Genomic Staging of Multifocal Lung Squamous Cell Carcinomas Is Independent of the Comprehensive Morphologic Assessment.

INTRODUCTION: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment. METHODS: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of the study cases was characterized by the HTG EdgeSeq Precision Immuno-Oncology Panel. RESULTS: By WES data, 11 cases were classified as SPLC and seven cases as IPM. Two cases were technically suboptimal. Analysis revealed marked genomic and immunogenic heterogeneity, but immune gene expression profiles highly correlated with mutation profiles. Tumors classified as IPM have a large number of shared mutations (ranging from 33.5% to 80.7%). The agreement between individual morphologic assessments for each case and WES was 58.3%. One case was unanimously interpreted morphologically as IPM and was in agreement with WES. In a further 17 cases, the number of pathologists whose morphologic interpretation was in agreement with WES ranged from two (one case) to 15 pathologists (one case) per case. Pathologists showed a fair interobserver agreement in the morphologic staging of multiple LSCCs, with an overall kappa of 0.232. CONCLUSIONS: Staging of multifocal LSCC based on morphologic assessment is unreliable. Comprehensive genomic analyses should be adopted for the staging of multifocal LSCC.

Hantzsch Ester as Efficient and Economical NAD(P)H Mimic for In Vitro Bioredox Reactions.

Biocatalysis has emerged as a valuable and reliable tool for industrial and academic societies, particularly in fields related to bioredox reactions. The cost of cofactors, especially those needed to be replenished at stoichiometric amounts or more, is the chief economic concern for bioredox reactions. In this study, a readily accessible, inexpensive, and bench-stable Hantzsch ester is verified as the viable and efficient NAD(P)H mimic by four enzymatic redox transformations, including two non-heme diiron N-oxygenases and two flavin-dependent reductases. This finding provides the potential to significantly reduce the costs of NAD(P)H-relying bioredox reactions.

A tailored LNA clamping design principle: Efficient, economized, specific and ultrasensitive for the detection of point mutations.

In the development of personalized medicine, the ultrasensitive detection of point mutations that correlate with diseases is important to improve the efficacy of treatment and guide clinical medication. In this study, locked nucleic acid (LNA) was introduced as an amplification suppressor of a massive number of wild-type alleles in an amplification refractory mutation system (ARMS) to achieve the detection of low-abundance mutations with high specificity and sensitivity of at least 0.1%. By integrating the length of clamp, base type, number and position of LNA modifications, we have established a "shortest length with the fewest LNA bases" principle from which each LNA base would play a key role in the affinity and the ability of single base discrimination could be improve. Finally, based on this LNA design guideline, a series of the most important single point mutation sites of epidermal growth factor receptor (EGFR) was verified to achieve the optimal amplification state which as low as 0.1% mutation gene amplification was not affected under the wild gene amplification was completely inhibited, demonstrating that the proposed design principle has good applicability and versatility and is of great significance for the detection of circulating tumor DNA.

Forecast of the incidence, prevalence and burden of end-stage renal disease in Nanjing, China to the Year 2025.

BACKGROUND: There are limited data on the trends of incidence or prevalence of end stage renal disease (ESRD) in China. To assist in future planning for the ESRD program, the trends of incidence, prevalence and health care costs were analyzed and forecasted to the year 2025 by modeling of historical data from 2004 through 2014. METHODS: Nanjing urban employee basic medical insurance (NJUEBMI) data were obtained from the Nanjing Medical Insurance Information System from 2004 to 2014. The time series forecasting system in SAS 9.4 was used. Each variable was independently forecasted by the fittest model, which was selected automatically or manually. RESULTS: The forecasting models demonstrated mean percent errors of -2.49 to 5.62 %, relative to the observed values. The R-square values for the forecasting models ranged from 0.756 to 0.997. On the basis of trends in the historical data, the models projected that the average annual increase in the NJUEBMI population was 4.77 %, with forecasted values of 5,029,270 in 2025 (95 % CI, 4,960,423-5,098,117). The incidence and prevalence of ESRD were projected to increase by 1.19 and 1.95 % annually and were expected to reach 250.5 pmp (95 % CI, 247.7-253.3) and 1505 pmp(95 % CI, 1450-1560) by 2025. Additionally, the costs associated with ESRD were forecasted to increase at a growth rate of 5.80 % for healthcare costs and 7.25‰ for per capita medical expenses, with forecasted values of ¥600.3 million ($92.4 million) (95 % CI, 541.8-658.9) and ¥99.0 thousand ($15.2 thousand) (95 % CI, 98.6-99.3), respectively, by 2025. The incidence and prevalence of kidney transplantation were projected to decrease by 6.58 and 9.79 % annually. CONCLUSIONS: These projections suggest that the incidence, prevalence, healthcare costs, and per capita medical expenses of ESRD would increase in the NJUEBMI population. They provide a basis for discussing the trends of ESRD in China and facing the challenges from the ESRD program.

Epidemiological Study of RRT-Treated ESRD in Nanjing - A Ten-Year Experience in Nearly Three Million Insurance Covered Population.

BACKGROUND: The growing burden of end-stage renal disease (ESRD) has been a great challenge to the health care system of China. However, the exact epidemiological data for ESRD in China remain unclear. We aimed to investigate the epidemiology of ESRD treated by renal replacement therapy (RRT) in Nanjing based on analysing ten-year data of Nanjing three million insurance covered population. METHODS: Using the electronic registry system of Urban Employee Basic Medical Insurance (UEBMI), we included all subjects insured by UEBMI in Nanjing from 2005 to 2014 and identified subjects who developed ESRD and started RRT in this cohort. RESULTS: The UEBMI population in Nanjing increased from 1,301,882 in 2005 to 2,921,065 in 2014, among which a total of 5,840 subjects developed ESRD and received RRT. Over the 10-year period, the adjusted incidence rates of RRT in the UEBMI cohort gradually decreased from 289.3pmp in 2005 to 218.8pmp in 2014. However, the adjusted prevalence rate increased steadily from 891.7pmp in 2005 to 1,228.6pmp in 2014. The adjusted annual mortality rate decreased from 138.4 per 1000 patient-years in 2005 to 97.8 per 1000 patient-years in 2014. The long-term survival rate fluctuated over the past decade, with the 1-year survival rate ranging from 85.1% to 91.7%, the 3-year survival rate from 69.9% to 78.3% and the 5-year survival rate from 58% to 65.4%. CONCLUSION: Nanjing is facing an increasing burden of ESRD with its improvement of medical reform. The ten-year complete registry data on RRT in urban employees in Nanjing provided a unique opportunity to understand the real threat of ESRD confronting China during its process of health care transition.