Clinical Observation of Erlotinib in the Treatment of Advanced Non-small Cell Lung Cancer: A Report of 92 Eases

Background and objective Erlotinib, a selective inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved effective in local advanced or metastatic non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the efficacy and safety of erlotinib for the treatment of advanced NSCLC. Methods Ninety-two patients with advanced NSCLC who had failed or not tolerated or refused chemotherapy received 150 mg oral doses of erlotinib once daily until the disease progression or intolerable toxicity. Results Among the 92 NSCLC patients, 2 patient got complete response (2.2%), 22 partial response (23.9%), 48 stable disease (52.2%) and 20 progressive disease (21.7%). The overall response rate and the disease controlled rate of erlotinib was 26.1% (24/92) and 78.3% (72/92), respectively. The response rate of erlotinib were significantly higher in rash and ECOG 0-1 than no rash and ECOG ≥ 2. The disease controlled rate of erlotinib was significantly higher in female and non-smokers than male and smokers (P < 0.05). The response rate of erlotinib did not show significant differences within pathological type or previous treatment. The most common side effects were rash and diarrhea with 84.8% and 31.5%, respectively, but usually were mild. Conclusion Erlotinib is effective and safe in the treatment of advanced NSCLC patients

COMPATIBILITY EVALUATION OF BZ25-1 CRUDE OILS IN BOHAI BAY, CHINA

ABSTRACT BZ25-1 oilfield is located in the southeast of Bohai bay which geographically lies between 119 o 00′to 119 o 15′east longitude and 38 o 10′to 38 o 20′north latitude. It has two oil blocks, including Shahejie (SHJ) waxy oil and Minghuazhen (MHZ) heavy oil, with six wellhead platforms WHPA~WHPF and six submarine pipelines. Therein, the WHPC-WHPB and WHPB-SPM (Single Point Mooring) pipelines transport the mixture of the two produced crude oils. However, the mixing of the two oils will certainly bring out a change in their components and properties, which directly affects the safe operation of the submarine pipelines and offshore production facilities. Therefore, this paper compounds three kinds of MHZ/SHJ mixed oils with blending ratios of 1:1, 3:1 and 9:1, mainly studies how the components, rheological and thermophysical properties of the oil mixtures change with the blending ratio. The major objective of this study is to evaluate the compatibility of the two crude oils and provide a theoretical basis for the production optimization and risk elusion of the oilfield. The results of the study show that the components and properties of SHJ crude oil are quite different from those of MHZ oil, the flow behavior of SHJ oil is more sensitive to temperature. As MHZ oil in the compounds increases, the contents of asphaltene, resin, sulfur and carbon residue will increase except wax contents, their viscosities, densities and flash points will also increase, but their pour points, yield stresses, calorific values and other major thermophysical parameters will decrease. A blending ratio of 2~7:1 for MHZ to SHJ crude oil can be concluded to make the properties of the compounds meet the safe and economic requirements of the subsea pipeline and offshore facility operations and ensure the compatibility of the mixed oils. In actuality, the field operations have confirmed that the recommended blending ratio is reasonable and practicable

Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes

Autism spectrum disorder (ASD) is frequently comorbid with other neurological disorders such as intellectual disability (ID) or global development delay (GDD) and epilepsy. The pathogenesis of ASD is complex. So far, studies have identified more than 1000 ASD risk genes. Most of them were also reported to relate with other neurological diseases, and only several of them have been confirmed as pathogenic genes for autism. Little is known about the roles of these risk genes in neurological diseases with ASD. In the present study, we recruited a cohort of 158 neurological disorder probands with 163 variants of 48 ASD risk genes. Of these, 50 individuals (31.6%) were diagnosed with ASD. In the ASD patient subset, we identified several rarely reported candidate genes including DOLK, USH2A, and HUWE1. In a comparison of patients with neurological disorders with and without ASD, we found that ID/GDD was frequently comorbid with ASD whereas epilepsy was more common in the non-ASD group. Statistical analyses of all possible risk factors implicated that variants in synaptic genes, especially non-voltage-gated ion channel genes and in transcriptional and chromosome genes were related to ASD, but none of the investigated environmental factors was. Our results are useful for the future diagnosis and prognosis of patients with neurological disorders and emphasize the utility of genetic screening

Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy

Introduction: The concurrence of intellectual disability/global developmental delay and epilepsy (ID/GDD-EP) is very common in the pediatric population. The etiologies for both conditions are complex and largely unknown. The predictors of significant copy number variations (CNVs) are known for the cases with ID/GDD, but unknown for those with exclusive ID/GDD-EP. Importantly, the known predictors are largely from the same ethnic group; hence, they lack replication.Purpose: We aimed to determine and investigate the diagnostic yield of CNV tests, new causative CNVs, and the independent predictors of significant CNVs in Chinese children with unexplained ID/GDD-EP.Materials and methods: A total of 100 pediatric patients with unexplained ID/GDD-EP and 1,000 healthy controls were recruited. The American College of Medical Genetics guideline was used to classify the CNVs. Additionally, clinical information was collected and compared between those with significant and non-significant CNVs.Results: Twenty-eight percent of the patients had significant CNVs, 16% had variants of unknown significance, and 56% had non-significant CNVs. In total, 31 CNVs were identified in 28% (28/100) of cases: 25 pathogenic and 6 likely pathogenic. Eighteen known syndromes were diagnosed in 17 cases. Thirteen rare CNVs (8 novel and 5 reported in literature) were identified, of which three spanned dosage-sensitive genes: 19q13.2 deletion (ATP1A3), Xp11.4-p11.3 deletion (CASK), and 6q25.3-q25.3 deletion (ARID1B). By comparing clinical features in patients with significant CNVs against those with non-significant CNVs, a statistically significant association was found between the presence of significant CNVs and speech and language delay for those aged above 2 years and for those with facial malformations, microcephaly, congenital heart disease, fair skin, eye malformations, and mega cisterna magna. Multivariate logistic regression analysis allowed the identification of two independent significant CNV predictors, which are eye malformations and facial malformations.Conclusion: Our study supports the performance of CNV tests in pediatric patients with unexplained ID/GDD-EP, as there is high diagnostic yield, which informs genetic counseling. It adds 13 rare CNVs (8 novel), which can be accountable for both conditions. Moreover, congenital eye and facial malformations are clinical markers that can aid clinicians to understand which patients can benefit from the CNV testing and which will not, thus helping patients to avoid unnecessary and expensive tests

The Effect of Cross-Boundary Supply on the Accessibility of Public Services in Urban Governance: An Example of Shanghai

Due to regional variations in urban governance and the division of functions across different government departments, administrative divisions have caused serious fragmentations in local governance and raised serious obstacles to the standardization and equitable delivery of public services within communities. Existing studies have put forward solutions to the problem of governance fragmentation that prioritize optimizing organizational structures. However, these studies neglect to take into account the impact of administrative divisions on public service supply. Current developments in information technology (IT) have brought new opportunities to urban governance. In this study, we take the Community Public Service Centers (CPSCs) of Shanghai as an example to illustrate the impact of administrative divisions on the equitable delivery of public services. We then explore the use of IT-driven implementation of cross-boundary public services to establish an innovative urban governance model that improves the accessibility of public services. The study found that the cross-boundary supply with the support of IT will effectively improve the equitable delivery of public services. This research will provide references for improving the accessibility of public services, the efficiency of resource allocation, and the promotion of the equitable delivery of public services among communities—all of which contribute to the optimization of urban governance

The Effect of Cross-Boundary Supply on the Accessibility of Public Services in Urban Governance: An Example of Shanghai

Due to regional variations in urban governance and the division of functions across different government departments, administrative divisions have caused serious fragmentations in local governance and raised serious obstacles to the standardization and equitable delivery of public services within communities. Existing studies have put forward solutions to the problem of governance fragmentation that prioritize optimizing organizational structures. However, these studies neglect to take into account the impact of administrative divisions on public service supply. Current developments in information technology (IT) have brought new opportunities to urban governance. In this study, we take the Community Public Service Centers (CPSCs) of Shanghai as an example to illustrate the impact of administrative divisions on the equitable delivery of public services. We then explore the use of IT-driven implementation of cross-boundary public services to establish an innovative urban governance model that improves the accessibility of public services. The study found that the cross-boundary supply with the support of IT will effectively improve the equitable delivery of public services. This research will provide references for improving the accessibility of public services, the efficiency of resource allocation, and the promotion of the equitable delivery of public services among communities—all of which contribute to the optimization of urban governance

Integration of ATAC-Seq and RNA-Seq identifies key genes and pathways involved in the neuroprotection of S-adenosylmethionine against perioperative neurocognitive disorder

The gene-regulatory landscape is highly dynamic in healthy and diseased brains. DNA methylation is a well-known epigenetic modification that regulates gene expression, and our previous study demonstrated that S-adenosylmethionine (SAM), a methylome modulator, was a neuroprotectant against perioperative neurocognitive disorder (PND). However, the underlying mechanism remains to be elucidated. Here, we integrated an assay for transposase-accessible chromatin by sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to identify the key genes and pathways involved in the neuroprotection of SAM against PND. Our RNA-seq data demonstrated that genes involved in biological processes such as Wnt signaling, inflammatory response, transcription and long-term potentiation likely mediate the neuroprotection of SAM. Our ATAC-seq data provided comprehensive maps of chromatin accessibility changes induced by laparotomy and laparotomy + SAM treatment, and functional annotation of the regions with high variations in chromatin accessibility highlighted the role of the Wnt signaling pathway in PND pathogenesis and SAM treatment. Further motif analysis identified key transcription factors (e.g., CTCF, TFDP1, TCFL5, KLF15, ZBTB14, TFAP2E) that may participate in the neuroprotection of SAM. In conclusion, the current study provides an epigenomic perspective to understand the pathogenesis of PND and its treatment by SAM