Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

A large number of data show that the prevalence rate of alcoholic liver injury （ALI） is increasing year by year， and it has become one of the main causes of death due to chronic liver diseases such as liver cancer and liver cirrhosis. Quitting drinking is the main method for the prevention of ALI in modern medicine， and the main treatment methods include Western medicine with antioxidant and anti－fibrotic effects and nutritional support. However， Western medicine tends to have an unsatisfactory treatment effect and can only alleviate initial symptoms， and severe ALI still requires surgical treatment. Studies have shown that the monomers extracted from natural drugs and foods have obvious preventive and therapeutic effects on ALI， with high safety and easy access. Therefore， this article systematically summarizes the main natural drug and food monomers used for the prevention and treatment of ALI and proposes the idea of the combination of drug and food for the prevention and treatment of ALI from the perspective of paying attention to the whole process of health， in order to explore more effective prevention， health care， and treatment methods and provide ideas for research on the prevention and control of ALI.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

We developed a high-efficiency microfluidic chip for extracting exosomes from human plasma. We collected peripheral blood from normal human, designed and fabricated a microfluidic chip based on nanoporous membrane and agarose gel electrophoresis to isolate exosomes. The extracted exosomes were characterized by transmission electron microscopy, nanosight and Western blotting, the morphology, concentration and particle size of exosomes were identified and analyzed. Meanwhile, we used ultracentrifugation and microfluidic chip to isolate exosomes separately. The particle size and concentration of the exosomes extracted by two methods were compared and analyzed, and their respective extraction efficiency was discussed. Finally, the expression level of miRNA-21 in exosomes was analyzed by RT-PCR. The microfluidic chip isolated (in 1 hour) high-purity exosomes with size ranging from 30-200 nm directly from human plasma, allowing downstream exosomal miRNA analysis. By comparing with ultracentrifugation, the isolation yield of microfluidic chip was 3.80 times higher than ultracentrifugation when the volume of plasma sample less than 100 μL. The optimized parameters for exosome isolation by gel electrophoresis microfluidic chip were: voltage: 100 V; concentration of agarose gel: 1.0%; flow rate of injection pump: 0.1 mL/h. The gel electrophoresis microfluidic chips could rapidly and efficiently isolate the exosomes, showing great potential in the research of exosomes and cancer biomarkers.
Exosomes ; Humans ; MicroRNAs/genetics* ; Microfluidics ; Plasma ; Ultracentrifugation

Accurate detection of low frequency mutations from plasma cell-free DNA in blood using targeted next generation sequencing technology has shown promising benefits in clinical settings. Duplex sequencing technology is the most commonly used approach in liquid biopsies. Unique molecular identifiers are attached to each double-stranded DNA template, followed by production of low-error consensus sequences to detect low frequency variants. However, high sequencing costs have hindered application of this approach in clinical practice. Here, we have developed an improved duplex sequencing approach called SinoDuplex, which utilizes a pool of adapters containing pre-defined barcode sequences to generate far fewer barcode combinations than with random sequences, and implemented a novel computational analysis algorithm to generate duplex consensus sequences more precisely. SinoDuplex increased the output of duplex sequencing technology, making it more cost-effective. We evaluated our approach using reference standard samples and cell-free DNA samples from lung cancer patients. Our results showed that SinoDuplex has high sensitivity and specificity in detecting very low allele frequency mutations. The source code for SinoDuplex is freely available at https://github.com/SinOncology/sinoduplex.

The optometrist education system in the United States has a history of more than 100 years and has become a complete and mature system. It contains five parts: optometry admission test (OAT); a complete curriculum of optometry, including basic medical lectures, optometric theories and skills, large amount of clinical practices; the National Board Exam of Optometry (NBEO) which is mandatory for every licensed optometrist/practitioner, a one-year optional resident program; continue education in every year for renewing optometric licenses. We analyzed differents such as the enrollment requirements, the training time, the graduation requirements and the career perspective of the optometry education system between China and the United States were analyzed, we want to develop a optometrist training system with Chinese characteristics.

OBJECTIVE:To establish a method for the determination of related substances in Cabazitaxel injection. METHODS:HPLC method was used. The determination was performed on Agilent Eclipse XDB-C18column with mobile phase consisted of water-acetonitrile-ethanol(gradient elution)at the flow rate of 1.0 mL/min. The column temperature was 35 ℃,and the detection wavelength was set at 230 nm. The sample size was 20 μ L. Established method was used to determine related substances in 3 batches of Cabazitaxel injection. RESULTS:The linear relationship of cabazitaxel were 0.039-11.60 μ g/mL(r=0.999 8,n=7). The detection limit was 2×10-4μg,and quantitation limit was 8×10-4μg. RSD of precision and reproducibility tests were all lower than 10.0%(n=6). The amount of single impurity in 3 batches of samples ranged 0.07%-0.08%,and total amount of impurities were 0.26%-0.29%. CONCLUSIONS:Established method is simple,accurate and reliable,can be used for the determination of related substances in Cabazitaxel injection.

OBJECTIVE:To establish a method for simultaneous determination of 6 residual organic solvents in aprepitant raw material as methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether and tetrahydrofuran.METHODS:Headspace capillary gas chromatography was adopted.The determination was performed on DB-624 capillary column using temperature programming.The temperature of injector port was 180 ℃,and flame ionization detector was used with temperature of 260 ℃.Nitrogen was used as carrier gas with flow rate 3.0 mL/min.The spilt ratio was 5 ∶ 1,and head-space injection volume was 1.0 mL.The head-space equilibrium temperature was set at 80 ℃,and equilibrium time was 40 min.RESULTS:The linear ranges of methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether,tetrahydrofuran were 6.052-605.232 μ g/mL (r=0.999 9),9.987-998.718 μg/mL(r=0.999 9),9.998-999.768 μg/mL(r=0.999 8),9.986-998.634 μg/mL(r=0.999 9),9.991-999.090 μg/mL (r=0.999 7),1.461-146.133 μg/mL(r=0.999 5),respectively.The limits of quantitation were 1.782 1,2.079 0,0.749 8,1.777 8,0.223 1,0.607 0 μg/mL;the limits of detection were 0.594 0,0.693 0,0.249 9,0.592 6,0.074 4,0.202 3 μg/mL,respectively.RSD of precision test was lower than 2.0％.Only acetone and isopropyl alcohol were detected in stability test and reproducibility tests,RSD＜2.0％.Their recoveries were 99.34-100.75％ (RSD=0.52％,n=9),98.20％-100.24％ (RSD=0.69％,n=9),98.07％-100.07％ (RSD=0.84％,n=9),99.86％-101.32％ (RSD=0.58％,n=9),97.87％-104.02％ (RSD=2.13％,n=9),98.26 ％-100.58 ％ (RSD =0.75 ％,n =9),respectively.CONCLUSIONS:The established method is simple,accurate and reproducible,and can be used for simultaneous determination of 6 residual organic solvents in aprepitant raw material.

Objective To establish a method of gas chromatography with head-space sampling for determination of five residual solvents ( acetone, ethyl acetate, isopropanol, dichloromethane, acetonitrile ) in raw material drug of cefotiam hexetil hydrochloride. Methods Agilent DB-624 capillary column(30 m×0.53 mm,3.0 μm)was used,with FID served as detector and DMF as the solvent. Results Linear relationships were obtained for the 5 residual solvents in their respective concentration ranges ( r=0.999 6-0.999 9,n=5) ,and the detection range was from 0.071 to 0.847μg. The stabilities measured as relative standard deviations ( RSD) for the 5 residual solvents were from 0.40% to 2.12% ( n=3) . The average recovery rates were 99.03% to 103.33%,and RSD were 0.54% to 3.41% ( n=3) . Conclusion The method is simple,sensitive and accurate for the residual solvent analysis in raw material drug of cefotiam hexetil hydrochloride.

Objective To comprehensively evaluate the effect of the program of treatment and assistance to advanced schis-tosomiasis patients in Hunan Province from 2004 to 2013. Methods The fund investment of the program,the profits of hospi-tals and the improvement of the patients’health were investigated by data collection and questionnaire survey. The evaluation index system of treatment and assistance to advanced schistosomiasis in Hunan Province was constructed by the Delphi method and analytic hierarchy process,and the program was assessed comprehensively. Results The evaluation index system includ-ing 6 primary indices and 33 secondary indices was established. Among all the primary indices,the score of the treatment and assistance(22.25)was the highest,and that of the satisfaction assessment(8.15)was the lowest,and the score of the compre-hensive assessment was 87.06. The average cure rate of the patients was 13.08%from 2004 to 2013. More than 60%of the pa-tients’disease condition got better,and nearly 70%of the patients’psychological condition improved,and more than 70%of patients’self-help ability and social contact improved,as well as family happiness increased. In addition,the annual average cost for caretakers decreased by 2000 Yuan,and the profits of all the fixed-point hospitals for treatment and assistance in-creased. Conclusion The effectiveness and efficiency of the treatment and assistance to advanced schistosomiasis patients in Hunan Province is obvious,and the government should continuously invest in the program.