Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure.

AIMS: The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA. METHODS AND RESULTS: A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the '2021 Universal Definition of HF' criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76-0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07-0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05). CONCLUSIONS: The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

Establishment and Validation of the Nomogram Model and the Probability of Silent Cerebral Infarction After Ablation Atrial Fibrillation.

BACKGROUND: The objective of this study is to establish and validate a nomogram model for predicting the probability of silent cerebral infarction following ablation of atrial fibrillation. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 238 patients with atrial fibrillation who underwent radiofrequency ablation in our hospital from October 2019 to December 2022. LASSO regression and multivariate logistics regression analysis were used to assess the independent risk factors for silent cerebral infarction after ablation. The AUC of the predictive model was 0.733 (95% CI, 0.649-0.816) and the internal validation (bootstrap = 1000) of the bootstrap method was 0.733 (95% CI 0.646-0.813). The Hosmer-Lemeshow test yields an insignificant p-value of X-squared = 10.212 and p-value = 0.2504, thus indicating an insignificant difference between predicted and observed values and good calibration results. The clinical impact curve (CIC) and clinical decision curve also prove that this graph is useful in the clinical setting. CONCLUSION: We developed an easy-to-use nomogram model to predict the probability of silent cerebral infarction following radiofrequency ablation of atrial fibrillation. This model can provide a valid assessment of the probability of postoperative silent cerebral infarction in patients undergoing radiofrequency ablation of atrial fibrillation.

Association between estimated pulse wave velocity and risk of diabetes: A large sample size cohort study.

BACKGROUND AND AIM: Estimated pulse wave velocity (ePWV) measurements have good agreement with PWV measurements. However, the relationship between ePWV and the risk of new-onset diabetes remains unclear. Therefore, this study aimed to investigate whether ePWV was associated with new-onset diabetes. METHODS AND RESULTS: Based on a secondary analysis of the Chinese Rich Health Care Group's cohort study, 211,809 participants who met the criteria were enrolled and divided into four groups based on the ePWV quartiles. Diabetes events are of interest as a result of the study. Over a mean follow-up of 3.12 years, 3000 male (1.41%) and 1173 female (0.55%) patients were diagnosed with new-onset diabetes. The cumulative incidence curves based on quartile subgroups showed that the Q4 group had a significantly higher overall incidence of diabetes than the other subgroups. A multivariate Cox regression analysis showed that ePWV was an independent predictor of new-onset diabetes (hazard ratio, 1.233; 95% confidence interval, 1.198-1.269; P < 0.001). The receiver operating characteristic curve showed that the predictive value was higher than for age and blood pressure. The ePWV was treated as a continuous variable using MaxStat, which identified that the best cut-off point for diabetes risk was 8.47 m/s. A stratified analysis showed that the association between ePWV and the risk of diabetes remained significant in multiple strata. CONCLUSIONS: An elevated ePWV was independently associated with an increased risk of developing diabetes in Chinese adults. Thus, ePWV may be a reliable indicator of the risk of early diabetes.

Soil heavy metal pollution and risk assessment associated with the Zn-Pb mining region in Yunnan, Southwest China.

The environmental assessment and identification of sources of heavy metals in Zn-Pb ore deposits are important steps for the effective prevention of subsequent contamination and for the development of corrective measures. The concentrations of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in soils from 40 sampling points around the Jinding Zn-Pb mine in Yunnan, China, were analyzed. An environmental quality assessment of the obtained data was performed using five different contamination and pollution indexes. Statistical analyses were performed to identify the relations among the heavy metals and the pH in soils and possible sources of pollution. The concentrations of As, Cd, Pb, and Zn were extremely high, and 23, 95, 25, and 35% of the samples, respectively, exceeded the heavy metal limits set in the Chinese Environmental Quality Standard for Soils (GB15618-1995, grade III). According to the contamination and pollution indexes, environmental risks in the area are high or extremely high. The highest risk is represented by Cd contamination, the median concentration of which exceeds the GB15618-1995 limit. Based on the combination of statistical analyses and geostatistical mapping, we identified three groups of heavy metals that originate from different sources. The main sources of As, Cd, Pb, Zn, and Cu are mining activities, airborne particulates from smelters, and the weathering of tailings. The main sources of Hg are dust fallout and gaseous emissions from smelters and tailing dams. Cr and Ni originate from lithogenic sources.

Clinical characteristics associated with non-small-cell lung cancer harboring ALK rearrangements in Chinese patients.

AIM: The ALK inhibitor, crizotinib, has demonstrated effectiveness in patients with non-small-cell lung cancer harboring ALK rearrangements. As few studies of the clinical characteristics of Chinese patients with ALK rearrangements have been reported, we conduct this study to gain more understanding in such area among Chinese patients. PATIENTS & METHODS: We undertook a retrospective study of 288 non-small-cell lung cancer patients admitted to our institution over a period of 4.5 years. RESULTS: Following testing, 14.9% of the patients (43/288) were found to be ALK fusion gene positive. Patient data including gender, age, smoking status, EGFR mutation status and medical imaging data were collected and analyzed. CONCLUSION: The findings suggested that patients with ALK rearrangements are more likely to be young, have EGFR wild-type, and more likely to exhibit mucus secretion, solid tumor growth, lymph node metastasis and pleural metastasis.

[Determination of Alcoholysis Degree and Volatile Matter of Poly-Vinyl Alcohol Using Diffuse-Reflection Near Infrared Spectroscopy].

A new method using reflection NIR technology was developed to determine the alcoholysis degree and volatile matter of Poly-vinyl alcohol (PVA). 120 samples were used in this research. NIR spectra of the sample were scanned by the spectrometer from 1 000 to 1 800 nm. The alcoholysis degree and volatile matter were determined by the national standard method of volumetric and gravimetric method respectivily. Partial least squares (PLS1) was used to establish the quantitative correction model of alcoholysis degree and volatile matter of PVA. The corrected relationship (Rc) of alcoholysis degree and volatile matter was 0.976 and 0.981 respectively. The corrected standard deviation(SEC) was 0.176 and 0.197. The predicted relationship (R(p)) was 0.967 and 0.969. The predicted deviation(SEP) was 0.202 and 0.193. The test for actual samples showed that the NIR method was fitted for the requirement of PVA analysis.

Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. METHODS: Here, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR. RESULTS: A total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB + PPROM), as compared to those from full-term labor (FTB + PROM) and from premature rupture of membranes (PPROM + PROM), as compared to those from non-rupture of membranes (sPTB + FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM. CONCLUSION: Differentially expressed lncRNAs that were identified from the human placentas of sPTB and PPROM may regulate their associated mRNAs through differential mechanisms and connect the ubiquitin-proteasome system with infection-inflammation pathways. Although the detailed mechanisms by which lncRNAs regulate their associated mRNAs in sPTB and PPROM are yet to be clarified, our findings open a new approach to explore the pathogenesis of sPTB and PPROM.

Factors influencing the quality of preconception healthcare in China: applying a preconceptional instrument to assess healthcare needs.

BACKGROUND: Preconception care is defined as the promotion of the health and well-being of a woman and her partner before pregnancy. Improving preconception health can result in improved reproductive health outcomes. China has issued latest version official guideline for preconception care in 2011. The objective of this cross-sectional study is to determine whether there is a variation in the quality of preconception healthcare services in distinct eastern and northern populations of China, and what factors are associated with such variation. METHODS: A cross-sectional survey using our previously developed preconception instrument was conducted. Women at reproductive age planning for pregnancy were surveyed along with their partners at hospitals during their pre-pregnancy health examination. Data collected include general health/life profiles, pregnancy history, alcohol/tobacco/drug exposures, immunizations, micronutrient supplements and the demands in preconception care. After quality assessment, statistical analysis were applied to evaluate the variations in preconception factors between people from Hebei and Jiangsu Provinces. RESULTS: 3202 women of reproductive age in from eastern province, Jiangsu, and in a northern province, Hebei, participated this study. 2806 of them and their partners have completed the questionnaire, at a rate of 87.6%, 1011 were from Jiangsu and 1795 were from Hebei. Statistical significance was obtained for maternal age (P < 0.001), body mass index (u =13.590, P <0.001), education (χ2 = 916.33, P < 0.001), occupation (χ2 = 901.78, P < 0.001), health status/common disease, immunization status, and need for preconception care. CONCLUSIONS: For a country as large as China, the centralized guideline for standardized preconception healthcare does have a very crucial positive role in reproductive healthcare, but it may not be suited for all populations. Regional authorities should consider the demographics and healthcare needs of the local population and modify the centralized guideline accordingly, as well as provide a better education and professional services for the public, to improve the quality of preconception services at both the regional and the national level.

Preconception health assessment in China, Lebanon and the Philippines: applicability to other countries.

To test the utility of a preconception checklist tool in identifying preconception health needs of women in three countries; China, Lebanon and the Philippines. An academic medical center within each country participated in the development and testing of a preconception checklist tool, which was administered over a 6 month period to selected target groups in each country. The checklist provided valuable data on the preconception health of 6,530 women. Aggregated data identified common preconception health needs across all countries, including provision of modern contraceptives and adequate immunization coverage; HIV and STI screening; treatment for anemia; and counseling for maintenance of a healthy weight. A preconception checklist tool was found to be useful in distinct cultural settings. The study was a pilot. Future steps include validation and standardization of the checklist, data from which could be used to help shape preconception care policies and implementation strategies.

Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms.

The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5'-flap or 5'-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found.

A proteomic study of Hutchinson-Gilford progeria syndrome: Application of 2D-chromotography in a premature aging disease.

The Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease characterized by segmental premature aging. Applying a two-dimensional chromatographic proteomic approach, the 2D Protein Fractionation System (PF2D), we identified 30 differentially expressed proteins in cultured HGPS fibroblasts. We categorized them into five groups: methylation, calcium ion binding, cytoskeleton, duplication, and regulation of apoptosis. Among these 30 proteins, 23 were down-regulated, while seven were up-regulated in HGPS fibroblasts as compared to normal fibroblasts. Three differentially expressed cytoskeleton proteins, vimentin, actin, and tubulin, were validated via Western blotting and characterized by immunostaining that revealed densely thickened bundles and irregular structures. Furthermore in the HGPS cells, the cell cycle G1 phase was elongated and the concentration of free cytosolic calcium was increased, suggesting intracellular retention of calcium. The results that we obtained have implications for understanding the aging process.

The overall survival benefit in Chinese ALK+ NSCLC patients received targeted therapies.

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement is a series of mutations of non-small cell lung cancer (NSCLC) patients. Since 2011, multiple ALK inhibitors (ALKis) have been developed and launched for targeted therapy. In this study, we sought to investigate different strategies of sequential applying the ALKis and their clinical benefits to the overall survival (OS). Methods: A total of 176 patients with advanced NSCLC (stage IIIB-IV) harboring the ALK rearrangement were included in this cohort study. They were diagnosed between February 1, 2012 and November 19, 2019 at Peking University Cancer Hospital. Clinical characters were reviewed from patients' records. Strategies of drugs, progression-free survival (PFS) and OS were collected during the follow-ups. The Kaplan-Meier method and multivariate Cox proportional-hazard analysis were used to conduct the analyses survival and to examine the relationship between the variables and OS. Results: A significantly longer OS was observed either in patients treated with crizotinib [N=106, median OS (mOS): 32.9 months] or in patients treated with a next-generation ALKi [N=34, mOS: not reached (NR)] as the initial ALKi, compared with patients treated with conventional chemotherapy but no ALKi (N=36, mOS: 10.3 months, P<0.001). After disease progression with initial crizotinib, patients who received no ALKi had shorter OS than those who received only crizotinib beyond progressive disease (CBPD) (mOS: 9.7 vs. 20.3 months; P=0.015), only subsequent next-generation ALKis (mOS: 9.7 vs. 41.1 months; P<0.001), and CBPD followed with subsequent next-generation ALKis (mOS: 9.7 months vs. NR; P<0.001). Patients treated with 2 types of ALKi had better survival than those treated with 1 ALKi (mOS: 45.8 vs. 21.3 months, P=0.003), but no such survival benefit was observed in patients treated with ≥3 ALKis (P=0.366). Conclusions: ALKis have been shown to be clinically effective in treating NSCLC patients with ALK rearrangements. In the case of disease progression with crizotinib, either of CBPD or sequential other ALKis can extend patients' OS. The sequential application of multiple ALKis was found to be better than it of single ALKi in prolonging OS. However, the question of which inhibitor to select as the initial inhibitor needs to be examined further in future studies.

Comprehensive analysis of alfa defensin expression and prognosis in human colorectal cancer.

Introduction: Colorectal cancer (CRC) is a serious threat to human health. Screening new biomarkers can provide basis for improving the prognosis and individualized treatment of CRC. Although some members of the defensin family were found increased in pancreatic cancer and CRC, their exact function and clinical significance remain unclear. Methods: In this study, the expression, correlation, mutation, and functional enrichment of several defensin family members in pancreatic cancer and CRC were analyzed using tumor public databases and verified in several patients. Results: Results showed no significant correlation between the expression levels of DEFA1-4 and CRC. The expression levels of DEFA5 and DEFA6 significantly increased in CRC tissues compared with those in normal tissues. DEFA5 may be associated with better prognosis of CRC, while DEFA6 may be associated with poor prognosis. Immunohistochemistry (IHC) experiments showed that the expression of DEFA6 was significantly higher in adenoma than in normal mucosa and slightly higher in carcinoma than in normal mucosa. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that DEFAs were closely related to hsa05202: transcriptional misregulation in cancer and Hsa04015: Rap1 signaling pathway. DEFA5 may be a stable and good prognostic marker, and DEFA6 may be a poor prognostic marker in CRC of metastasis. Conclusion: Overall, DEFA5 and DEFA6 have a certain degree of sensitivity and specificity in predicting CRC.

DEAD-box proteins from Escherichia coli exhibit multiple ATP-independent activities.

DEAD-box proteins (DBPs) are a widespread class of ATP-dependent RNA helicases that play a key role in unwinding RNA duplexes. In recent years, certain DBPs have also been found to exhibit activities that do not require ATP. To gain a better understanding of prokaryotic RNA metabolism, we investigated whether Escherichia coli DBPs harbor any ATP-independent activities. We show that each of the four E. coli DBPs tested in this study can accelerate the association of cRNA molecules, can stimulate strand displacement, and can function as an RNA chaperone without utilizing ATP. To the best of our knowledge, these prokaryotic DBPs constitute the first examples of proteins that harbor each of these three activities. The identification of these auxiliary functions indicates that the E. coli DBPs are versatile factors that possess significant RNA remodeling activity in addition to their canonical RNA helicase activity and might therefore participate in a greater variety of cellular processes than has been previously appreciated.

Identification of differentially expressed transcripts and translatants targeted by knock-down of endogenous PCBP1.

PCBP1 is a member of the hnRNP family and participates in the regulation of transcription and translation. Previously, we identified transcripts targeted by overexpression of exogenous PCBP1. To further determine if these altered transcripts may also be targeted by a lack of PCBP1, we depleted endogenous PCBP1 in human SH-SY5Y cells. We identified 941 transcripts with the Affymetrix and 1362 with the Agilent expression platforms. There were 375 transcripts identified by both platforms, including 328 down-regulated and 47 up-regulated. The identified transcripts could be grouped into neuronal, cell signaling, metabolic, developmental, and differentiation categories, with pathway involvement in Wnt signaling, TGF beta signaling, translation factors and nuclear receptors. A proteomic profiling study with a two-dimensional chromatographic platform showed global translational changes over a range of isoelectric points (pI)=4.84-8.42. This study identifies the transcripts affected by knock-down of endogenous PCBP1 and compares them to the transcripts affected by overexpression of PCBP1.

Targeted pre-mRNA modification for gene silencing and regulation.

Most eukaryotic box C/D small nucleolar (sno) or Cajal body-specific RNAs guide base pairing with target RNAs and direct site-specific 2'-O-methylation. We designed an artificial C/D RNA to target the branch point adenosine of ACT1 pre-mRNA to block its splicing. Saccharomyces cerevisiae expressing this guide RNA gene controlled by a GAL1 promoter grew normally on dextrose but not on galactose medium. The pre-mRNA was specifically 2'-O-methylated, prohibiting maturation of ACT1 mRNA. Targeting other adenosines in this region while maintaining almost identical complementarity did not affect ACT1 mRNA level or cell growth, suggesting that targeting the branch-point adenosine was truly 2'-O-methylation-specific rather than an antisense effect; moreover, only the 3'-most branch site adenosine served as the branch point. We targeted other essential intron-containing genes, and observed a similar phenotype. We demonstrated that a Box C/D RNA can guide modification at the pre-mRNA branch point, thus silencing its expression and inducing cell death.

Factors Affecting COVID-19 Preventive Behaviors among University Students in Beijing, China: An Empirical Study Based on the Extended Theory of Planned Behavior.

Higher education institutions (HEIs), among other social systems, have an irreplaceable role in combating COVID-19. However, we know little about institutional and individual factors that might facilitate university students' beliefs and behaviors toward preventive behaviors for COVID-19 within the higher education context. Our study applies an extended theory of planned behavior (TPB) model to investigate the structural relationships among the institutional climate, attitudes, subjective norms, perceived behavioral control and preventive behaviors of university students and to detect the moderating impacts of perceived risk on the structural model. Data were collected from 3693 university students at 18 universities in Beijing, China through an online survey. Structural equation modeling (SEM) and multigroup analysis were performed to examine the empirical model. The results reveal that (1) the institutional climate has a significant, direct effect on preventive behaviors for COVID-19 among university students, (2) the TPB components, namely attitudes, subjective norms and perceived behavioral control, partially mediate the relationship between the institutional climate and preventive behaviors for COVID-19, and (3) perceived risk moderates several paths in the model. Theoretical and practical implications are offered, and recommendations for future research are outlined.

FOXI1 inhibits gastric cancer cell proliferation by activating miR-590/ATF3 axis via integrating ChIP-seq and RNA-seq data.

FOXI1 plays a key role in the development of gastric cancer. However, the whole genome FOXI1 binding sites and its target genes are unclear. In the present study, we used ChIP-seq and RNA-seq technologies to identify the target gene of FOXI1. Firstly, ChIP-seq data showed that, 4476 unique peaks in the genome region were captured. Most of these binding peaks are located in introns or intergenic regions. We annotated all the peaks to the nearest gene and identified 404 genes as FOXI1 binding genes. KEGG and GO analysis showed that FOXI1 binding gene to be correlated with the cellular process, cell part, cell, binding, single-organism process. Further, we performed FOXI1-overexpressed RNA-seq experiment. We comprehensively analyzed the ChIP-seq and RNA-seq data and take the intersection of two databases, several genes were identified. ATF3 was selected from the intersection since ATF3 was the most enriched mRNA after FOXI1 overexpressed. ChIP-qPCR and luciferase report gene were used to validate that ATF3 was target gene of FOXI1. Intriguely, ATF3 protein was significantly downregulated after FOXI1 overexpressed. We found FOXI1 can also bind to the promoter of miR-590 and active it which directly target ATF3. The binding site between FOXI1 and miR-590 was verified by ChIP-qPCR and luciferase report gene, and the target relationship between miR-590 and ATF3 was confirmed by dual-luciferase reporter gene. In conclusion, our data identified the genome binding sites of FOXI1, and provide evidence that FOXI1 inhibits gastric cancer cell proliferation by activating miR-590/ATF3 axis.

Incorporation of 5-fluorouracil into U2 snRNA blocks pseudouridylation and pre-mRNA splicing in vivo.

5-fluorouracil (5FU) is an effective anti-cancer drug, yet its mechanism of action remains unclear. Here, we examine the effect of 5FU on pre-mRNA splicing in vivo. Using RT-PCR, we show that the splicing of a number of pre-mRNAs is inhibited in HeLa cells that have been exposed to a low dose of 5FU. It appears that this inhibitory effect is not due to its incorporation into pre-mRNA, because partially or fully 5FU-substituted pre-mRNA, when injected into Xenopus oocytes, is spliced just as well as is the unsubstituted pre-mRNA. Detailed analyses of 5FU-treated cells indicate that 5FU is incorporated into U2 snRNA at important naturally occurring pseudouridylation sites. Remarkably, 5FU incorporation effectively blocks the formation of important pseudouridines in U2 snRNA, as only a trace of pseudouridine is detected when cells are exposed to a low dose of 5FU for 5 days. Injection of the hypopseudouridylated HeLa U2 snRNA into U2-depleted Xenopus oocytes fails to reconstitute pre-mRNA splicing, whereas control U2 isolated from untreated or uracil-treated HeLa cells completely reconstitutes the splicing. Our results demonstrate for the first time that 5FU incorporates into a spliceosomal snRNA at natural pseudouridylation sites in vivo, thereby inhibiting snRNA pseudouridylation and splicing. This mechanism may contribute substantially to 5FU-mediated cell death.

Analysis of the birth defects among 61 272 live born infants in Beijing.

OBJECTIVE: To investigate the birth defect condition in Haidian district of Beijing city, 61,272 live-born infants who were delivered in Haidian Maternal and Child Health Hospital from 2003 to the March of 2009 are analyzed. METHODS: Data was collected from the hospital's medical records and from the birth defect surveillance. RESULTS: Among the newborns studied, 1 076 were found having birth defect (17.56 per thousand). The most common birth defects are congenital heart defect, followed by dysmorphosis of external ear, polydactyly, hypospadia, cleft lip and palate. In addition, three birth defects that are not included in the birth defect surveillance list were enorchia, renal agenesis and giant hemangioma. The birth defect rates of preterm and small for gestational age infants are significantly higher than it of the term infants. The birth defect patterns for these two types of abnormal infants are distinct. CONCLUSION: We have determined the pattern of birth defects in Beijing, which may help in policy-making regarding the prevention and intervention of birth defects.