The intracellular retention of nanotherapeutics is essential for their therapeutic activity. The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors. However, strategies for the intracellular immobilization of nanoparticles are limited. Herein, a cisplatin prodrug was synthesized and utilized as a glutathione (GSH)-activated linker to induce aggregation of the cisplatin prodrug/IR820/docetaxel nanoassembly. The nanoassembly has been reprogrammed with peptide-containing moieties for tumor-targeting and PD-1/PD-L1 blockade. The aggregation of the nanoassemblies is dependent on GSH concentration. Evaluations

Objective:To investigate the levels of periphreal blood free carnitine and amino acids in healthy pregnant women in the third trimester and their association with maternal, fetal, and neonatal cardiac function and structure.Methods:This prospective descriptive study included healthy singleton pregnancies who underwent routine obstetric examination and delivered in two district maternal and child health hospitals (one in the urban and one in the suburb an area) in Beijing from June 2017 to February 2018. All recruiters had serology Down's syndrome screening test at (18±1) gestational weeks. Besides measurement of amino acids and free carnitine levels in whole blood and urine samples by liquid chromatography-tandem mass spectrometry, all cases underwent maternal and fetal echocardiography at (35±1) weeks of gestation. And neonatal echocardiography was performed after delivery to assess the heart function and structure. Antenatal factors were also collected, including maternal education background, age at first marriage and conception, gravidity, and folic acid supplement in early pregnancy. Statistical analysis was performed using t-test, ANOVA, Chi-square test, Pearson correlation coefficient, and Kappa test. Results:A total of 493 mother-neonate dyads were enrolled in this study. Blood free carnitine levels in the healthy pregnant women in the third trimester ranged from 5.09 to 59.17 μmol/L (reference value: 10.00-50.00 μmol/L) with an average value of (13.03±3.87) μmol/L. None was found with structural abnormalities by cardiac ultrasound, showing an average left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) of (45.70±3.08) mm and (29.17±3.12) mm, respectively, and left ventricular ejection fraction (LVEF) of all cases were over 55%. No cardiac malformation was detected by the third-trimester fetal echocardiography. The average birth weight of the 493 newborns was (3 340±313) g. Those whose birth weight <2 500 g and >4 000 g were accounted for 1.0% (5 cases) and 3.0% (15 cases) with the average maternal blood free carnitine level of (13.25±2.17) μmol/L (10.46-19.21 μmol/L) and (12.64±2.50) μmol/L (8.78-17.73 μmol/L) ( t=0.42, P>0.05). The average LVEDD and LVESD of the 493 newborns were (17.21±1.27) mm and (11.03±1.30) mm, respectively. For the 64 newborns (13.0%) whose LVEF<60%, the maternal blood free carnitine level was (12.93±2.78) μmol/L (7.34-22.13 μmol/L), showing no statistical difference ( t=-0.29, P>0.05) with those 59 neonates (12.0%) whose LVEF over 75% and maternal carnitine level of (13.09±3.24) μmol/L (8.66-27.49 μmol/L). All cases were divided into four groups based on the quartiles of maternal blood free carnitine level and no significant difference in maternal or neonatal LVEDD or LVEF was observed among these groups (all P>0.05). Conclusions:Blood free carnitine concentration in healthy pregnant women in the third trimester is at the lower limit of normal range, and no significant effect on maternal cardiac function and fetal cardiac structure is seen. However, the effect of low maternal carnitine level in the third trimester on children's myocardial function and whether carnitine should be supplemented in the third trimester are worthy of further investigation with larger sample size.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective:To investigate the normal range of exhaled nitric oxide in healthy children aged 6-18 in Jinan.Methods:The healthy school children aged 6-18 in Jinan from October 11 to 26, 2017 were selected for questionnaire survey, physical examination and exhaled nitric oxide test.The levels of mouth exhaled nitric oxide at the flow rate of 50 mL/s (FeNO 50) and mouth exhaled nitric oxide at the flow rate of 200 mL/s(FeNO 200), alveolar nitric oxide (CaNO), and nasal exhaled nitric oxide at the flow rate of 10 mL/s(FnNO 10) were measured by the electroche-mical method.The distributions of FeNO 50, FeNO 200, CaNO and FnNO 10 were analyzed, and their correlations with gender, age, height and body mass index (BMI) were discussed by the multiple linear regression model. Results:A total of 772 healthy children were enrolled in this study, including 364 males and 408 females, with a median age of 12.1(11.8-12.3) years old, a median height of 154.8(153.6-156.0) cm, and a median BMI of 20.3 (20.0-20.6) kg/m 2. The measured values of FeNO 50, FeNO 200, CaNO and FnNO 10 fluctuated in the range of 3.0-168.0 ppb, 2.0-44.0 ppb, 0.5-44.2 ppb and 0-1 253.0 ppb, respectively.FeNO 50, FeNO 200 and CaNO values showed skewed a distribution, and their 95% upper limits were 35.0 ppb, 13.3 ppb and 8.5 ppb, respectively.The geometric mean(95% CI) of FeNO 50 in males (95% CI)[14.6 (13.7-15.5) ppb] was significantly higher than that in females [13.3(12.7-14.0) ppb], and the difference was statistically significant ( Z=1.470, P=0.027). The multiple linear regression results suggested that, FeNO 50 was positively correlated with age and height ( β=0.023, 0.007, respectively, all P<0.05), and negatively correlated with BMI ( β=-0.016, P<0.05). The geometric mean (95% CI) of FeNO 200in males[7.1 (6.8-7.4) ppb] was significantly higher than that in females[6.4 (6.1-6.6) ppb], and the difference was statistically significant( Z=1.747, P=0.004). The multiple linear regression results suggested that, FeNO 200 was positively correlated with height ( β=0.005) and negatively correlated with gender(female β=-1.126) (all P<0.05). There was no significant difference between male and female in CaNO, which had no correlation with gender, age, height and BMI (all P>0.05). FnNO 10 showed a normal distribution, with a mean value of 456.2 ppb, 95% CI of 29.3-863.4 ppb.The geometric mean (95% CI) of FnNO 10 in males [408.7 (377.1-443.0) ppb] was significantly higher than that in females [368.8 (339.0-401.3) ppb], and the difference was statistically significant ( Z=1.722, P=0.005). The multiple linear regression results indicated that FnNO 10 was related to gender ( β=-36.098, P<0.05), and not correlated with age, height and BMI (all P>0.05). Conclusions:The normal ranges of FeNO 50, FeNO 200, CaNO and FnNO 10 in healthy children aged 6-18 in Jinan are 3.0-35.0 ppb, 2.0-13.3 ppb, 0.5~8.5 ppb and 29.3-863.4 ppb, respectively.FeNO 50 is correlated with age, height and BMI.FeNO 200 is correlated with gender and height.CaNO and FnNO 10 are not correlated with age, height or BMI.

Objective:To investigate the normal range of exhaled nitric oxide (FeNO) in 6-18-year-old children in China, so as to provide a data base for the establishment of FeNO standards for Chinese children.Methods:A multi-center study was conducted on 5 949 children aged 6-18 (3 101 males and 2 848 females) in 16 pro-vinces of 7 administrative districts in China.According to the technical standard recommended by American Thoracic Society/European Respiratory Association, FeNO was measured, and the relationship of FeNO with the sex, age, height, weight, body mass index and region was discussed.Results:The geometric mean FeNO value of Chinese children aged 6-18 was 14.1 ppb, and its 95% confidence interval (skewness distribution) was 1.0-38.2 ppb.The geometric mean FeNO values of children aged 6-11 and 12-18 were 13.1 ppb and 15.7 ppb, respectively, and their 95% confidence intervals (skewness distribution) were 1.0-38.1 ppb and 2.0-38.2 ppb.For children at and under 11 years old, FeNO decreased with age, with a mean decline of 1 ppb per year.The multiple linear regression results suggested that there was a significant correlation between FeNO and age for children aged 6-11, and FeNO of children aged 12-18 was significantly correlated with the gender, height, and region(all P<0.01). Conclusions:FeNO values of Chinese children and adolescents in this study are higher than those obtained by the previous study conducted from 2010 to 2012.For children aged 12-18, 16 ppb is recommended as the clinical cut-off point.For children at or under 11 years old, the influence of age on FeNO should be considered, and the cut-off point of FeNO decreases by 1 ppb as the age is reduced by one year.

Objective To screen a Madin-Darby canine kidney (MDCK) cell line for H5N1 influ-enza virus isolation and to evaluate its safety in vaccine production. Methods MDCK cells were cloned by the method of limiting dilution. Hemagglutination test was used to screen MDCK cells that were suitable for H5N1 influenza virus production. Tests for analyzing the characteristics, extraneous agents, endogenous agents and tumorigenicity of MDCK cells were performed according to Chinese Pharmacopeia Volume Ⅲ. Results A total of 108 MDCK cell lines were obtained and three of them were selected after hemagglutina-tion test. G1 cells were chosen following further screening with tumorigenicity test and receptor abundance analysis. The average number of chromosomes of the MDCK-G1 cells was 78±4. No bacteria, fungi or myco-plasma contamination was detected. In experimental group, each nude mouse was injected with 1×107/ml viable cells to observe their tumorigenicity. Twelve weeks after cell injection, no node was found at injection sites or in gross anatomy. There was no significant difference between the experimental and negative control groups. The result of the tumorigenicity test was negative. No node formation was found after injecting nude mice with cell lysate or cellular DNA collected from equivalent amount of cells. It was indicated that the MDCK-G1 cells were of low-oncogenic potential. Conclusions The MDCK-G1 cell line could be used as a substrate to produce H5N1 influenza virus vaccine.

Objective To evaluate the quality of Radix et Caulis Ilicis Asprellae from Pingyuan planting base and Chinese herbal medicine market. Methods The water- and alcohol-soluble extracts from 19 batches of Radix et Caulis Ilicis Asprellae medicinal materials were detected according to Appendix ⅨH, ⅩA of the Chinese Pharmacopoeia ( 2010 edition). And the quality of the medicinal materials was evaluated by microscopic identification technology according to the method for Radix et Caulis Ilicis Asprellae recorded in Guangdong Provincial Chinese Medicine Standard, and then thin layer chromatography ( TLC) was optimized to establish the high performance liquid chromatography (HPLC) fingerprint. The HPLC was performed on Waters XBridgeTM C18 column (250 mm × 4.6 mm, 5μm) with acetonitrile(A)-0.2% (v/v) phosphorus acid (B) as the mobile phase by gradient elution, flow rate was 1.0 mL/min, and detection wavelength was 220 nm. Results The results of sample characters, TLC and microscopic identification showed that the samples of Radix et Caulis Ilicis Asprellae in Chinese herbal medicine markets were certified products, but stems and roots were blended. Seven common peaks were showed by HPLC and confirmed by similarity analytical software. The similarity of 15 batches of planting base samples was all above 0.9. Of 19 batches of the commercial samples, the similarity of 11 batches was above 0.9. The alcohol-soluble extract contents were in the range of 64.55 mg/g to 186.18 mg/g. Conclusion The medicinal materials of Radix et Caulis Ilicis Asprellae from Chinese herbal medicine market are certified products, but the qualities vary greatly for the blending of stems and roots and inadequate growth years. The quality of materials from planting base is better. The established method is helpful for the quality evaluation and control of Radix et Caulis Ilicis Asprellae.

OBJECTIVETo screen out serum differential proteins between vinyl chloride monomer (VCM)-exposed workers and healthy controls by proteomics and analyze the functions of differential proteins, and to provide a basis for elucidating the pathogenesis of diseases caused by VCM exposure and searching for the protein biomarkers.

METHODSFasting venous blood was collected from 125 VCM-exposed workers and 40 healthy controls according to accumulated exposure doses. Proteins were precipitated by acetone precipitation. These proteins were identified by 2D-nano LC-ESI-TOF/MS and quantified by isobaric tags for relative and absolute quantitation. The functions of differential proteins were analyzed by gene ontology.

RESULTSA total of 596 proteins were identified, including 194 quantified proteins. There were 21 differential proteins according to the screening criteria (19 upregulated proteins and 2 downregulated proteins), including complement, apolipoprotein, and glycoprotein. The functions of these differential proteins were binding, enzyme regulator activity, catalytic activity, and transporter activity, and they were involved in the biological processes including immune system process and response to stimulus.

CONCLUSIONThe complement, apolipoprotein, and glycoprotein identified in the proteomics may be related to liver injury caused by VCM exposure, and they could be used as candidate protein biomarkers of diseases caused by VCM exposure.

Biomarkers ; blood ; Blood Proteins ; analysis ; Humans ; Liver ; injuries ; Occupational Exposure ; Proteins ; metabolism ; Proteomics ; Vinyl Chloride ; toxicity

Curcumin can induce cell apoptosis in human chondrosarcoma cells through extrinsic death receptor pathway,inhibit proliferation of lung cancer cells by inducing cell cycle arrest,and can suppress proliferation and induce apoptosis in cholangiocarcinoma cells through blocking multiple signaling pathways,suppress the formation of tumor blood vessels by reducing the expression of vascular endothelial growth factor in Ehrlich ascites cancer cells,inhibit breast cancer cell motility and invasiveness by regulating the expression of adhesion molecules and increase the sensitivity of chemotherapy drugs to cancer cells by regulating the expression of multidrug resistance related genes.Curcumin has explored new approaches for the treatment of tumor.

For optimal adaptive cultivation region selection, we used ecology factors characterized Duolun region as model area to carry out the adaptive habitat division of Paeonia lactiflora. Similar priority comparison of ecology factors.in 91 cities were calculated by Fuzzy methods, then, distance of the ecology factors were transferred to spacial model by geography information system (,GIS) and modified by soil utilization map of China. The results showed that P. lactiflora were mainly distributed in the Daxing'an Mountain, Changbaishan and qinling range which were divided into six grades of suitable regions belonging to three geographical distributed units. The most similar areas to Duolun were Huade, Xilinhaote, Suolun and Zhangbei. P. lactiflora's distribution and quality are relevant with longitude and latitude, and temperature and rainfall.
China ; Environment ; Fuzzy Logic ; Paeonia ; classification ; growth & development ; Temperature