention and previous operation was 5.0 (0.6, 7.0) years. One patient did not tolerate the operation and occlude was not implanted in this patient. The success rate of transcatheter intervention was 93.3% (14/15). The average operation time was (126.7±56.4)min, and X ray exposure time was (21.0±10.0)min, and median hospitalization time was 7.0 (6.0, 10.0)d. The main post-operative complications included 1 case of hemoptysis, 1 case of acute renal failure, 1 case of hematuria and 4 cases of blood transfusion. The median follow-up time was 7.0 (4.0, 12.0) months. During the follow-up, there was no death and no serious complications. One month after the procedure, left ventricular ejection fraction significantly increased to(52.1±4.3)%, and median mitral regurgitation significantly reduced to 0.5 (0, 2.0)ml (all P<0.05). CONCLUSION: The interventional therapy for PVL after mitral valve replacement is safe and effective, and further studies are warranted to observe the long-term effect of this procedure.

Structure and polymorphism of novel X-chromosome short tandem repeat loci in a Chinese Han population.

Recently, 5 novel X-chromosome short tandem repeat (X-STR) loci with high degrees of polymorphism were examined. In this study, we investigated the genetic distribution of these loci in a Chinese Han population. The 5 X-STR loci were successfully examined by polyacrylamide gel electrophoresis in a total of 200 unrelated Shaanxi Han individuals (100 males and 100 females). Hardy-Weinberg equilibrium tests revealed no significant deviation from expected values (P > 0.05) for all 5 X-STR loci in the Shaanxi Han population.The loci were named DXS-p11.3, DXS-q12, DXS-q13.3, DXS-q22.1, and DXS-q25 and were found to contain 6, 8, 7, 7, and 5 alleles, respectively. In addition, 17, 21, 18, 19, and 11 genotypes, respectively, were detected in the female samples. The heterozygosities of the 5 X-STR loci were 0.75, 0.74, 0.74, 0.72, and 0.56, respectively. The polymorphic information contents of the 5 X-STR loci were 0.70, 0.69, 0.69, 0.68, and 0.51, respectively. The individual discrimination values of the 5 X-STR loci were 0.88, 0.86, 0.88, 0.87, and 0.74, respectively. Five new X-chromosome STR loci with high degrees of polymorphism were observed in our lab. The results of this study are important for forensic individual identification, paternity identification, and population genetics research.

Regulators of G-protein signaling 9 genetic variations in Chinese subjects with schizophrenia.

To identify single-nucleotide polymorphisms that contribute to the genetic susceptibility to schizophrenia, we examined the potential association between schizophrenia and 9 single nucleotide polymorphisms (rs1530351, rs4791230, rs2869577, rs8077696, rs8070231, rs2292592, rs9916525, rs1122079, and rs4790953) in the G-protein signaling 9 gene. The participants included 395 schizophrenia subjects and 400 healthy controls. The selected single nucleotide polymorphisms were genotyped using mass spectrometry techniques. The allelic or genotypic frequencies of the rs4791230 (promoter region) polymorphisms in subjects with schizophrenia were significantly different from those in healthy controls. The subjects with schizophrenia had a significantly higher frequency of the G allele (P = 0.030, odds ratio = 1.589, 95% confidence interval = 1.042-2.422) of rs4791230. Strong linkage disequilibrium was observed in 4 blocks (D' > 0.9). Significantly fewer T-A (rs1530351-rs4791230) haplotypes (P = 0.029) were found in subjects with schizophrenia. These findings suggest a role of G-protein signaling 9 polymorphisms in schizophrenia among Han Chinese and may be informative for future genetic or neurobiological studies on schizophrenia.

Single-nucleotide polymorphisms in dopamine receptor D1 are associated with heroin dependence but not impulsive behavior.

Previous studies suggested that dopamine receptors may be associated with drug dependence and impulsive behavior. In this study, we examined whether dopamine receptor D1 (DRD1) is associated with heroin dependence and the impulsive behavior in patients with heroin dependence. The participants included 367 patients with heroin dependence and 372 healthy controls from a Chinese Han population. We examined the potential association between heroin dependence and 8 single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326, rs265981, rs10078714, rs10078866) of DRD1, and the associations between single single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with the healthy controls, heroin dependence patients showed a significantly lower frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no association was observed between haplotypes and heroin dependence in the 2 blocks. This genetic behavior correlation study showed that the 2 single-nucleotide polymorphisms, rs5326 and rs265981, were not associated with the impulsive behavior in patients with heroin dependence. These findings indicate that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han population and may be informative for future genetic or biological studies on heroin dependence.

Dopamine receptor D1 but not D3 essential for morphine-induced conditioned responses.

Recent studies indicate the involvement of dopamine receptors D1 and D3 in the regulation of locomotor stimulant and conditioned responses to morphine in mice. Moreover, expression of brain-derived neurotrophic factor (BDNF) may be modulated by D1 and D3 receptor activities in the nucleus accumbens (NAc) and prefrontal cortex (PFC). However, the underlying interactions between D1 and D3 receptors and BDNF in the expression of behavioral responses controlled by drug-associated cues have not yet been fully elucidated. In this study, we used dopamine receptor mutant mice to explore the roles of the D1 and D3 receptors in locomotion and morphine-induced place preference; furthermore, we investigated the effects of morphine on BDNF expression in the NAc and PFC of the mouse brain. Our results show that D1 receptor but not D3 receptor mutant mice had decreased sensitivity to acute morphine-induced (10 mg/kg) locomotion (D1: 3814.82 ± 319.9 cm vs D3: 8089.64 ± 967.4 cm). Furthermore, D1 receptor mutant mice did not acquire morphine-conditioned place preference (D1: -18.3 ± 59.9, D3: 217.7 ± 64.1) and showed decreased BDNF expression in the NAc (D1: 0.33 ± 0.07 fold, D3: 2.21 ± 0.18 fold) and PFC (D1: 0.74 ± 0.15 fold, D3: 1.68 ± 0.22 fold) compared with wild-type and D3 receptor mutant mice. These findings suggest that the D1 receptor is necessary for the induction of cue-associated morphine seeking and modulates locomotor habituation processes in response to acute morphine. The dopamine receptor D1 but not the D3 is also critical for morphine-induced BDNF expression in the NAc and PFC.

Association of the VRK2 gene rs3732136 polymorphism with schizophrenia in a Northwest Chinese Han population.

Previous studies have found that the vaccinia related kinase 2 gene (VRK2) polymorphism was associated with schizophrenia (SCZ) in the worldwide population. This association was further supported by VRK2 mRNA expression patterns and brain structure variations. Here, we analyzed four single nucleotide polymorphisms (SNPs) of the VRK2 gene in a total population of 893 samples, consisting of 360 patients with SCZ and 533 healthy controls of Han Chinese descent using the SNPscan method. Single SNP, haplotype, and gender-specific association analyses were performed. We found that rs3732136 was significantly associated with SCZ (P = 0.042; odds ratio = 1.25; 95% confidence interval = 1.01-1.55). Further genotype and haplotype association analyses suggested a similar pattern. Our data provide preliminary evidence that the VRK2 gene might play a major role in the development of SCZ in the Northwest Chinese Han population.

Characterization of a TIR-NBS-LRR gene associated with downy mildew resistance in grape.

Grapevine downy mildew, caused by Plasmopara viticola, is a devastating disease that results in considerable economic losses as well as environmental damage through the repeated application of fungicides. The nucleotide-binding site leucine-rich repeat gene family functions in plant immunoactivity against various pathogens and pests. In this study, the 5' and 3' ends of the resistance gene homology fragment RGA5 were obtained by rapid amplification of cDNA ends. The 4282-base pair full-length cDNA was obtained using gene-specific primers, and the corresponding 1335-amino acid protein sequence contained characteristic nucleotide-binding site leucine-rich repeat domains of plant resistance proteins, including the toll-interleukin receptor type region. Expression of RGA5 during P. viticola infection and abiotic stress was investigated using quantitative real-time polymerase chain reaction. The results showed that treatment with P. viticola and 4 abiotic stimuli (salicyclic acid, methyl-jasmonate, abscisic acid, H2O2) significantly induced RGA5 within 12 days of inoculation. Therefore, RGA5 may play a critical role in protecting grapevines against P. viticola via signaling pathways involving these molecules.

Functional polymorphisms of the glutamate receptor N-methyl D-aspartate 2A gene are associated with heroin addiction.

Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.

Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy.

This study explored the clinical significance of silencer of death domain (SODD) expression in childhood acute lymphoblastic leukemia (ALL) and its influence on chemotherapy as well as the effect of SODD expression on apoptosis of leukemic cells. The expression of SODD proteins in different ALL groups was determined by immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and transferred to Jurkat cells, and the effects of SODD expression on cell proliferation and apoptosis were analyzed using the MTT and FCM methods. The expressions of SODD, Phospho-NF-κB-P65, Bcl-2, and Caspase 3 were detected by Western blot analysis. The expression of SODD proteins was significantly higher in the ALL groups than in the control group (P < 0.05). The positive expression rate of SODD was significantly higher in refractory/relapsed and clinical high-risk groups than in standard-risk, initial treatment, and complete remission groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with down-regulated SODD expression induced by SODD-interfering plasmid transfection. The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD expression was high in the ALL children. These findings indicated that SODD over-expression might be correlated with the clinical classification, curative effect, and prognosis of ALL cells. Microtubule-targeting drugs can specifically down-regulate SODD expression in leukemic cells, thereby increasing the sensitivity of leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD expression tends to reduce sensitivity.

[Incidence of common gene mutations in early-onset colorectal cancer and the association with cancer survival: a meta-analysis].

Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

[Updates of colonoscopy surveillance guidelines after screening and polypectomy, and related research progress].

With the widespread application of colorectal cancer screening, the surveillance and management of the increasing number of screened population has become a pivotal aspect in preventing and controlling colorectal cancer. In recent years, researches have been conducted on the risk of colorectal cancer incidence and mortality in the population after screening. At the same time, various organizations in Europe and the United States have continuously updated colonoscopy surveillance after screening and polypectomy based on the latest research evidence. In this review, we summarized the current progress of studies on colorectal cancer risk in post-screening colorectal cancer populations and the key points of relevant guideline updates, in order to provide a reference for conducting relevant studies and formulating surveillance guidelines or consensus in China.

[Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center].

Objective: To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC. Methods: Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ2 tests (categorical variates) were performed to compare differences in epidemiological features. Results: A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m2 vs. 22.9 kg/m2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher (P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ2=46.9,P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850,P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions: This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.

Roles of functional NFKB1 and ß-TrCP insertion/deletion polymorphisms in mRNA expression and epithelial ovarian cancer susceptibility.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological cancers. Nuclear factor-kappa B (NF-κB) is involved in carcinogenesis and in the development of EOC. The ß-transducin repeat-containing protein (ß-TrCP) is a positive regulator of the NF-κB signaling pathway. Recent studies have indicated that the -94 ins/del ATTG polymorphism in the promoter region of the NFKB1 gene, and the 9N ins/del polymorphism in the 3'-untranslated region of the ß-TrCP gene are associated with increased susceptibility to a variety of cancers. We examined a potential association between these two polymorphisms and EOC. Genotypes were determined for 187 patients with EOC and 221 healthy control subjects, using the MassARRAY system. We found a significant association between the -94 ins/del ATTG genotype distribution and EOC. The frequency of the -94 del ATTG allele was significantly lower in EOC patients compared to healthy controls. The NF-κB mRNA level in cancer tissue was significantly correlated with -94 ins/del ATTG genotypes. Compared to the ATTG1/ATTG1 phenotype, the NF-κB mRNA level was 2.089 and 1.257 times higher in the ATTG2 (insertion)/ATTG2 homozygote and the ATTG1 (deletion)/ATTG2 heterozygote, respectively. However, we found no evidence of association between the 9N ins/del polymorphism of the ß-TrCP gene and EOC in this Chinese population. Based on these results, we suggest that the NF-κB -94 ins/del ATTG polymorphism is a risk factor for EOC susceptibility.

Reference charts and equations of fetal biometry for normal singleton pregnant women in Shaanxi, China.

OBJECTIVE: To construct reference charts and equations of fetal biometry for singleton pregnant women in Shaanxi, China. MATERIALS AND METHODS: This was a cross-sectional study involving 6,832 singleton pregnant women. One set of fetal ultrasonographic measurement data between the 16th to 41st gestational weeks (GW) was randomly selected from each pregnant woman, and biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) were recorded. Mean and standard deviation (SD) of BPD, AC, and FL were fitted by polynomial. Centile = Mean + Z(alpha) x SD was used to calculate centiles. Differences in the 50th centile of BPD, AC, and FL between Hong Kong, Korean, Italian and Shaanxi fetuses were compared. RESULTS: Mean of BPD, AC, and FL were well-fitted by quadratic polynomial, SD of BPD, AC and FL were fitted by linear regression. Equations for estimating mean and SD for BPD, AC, and FL from GW were obtained. Centiles for BPD,AC, and FL were calculated. From the 21st GW, the differences in BPD,AC, and FL between Hong Kong, Korean, Italian, and Shaanxi fetuses became larger. CONCLUSION: Fetal biometry reference charts and equations for estimating fetal size and GW could be used in obstetrics practice and research in Shaanxi, China.

Polymorphisms in the glutamate decarboxylase 1 gene associated with heroin dependence.

The GAD1 gene encodes the 67-kDa glutamic acid decarboxylase isoform (GAD67), the rate-limiting enzyme responsible for γ-aminobutyric acid (GABA) biosynthesis from glutamic acid, and may be involved in the development of drug dependence. To identify markers contributing to the genetic susceptibility to heroin dependence, this study examined the potential association between heroin dependence and 15 single nucleotide polymorphisms (SNPs, rs1978340, rs3762556, rs3791878, rs3749034, rs11542313, rs2241165, rs2241164, rs769407, rs3749033, rs16858977, rs701492, rs16858988, rs4668331, rs7578661, rs769395) of GAD1 gene using the MassARRAY system. Participants included 370 heroin-dependent subjects and 389 healthy controls. The allelic or genotypic frequencies of the rs1978340 (promoter region), rs3791878 (promoter region), and rs11542313 (exon 3) polymorphisms in heroin addicts were significantly different from those in healthy controls. Strong linkage disequilibrium was observed in two blocks (D'>0.9). Significantly more C-C-C-C-A haplotypes (p=0.0053 after Bonferroni correction) and significantly fewer T-C-A-C-A haplotypes (p=0.0003 after Bonferroni correction) were found in heroin dependent subjects. These findings point to a role for GAD1 polymorphism in heroin dependence among Han Chinese, and may be informative for future genetic or neurobiological studies on heroin dependence.

Functional characterisation of a natural androgen receptor missense mutation (N771H) causing human androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is an X-linked disorder due to mutations of androgen receptor (AR) gene. Various AR mutations have been identified, and the characterisation of these mutations greatly facilitates our understanding of AR structure-function. In this study, we have analysed an AR missense mutation (N771H) identified in patients with AIS. Functional analysis of the mutant AR was performed by in vitro mutagenesis-cotransfection assays. Compared to the wild-type AR, the dose-response curve of dihydrotestosterone-induced transactivation activity in the mutant AR was greatly shifted to the right and significantly decreased. However, the maximal efficacy of transactivation activity in the mutant AR was similar to that of the wild type. Receptor binding assay indicated that the mutant AR had an approximately 2.5-fold lower binding affinity to dihydrotestosterone compared to the wild type. Western blot analysis showed that the size and the expression level of mutant AR in transfected cells were comparable to the wild type. These data underscore the importance of asparagine at amino acid position 771 of human AR in normal ligand binding and normal receptor function, and a mutation at this position results in androgen insensitivity in affected subjects.

Polymorphism G861C of 5-HT receptor subtype 1B is associated with heroin dependence in Han Chinese.

The serotoninergic (5-HT) system regulates neuronal activity in broad brain regions, and appears to be particularly important for modulating behavioral and physiological functions such as mood, emotion, sleep and appetite. Central 5-HT deregulation may be involved in many neuropsychological disorders, which include substance abuse and addiction. Previous studies suggest that genetic polymorphisms in some 5-HT receptor genes may relate to heroin dependency. Here we examined potential association between heroin dependence and four single nucleotide polymorphisms (SNPs) of 5-HT receptors (A-1438G and T102C of HTR(2A), and G861C and A1180G of HTR(1B)) in a cohort of Han Chinese. Participants included 303 heroin-dependent subjects who were recruited into the Methadone Maintenance Treatment (MMT) Program in the Xi'an Mental Health Center, and 300 healthy controls. The resulting data yielded a significantly higher frequency of the HTR(1B) G allele with G861C among the heroin-dependent subjects relative to controls (p=0.001 after Bonferroni correction). Further genotype and clinical phenotype correlation study of the G861C carriers showed that the amount of heroin self-injection was higher in patients with the GG genotype relative to CC and CG genotypes (p<0.01). These findings point to a role for HTR(1B) polymorphism in heroin dependence among Han Chinese, and may be informative for future genetic or neurobiological studies on heroin dependence.

Airtraq laryngoscope versus conventional Macintosh laryngoscope: a systematic review and meta-analysis.

The Airtraq laryngoscope is a single-use laryngoscope designed to facilitate tracheal intubation in patients with either normal or difficult airways. The aim of this systematic review and meta-analysis was to compare the Airtraq with the conventional Macintosh laryngoscope. Data were retrieved from Medline, Embase, the Cochrane register of controlled trials, and by a manual search of bibliographies. Twelve randomised controlled trials (published between 2006 and 2011) including 1061 patients met the inclusion criteria. The Airtraq reduced intubation time significantly (mean difference -15 s; 95% CI -25 to -4 s, p < 0.00001) used by both experienced anaesthetists and novices, and it increased the first attempt success rate only in novices (relative risk 1.25; 95% CI 1.05-1.49, p = 0.07). The incidence of oesophageal intubation (relative risk 0.12; 95% CI 0.03-0.48, p < 0.05) was significantly reduced by the Airtraq. We conclude that the Airtraq laryngoscope facilitates a more rapid and accurate intubation, especially when used by novices.