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Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5mg/mL LBP, 10 μM OXA) group (p < 0.05). Cells in the LBP + OXA (2.5mg/mL LBP, 10 μMOXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumormodels showed a decrease in tumor size. Therewas no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC. [ABSTRACT FROM AUTHOR]

Purpose: Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients. Methods: The genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated. Results: The highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-a2, IL- 1a, and IL-1b in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFa, IFNg, IL-1a, and IL-1b in the first serum samples from patients with ON1 compared to those with BA9 of subtype B. Conclusions: Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity. [ABSTRACT FROM AUTHOR]

Background: Bronchofiberscopy, a widely used procedure for the diagnosis of various pulmonary diseases within intensive care units, has a history of association with nosocomial infections. Between September and November 2009, an outbreak caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) was observed in the intensive care unit of a tertiary care hospital in Beijing, China. This study is aimed to describe the course and control of this outbreak and investigate the related risk factors. Methods: Clinical and environmental sampling, genotyping with repetitive extragenic palindromic polymerase chain reaction (REP-PCR), and case-control risk factor analysis were performed in the current study. Results: During the epidemic period, 12 patients were infected or colonized with MDR-Ab. Sixteen (72.7%) of twenty-two MDR-Ab isolates from the 12 patients and 22 (84.6%) of 26 MDR-Ab isolates from the bronchofiberscope and the healthcare-associated environment were clustered significantly into a major clone (outbreak MDR-Ab strain) by REP-PCR typing. Seven patients carrying the outbreak MDR-Ab strain were defined as the cases. Six of the seven cases (83%) received bronchofiberscopy versus four of the 19 controls (21%) (odds ratio, 22.5; 95% confidence interval, 2.07-244.84; P = 0.005). Several potential administrative and technical problems existed in bronchofiberscope reprocessing. Conclusions: Bronchofiberscopy was associated with this MDR-Ab outbreak. Infection control precautions including appropriate bronchofiberscope reprocessing and environmental decontamination should be strengthened. [ABSTRACT FROM AUTHOR]

To investigate whether and how the Beijing Olympic Games influenced the Chinese competitiveness towards foreigners, we conducted a three-wave longitudinal study and found that participants' competitiveness towards foreigners from five comparison target nations, particularly towards Japanese, South Koreans and Kenyans, was higher during the Games than before and/or after. We further found that nationalism predicted the competitiveness toward Japanese and South Koreans, but did not predict the competitiveness toward Americans, Russians and Kenyans. Additionally, we found that patriotism played little role in the effects of the Games on competitiveness towards foreigners. We herein discuss the relationship between national comparisons, nationalism and national conflict. [ABSTRACT FROM AUTHOR]

A novel polyomavirus (WU virus) has been identified in pediatric patients with acute respiratory tract infections (ARI), but its role as a respiratory pathogen has not yet been demonstrated. To investigate if WU virus is related to acute respiratory infections in infants and children in Beijing, specimens collected from 674 pediatric patients with ARI from April 2007 to May 2008 and from 202 children without ARI were used for this investigation. Common respiratory viruses were tested by virus isolation and/or antigen detection by indirect immunofluorescent assay followed by RT-PCR or PCR for other viruses associated with respiratory infections in specimens collected from patients with ARI before WU virus DNA was detected. WU virus DNA was detected by initial screening and secondary confirmation PCR for all specimens. The region encoding the VP2 gene of the virus was amplified from 17 WU-virus-positive clinical specimens, and sequence analysis was performed. Thirty-eight of 674 (5.6%) specimens from patients with ARI and 3 of 202 (1.5%) specimens from children without ARI yielded PCR products with the predicted molecular weight, using either screening or confirmation primer sets, indicating that these specimens were WU virus positive. However, more than 60% of the 38 WU-virus-positive specimens from patients with ARI were also positive for one or more respiratory viruses. The nucleotide and deduced amino acid sequences of the region encoding the VP2 gene from 17 Beijing WU viruses shared high homology (>98.5%) with sequences from GenBank and among themselves. The data indicated that WU virus in Beijing occurred 3.7 times more frequently in pediatric patients with ARI than in those without ARI ( p < 0.05). [ABSTRACT FROM AUTHOR]

Background. Chronic kidney disease (CKD) is a public health problem, while data from developing countries are limited. We sought to investigate the epidemiological features of kidney damage in metropolis-residing Chinese adults (>40 years old), and to determine the associated factors of CKD.Methods. Two thousand three hundred and fifty-three residents in one district of Beijing were interviewed and tested for albuminuria, reduced renal function, haematuria and pyuria. The associations between demographic characteristics, health characteristics and indicators of kidney damage were examined.Results. Albuminuria was detected in 6.2% of subjects; reduced renal function was found in 5.2% of subjects; haematuria was found in 0.8% and non-infective pyuria was found in 0.09%. Approximately, 11.3% (95% confidence interval: 10.0–12.8%) of subjects had at least one indicator of kidney damage. The awareness rate of CKD was only 7.2%. Systolic blood pressure and diabetes were independently associated with albuminuria. Age, diastolic blood pressure, hypercholesteraemia, hypertriglyceridaemia and hyperuricaemia were independently associated with reduced renal function.Conclusions. This is the first report on the prevalence of CKD in a community-based population within a developing country, determined using protocols recommended by kidney disease improving global outcomes (KDIGO). The prevalence of CKD in our population was close to the levels observed in developed countries, and the spectrum of CKD and associated factors were similar to developed countries. Results from this study suggest that strategies aimed at an intervention of hypertension and other metabolic disorders might prove effective in controlling the pandemic of CKD in China, as well as other developing countries. [ABSTRACT FROM AUTHOR]

Background. It is unclear whether ethnic disparity of the prevalence of chronic kidney disease (CKD) exists among native Chinese and American ethnicities. Methods. A stratified multistage clustered screening for CKD performed in Beijing in 2006 was compared with data from the National Health and Nutrition Examination Survey (NHANES) between 1999–2006 (participants aged ≥20 years, 13 626 Chinese, 9006 whites, 3447 African Americans, 4626 Hispanics). Serum creatinine from Beijing and NHANES were calibrated at the Cleveland Clinic Laboratory. The re-expressed abbreviated MDRD equation for Americans and its modified form for Chinese were used to estimate glomerular filtration rate (eGFR). Subjects with eGFR 17 mg/g for males or >25 mg/g for females. CKD was diagnosed if CRI or albuminuria was present. Results. Compared with American whites, African Americans and Hispanics, Chinese had a lower prevalence of adjusted albuminuria (12.10%, 16.33% and 14.16% versus 9.27%), CRI (9.46%, 5.18% and 3.11% versus 1.38%) and CKD (19.03%, 19.00% and 15.99% versus 10.25%). Moreover, Chinese hold the lowest risk of albuminuria when exposed to diabetes; the risk of CRI among Chinese when exposed to diabetes or hypertension was lower than that among African Americans, but similar to that among whites and Hispanics. Conclusions. The CKD prevalence was significantly different among native Chinese and American ethnicities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the relationship between metabolic syndrome and chronic kidney disease (CKD) in a study population from a developing country. PARTICIPANTS AND METHODS: The prevalence of metabolic syndrome (as most recently defined by the international Diabetes Federation) and CKD (defined as an estimated giomerular flitration rate of <60 mL/min per 1.73 m² and/or aibuminuria) was determined in 2310 study participants (age ⩾40 years) from Beijing, China, between May 12 and December 7, 2004. The relationship between metabolic syndrome and CKD was then analyzed. RESULTS: Participants with metabolic syndrome had a higher prevalence of CKD (15.4% vs 8.3%; P<.001) than those without the syndrome. As the number of metabolic syndrome traits increased, so did the prevalence of CKD. Strong unadjusted and adjusted associations were observed between metabolic syndrome and CKD. For participants without hypertension and diabetes, metabolic syndrome was also associated with CKD (odds ratio, 2.03; 95% confidence lnterval, 1.05-3.94). CONCLUSION: in these 2310 Chinese study participants aged 40 years and older, metabolic syndrome was associated with CKD. [ABSTRACT FROM AUTHOR]