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Objectives To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. Methods The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. Results The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47–10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P P P = 0.01), stress ulcer with gastraintestinal bleeding (SUB) (OR = 6.36, 95% CI: (1.45 ~ 28.01, P = 0.01) were significantly related the 10-year mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 (OR = 2.97,95% CI:1.46 ~ 6.03, P P = 0.03) were significantly related to the 10-year mortality of patients with STEMI and a CTO. Conclusions The presence of a CTO in a non-IRA, an age ≥ 65 years, an in-hospital Killip class ≥ 3, and the presence of renal insufficiency, and SUB were independent risk predictors for the long-term mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 and renal insufficiency were independent risk predictors for the long-term mortality of patients with STEMI and a CTO.

Impaired exercise following Fontan is a surrogate of morbidity. Single-center longitudinal data exist, but there is a lack of contemporary multi-center data. Ramp cycle ergometry was re-performed in consented participants who had originally participated in the Pediatric Heart Network’s Fontan cross-sectional study. Annualized change was evaluated at maximal and submaximal exercise. Associations between these outcomes and patient characteristics were analyzed. There were 336 participants in Fontan 3, mean age 23.2 years. Paired measurements of peak oxygen consumption (peak VO(2)) were available for 95; peak exercise data at Fontan 3 were available for 275. Percent-predicted peak VO(2) declined by 0.8 ± 1.7% per year (p < 0.001). At Fontan 3, the lowest performing peak VO(2) tertile had the highest rate of overweight and obesity (p < 0.001). Female gender was more prevalent in the highest performing tertile (p = 0.004). Paired data at the ventilatory anaerobic threshold (VO(2) at VAT) were available for 196; VAT data at Fontan 3 were available for 311. Percent-predicted VO(2) at VAT decreased by 0.8 ± 2.6% per year (p < 0.001). At Fontan 3, VO(2) at VAT was better preserved than peak VO(2) across all tertiles, with higher rates of overweight and obesity in the lower performing group (p = 0.001). Female gender (p < 0.001) and left ventricular morphology (p = 0.03) were associated with better performance. Submaximal exercise is better preserved than maximal in the Fontan population, but declined at the same rate over the study period. The overall longitudinal rate of decline in exercise performance is slower than what has been described previously.

Ruminants have a superficial implantation pattern. The extended conceptus attaches to the receptive endometrium to form the cotyledonary placenta. During the attachment, a large number of events occur at the maternal-fetal interface. However, the related molecular mechanisms have not been fully understood. Integrin beta8 (ITGB8) is a subunit of integrin beta involved in embryo implantation. In this study, we determined peri-implantation expression and regulation of ITGB8 in goat uterus. The mRNA and protein levels of ITGB8 were both high in goat endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) during the adhesion period (Days 16-19 of pregnancy). Such expression profile was opposite to that of microRNA-187 (miR-187). Then, we validated that miR-187 targeted the 3' untranslated region (UTR) of ITGB8 in primary goat endometrial epithelial cells (EECs). In EECs, inhibition of miR-187 resulted in not only up-regulated ITGB8 level but also reduced cell proliferation and focal adhesion kinase (FAK) activity. Moreover, ITGB8 and miR-187 were regulated by interferon tau (IFNT). Altogether, in goat, the miR-187/ITGB8 axis may be involved in conceptus attachment and is downstream of IFNT. Our results will help us better understand the mechanisms of ruminant implantation and may provide a useful tool to improve the reproduction ratio for ruminants.

Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.

Pregnancy success is closely related to the molecular mechanisms that control energy metabolism balance. However, the mechanisms have not been fully understood. Uncoupling protein 2 (UCP2) plays a physiological role by regulating energy metabolism in numerous tissues. In this study, we determined the expression and hormone regulation of UCP2 in goat uterus. UCP2 is expressed in the luminal and glandular epithelia of goat uterus during early pregnancy, as revealed by in situ hybridization and immunohistochemistry conducted on pregnant goats. The signals were detected from day 0 (D0) to D30 of pregnancy, though weak on D16 (the adhesion period). The low levels of UCP2 on D16 were confirmed by RT-qPCR and western blot. In goat uterus and endometrial epithelial cells (EECs), UCP2 was up-regulated by progesterone and estrogen. In addition, after goat EECs were treated with genipin (an inhibitor of UCP2), not only UCP2 expression but also cell proliferation was inhibited. Collectively, UCP2 is dynamically expressed in goat uterus and can affect EEC proliferation, suggesting that it may participate in regulating the energy metabolism balance of goat uterus during early pregnancy.

Streptococcus suis serotype 2 (S. suis 2) is an important swine pathogen and also an emerging zoonotic agent. HtpsA has been reported as an immunogenic cell surface protein on the bacterium. In the present study, we constructed an isogenic mutant strain of htpsA, namely ΔhtpsA, to study its role in the development and virulence of S. suis 2. Our results showed that the mutant strain lost its typical encapsulated structure with decreased concentrations of sialic acid. Furthermore, the survival rate in whole blood, the anti-phagocytosis by RAW264.7 murine macrophage, and the adherence ability to HEp-2 cells were all significantly affected in the ΔhtpsA. In addition, the deletion of htpsA sharply attenuated the virulence of S. suis 2 in an infection model of mouse. RNA-seq analysis revealed that 126 genes were differentially expressed between the ΔhtpsA and the wild-type strains, including 28 upregulated and 98 downregulated genes. Among the downregulated genes, many were involved in carbohydrate metabolism and synthesis of virulence-associated factors. Taken together, htpsA was demonstrated to play a role in the morphological development and pathogenesis of the highly virulent S. suis 2 05ZYH33 strain.

To make early predictions of preeclampsia before diagnosis, we developed and validated a new nomogram for the early prediction of preeclampsia in pregnant Chinese women. A stepwise regression model was used for feature selection. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. The signature, which consisted of 11 selected features, was associated with preeclampsia status (P < 0.1) for the development dataset. Predictors contained in the individualized prediction nomogram included BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator levels. The model showed good discrimination, with an area under the ROC curve of 0.8563 (95% CI: 0.8364-0.8761) and good calibration. The nomogram still had good discrimination and good calibration when applied to the validation dataset (area under ROC curve of 0.8324, 95% CI: 0.7873-0.8775). Decision curve analysis demonstrated that the nomogram was clinically useful. The nomogram presented in this study incorporates BMI, blood pressure, uterine artery ultrasound parameters, and serological indicators and can be conveniently used to facilitate the individualized prediction of preeclampsia.

Objective During pregnancy, inhibin A is mainly derived from the placenta and regulates the implantation and differentiation of embryos. Our aim was to assess whether second trimester serum inhibin A was associated with an increased risk of adverse pregnancy outcomes. Methods We investigated the serum levels of Inhibin A during the second trimester in pregnancy, and analyzed associations between the Inhibin A and the risk of adverse pregnancy outcome. 12,124 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Multivariate logistic regression analysis was conducted to estimate the relative risk between Inhibin A and adverse pregnancy outcome. Results Compared with the group without adverse pregnancy outcome, during the second trimester of pregnancy, age and Inhibin A were risk factors for pre-eclampsia, gestational diabetes mellitus and preterm delivery; Inhibin A was risk factors for low birth weight. Gravidity and Inhibin A were risk factors for macrosomia; while parity was a protective factor against pre-eclampsia, gestational hypertension and low birth weight. Conclusion Elevated Inhibin A levels in pregnancy are significantly associated with pre-eclampsia, GDM, macrosomia, low birth weight and preterm delivery.

Embryo implantation is crucial for a successful pregnancy. Although many essential molecular modulators and pathways have been identified, the precise mechanisms of the process in goat remain largely unknown. CCN2 is a connective tissue growth factor participating in many biological processes; however, its presence or function in goat uterus has not yet been reported. In this study, we determined the expression and regulation of CCN2 in goat uterus. CCN2 was not detected by in situ hybridization at ED0 (Day 0 of the estrous cycle), but at ED6 (metestrus), ED12 (dioestrus), and ED16 (proestrus), with high signals in luminal epithelium, superficial glands, and caruncula matrix. During early pregnancy, CCN2 was also detected in these locations on D0 and D6 (pre-receptive uterus). The signals significantly increased on D16 and D19 (receptive uterus), and remained at high levels on D25 and D30. Similarly, the RT-qPCR assays showed that the mRNA level of CCN2 was relatively low on D0 and D6, increased on D16, peaked on D19, and kept high thereafter. Moreover, CCN2 was up-regulated not only in ovariectomized ewes subcutaneously injected with 17β-estradiol and progesterone (separately or together), but also in cultured goat uterine epithelial cells treated with the two hormones or interferon tau (IFNτ). In conclusion, CCN2 expression may be induced by 17β-estradiol, progesterone, and IFNτ in the luminal epithelium of goat receptive uterus, suggesting that CCN2 is involved in goat embryo adhesion during early pregnancy.

Background. Grip-force performance can be affected by aging, and hand-grip weakness is associated with functional limitations of dasily living. However, using an appropriate digital hand-held dynamometer with continuous hand-grip force data collection shows age-related changes in the quality of hand-grip force control may provide more valuable information for clinical diagnoses rather than merely recording instantaneous maximal hand-grip force in frail elderly adults or people with a disability. Therefore, the purpose of this study was to indicate the construct validity of the digital MicroFET3 dynamometer with Jamar values for maximal grip-force assessments in elderly and young adults and confirmed age-related changes in the maximal and the quality of grip-force performance using the MicroFET3 dynamometer in elderly people. Methods. Sixty-five healthy young (23.3±4.5 years) and 50 elderly (69.5±5.8 years) adults were recruited and asked to perform a validity test of the grip-force maximum voluntary contraction (MVC) using both the dominant and nondominant hands with a Jamar dynamometer and a MicroFET3 dynamometer. Results. A strong correlation of maximal grip-force measurements was found between the MicroFET3 dynamometer and Jamar standard dynamometer for both hands in all participants (p<0.05). Although, the results showed that a lower grip force was measured in both hands by the MicroFET3 dynamometer than with the Jamar dynamometer by 49.9%~57% (p<0.05), but confidently conversion formulae were also developed to convert MicroFET3 dynamometer values to equivalent Jamar values for both hands. Both dynamometers indicated age-related declines in the maximum grip-force performance by 36.7%~44.3% (p<0.05). We also found that the maximal hand-grip force values generated in both hand by the elderly adults were slower and more inconsistent than those of the young adults when using the MicroFET3 dynamometer. Conclusions. This study demonstrated that the digital MicroFET3 dynamometer has good validity when used to measure the maximal grip force of both hands, and conversion formulae were also developed to convert MicroFET3 dynamometer force values to Jamar values in both hands. Comparing with the Jamar dynamometer for measuring grip force, the MicroFET3 dynamometer not only indicated age-related declines in the maximum grip-force performance but also showed slower and more inconsistent maximal hand-grip strength generation by the elderly.

Depression is one of the most frequent psychiatric symptoms observed in people during the development of Alzheimer's disease (AD). We hypothesized that genetic factors conferring risk of depression might affect AD development. In this study, we screened 31 genes, which were located in 19 risk loci for major depressive disorder (MDD) identified by two recent large genome-wide association studies (GWAS), in AD patients at the genomic and transcriptomic levels. Association analysis of common variants was performed by using summary statistics of the International Genomics of Alzheimer's Project (IGAP), and association analysis of rare variants was conducted by sequencing the entire coding region of the 31 MDD risk genes in 107 Han Chinese patients with early-onset and/or familial AD. We also quantified the mRNA expression alterations of these MDD risk genes in brain tissues of AD patients and AD mouse models, followed by protein-protein interaction network prediction to show their potential effects in AD pathways. We found that common and rare variants of L3MBTL2 were significantly associated with AD. mRNA expression levels of 18 MDD risk genes, in particular SORCS3 and OAT, were differentially expressed in AD brain tissues. 13 MDD risk genes were predicted to physically interact with core AD genes. The involvement of HACE1, NEGR1, and SLC6A15 in AD was supported by convergent lines of evidence. Taken together, our results showed that MDD risk genes might play an active role in AD pathology and supported the notion that depression might be the "common cold" of psychiatry.

Subglottic stenosis (SGS) is a common cause of obstructed airway in children, and the treatment of pediatric SGS, especially congenital SGS, remains a challenge for the otolaryngologist. Objective To analyze the outcomes of endoscopic management in young children with SGS. Methods We performed a retrospective review of treatment with endoscopic balloon dilation (EBD) or EBD combined with endoscopic anterior cricoid split (EACS) for young SGS children, from December 2008 to December 2015. The ages of patients ranged from 2 days to 12 years, median age was 5 months. The grade of them ranged from II to IV. Results For acute acquired SGS, 19 cases received EBD alone and the other 3 cases received EBD and EACS, the success rate was about 95.5%; For chronic acquired SGS, EBD and EACS was performed in 6 patients with a success rate of 66.7%; For congenital SGS, EBD and EACS was performed in 28 patients with a success rate of 85.7%. Overall, the success rate of endoscopic management in 56 young children was about 87.5%. Besides, No procedure-related complications were observed in any patients. Conclusions Endoscopic surgical technique offers a safe and effective approach for treatment of young children with SGS, especially in congenital SGS.

Background Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing. Methods We included 122 neonates and infants (0–180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200–300 pg ml−1), medium (400–500 pg ml−1), and high (600–700 pg ml−1) DEX plasma concentrations. Results Five of 122 subjects had adverse safety outcomes (4.1%; 95% confidence interval [CI], 1.8–9.2%). Two had junctional rhythm, two had second-/third-degree atrioventricular block, and one had hypotension. Clearance (CL) immediately postoperative and CL on CPB were reduced by approximately 50% and 95%, respectively, compared with pre-CPB CL. DEX clearance after CPB was 1240 ml min−1 70 kg−1. Age at 50% maximum clearance was approximately 2 days, and that at 90% maximum clearance was 18 days. Overall, 96.1% of measured DEX concentrations fell within the 5th–95th percentile prediction intervals in the PK model validation. Dosing strategies are recommended for steady-state DEX plasma levels ranging from 200 to 1000 pg ml−1. Conclusions When used with a careful dosing strategy, DEX results in low incidence and severity of adverse safety events in infants undergoing cardiac surgery with cardiopulmonary bypass. This validated PK model should assist clinicians in selecting appropriate dosing. The results of this phase 1 trial provide preliminary data for a phase 3 trial of DEX neuroprotection. Clinical trials registration NCT01915277.

Yue Huang, Xiao-Lin Yang, Yi-Hua Ni, Zheng-Min Xu Department of Otolaryngology-Head and Neck Surgery, Children’s Hospital of Fudan University, Shanghai, China Background: Geraniol is a monoterpene alcohol that has anti-fungal, anti-cancer and anti-nociceptive properties, but its anti-allergic rhinitis (AR) property is unclear.Methods: In this study, the anti-inflammatory role and its possible mechanisms of geraniol in human mast cell line (HMC-1) cells stimulated by inflammatory trigger phorbol 12-myristate 13-acetate plus A23187 (PMACI), as well as in ovalbumin (OVA)-induced AR mice models were investigated.Results: PMACI results in a significant increase in the production of proinflammatory cytokines, such as TNF-α, IL-1β, MCP-1, IL-6 and as well as histamine. Geraniol was found to inhibit both TNF-α, IL-1β and IL-6 protein and mRNA expressions at concentrations of 40, 80, 160μM. In OVA-induced AR models, geraniol treatment was able to suppress AR biomarkers (OVA-specific IgE and IL-1β as well as histamine) and nasal rub scores. Interestingly, p38, a member of the mitogen-activated protein kinase (MAPK) signaling family, was found to be increasingly hypophosphorylated as geraniol dose was increased. Similar decreases in the nuclear level of p65, a member of the nuclear factor kappa B (NF-κB) signaling pathway, were also observed.Conclusion: Our data highlights that the anti-inflammatory properties of geraniol on AR-related markers in activated HCM-1 cells and OVA-induced AR models may be mediated through the regulation of the MAPK/NF-κB signaling pathway. Keywords: geraniol, HMC-1, allergic rhinitis, PMACI

Drug-resistance of platinum remains a big challenge for effective treatment of patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are associated with multi-drug resistance. Our study aims on identifying role of miRNAs in drug-resistance of platinum in ovarian cancer. In present study, we compared the expression profiles of miRNAs between three pairs of platinum-resistant and platinum-sensitive ovarian tissues and found that miR-509-3p was significantly down-regulated in cisplatin-resistant ovarian cancer tissues. The different expression of miR-509-3p was further determined by RT-qPCR analyses of tissue samples from groups of 20 patients with cisplatin-sensitive ovarian cancer and 7 patients with cisplatin-resistant ovarian cancer. Functional studies demonstrated that miR-509-3p inhibitor decreased cell response to cisplatin (CDDP) and promoted cell survival in SKOV3 ovarian cancer cells. Furthermore, we found gene expression level of Golgi phosphoprotein-3 (GOLPH3) and wntless Wnt ligand secretion mediator (WLS) were regulated by miR-509-3p. The direct bindings of miR-509-3p to GOLPH3 and WLS genes were confirmed by dual-luciferase reporter assay. And the negative correlation between their expression levels in SKOV3 cells was further verified with RT-qPCR. Altogether, our data provide preliminary evidence, supporting that targeting miR-509-3p might be a potential therapeutic strategy for patients with platinum-resistant ovarian cancer.

Anhedonia and amotivation, the hallmarks of negative symptoms in schizophrenia, are believed to be due to "emotion-behavior decoupling," a failure in translating pleasure experience into appropriate goal-directed behavior. A number of studies have reported that long-term institutionalized schizophrenia patients suffer from more severe negative symptoms than community-dwelling patients, but few studies have investigated pleasure experience and motivational behavior in schizophrenia patients who have experienced long-term institutionalization. In this study, we recruited 26 long-term institutionalized schizophrenia patients, 27 community-dwelling schizophrenia patients, and 27 healthy controls. Participants were administered two specific computer-based tasks to assess anhedonia and amotivation. The Anticipatory and Consummatory Pleasure (ACP) Task was used to measure emotion-behavior decoupling and the Effort-Expenditure for Rewards Task (EEfRT) was used to measure amotivation related to rewards. Findings from the ACP Task showed that compared with healthy controls, the coupling between emotion experience and motivated behavior was significantly weaker in both clinical groups, suggesting that emotion-behavior decoupling could be a stable trait in schizophrenia patients. In the EEfRT, compared with both community-dwelling patients and healthy controls, institutionalized patients with schizophrenia failed to expend more effort to gain potential rewards even when reward probability increased. These findings further reveal the underlying mechanism of anhedonia and amotivation and their potential relationships with long-term institutionalization in patients with schizophrenia.

Background Long-term outcomes of very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are still unclear. The aim was to evaluate the long-term outcomes after VLST of DES, and to analyze the related factors of long-term outcomes in these patients. Methods From January 2006 to February 2013, patients with angiographically defined VLST were studied. The clinical characteristics, angiography and interventional data, and anti-platelet therapy protocols were analyzed. The patients were divided into two groups according to the occurrence of major adverse cardiac events (MACE) during follow-up. The clinical and interventional data between the two groups were compared. Results Sixty-two patients were enrolled consisting of 55 males and 7 females with an average age of 58.6 ± 10.2 (41–82) years. The mean time from first implantation of DES to occurrence of VLST was 38.7 ± 18.1 (12.5–84) months. One patient died in hospital. Sixty-one patients survived to discharge, and MACE occurred in 17 patients after a median follow-up of 32.1 ± 19.1 (median: 44, range 5–88) months. The total MACE rate was 29.0% (18/62), and Kaplan–Meier survival analysis showed the estimated MACE-free survival was 45.1%. The rate of implantation of an additional first-generation DES during the first VLST in the group with events was higher (44.4% vs.11.4%, respectively, p = 0.007). The percentage of continuous dual antiplatelet therapy (DAPT) at the longest available follow-up was higher in the event-free group (27.8% vs. 75.0%, respectively, p = 0.001). Multivariable Cox regression analysis revealed that the only independent predictors for freedom of MACE during long-term follow-up was continuous DAPT at the longest available follow-up [hazard ratio (HR) = 0.30, 95% CI: 0.09–0.97, p = 0.04]. Conclusions Long-term outcomes after VLST were unfavorable. Implantation of an additional first-generation DES might be avoided, and DAPT should be continued.

Background To determine the survival of patients with stroke for up to 10 years after a first-time stroke and to investigate whether stroke rehabilitation within the first 3 months reduced long-term mortality in these patients. Methods We used the medical claims data for a random sample of 1 million insured Taiwanese registered in the year 2000. A total of 7767 patients admitted for a first-time stroke between 2000 and 2005; 1285 (16.7%) received rehabilitation within the first 3 months after stroke admission. The other 83.3% of patients served as a comparison cohort. A Cox proportional hazards model was used to estimate the relative risk of mortality in relation to the rehabilitation intervention. Results In all, 181 patients with rehabilitation and 1123 controls died, representing respective mortality rates of 25.0 and 32.7 per 1000 person-years. Rehabilitation was significantly associated with a lower risk of mortality (hazard ratio .68, 95% confidence interval .58-.79). Such a beneficial effect tended to be more obvious as the frequency of rehabilitation increased ( P for the trend Conclusions Stroke rehabilitation initiated in the first 3 months after a stroke admission may significantly reduce the risk of mortality for 10 years after the stroke.

Alkaline phosphatase (AP) activity has been demonstrated in the uterus of several species, but its importance in the uterus, in general and during pregnancy, is yet to be revealed. In this study, we focused on identifying AP isozyme types and their hormonal regulation, cell type, and event-specific expression and possible functions in the hamster uterus during the cycle and early pregnancy. Our RT-PCR andin situhybridization studies demonstrated that among the knownAkp2,Akp3,Akp5, andAkp6murine AP isozyme genes, hamster uteri express onlyAkp2andAkp6; both genes are co-expressed in luminal epithelial cells. Studies in cyclic and ovariectomized hamsters established that while progesterone (P4) is the major uterineAkp2inducer, both P4and estrogen are strongAkp6regulators. Studies in preimplantation uteri showed induction of both genes and the activity of their encoded isozymes in luminal epithelial cells during uterine receptivity. However, at the beginning of implantation,Akp2showed reduced expression in luminal epithelial cells surrounding the implanted embryo. By contrast, expression ofAkp6and its isozyme was maintained in luminal epithelial cells adjacent to, but not away from, the implanted embryo. Following implantation, stromal transformation to decidua was associated with induced expressions of onlyAkp2and its isozyme. We next demonstrated that uterine APs dephosphorylate and detoxify endotoxin lipopolysaccharide at their sites of production and activity. Taken together, our findings suggest that uterine APs contribute to uterine receptivity, implantation, and decidualization in addition to their role in protection of the uterus and pregnancy against bacterial infection.

Background and Purpose: Vascular endothelial growth factor (VEGF) plays a key role in the development of cerebral infarction as a major mediator of angiogenesis. The aim of this study was to investigate whether the VEGF gene polymorphisms were associated with the risks of acute cerebral infarction. Methods: We examined the distribution of three single nucleotide polymorphisms (SNPs), –1154G/A, 936C/T and –2578C/A, in the promoter and coding region of the VEGF gene in DNA samples from 147 Chinese patients with acute cerebral infarction and 131 control subjects. Results: There was nosignificant difference in allele and genotype distributions of –1154G/A, 936C/T and –2578C/A with the risk of acute cerebral infarction when compared with controls. However, haplotype analysis from the above-mentioned three polymorphisms showed that haplotype ACC was significantly lower in patients with acute cerebral infarction (0.020) than in controls (0.054) (p = 0.034). Conclusions: These data suggested that the –1154/, 936/ and –2578/ ACC haplotype was associated with the risk of acute cerebral infarction with an OR of 0.361, and it may reduce the risk of acute cerebral infarction through the regulation of VEGF expression.

Background: The clinical application has widespread disagreement on the different regimens of neoadjuvant chemotherapy (NCT) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). We conducted a network meta-analysis (NMA) to evaluate the efficacy of the different NCT regimens in the treatment of NPC. Methods: A systematic literature search was performed using PubMed, Embase, and Cochran Library. Totally, 31 randomized controlled trials (RCTs) (n = 4062) met study selection criteria and were incorporated in this NMA study. Results: Our study showed that certain NCT regimens improved the prognosis of patients, and found out the relative best solution for each endpoint, such as paclitaxel, carboplatin, and gemcitabine for 1-year overall survival (OS) rate, cisplatin, calcium folinate, and 5-fluorouracil for 2-year OS rate, vinorelbine and cisplatin (NP) for 3-year OS rate, cyclophosphamide, cisplatin, and 5-fluorouracil for 5-year OS rate, NP for complete remission rate, cisplatin and gemcitabine for overall remission rate of the primary tumor. In addition, for certain grade 3 and above toxicity, the results of the NMA reflected certain NCT regimens can reduce toxicity of chemoradiotherapy (CRT) to a minimum, such as NP for anemia, mucositis, and thrombocytopenia, paclitaxel, epirubicin, and cisplatin for neutropenia and skin toxicity. Conclusion: Our NMA showed that certain cisplatin-based NCT regimens improved the prognosis of patients with NPC and reduced the toxicity of CRT. However, in view of survival rate and response rate, the best NCT regimen is not entirely consistent. Therefore, which NCT regimen will benefit most patients will need further explored.

Eight cellular homologs of the inhibitors-of-apoptosis proteins (IAP) have been identified in humans and of them, the X-linked IAP (XIAP) is the most potent. XIAP-associated factor 1 (XAF1) is a newly discovered XIAP-binding protein that negatively regulates the caspase-inhibiting activity of XIAP. It is either not expressed or present at extremely low levels in many cancer cell lines. The aims of the present study were: (i) to investigate the expression of XAF1 in human colorectal cancers (CRC) both in vitro and in vivo, and (ii) to evaluate the possibility of XAF1 as a new tumor marker.The expression of XAF1 in four human colon cancer cell lines (Colo205, Colo320, SW1116, LoVo) and in samples from 70 patients with CRC was analyzed by reverse transcriptase-polymerase chain reaction. XAF1 concentrations were also detected in the peripheral circulation of the 70 patients, as well as three traditional circulating cancer-associated antigens.A low concentration of XAF1 mRNA was detectable in the three colon cancer cell lines other than Colo205, which showed the strongest expression of XAF1. The expression of XAF1 in tissue was relatively lower in primary CRC compared with a relatively higher level in benign colorectal tumors (P0.01). Although the XAF1 expression in circulation of those with CRC was also lower than in those with benign tumors, there was no statistical significance (P0.05).The present results suggest that the low expression of XAF1 in tumor tissue coincides with a similar level in the peripheral circulation, which contributes at least part to the malignant behavior of CRC. Integrating the XAF1 relative expression value with the other three traditional tumor biomarkers created a four-parameter assay that significantly improved the rate of diagnosis of CRC.

The aim of this study was to examine the expression and regulation of peroxisome proliferator-activated receptor (PPAR) PPARδ gene in mouse uterus during early pregnancy by in situ hybridization and immunohistochemistry. PPARδ expression under pseudopregnancy, delayed implantation, hormonal treatment, and artificial decidualization was also investigated. There was a very low level of PPARδ expression on days 1–4 of pregnancy. On day 5 when embryo implanted, PPARδ expression was exclusively observed in the subluminal stroma surrounding the implanting blastocyst. No corresponding signals were seen in the uterus on day 5 of pregnancy. There was no detectable PPARδ signal under delayed implantation. Once delayed implantation was terminated by estrogen treatment and embryo implanted, a strong level of PPARδ expression was induced in the subluminal stroma surrounding the implanting blastocyst. Estrogen treatment induced a moderate level of PPARδ expression in the glandular epithelium, while progesterone treatment had no effects in the ovariectomized mice. A strong level of PPARδ expression was seen in the decidua on days 6–8 of pregnancy. PPARδ expression was also induced under artificial decidualization. These data suggest that PPARδ expression at implantation sites require the presence of an active blastocyst and may play an essential role for blastocyst implantation. Mol. Reprod. Dev. 66: 218–224, 2003. © 2003 Wiley-Liss, Inc.

Leukemia inhibitory factor (LIF) is essential for implantation of mouse embryos. The aim of this study was to assess the expression and regulation of LIF receptor (LIFR) and gp130 mRNA in mouse uterus during early pregnancy using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). A strong level of LIFR mRNA signal was detected in the luminal epithelium on day 5 of pregnancy. On day 6-8 of pregnancy, LIFR signal was mainly localized in the decidua. LIFR signal in the luminal epithelium of ovariectomized mouse was slightly stimulated by a combination of progesterone and estrogen. By RT-PCR, LIFR mRNA signal was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 5. A low level of gp130 mRNA signal was seen in the glandular epithelium on day 3 of pregnancy and reached a high level on day 4 of pregnancy. gp130 signal in the decidua appeared on day 6 of pregnancy and reached a high level on day 7 and 8 of pregnancy. After the ovariectomized mouse was treated with a combination of progesterone and estrogen, a strong gp130 signal was observed in the glandular epithelium, while no signal was detected after progesterone or estrogen treatment alone. By RT-PCR analysis, gp130 mRNA was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 4 of pregnancy. Additionally, a high level of LIFR and gp130 mRNA signal was detected in the decidua under artificial decidualization compared to the control uninjected horn. The co-expression of a high level of LIFR and gp130 mRNA in the decidua may play a key role during the decidualization and placentation.

Protein tyrosine phosphatase (PTP)‑α regulates the phosphorylation of focal adhesion kinase (FAK), which is important in cellular signal transduction and integration of proteins. It has been demonstrated that a FAK‑Del33 mutation (deletion of exon 33; KF437463) in breast cancer tissues regulates cell migration through FAK/Src signaling activation. However, the detailed pathway for Src activation with FAK‑Del33 remains to be elucidated. The present study used a retroviral expression system to examine changes in PTPα phosphorylation affected by the FAK‑Del33 protein in breast cancer cells. Small interfering (si)RNA targeting PTPα interfered with the phosphorylation of Src. Wound‑healing and migration assays were performed to identify cell morphology and quantitative analysis was performed by examining band color depth in western blot analysis. Significant differences were observed in the phosphorylation level of PTPα at Tyr789 between the FAK‑Del33 and the wild‑type breast cancer cells, suggesting that FAK regulated the phosphorylation level of PTPα at Tyr789 in breast cancer mutant FAK‑Del33 cells. The gene expression profile with FAK siRNA did not alter the levels of phosphorylation in other mutants, including autophosphorylation disability (Y397F), ATP kinase dominant negative (K454R) and protein 4.1, ezrin, radixin, moesin domain attenuate (Δ375). FAK RNAi inhibited the activity of the FAK‑Del33 at the Src site and rescued the elevated cell migration and invasion. The present study demonstrated for the first time, to the best of our knowledge, an increase in the phosphorylation level of PTPα‑Tyr789 by its upstream activator, FAK‑Del33, leading to Src activation in certain breast cancer cells, which has significant implications for metastatic potential.

OBJECTIVE: The aim of this study was to compare the 2-year clinical outcomes of overlapping second-generation everolimus-eluting stents (EES) with those of overlapping resolute zotarolimus-eluting stents (R-ZES) in the treatment of long coronary artery lesions. MATERIALS AND METHODS: This retrospective analysis included 256 patients treated with overlapping EES (n=121) and R-ZES (n=135) for long coronary artery lesions (total stent length per lesion ≥34 mm). Study endpoints included major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction, and target-vessel revascularization (TVR), as well as target-lesion revascularization and definite stent thrombosis separately at 2 years. RESULTS: In the two groups, the mean age was older and the average number of disease vessel was higher in the R-ZES group. The mean lesion length and total stent length per lesion were longer in the R-ZES group. EES were more frequently implanted in the left anterior descending coronary artery. No significant differences in the estimated MACE (5.8% for EES vs. 8.1% for R-ZES; P=0.548) or TVR (3.4% for EES vs. 4.0% for R-ZES; P=0.806) rates were noted between the two groups at 2-year follow-up. The incidence of definite stent thrombosis was low and similar in both groups (0.83% for EES vs. 0% for R-ZES; P=0.473). No significant differences were noted with respect to MACE or TVR between the two groups following propensity score matching. CONCLUSION: Stent overlap with second-generation EES or R-ZES was associated with low rates of MACE, TVR, and stent thrombosis at 2-year follow-up. Our results suggest that the use of overlapping EES or R-ZES in long coronary lesions is associated with good long-term clinical outcomes. These results need to be validated with randomized controlled trials.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for development of hypertension. Epidemiological surveys have found that risk of cardiovascular diseases increased in postmenopausal women. However, it is not well known about the profiles of hypertension of women with OSAHS in their different reproductive stages. This study aimed to investigate the difference of blood pressure profile between pre and postmenopausal women with OSAHS. Women who were tested by polysomnography (PSG) (n = 207) in Ruijin Hospital were recruited in the study. The subjects were divided into two groups of premenopausal women (24 with and 30 without OSAHS), and two groups of postmenopausal women (116 with and 37 without OSAHS). Among the groups, the differences of demographic and PSG variables were compared. The factors influencing blood pressure were further studied. The prevalence of hypertension (56.9 %) in postmenopausal OSAHS patients was higher than the other three groups. Among OSAHS patients, both average systolic blood pressure (SBP) and diastolic blood pressure (DBP) of postmenopausal women were higher than those of premenopausal ones [(129.9 ± 16.16 mmHg vs. 123.7 ± 18.89), (84.96 ± 9.88 mmHg vs. 78.81 ± 10.34), P = 0.05, P

To develop the national neglect norms for urban primary school students in China.According to multi-stage stratified cluster sampling principle, 24 cities of 13 provinces (municipalities) in China were selected during December 1 to 31, 2008. A total of 1491 students in grade 1 - 3 and 2236 students in grade 4 - 6 were selected. Questionnaire was designed by authors and the final norms were determined through several statistical analysis methods, such as item analysis method, factor analysis method, reliability analysis method. The reliability analysis and validity analysis were used to test the stability and reliability of the norms. The evaluation criteria of the scale was determined by the percentile method, then the initial development of the norm was completed.The two questionnaires of grade 1 - 3 and grade 4 - 6 students consisted of 55 and 57 items, respectively, whose item loadings were ranged from 0.301 to 0.687 and 0.321 to 0.730, which met the statistical requirements. For grade 1 - 3 students, the scale's total Cronbach α coefficients was 0.914, the total split-half reliability coefficients was 0.896, the Cronbach α coefficients of four level was above 0.737 except medical and social neglect, split-half reliability was ranged from 0.461 to 0.757; for grade 4-6 students, the scale's total Cronbach α coefficients was 0.916, split-half reliability was 0.883, except social neglect, the Cronbach α coefficients of other level was ranged 0.457 to 0.856, split-half reliability was ranged from 0.500 to 0.798. The total neglect cut-off score of the two scales grade 1-3 and 4-6 were 125 and 155, respectively.The structure of two norms was reasonable. The scales have good stability and reliability.

To investigate the relationship between the promoter polymorphism of IL-4 and IL-6 and chronic rhinosinusitis (CRS).One hundred and twenty-three patients with CRS and 239 healthy controls in Shanghai region were chosen in this study. The genotype of IL-4 gene -33TC and -590CT were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and the genotype of IL-10 gene -1082AG was determined using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Statistical calculations were performed using SAS 8.2 software.Significant differences were found in genotype distribution of -33TC and -590CT between the CRS group and the control group (χ2=6.6013, P=0.0102, χ2=6.6013, P=0.0304), and -33TC remained significant following application of the Bonferroni correction (P0.025). The relative risks of CRS with -33TC and -590CT were 1.818(P=0.0236, 95%CI 1.084-3.050) and 1.838 (P=0.0147, 95%CI 1.127-2.997). There was linkage disequilibrium (LD) between the -33TC and -590CT. The coefficient of linkage disequilibrium (D') was 0.77 and the related coefficient (r2) was 0.54. The -33T/-590T haplotype was associated with CRS and the relative risk was 1.653 (P=0.0130, 95%CI 1.107-2.469). There were only two genotypes of IL-10 gene-1082AG and the frequencies of the AA and AG genotypes were not different between the CRS and control groups.The promoter polymorphism of IL-4 -33TC and -590CT were associated with the susceptibility of CRS and the -33T/-590T haplotype was a risk factor for CRS, but there were no association between the -1082AG and CRS.

Embryo implantation into the maternal uterus is a crucial step for the successful establishment of mammalian pregnancy. Following the attachment of embryo to the uterine luminal epithelium, uterine stromal cells undergo steroid hormone-dependent decidualization, which is characterized by stromal cell proliferation and differentiation. The mechanisms underlying steroid hormone-induced stromal cell proliferation and differentiation during decidualization are still poorly understood. Ribonucleotide reductase, consisting of two subunits (RRM1 and RRM2), is a rate-limiting enzyme in deoxynucleotide production for DNA synthesis and plays an important role in cell proliferation and tumorgenicity. Based on our microarray analysis, Rrm2 expression was significantly higher at implantation sites compared with interimplantation sites in mouse uterus. However, the expression, regulation, and function of RRM2 in mouse uterus during embryo implantation and decidualization are still unknown. Here we show that although both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells undergoing decidualization, only RRM2 is regulated by progesterone, a key regulator of decidualization. Further studies showed that the induction of progesterone on RRM2 expression in stromal cells is mediated by the AKT/c-MYC pathway. RRM2 can also be induced by replication stress and DNA damage during decidualization through the ATR/ATM-CHK1-E2F1 pathway. The weight of implantation sites and deciduoma was effectively reduced by specific inhibitors for RRM2. The expression of decidual/trophoblast prolactin-related protein (Dtprp), a reliable marker for decidualization in mice, was significantly reduced in deciduoma and steroid-induced decidual cells after HU treatment. Therefore, RRM2 may be an important effector of progesterone signaling to induce cell proliferation and decidualization in mouse uterus.

BACKGROUND: Junctional adhesion molecule 2 (Jam2) is a member of the JAM superfamily. JAMs are localized at intercellular contacts and participated in the assembly and maintenance of junctions, and control of cell permeability. Because Jam2 is highly expressed in the luminal epithelium on day 4 of pregnancy, this study was to determine whether Jam2 plays a role in uterine receptivity and blastocyst attachment in mouse uterus. METHODOLOGY/PRINCIPAL FINDINGS: Jam2 is highly expressed in the uterine luminal epithelium on days 3 and 4 of pregnancy. Progesterone induces Jam2 expression in ovariectomized mice, which is blocked by progesterone antagonist RU486. Jam2 expression on day 4 of pregnancy is also inhibited by RU486 treatment. Leukemia inhibitory factor (LIF) up-regulates Jam2 protein in isolated luminal epithelium from day 4 uterus, which is blocked by S3I-201, a cell-permeable inhibitor for Stat3 phosphorylation. Under adhesion assay, recombinant Jam2 protein increases the rate of blastocyst adhesion. Both soluble recombinant Jam2 and Jam3 can reverse this process. CONCLUSION: Jam2 is highly expressed in the luminal epithelium of receptive uterus and up-regulated by progesterone and LIF via tyrosine phosphorylation of Stat3. Jam2 may play a role in the interaction between hatched blastocyst and receptive uterus.

Primary percutaneous coronary intervention (PCI) is the best treatment of choice for acute ST segment elevation myocardial infarction (STEMI). This study aimed to determine the clinical outcomes of tirofiban combined with the low molecular weight heparin (LMWH), dalteparin, in primary PCI patients with acute STEMI.From February 2006 to July 2006, a total of 120 patients with STEMI treated with primary PCI were randomised to 2 groups: unfractionated heparin (UFH) with tirofiban (group I: 60 patients, (61.2 ± 9.5) years), and dalteparin with tirofiban (group II: 60 patients, (60.5 ± 10.1) years). Major adverse cardiac events (MACE) during hospitalization and at 4 years after PCI were examined. Bleeding complications during hospitalization were also examined.There were no significant differences in sex, mean age, risk factors, past history, inflammatory marker, or echocardiography between the 2 groups. In terms of the target vessel and vascular complexity, there were no significant differences between the 2 groups. During the first 7 days, emergent revascularization occurred only in 1 patient (1.7%) in group I. Acute myocardial infarction (AMI) occurred in 1 (1.7%) patient in group I and in 1 (1.7%) in group II. Three (5.0%) patients in group I and 1 (1.7%) in group II died. Total in-hospital MACE during the first 7 days was 4 (6.7%) in group I and 2 (3.3%) in group II. Bleeding complications were observed in 10 patients (16.7%) in group I and in 4 patients (6.7%) in group II, however, the difference was not statistically significant. No significant intracranial bleeding was observed in either group. Four years after PCI, death occurred in 5 (8.3%) patients in group I and in 4 (6.7%) in group II. MACE occurred in 12 (20.0%) patients in group I and in 10 (16.7%) patients in group II.Dalteparin was effective and safe in primary PCI of STEMI patients and combined dalteparin with tirofiban was effective and safe without significant bleeding complications compared with UFH. Although there was no statistically significant difference, LMWH decreased the bleeding complications compared with UFH.

The objective of this study was to evaluate the effects of musical intervention on preoperative anxiety and vital signs in patients undergoing day surgery.Studies and systematic meta-analyses have shown inconclusive results of the efficacy of music in reducing preoperative anxiety. We designed a study to provide additional evidence for its use in preoperative nursing care.Randomised, controlled study.Patients (n = 183) aged 18-65 admitted to our outpatient surgery department were randomly assigned to either the experimental group (music delivered by earphones) or control group (no music) for 20 minutes before surgery. Anxiety, measured by the State-Trait Anxiety Inventory, and vital signs were measured before and after the experimental protocol.A total of 172 patients (60 men and 112 women) with a mean age of 40·90 (SD 11·80) completed the study. The largest number (35·7%) was undergoing elective plastic surgery and 76·7% of the total reported previous experience with surgery. Even though there was only a low-moderate level of anxiety at the beginning of the study, both groups showed reduced anxiety and improved vital signs compared with baseline values; however, the intervention group reported significantly lower anxiety [mean change: -5·83 (SD 0·75) vs. -1·72 (SD 0·65), p0·001] on the State-Trait Anxiety Inventory compared with the control group.Patients undergoing day surgery may benefit significantly from musical intervention to reduce preoperative anxiety and improve physiological parameters.Finding multimodal approaches to ease discomfort and anxiety from unfamiliar unit surroundings and perceived risks of morbidity (e.g. disfigurement and long-term sequelae) is necessary to reduce preoperative anxiety and subsequent physiological complications. This is especially true in the day surgery setting, where surgical admission times are often subject to change and patients may have to accommodate on short notice or too long a wait that may provoke anxiety. Our results provide additional evidence that musical intervention may be incorporated into routine nursing care for patients undergoing minor surgery.

This prospective random control study was performed to compare the efficacy and safety of primary percutaneous coronary intervention (PCI) with biodegradable polymer (Excel) and with durable polymer (Cypher Select) sirolimus-eluting stents in patients with acute ST-elevation myocardial infarction (STEMI).Consecutive patients with STEMI underwent primary PCI were randomly divided into Cypher group (n = 113) and Excel group (n = 115). The primary endpoints were major adverse cardiac events (MACE, including death, reinfarction and target vessel revascularization) within 12 months. The second endpoints included late luminal loss and restenosis at 9 months.Angiographic follow-up data at 9 months were available in 43 (38%) patients in Cypher group and 48 (42%) in Excel group. The rates of in-stent restenosis and in-segment restenosis were 2.3% vs. 2.1% (P = 0.937) and 4.7% vs. 6.3% (P = 0.738), respectively. The late luminal loss of in-stent and in-segment were (0.17 ± 0.26) mm vs. (0.18 ± 0.33) mm (P = 0.483) and (0.19 ± 0.36) mm vs. (0.20 ± 0.42) mm (P = 0.419), respectively. There were no significant differences in death (3.5% vs. 2.6%, P = 0.692), reinfarction (1.8% vs. 2.6%, P = 0.658), target vessel revascularization (1.8% vs. 2.6%, P = 0.658), MACE (5.3% vs. 6.1%, P = 0.788) or stent thrombosis (4.4% vs. 3.5%, P = 0.692) at 12 months between Cyper group and Excel group.Excel and Cypher Select stents may have similar mid-term efficacy and safety in patients with STEMI treated with primary PCI.Further investigation is warranted to validate the long-term efficacy and safety.

To explore the prognostic impact of post primary percutaneous coronary intervention (PCI) reperfusion status on outcome in patients with acute ST-elevation myocardial infarction (STEMI).A retrospective analysis was performed in 964 patients undergoing primary PCI for STEMI. Electrocardiogram and TIMI myocardial perfusion grade (TMPG) were analyzed by reader blinded to the clinical course. Patients were divided to four groups according to ST segment resolution (STR) and TMPG: group A were patients with good STR and TMPG(425/964), group B were patients with poor STR and good TMPG (239/964), group C were patients with good STR and poor TMPG (113/964) and group D were patients with poor STR and TMPG (113/964).Although TIMI grade III flow was achieved after mechanical reperfusion, abnormal reperfusion was still present in about 1/3 patients as shown by poor STR or TMPG. Older age, cardiac dysfunction and diabetes, prolonged time of pain to balloon/emergency room are independent risk factors for abnormal reperfusion post PCI. Major adverse cardiac events events in hospital (RR = 64. 63, P0.01) and during follow up (RR = 11.69, P0.01) were significantly higher in group D than in group A.Poor post PCI reperfusion status is associated with higher in hospital and during follow up major adverse cardiac events event in STEMI patients.

The clinical outcome of percutaneous coronary intervention (PCI) is poorer in women than that in men. This study aimed at comparing the impact of gender difference on the strategy of primary PCI in patients with acute ST-segment elevation myocardial infarction (STEMI).Two hundred and fifty-nine patients with STEMI who underwent primary PCI within 12 hours of symptom onset were enrolled. The male group consisted of 143 men aged55 years, and a female group included 116 women without age limitation. Procedural success was defined as residual stenosis20% with thrombolysis in myocardial infarction flow grade2 and without death, emergency bypass surgery or disabling cerebral events during the hospitalization. The rate of major adverse cardiac events (MACE), including death, nonfatal myocardial infarction and target vessel revascularization during follow-up, was recorded.Female patients were more hypertensive and diabetic and with fewer cigarette smokers than male counterparts. The prevalence of angiographic 3-vessel disease was higher in the female group, but the procedural success rate was comparable between the two groups (94.4% vs 92.2%). The occurrence rate of MACE did not differ during the hospitalization (4.2% vs 6.0%, P = 0.50), but was significantly higher in the female group during follow-up (mean (16.0 +/- 11.2) months) than that in the male group (5.4% vs 0.7%, P = 0.02).Despite a similar success rate of primary PCI and in-hospital outcomes in both genders, female patients with acute STEMI still have a worse prognosis during the long-term follow-up.

To observe the safety and long-term efficacy of Cypher stent versus bare metal stents (BMS) in patients with STEMI.From Dec 2002 to Mar 2005, clinical and angiographic data of 407 consecutive patients with STEMI treated with Cypher stent (n = 131) or BMS (n = 276) were analyzed and followed up for a mean period of 28.7 +/- 11.7 months. Major adverse cardiac events (MACE): death, nonfatal reinfarction and target lesion revascularization (TLR) during follow up was compared between two groups.Compared with the BMS group, diameter of vessels were significantly smaller (3.0mm vs. 3.2mm, P = 0.00), the incidence of MACE (6.1% vs. 12.7%, P = 0.04) and total mortality (1.5% vs. 6.9%, P = 0.02) were significantly lower in the Cypher group. The relative risk for MACE in Cypher group was 0.61 (P0.05), while there was no significant difference in the rate of stent thrombosis, rate of target lesion revascularization and restenosis.Utilization of Cypher in the setting of primary PCI for STEMI was safe and improved the long-term clinical outcomes compared to BMS.

To investigate the clinical and angiographic morphologic features leading to worse myocardial reperfusion in patients with acute ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Clinical and angiographic data were collected and logistic regression analysis performed in 964 STEMI patients undergoing primary PCI.Logistic regression analysis showed that non-anterior myocardial infarction, pain to balloon time and degree of cardiac dysfunction were clinical predictive factors while fade-out type of angiographic morphology, ie, presence of accumulated thrombus proximal to the occlusion was angiographic predictive factor of worse reperfusion for STEMI patients post PCI.These predictive clinical and angiographic morphologic factors in STEMI patients for worse myocardial reperfusion post PCI could help to identify patients at high risk post PCI.

To observe the effect of reperfusion therapy on the prognosis of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) in reperfusion era.89 cases of AMI with CS were included with 57 male and 32 female. 50 cases received conservative therapy and 39 cases reperfusion therapy. 28 of the 39 cases had successful reperfusion and 11 cases failed. 18 patients had intra-aortic balloon pump (IABP) within 1 hour of CS, they constituted an early group; 35 patients treated with IABP 1 hour after CS were of a late group. A group of 36 cases were not treated with IABP (no IABP group).The mortality of the early group with IABP was significantly lower than that of the late and no IABP group (33.3% vs. 74.2% vs. 86.1%, P0.01). The mortality of the group with successful reperfusion was significantly lower than that of unsuccessful reperfusion and conservative no IABP group (42.8% vs. 81.8% vs. 84.0% , P0.01). logistic regression analysis showed that successful reperfusion therapy (OR 4.232, 95% CI 1. 07 - 12.730, P = 0.01) and THE TIME of using IABP (OR 0.22, 95% CI 0.063 - 0.764, P =0.017) were independent risk factors for death.Early successful reperfusion and early institution of IABP were the most important therapeutic measures for reducing mortality of AMI complicated by CS.

To examine the mRNA expression of the linker for activation of T cell (LAT) and its upstream regulatory factors (Syk, Lck and ZAP-70) in the peripheral blood T cells of asthmatic patients.Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of LAT and its upstream regulatory factors (Syk, Lck and ZAP-70) in 20 asthmatic patients and 20 nonallergic subjects. The results of LAT transcription level were confirmed by real-time RT-PCR Results were expressed as x +/- s. Differences between groups were assessed for significance by t test.Compared with nonallergic subjects, a significant decrease of mRNA expression of LAT gene was observed in T cells of asthmatic patients (0.54 +/- 0.14 vs 0.72 +/- 0.17, t = 3.11, P0.01), which was verified by real-time RT-PCR (0.0065 +/- 0.0066 vs 0.0124 +/- 0.0045, t =0.0022, P0.01). The Lck and ZAP-70 gene transcription levels were significantly up-regulated (Lck: 0.71 +/- 0.16 vs 0.53 +/- 0.17, t = 3.18, P0.01; ZAP-70: 1.05 +/- 0.41 vs 0.82 +/- 0.27, t = 2.10, P0.05).A significant decrease of mRNA expression of LAT gene in T cells of asthmatic patients may be due to the up-regulation of its upstream regulatory factors (Lck and ZAP-70). The abnormal mRNA expression of LAT, Lck and ZAP-70 genes may be involved in the pathogenesis of asthma.

MicroRNAs (miRNAs) are 21-24-nucleotide non-coding RNAs found in diverse organisms. Although hundreds of miRNAs have been cloned or predicted, only very few miRNAs have been functionally characterized. Embryo implantation is a crucial step in mammalian reproduction. Many genes have been shown to be significantly changed in mouse uterus during embryo implantation. However, miRNA expression profiles in the mouse uterus between implantation sites and inter-implantation sites are still unknown. In this study, miRNA microarray was used to examine differential expression of miRNAs in the mouse uterus between implantation sites and inter-implantation sites. Compared with inter-implantation sites, there were 8 up-regulated miR-NAs at implantation sites, which were confirmed by both Northern blot and in situ hybridization. miR-21 was highly expressed in the subluminal stromal cells at implantation sites on day 5 of pregnancy. Because miR-21 was not detected in mouse uterus during pseudopregnancy and under delayed implantation, miR-21 expression at implantation sites was regulated by active blastocysts. Furthermore, we showed that Reck was the target gene of miR-21. Our data suggest that miR-21 may play a key role during embryo implantation.

To screen and identify the genes of activated memory CD(4)(+) T cells in asthma.Differential display polymerase chain reaction (DDPCR) was utilized to identify genes of memory CD(4)(+) T cells after activation from asthmatic patients and normal individuals, and the mRNA levels of the differentially expressed genes were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).Nineteen differentially expressed cDNA fragments were isolated. The homology analysis indicated that two fragments possessed a high degree of homology with interleukin-7 (IL-7) mRNA and MM-1 mRNA. RT-PCR confirmed that IL-7 mRNA and MM-1 mRNA levels were increased in memory CD(4)(+) T cells after activation in asthmatic patients (0.390 +/- 0.029, 0.629 +/- 0.047, F = 983, 1264 respectively, all P0.05).The up-regulated expression of IL-7 and MM-1 genes in memory CD(4)(+) T cells after activation may be a molecular mechanism that differentiates the response to allergens of asthma patients from normal individuals.

To investigate the differential expression and regulation of Gstm2 in mouse uterus during early pregnancy.Experimental animal study.University research laboratory.Sexually mature female Kunming white strain mice.Delayed and activated implantation, pseudopregnancy, hormonal treatment.The expression of Gstm2 mRNA was detected by in situ hybridization and reverse-transcription polymerase chain reaction (RT-PCR).By in situ hybridization, there were a low level of Gstm2 expression in luminal epithelium on day 3 and a strong level in the luminal epithelium on day 4 during early pregnancy. The expression pattern of Gstm2 in the pseudopregnant uterus was similar to that during early pregnancy. By RT-PCR, Gstm2 was strongly detected in the uteri on days 3 and 4 of pregnancy and pseudopregnancy. Gstm2 expression was strongly detected in the luminal epithelium under delayed implantation, but not seen after delayed implantation was activated by estrogen. In the ovariectomized mouse uterus, Gstm2 expression was strongly up-regulated by progesterone via progesterone receptor.The results showed that Gstm2 was highly expressed in the uterine luminal epithelium during preimplantation period and up-regulated by progesterone.

To investigate the single nucleotide polymorphism (SNP), the distribution of their haplotypes and linkage disequilibrium of hepatic lipase (HL) gene promoter 250G/A, 514C/T, 710T/C and 763A/G in cerebral infarction patients of Shanghai.Peripheral blood sample were collected from 133 patients with cerebral infarction and 112 healthy controls in Shanghai. The HL gene polymorphism was analyzed by polymerase chain reaction- restriction fragment length polymorphism.There were statistically significant differences in genotype and allele frequencies between the healthy controls and the patients with cerebral infarction in -250G/A and -514C/T genotypes and allele frequencies (all P0.05). However, there were no significant differences in genotype and allele frequencies in -710T/C and -763A/G between the healthy controls and the patients with cerebral infarction (all P0.05). Besides, there was a strong linkage disequilibrium between -250G/A and -514C/T, -710T/C, and -763A/G respectively, between -514C/T and -710T/C and -763A/G respectively, and between -710T/C and -763A/G. When the haplotypes were -250G/-514C, -250G/-710C, -250G/-763G, -514C/-710C, and 514C/-763G respectively, the frequencies in the cerebral infarction group were significantly lower than that in the healthy controls. When the haplotype was -250A/-514T, -250A/-710T, -250A/-710C, -250A/-763G, -514T/-710C, -514T/-763G, and -710T/-763G respectively, the frequencies in the cerebral infarction group were significantly higher than those in the healthy controls.There are significant haplotypes and linkage disequilibrium among the four SNPs of HL gene in the cerebral infarction patients of Shanghai. The haplotypes GC, GG, and CC lower the incidence rate of cerebral infarction, while the haplotypes AT, AC, AG, TC, and TG increase the incidence rate of cerebral infarction.

Postconditioning has been shown to reduce infarct size during reperfusion (72 hours). However, it is unknown whether the infarct size reduction with postconditioning is a long-term effect after clinical percutaneous coronary intervention (PCI). The present study tested the hypothesis that postconditioning during primary PCI preserves global cardiac function and reduces infarct size in patients after prolonged reperfusion.Fortyone patients undergoing PCI were randomly assigned to a control (n = 18) or postconditioning (n = 23) group within 90 minutes after admission. After predilatation, in the Control group, no intervention was applied in the first 3 minutes of reperfusion, while in the Postconditioning group, three cycles of 30-second angioplasty balloon deflation and 30-second inflation were repetitively applied.There was a trend toward increased ejection fraction quantified by echocardiography in the Postconditioning group compared to that in the Control group (54 +/- 12.9% vs. 44 +/- 16.7%; p0.05). Infarct size represented by the area under the curve of creatine-kinase activity during the first 72 hours of reperfusion was significantly less by 27% in the Postconditioning group than that in the Control group (58,002 +/- 593 vs. 79,787 +/- 681; p = 0.04). After 7 days of reperfusion, infarct size quantified by single-photon emission computed tomography was 27% smaller in the Postconditioning group than that measured in the Control group (31.3 +/- 8.6% vs. 22.8 +/- 6.7% of left ventricle; p0.05).This study demonstrates that postconditioning following PCI significantly protects the heart against ischemia/reperfusion-induced injury. More importantly, this study indicates that protection with postconditioning is still apparent 1 week following reperfusion, suggesting long-term protection.

To compare the effects on MACE of intracoronary or intravenous tirofiban bolus administration in patients with acute ST-elevation myocardial infarction (STEMI).A total of 60 consecutive STEMI patients ready to receive primary PCI were randomly assigned to intracoronary tirofiban bolus (10 microg/kg) prior to the first balloon inflation (Group IC) or to intravenous tirofiban bolus at the same dose prior to coronary angiography (Group IV), followed by a 36-hours IV tirofiban (0.15 microg . kg(-1) . min(-1)) infusion for all patients. Clinical and angiographic features between 2 groups before and after PCI were analyzed.Fifty-four out of 60 STEMI patients accomplished the study. Group IC was superior to Group IV in terms of TIMI flow grade, TIMI myocardial perfusion grade, ST-segment resolution, the distal embolism of IRA immediately after PCI and ejection fraction at 5 - 7 days after the PCI. The in-hospital MACE rate and bleeding complications were similar between the groups while, the combined incidence of MACE during follow-up was significantly lower in the Group IC compared with Group IV (7.1% versus 30.8%; P = 0.02).Intracoronary bolus application of tirofiban is associated with superior clinical prognosis compared with the standard intravenous bolus application of tirofiban in patients with STEMI undergoing primary PCI.

To observe the safety and efficiency of ultra-early glycoprotein IIb/IIIa receptor blockade tirofiban use in patients with acute ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI).From April 2005 to April 2006, 158 consecutive AMI patients (117 males, mean age of 58.8 +/- 25.2 years) were randomly received tirofiban (10 microg/kg bolus i.v. followed by 0.15 microgxkg(-1)xmin(-1) for 36 hours) before PCI in emergency room (early, n = 78) or immediately before PCI in catheterization lab (late, n = 80). Clinical and angiographic features between 2 groups before and after PCI were analyzed.Baseline clinical characteristics before PCI were similar between the two groups. Tirofiban was administered 39.8 minutes earlier in early group than that in the late group. The TIMI 3 flow rate (23.1% vs. 10.0%, P = 0.032) and the combined TIMI 2 or 3 flow rate (39.7% vs. 23.8%, P = 0.040) at initial angiography before PCI were significantly higher in early group than that in late group. However, TIMI 3 flow rate, myocardial Blush grade or corrected TIMI frames immediately after PCI were similar between the groups. The combined incidence of death or recurrent MI as well as bleeding complications or thrombocytopenia rate during early follow-up were similar between the groups (P0.05).Early initiation of tirofiban in patients with acute STEMI treated by primary PCI was safe. A better patency (TIMI 3 and TIMI 2-3 flow) in infarct related artery was obtained in patients with early tirofiban administration.

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.

To analysis the genetic mode of Rh DEL phenotype and RHD 1227A allele in Zhejiang Han population through family investigations.Rh DEL phenotypes were identified by a serologic adsorption-elution method. Two polymerase chain reaction-sequence specific prime (PCR-SSP) methods which detectED RHD 1227A allele and Rhesus hybrid box, respectively, and a nucleotide sequencing method focused on the exon 9 of RHD 1227A allele were employed to determine the zygosity of RHD allele.All five probands with Rh DEL phenotype harbored a RHD 1227A allele and had a RHD allele deletion, and they were RHD 1227A/RHd heterozygote. One of the parent members was found to contain a RHD 1227A allele and a normal RHD allele in pedigree 1, 2 and 3, respectively. Thus, they were RHD 1227A/RHD heterozygotes and presented normal D positive phenotype. The son of proband No 1. inherited the RHD 1227A allele and presented a normal D positive phenotype due to a RHD 1227A/RHD heterozygote; The offsprings of proband No. 2, No. 4, and No. 5 did not inherit RHD 1227A allele and presented a normal D positive phenotype.RHD 1227A allele is an important genetic marker of Rh DEL phenotype; RHD 1227A is recessive to normal RHD allele and dominant to RHd allele; RHD 1227A allele is an ancestral, but not a spontaneously mutated allele.