Genomic epidemiology of the Los Angeles COVID-19 outbreak

Los Angeles (LA) County has sustained a large outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To learn about the transmission history of SARS-CoV-2 in LA County, we sequenced 142 viral genomes from unique patients seeking care at UCLA Health System. 86 of these genomes are from samples collected before April 19, 2020. We found that the early outbreak in LA, as in other international air travel hubs, was seeded by multiple introductions of strains from Asia and Europe. We identified a US-specific strain, B.1.43, which has been found predominantly in California and Washington State. While samples from LA County carry the ancestral B.1.43 genome, viral genomes from neighbouring counties in California and from counties in Washington State carry additional mutations, suggesting a potential origin of B.1.43 in Southern California. We quantified the transmission rate of SARS-CoV-2 over time, and found evidence that the public health measures put in place in LA County to control the virus were effective at preventing transmission, but may have been undermined by the many introductions of SARS-CoV-2 into the region. Our work demonstrates that genome sequencing can be a powerful tool for investigating outbreaks and informing the public health response. Our results reinforce the critical need for the U.S. to have coordinated inter-state responses to the pandemic.

Swab-Seq: A high-throughput platform for massively scaled up SARS-CoV-2 testing

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to the high rates of transmission by individuals who are asymptomatic at the time of transmission1, 2. Frequent, widespread testing of the asymptomatic population for SARS-CoV-2 is essential to suppress viral transmission. Despite increases in testing capacity, multiple challenges remain in deploying traditional reverse transcription and quantitative PCR (RT-qPCR) tests at the scale required for population screening of asymptomatic individuals. We have developed SwabSeq, a high-throughput testing platform for SARS-CoV-2 that uses next-generation sequencing as a readout. SwabSeq employs sample-specific molecular barcodes to enable thousands of samples to be combined and simultaneously analyzed for the presence or absence of SARS-CoV-2 in a single run. Importantly, SwabSeq incorporates an in vitro RNA standard that mimics the viral amplicon, but can be distinguished by sequencing. This standard allows for end-point rather than quantitative PCR, improves quantitation, reduces requirements for automation and sample-to-sample normalization, enables purification-free detection, and gives better ability to call true negatives. After setting up SwabSeq in a high-complexity CLIA laboratory, we performed more than 80,000 tests for COVID-19 in less than two months, confirming in a real world setting that SwabSeq inexpensively delivers highly sensitive and specific results at scale, with a turn-around of less than 24 hours. Our clinical laboratory uses SwabSeq to test both nasal and saliva samples without RNA extraction, while maintaining analytical sensitivity comparable to or better than traditional RT-qPCR tests. Moving forward, SwabSeq can rapidly scale up testing to mitigate devastating spread of novel pathogens.

Heterogeneity of EGFR mutations in non-small cell lung cancer / 肿瘤研究与临床

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown great efficacy in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR-mutation positive tumors.However,the response to EGFR-TKI is quite different even in EGFR-mutation positive patients.Besides that,different lesions in same patient can also show different response to EGFR-TKI.These phenomena might be associated with the heterogeneity of EGFR mutations,which involves intratumoral heterogeneity,intertumoral heterogeneity,and the heterogeneity before and after treatment.The article introduces the advance in heterogeneity of EGFR mutations from these three aspects.

Cellular response of RAW 264.7 to spray-coated multi-walled carbon nanotube films with various surfactants.

The increasing role of carbon nanotubes (CNTs) in various biological applications has led to a number of studies on the cytotoxicity of solution-phase CNTs, but few studies are available concerning the cytotoxicity of CNT films. Herein, we studied the potential health effect of CNT films fabricated with three commercial surfactants (sodium cholate, sodium dodecyl sulfate, and triton X-100). Multi-walled carbon nanotube-surfactant dispersions were coated onto substrates through air-spray technique. Cellular morphology, MTT assays, as well as the expression of TNF-α and IL-1ß of RAW 264.7 cells cultured on the spray-coated CNT films were evaluated for cytotoxicity. It was found that the cytotoxicity of the CNT films was largely dependent on the type of surfactant used and could be significantly reduced by mild washing steps.

Capillary electrophoresis with inhibited electrochemiluminescent detection for the trace analysis of epinephrine and dopamine / 药物分析学报

In this paper, a novel electrochemiluminescent (ECL) detection approach was developed for highly sensitive detection of ECL inhibitors based on the ECL inhibition of Ru(bpy)32+/2-(Dibutylamino)ethanol (DBAE) system. A microfluidic ECL detection cell was fabricated to couple with the capillary electrophoresis system, the electrochemical system and the postcolumn injection system. Both Ru(bpy)32+ and DBAE solutions were injected directly to the working electrode surface by a micro-infusion system to obtain a high and stable ECL signal. The performance of this setup was demonstrated by the analysis of two typical ECL inhibitors, dopamine and epinephrine. Under the optimal conditions, the limit of detection (LOD) for dopamine and epinephrine was 50nM and 5nM respectively. The proposed method was also successfully used for the trace analysis of dopamine and epinephrine in human serum samples.

Evaluation of serum gamma-glutamyltransferase assays by using the International Federation of Clinical Chemistry and Laboratory Medicine reference method / 中华检验医学杂志

Objective To evaluate the measurement accuracy of serum gamma-glutamyltransferase (GGT) assays manufactured in China. Methods The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method for GGT was set up and, after verification, was used to evaluate the performance of routine assay systems made in China. The evaluation was performed twice before and after a calibration by a common serum calibrator. Results For the reference measurement, the within run and total CVs were all less than 1%. The biases with the target values of IFCC External Quality Assessment Scheme for Reference Laboratories (RELA) were all within the limit of equivalence. Before a calibration with a common calibrator, the largest biases of results of GGT of the routine tasting systems compared with reference method at three medical decide levels were -47.53%, -34.11% and -30.07% respectively, and the averaged biases were 14.53% ,12.88% and 12.48%. After calibrating by fresh serum calibrator,the largest biases were reduced to - 17.63%, -5.88% and -4.08% ,the averaged biases were reduced to 7.50%, 2.70% and 1.87%. Conclusion The performance of GGT measurements can be effectively improved by using a common fresh serum calibrator that has a value assigned with the reference method.