Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1

Objective： Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 （BRCA1） gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 （RRM1） gene overexpression enhances resistance to gemcitabine. To further examine the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer （NSCLC）, we performed this non-randomized phase II clinical trial which tested the hypothesis that customized therapy would confer improved outcome over non-customized therapy. Methods： RNA was isolated from fresh tumor tissue. Patients received chemotherapy regimen based on their BRCA1 and RRM1 mRNA levels： both low-cisplatin plus gemcitabine （GP）; both high-vinorelbine plus cisplatin （NP）; BRCA1 low and RRM1 high-cisplatin plus docetaxel （TP）; BRCA1 high and RRM1 low-vinorelbine plus gemcitabine （GN）. Results： From Dec 2005 to Nov 2008, 94 metastatic and locally advanced NSCLC patients from our institute were enrolled in this study. The median age was 58 years old. Among them, 21 patients received GP, 30 patients received TP and 43 patients received NP chemotherapy. GP group had a higher response rate, and longer median time to progression （TTP） and median overall survival （OS） time than the other 2 groups. The response rates in the GP, TP and NP groups were 42.9%, 36.7% and 27.9%, respectively （P=0.568）. The median TTP was 5.6, 5.0, 4.8 months （P=0.975）, respectively, and the median OS time was 12.5, 11.0, 9.7 months （P=0.808）, respectively. Conclusion： Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with higher response rate and longer TTP and OS time in the GP group. This suggests that BRCA1 and RRM1 mRNA levels could be used as biomarkers in individual therapy in NSCLC.

Abundance and significance of neuroligin-1 and glutamate in Hirschsprung's disease

AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate(Glu) in Hirschsprung's disease(HSCR).METHODS: Ninety children with HSCR and 50 children without HSCR matched for similar nutritional status, age and basal metabolic index were studied. The expression and localization of neuroligin-1 and Glu were assessed using double-labeling immunofluorescence staining of longitudinal muscles with adherent myenteric plexus from the surgically excised colon of children with HSCR. Western blot analysis, quantitative real-time PCR(q RT-PCR) and immunohistochemistry were performed to evaluate the abundance of neuroligin-1 and Glu in different HSCR-affected segments(ganglionic, transitional, and aganglionic segments). Enzyme-linked immunosorbent assay(ELISA) was used to detect and compare serum Glu levels in the long-segment HSCR, short-segment HSCR and non-HSCR samples.RESULTS: Neuroligin-1 and Glu were co-expressed highest to lowest in the ganglionic, transi tional and aganglionic segments based on Western blot(neuroligin-1: 0.177 ± 0.008 vs 0.101 ± 0.006, 0.177 ± 0.008 vs 0.035 ± 0.005, and 0.101 ± 0.006 vs 0.035 ±0.005, P < 0.005; Glu: 0.198 ± 0.006 vs 0.115 ± 0.008, 0.198 ± 0.006 vs 0.040 ± 0.003, and 0.115 ± 0.008 vs 0.040 ± 0.003, P < 0.005) and q RT-PCR(neuroligin-1: 9.58 × 10-5 ± 9.94 × 10-6 vs 2.49 × 10-5 ± 1.38 × 10-6, 9.58 × 10-5 ± 9.94 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, and 2.49 × 10-5 ± 1.38 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, P < 0.005). Serum Glu level was the highest to lowest in the non-HSCR, short-type HSCR and long-type HSCR samples based on ELISA(in nmol/μL, 0.93 ± 0.31 vs 0.57 ± 0.25, 0.93 ± 0.31 vs 0.23 ± 0.16, and 0.57 ± 0.25 vs 0.23 ± 0.16, P < 0.005).CONCLUSION: Neuroligin-1 and Glu may represent new markers of ganglion cells, whose expression may correlate with the pathogenesis, diagnosis, differential diagnosis or classification of HSCR.

Surgical outcomes of bladder augmentation: A comparison of three different augmentation procedures

BACKGROUND Augmentation cystoplasty is indispensable in many pediatric diseases,especially neurogenic bladder.Various methods and materials are used to augment the bladder,and these methods are associated with different shortcomings and complications.AIM The present study reported the mid-term outcomes of patients undergoing various bladder augmentation procedures in a single institution,and assessed whether seromuscular cystoplasty lined with urothelium(SCLU)provided better urodynamic results than auto-augmentation(AA).METHODS A retrospective review of 96 patients undergoing various augmentation methods between 2003 and 2018 was performed.The patients were divided into three groups according to the type of augmentation,and their outcomes were compared.All patients developed neurogenic bladder due to myelomeningocele or sacrococcygeal teratoma.The clinical data of all patients were collected.RESULTS The mean ages at surgery in the three groups(standard cystoplasty[SC],SCLU,AA)were 10.8,7.5,and 4.8 years,respectively,with mean follow-ups of 36,61,and 36 mo,respectively.The mean preoperative and postoperative bladder capacities of the SC,SCLU,and AA groups were 174±11.7 vs.387±13.7(P<0.0001),165±12.2 vs.240±14.7(P=0.0002),and 138±16.7 vs.181±9.9(P=0.0360),respectively.Compared with the AA group,the SCLU procedure did not have better postoperative urodynamic parameters.Incontinence was reduced in most patients.The mean times of clean intermittent catheterization per day in the SC,SCLU,and AA groups were 5.6,7.8,and 8.2,respectively.The main complications of the SC group were recurrent urinary tract infections(8%)and bladder calculi(6%).Re-augmentation was done in patients in the SCLU(8)and AA(3)groups.CONCLUSION SC provided sufficient bladder capacity and improved compliance with acceptable complications.After AA and SCLU,the patients acquired limited increases in bladder capacity and compliance with a high rate of re-augmentation.Compared with AA,SCLU did not yield better postoperative urodynamic parameters.

Mechanically robust stretchable organic optoelectronic devices built using a simple and universal stencil-pattern transferring technology

Stretchable electronic and optoelectronic devices based on controllable ordered buckling structures exhibit superior mechanical stability by retaining their buckling profile without distortion in repeated stretch-release cycles.However,a simple and universal technology to introduce ordered buckling structures into stretchable devices remains a real challenge.Here,a simple and general stencil-pattern transferring technology was applied to stretchable organic lightemitting devices(SOLEDs)and polymer solar cells(SPSCs)to realize an ordered buckling profile.To the best of our knowledge,both the SOLEDs and SPSCs with periodic buckles exhibited the highest mechanical robustness by operating with small performance variations after 20,000 and 12,000 stretch-release cycles between 0%and 20%tensile strain,respectively.Notably,in this work,periodic-buckled structures were introduced into SPSCs for the first time,with the number of stretch-release cycles for the SPSCs improved by two orders of magnitude compared to that for previously reported random-buckled stretchable organic solar cells.The simple method used in this work provides a universal solution for low-cost and high-performance stretchable electronic and optoelectronic devices and promotes the commercial development of stretchable devices in wearable electronics.