Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles: Sequential Embryo Transfer or Double-blastocyst Transfer?

OBJECTIVE: Both sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes. METHODS: Totally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes. RESULTS: GQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267-5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482-6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218-13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT. CONCLUSION: SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Remote regulation of rs80245547 and rs72673891 mediated by transcription factors C-Jun and CREB1 affect GSTCD expression.

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is influenced by genetic factors. The genetic signal rs10516526 in the glutathione S-transferase C-terminal domain containing (GSTCD) gene is a highly significant and reproducible signal associated with lung function and COPD on chromosome 4q24. In this study, comprehensive bioinformatics analyses and experimental verifications were detailly implemented to explore the regulation mechanism of rs10516526 and GSTCD in COPD. The results suggested that low expression of GSTCD was associated with COPD (p = 0.010). And C-Jun and CREB1 transcription factors were found to be essential for the regulation of GSTCD by rs80245547 and rs72673891. Moreover, rs80245547T and rs72673891G had a stronger binding ability to these transcription factors, which may promote the allele-specific long-range enhancer-promoter interactions on GSTCD, thus making COPD less susceptible. Our study provides a new insight into the relationship between rs10516526, GSTCD, and COPD.

Single­nucleotide polymorphism rs6592645 confers asthma risk through regulating LRRC32 expression.

Asthma is a complex disease, often with evident genetic predisposition; for example, the single-nucleotide polymorphism (SNP) rs7130588 was significantly associated with asthma by genome-wide association study (GWAS). Analysis of 1000 Genomes Project data suggests that there is another SNP, rs6592645, in complete linkage disequilibrium with rs7130588 and should present the same signal in GWAS. However, the causal SNP and the mechanism for the association between rs7130588 and asthma remain to be elucidated. In the presents study, results from dual-luciferase assays indicated that the A/G alleles of rs7130588 failed to present significantly different reporter gene expression. By contrast, A allele of rs6592645 presented a significant increase in relative luciferase activity than G allele, thus suggesting that rs6592645 may be a causal SNP. Using chromosome conformation capture, the enhancer region containing rs6592645 was observed to interact with promoter region of leucine-rich repeat-containing 32 (LRRC32). Gene expression quantification suggested that LRRC32 expression is significantly increased in lung tissue of patients with asthma and is dependent on the genotype of this locus, thus verifying that LRRC32 may be involved in asthma onset and that rs6592645 can regulate LRRC32 expression. Through chromatin immunoprecipitation, transcription factor 3 (TCF3) was identified to bind to rs6592645 surrounding region and the interaction between TCF3 and rs6592645 surrounding region was investigated. Results from the present study may improve our understanding of the mechanism by which the genetic variation in this locus might influence asthma susceptibility.

Convergent Evidence Supports TH2LCRR as a Novel Asthma Susceptibility Gene.

Asthma is a common, complex disease with apparent genetic predispositions, and previous genome-wide association studies suggest that rs1295686 within the IL13 (IL-13) gene is significantly associated with asthma. Analysis of the data provided by the 1,000 Genomes Project indicated an additional four SNPs in nearly complete linkage disequilibrium with rs1295686 in White people. However, the causal SNPs and the associated mechanism remain unclear. To investigate this issue, functional genomics approaches were utilized to analyze the functions of these SNPs. Dual-luciferase assays indicated that the functional SNP is not rs1295686 but a haplotype consisting of three other SNPs: rs1295685, rs848, and rs847. Through chromosome conformation capture, it was found that the enhancer containing the three functional SNPs interacts with the promoter of TH2LCRR (T helper type 2 locus control region associated RNA), a recently identified long noncoding RNA. RNA-seq data analysis indicated that TH2LCRR expression is significantly increased in patients with asthma and is dependent on the genotype at this locus, indicating that TH2LCRR is a novel susceptibility gene for asthma and that these SNPs confer asthma risk by regulating TH2LCRR expression. By chromatin immunoprecipitation, the related transcription factors that bind in the region surrounding these three SNPs were identified, and their interactions were investigated by functional genomics approaches. Our effort identified a novel mechanism through which genetic variations at this locus could influence asthma susceptibility.

Identification of rs11615992 as a novel regulatory SNP for human P2RX7 by allele-specific expression.

P2RX7 (purinergic receptor P2X 7) is an important membrane ion channel and involved in multiple physiological processes. One non-synonymous SNP on P2RX7, rs3751143, had been proven to reduce ion channel function and further associated with multiple diseases. However, it was still unclear whether there were other cis-regulatory elements for P2RX7, which might further contribute to related diseases. Allele-specific expression (ASE) is a robust and sensitive approach to identify the potential functional region in human genome. In the current study, we measured ASE on rs3751143 in lung tissues and observed a consistent excess of A allele over C (P = 0.001), which indicated that SNP(s) in linkage disequilibrium (LD) could regulate P2RX7 expression. By analyzing the 1000 genomes project data for Chinese, one SNP locating ~ 5 kb away and downstream of P2RX7, rs11615992, was disclosed to be in strong LD with rs3751143. The dual-luciferase assay confirmed that rs11615992 could alter target gene expression in lung cell line. Through chromosome conformation capture, it was verified that the region surrounding rs11615992 could interact with P2RX7 promoter and effect as an enhancer. By chromatin immunoprecipitation, the related transcription factor POU2F1 (POU class 2 homeobox 1) was recognized to bind the region spanning rs11615992. Our work identified a novel long-distance cis-regulatory SNP for P2RX7, which might contribute to multiple diseases.

Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases.

SCGB1A1 (secretoglobin family 1A member 1) is an important protein for multiple pulmonary diseases, especially asthma, chronic obstructive pulmonary disease, and lung cancer. One single-nucleotide polymorphism (SNP) at 5'-untranslated region of SCGB1A1, rs3741240, has been suggested to be associated with reduced protein expression and further asthma susceptibility. However, it was still unclear whether there were other cis-regulatory elements for SCGB1A1 that might further contribute to pulmonary diseases. Allele-specific expression (ASE) is a novel approach to identify the functional region in human genome. In the present study, we measured ASE on rs3741240 in lung tissues and observed a consistent excess of G allele over A (P < 10-6), which indicated that this SNP or the one(s) in linkage disequilibrium (LD) could regulate SCGB1A1 expression. By analyzing 1000 Genomes Project data for Chinese, one SNP locating ~10.2 kb away and downstream of SCGB1A1, rs2509956, was identified to be in strong LD with rs3741240. Reporter gene assay confirmed that both SNPs could regulate gene expression in the lung cell. By chromosome conformation capture, it was verified that the region surrounding rs2509956 could interact with SCGB1A1 promoter region and act as an enhancer. Through chromatin immunoprecipitation and overexpression assay, the related transcription factor RELA (RELA proto-oncogene, NF-kB subunit) was recognized to bind the region spanning rs2509956. Our work identified a novel long-distance cis-regulatory SNP for SCGB1A1, which might contribute to multiple pulmonary diseases.

1H-NMR-based metabolic profiling of healthy individuals and high-resolution CT-classified phenotypes of COPD with treatment of tiotropium bromide.

BACKGROUND: Heterogeneity of COPD results in different therapeutic effects for different patients receiving the same treatment. COPD patients need to be individually treated according to their own characteristics. The purpose of this study was to explore the differences in different CT phenotypic COPD by molecular metabolites through the use of metabolomics. METHODS: According to the characteristics of CT imaging, 42 COPD patients were grouped into phenotype E (n=20) or phenotype M (n=24). Each COPD patient received tiotropium bromide powder for inhalation for a therapeutic period of 3 months. All subjects were assigned into phenotype E in pre-therapy (EB, n=20), phenotype E in post-therapy (EA, n=20), phenotype M in pre-therapy (MB, n=22), phenotype M in post-therapy (MA, n=22), or normal control (N, n=24). The method of metabolomics based on 1H nuclear magnetic resonance (1H-NMR) was used to compare the changes in serum metabolites between COPD patients and normal controls and between different phenotypes of COPD patients in pre- and post-therapy. RESULTS: Patients with COPD phenotype E responded better to tiotropium bromide than patients with COPD phenotype M in terms of pulmonary function and COPD assessment test scores. There were differences in metabolites in COPD patients vs normal control people. Differences were also observed between different COPD phenotypic patients receiving the treatment in comparison with those who did not receive treatment. The changes of metabolites involved lactate, phenylalanine, fructose, glycine, asparagine, citric acid, pyruvic acid, proline, acetone, ornithine, lipid, pyridoxine, maltose, betaine, lipoprotein, and so on. These identified metabolites covered the metabolic pathways of amino acids, carbohydrates, lipids, genetic materials, and vitamin. CONCLUSION: The efficacy of tiotropium bromide on COPD phenotype E is better than that of phenotype M. Metabolites detected by 1H-NMR metabolomics have potentialities of differentiation of COPD and healthy people, discrimination of different COPD phenotypes, and giving insight into the individualized treatment of COPD.

rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations.

Lung cancer is a common cancer in human and has presented significant genetic predisposition. Previous genome-wide association study observed that rs401681 within CLPTM1L (CLPTM1 like) was significantly associated with lung cancer. By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer. However, the real causal SNP and mechanism for the association were still not clear. The following plasmid construction, mutagenesis, transient transfection and luciferase reading indicated that both SNPs could regulate gene expression in lung/bronchial epithelium Beas-2B cell line. By chromosome conformation capture, it was identified that the segment containing these two SNPs could interact with TERT (telomerase reverse transcriptase) promoter, thus indicating that these SNPs confer lung cancer risk by regulating TERT expression instead of CLPTM1L. Through chromatin immunoprecipitation, the transcript factors HNF4A (hepatocyte nuclear factor 4 alpha) and MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) were recognized for the regions spanning rs401681 and rs402710, respectively. Our results uncovered a complete link between these two SNPs and lung cancer.

A functional SNP upstream of the ADRB2 gene is associated with COPD.

Background: Previous studies have suggested that ß2-adrenergic receptor (ADRB2) is associated with COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet. Methods: In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively. Results: One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034). The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1. In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017). Conclusion: Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.

Metabolic changes of different high-resolution computed tomography phenotypes of COPD after budesonide-formoterol treatment.

BACKGROUND: Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system. Metabolic profiling of different high-resolution computed tomography (HRCT) phenotypes of COPD patients before and after treatment may identify discriminatory metabolites that can serve as biomarkers and therapeutic agents. PATIENTS AND METHODS: 1H nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics was performed on a discovery set of plasma samples from 50 patients with stable COPD. Patients were assigned into two groups on the basis of HRCT findings including phenotype E (n=22) and phenotype M (n=28). After budesonide-formoterol treatment (160/4.5 µg ×2 inhalations twice daily for 3 months), clinical characteristics and metabolites were then compared between phenotype E pretreatment and posttreatment, phenotype M pretreatment and posttreatment, phenotype E pretreatment and phenotype M pretreatment, and phenotype E posttreatment and phenotype M posttreatment. RESULTS: Inhaled budesonide-formoterol therapy for both phenotype E (emphysema without bronchial wall thickening) and phenotype M (emphysema with bronchial wall thickening) was effective. However, phenotype E and phenotype M were different in response to therapy. Patients with phenotype M in response to therapeutic effects were significantly greater compared with phenotype E. Certain metabolites were identified, which were closely related to the treatment and phenotype. Metabolic changes in phenotype E or phenotype M after treatment may be involved with adenosine diphosphate (ADP), guanosine, choline, malonate, tyrosine, glycine, proline, l-alanine, l-valine, l-threonine leucine, uridine, pyruvic acid, acetone and metabolism disturbance. Metabolic differences between phenotype E and phenotype M in pretreatment and posttreatment covered glycine, d-glucose, pyruvic acid, succinate, lactate, proline, l-valine and leucine. CONCLUSION: Bronchial wall thickening in COPD may be an indicator for predicting the better response to the treatment with bronchodilator and corticosteroid. The identification of metabolic alterations provides new insights into different HRCT phenotypes and therapeutic assessment of COPD.

Relationship between PPARα mRNA expression and mitochondrial respiratory function and ultrastructure of the skeletal muscle of patients with COPD.

Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.

Intramedullary Nailing Combined with Bone Grafting for Benign Lesions of the Proximal Femur.

OBJECTIVE: To evaluate the effectiveness of intramedullary nailing for benign lesions of the proximal femur. METHOD: A retrospective analysis was carried out on 68 cases of benign lesions in the proximal femur at our hospital from April 2002 to April 2013 (38 men and 30 women). Mean age at surgery was 35.5 years (range, 22-56 years). The cases were divided into two groups: curettage of the lesion with bone grafting only as the grafting group (32 cases) and internal fixation after removal of the lesion as the fixation group (36 cases). For the grafting group, lesions were scraped out, deactivated and washed thoroughly with normal saline, then the allogeneic bone was implanted. For the fixation group, after the lesions were scraped, the intramedullary nails were implanted, and allogeneic bone was implanted into the scraped cavity with compaction. RESULTS: Pathological examination showed that 24 out of 68 cases (35.3%) had simple bone cysts (suffered from pathological fracture in 2 cases); 21 (30.9%) fibrous dysplasia; 18 (26.5%) aneurysmal bone cysts; 3 (4.4%) chondroblastoma, 2 (2.9%) out of which were combined with aneurysmal bone cysts. All patients were followed up for 12-96 months (56 months for mean). In the grafting group, 4 patients had postoperative complications (1 pathological bone fractures and 3 deep vein thrombosis), but only 1 patient of the fixation group (deep vein thrombosis) (P < 0.05). The average bedridden time after surgery was 11.4 ± 7.6 days for the grafting group, and for the other group was 7.5 ± 5.4 days ( P < 0.05). CONCLUSION: Both treatments are effective for benign lesions in the proximal femur, but the fixation group facilitated the functional recovery of patients and reduced postoperative complications.

Silencing of Btbd7 Inhibited Epithelial-Mesenchymal Transition and Chemoresistance in CD133+ Lung Carcinoma A549 Cells.

Cancer stem cells (CSCs) are responsible for tumorigenesis and recurrence, so targeting CSCs is an effective method to potentially cure cancer. BTB/POZ domain-containing protein 7 (Btbd7) has been found in various cancers, including lung cancer and liver cancer, but the role of Btbd7 in non-small cell lung cancer (NSCLC), CSC self-renewal, and chemoresistance is still unknown. Therefore, in this study we found that the ratio of tumor sphere formation and stem cell transcription factors in CD133+ cells was dramatically enhanced compared to parental cells, which indicated successful sorting of CD133+ cells from A549. Meanwhile, Btbd7 and the markers of the epithelial-mesenchymal transition (EMT) process were more highly expressed in CD133+ cells than in parental cells. Silencing of Btbd7 significantly inhibited the self-renewal and EMT process in CD133+ cells. Furthermore, we found that downregulation of Btbd7 promoted cell apoptosis and increased the sensitivity to paclitaxel in CD133+ and parental cells. In conclusion, our results suggest that Btbd7 is a promising agent for the inhibition of survival and chemoresistance of cancer stem-like cells of NSCLC, which may act as an important therapeutic target in NSCLC.

Effect of oral N-acetylcysteine on COPD patients with microsatellite polymorphism in the heme oxygenase-1 gene promoter.

BACKGROUND: Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients. N-acetylcysteine (NAC), an antioxidant/mucous modifier, has shown an uncertain benefit in COPD patients. We hypothesized that this polymorphism could be associated with the effectiveness of oral NAC. METHODS: A total of 368 patients with COPD were recruited and the polymorphisms of their HO-1 gene promoter were classified into three subclasses according to the number of (GT)n repeats, as previously reported: class S (<27 (GT)n repeats), class M (27-32 (GT)n repeats), and class L (>32 (GT)n repeats). These subjects were then classified as L+ group (with the L allele: L/L, L/M, L/S) and L- group (without the L allele: M/M, M/S, S/S). All the patients were allocated to standard therapy plus NAC 600 mg bid over a 1-year period and were observed over that year. RESULTS: The L- group saw improvements in forced expiratory volume in 1 second (FEV1) (from 1.44±0.37 to 1.58±0.38, P=0.04) and FEV1% predicted (from 56.6±19.2 to 59.7±17.2, P=0.03). No improvement was found in forced vital capacity of each group and the decline of forced vital capacity in both of the groups was not statistical significant. The number of yearly COPD exacerbations of the L- group was 1.5±0.66 which was lower than the 2.1±0.53 of the L+ group (P<0.01). For the changes of St George's Respiratory Questionnaire (SGRQ) score, only the activity score of the L- group was more significant than that of the L+ group (P=0.02). The improvement of the outcome of 6-minute walking distance test in L- group (from 290.1±44.9 meters to 309.7±46.9 m) was higher than that in the L+ group (from 289.7±46.2 m to 300.3±44.2 m) (P=0.03). CONCLUSION: A 600 mg bid oral NAC treatment for 1-year on COPD patients without the L allele can improve the FEV1, FEV1% predicted, the SGRQ activity score, and the result of 6-minute walking distance test, and the exacerbation rate of the L allele carrier in COPD patients is much higher than in the COPD patients without the L allele.

Nonlinear Inertia Weighted Teaching-Learning-Based Optimization for Solving Global Optimization Problem.

Teaching-learning-based optimization (TLBO) algorithm is proposed in recent years that simulates the teaching-learning phenomenon of a classroom to effectively solve global optimization of multidimensional, linear, and nonlinear problems over continuous spaces. In this paper, an improved teaching-learning-based optimization algorithm is presented, which is called nonlinear inertia weighted teaching-learning-based optimization (NIWTLBO) algorithm. This algorithm introduces a nonlinear inertia weighted factor into the basic TLBO to control the memory rate of learners and uses a dynamic inertia weighted factor to replace the original random number in teacher phase and learner phase. The proposed algorithm is tested on a number of benchmark functions, and its performance comparisons are provided against the basic TLBO and some other well-known optimization algorithms. The experiment results show that the proposed algorithm has a faster convergence rate and better performance than the basic TLBO and some other algorithms as well.

Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes.

BACKGROUND: The role of the antioxidant N-acetylcysteine (NAC) in the treatment of chronic obstructive pulmonary disease (COPD) has not been clarified as yet. In early studies, we found that the proportion of smokers with COPD having extremely slow/slow microsomal epoxide hydrolase (EPHX1) enzyme activity is significantly higher than that in healthy smokers. The purpose of this study was to evaluate whether different EPHX1 enzyme activity is related to differential therapeutic effects of treatment with NAC in COPD. METHODS: A total of 219 patients with COPD were randomly allocated to an extremely slow/slow EPHX1 enzyme activity group (n=157) or a fast/normal EPHX1 enzyme activity group (n=62) according to their EPHX1 enzyme activity. Both groups were treated with NAC 600 mg twice daily for one year. The main study parameters, including forced expiratory volume in one second (FEV1), St George's Respiratory Questionnaire (SGRQ), and yearly exacerbation rate, were measured at baseline and at 6-month intervals for one year. RESULTS: Both FEV1 and SGRQ symptom scores were improved after treatment with NAC in the slow activity group when compared with the fast activity group. Further, changes in FEV1 and SGRQ symptom score in patients with mild-to-moderate COPD were more significant than those in patients with severe-to-very severe COPD. The yearly exacerbation rates were reduced in both groups, but the reduction in the slow activity group was significantly lower than in the fast activity group. CONCLUSION: NAC treatment in COPD patients with extremely slow/slow EPHX1 enzyme activity improves FEV1 and the SGRQ symptom score, especially in those with mild-to-moderate COPD, and polymorphism in the EPHX1 gene may have a significant role in differential responses to treatment with NAC in patients with COPD.

[Relationship between mitochondrial cytochrome oxidase mRNA expression and maternal inheritance of asthma].

OBJECTIVE: To explore the relationship between the mRNA expression level of mitochondrial cytochrome oxidase and the maternal inheritance of asthma. METHODS: From January to December 2009, 220 asthma patients, 162 patient kins and 260 healthy subjects were recruited from Departments of Respiratory Critical Care Medicine and Pediatric Medicine at First Affiliated Hospital, Kunming Medical College. Lung function tests were performed and serum IgE level measured. The polymorphism of mitochondrial cytochrome oxidase gene polymorphisms was detected by direct sequencing. And the peripheral level of COX mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: No significant difference existed in age, gender among 3 groups. For 3 groups, the first second forced expiratory volume (FEV1)/forced vital capacity (FVC) were 90.6 ± 6.2, 92.3 ± 2.3, 102.3 ± 2.3 and FEV1 percentage of expected value (FEV1%) were (82.9 ± 10.8)%, (94.8 ± 5.4)% and (98.3 ± 8.6)% respectively. The lung function was not significant difference among three groups. The mRNA expression level of mitochondrial cytochrome oxidase in peripheral blood were 0.357 ± 0.217, 0.637 ± 0.473 and 0.975 ± 0.260 in the asthma, kin and control groups respectively. No significant difference existed in the expression level of COX3 mRNA among 3 groups (F = 21.45, P = 0.012). The serum level of lgE was the highest for the asthma patients. And it was significantly higher in the asthma group than that in the control group ((283.6 ± 62.4) vs (52.3 ± 13.7) µg/L, F = 48.31, P < 0.05). Moreover, the serum level of IgE was significantly higher in the kin group than that in the control group ((116.4 ± 57.5) vs (52.3 ± 13.7) µg/L, F = 20.45, P < 0.05). However, there was a negative correlation between the mRNA expression level of mitochondrial cytochrome oxidase and the serum level of IgE among 3 groups. CONCLUSIONS: The down-regulated mRNA expressin of mitochondrial cytochrome oxidase may participate in allergic inflammation by regulating the level of IgE. And the maternal inheritance of asthma is in effect.

Replication study in Chinese Han population and meta-analysis supports association between the MBL2 gene polymorphism and HIV-1 infection.

Mannose-binding lectin (MBL) plays an important role in immunity to HIV-1 infection. The exon1 coding polymorphisms of the MBL2 gene have been implicated in the susceptibility to HIV-1 infection, but the results were controversial. In the present study, a case-control study in a Chinese population was conducted to replicate the association, and then a meta-analysis combing our new data and published data was performed to clarify these findings. In total, 15 studies consisting 2219 HIV-1 patients and 2744 controls were included. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were assessed in the main analyses. By dividing the controls into two groups, healthy controls and HIV-1 exposed but seronegative (HESN) controls, we explored different genetic models and allelic model to detect the association. By using the healthy controls, we found that the MBL2 exon 1 polymorphisms were associated with hosts' susceptibility to HIV-1 infection in dominant model (p=0.01, 95% CI 1.05-1.43), recessive model (p<0.0001, 95% CI 1.35-2.28), allelic model (p<0.0001, 95% CI 1.12-1.37) and O/O vs. A/A model (p<0.00001, 95% CI 1.40-2.38). In the subgroup analysis by ethnicity, significant elevated risks were found in Caucasians (recessive model: p<0.0001, 95% CI 1.36-2.51), but not in Asians (recessive model: p=0.10, 95% CI 0.91-2.77). Collectively, our findings from our case-control replication study and meta-analysis suggested that the MBL2 gene exon 1 coding variants were associated with hosts' susceptibility to HIV-1 infection, especially in Caucasians, but not in Asians.

The VNTR polymorphism of the CLEC4M gene and susceptibility to HIV-1 infection in Han Chinese population.

C-type lectin domain family 4, member M (CLEC4M, also known as DC-SIGNR) is a C-type lectin that functions as a transreceptor for human immunodeficiency virus-1 (HIV-1). The relationship between variable number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and susceptibility to HIV-1 infection has been under debate. In the present study, a cohort of 287 HIV-1 seropositive patients and 388 ethnically age-matched healthy controls from Han Chinese population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. A total of 11 genotypes and 5 alleles were found in our population. A cross-sectional comparison between HIV-1 seropositive patients and healthy controls did not reveal significant differences with regards to DC-SIGNR genotype distribution, allele frequencies and homozygotes proportion. In addition, previous studies showed that DC-SIGNR might play different roles in different HIV infection routes. We stratified the patients into two subgroups: sexual contact patients and intravenous drug abuser/blood transfusion patients. Our results showed the frequencies of DC-SIGNR genotypes/alleles in these two subgroups were similar. To our knowledge, this is the first study performed in Northern Chinese. Our findings suggested that DC-SIGNR neck region VNTR polymorphism was not directly associated with hosts' predisposition for HIV-1 infection and not associated with the HIV-1 routes of infection. By lack of HIV-1 exposed seronegative (HESN) individuals and relative small sample size in present study made our conclusions not strong enough. In addition, the role of the DC-DIGNR neck region in different HIV-1 infection routes remains open for future study.

[Application of half-dose depot long-acting triptorelin in postoperative adjuvant therapy for endometriosis].

OBJECTIVE: To evaluate the efficacy and adverse effects of half-dose depot long-acting triptorelin in the therapy of endometriosis. METHODS: The efficacy and adverse effects of routine-dose or half-dose triptorelin in postoperative endometriosis patients were prospectively observed. A total of 186 postoperative patients with moderate or severe endometriosis received an intramuscular injection of triptorelin every 28 days for 6 times. They were randomly divided into 3 groups, i.e. half-dose group (n = 99): 1.875 mg each time; "draw-back" group (n = 52): 3.75 mg first time, then 1.875 mg each time; and routine-dose group (n = 35): 3.75 mg each time. RESULTS: Amenorrhea was effectively induced in all patients after the second injection. There was no significant difference in the rate of serum E2 level at Day 28 of every injection below the upper limit of "estrogen threshold (110 - 146 pmol/L)" not stimulating ectopic endometrium proliferation among half-dose group, "draw-back" group and routine-dose group (99% vs 100% and 99.0%, P > 0.05), the percentage of E2 < 37 pmol/L in E2 < 110 pmol/L in half-dose group was significantly lower than that in "draw-back" and routine-dose groups after 2-5(th) injection (69% vs 79% and 85%, P < 0.01), but there was no significant difference after first half-dose and routine-dose injection (71% vs 73%, P > 0.05). No significant difference existed in the rate of pelvic pain relief during the first returning menstruation and the recurrence rate of endometriosis within 1 year postoperation among three groups (both P > 0.05). However, the incidences of menopausal syndrome and severe menopausal syndrome in half-dose group were significantly lower than those in "draw-back" and routine-dose groups (both P < 0.01). And the incompletion rate of six-time drug for severe menopause syndrome was also significantly lower (P < 0.05) while the completion rate of six-time drug use in half-dose group was significantly higher (P < 0.05). CONCLUSION: As a postoperative adjuvant, half-dose depot triptorelin therapy is efficacious for endometriosis. It reduces menopausal syndrome and treatment cost and enhances patient compliance.