Effects of subitems in the colorectal cancer screening protocol on the Chinese colorectal cancer screening program: an analysis based on natural community screening results.

BACKGROUND: To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. METHODS: CRC screening results (scenario A) from Jiashan County, China, (2007-2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B-G (by selecting some items at the first stage of screening) for analysis. RESULTS: Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B-E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. CONCLUSION: The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.

Protamine-gold nanoclusters as peroxidase mimics and the selective enhancement of their activity by mercury ions for highly sensitive colorimetric assay of Hg(II).

We certify that protamine-gold nanoclusters (PRT-AuNCs) synthesized by one-pot method exhibit peroxidase-like activity. The catalytic activity of PRT-AuNCs followed typical Michaelis-Menten kinetics and exhibited higher affinity to 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate compared to that of natural horseradish peroxidase. Meanwhile, we found that Hg(II) could dramatically and selectively enhance the peroxidase-like activity of PRT-AuNCs, and the enhanced mechanism by Hg(II) was demonstrated to be generation of the cationic Au species and the partly oxidized Au species (Auδ+) by Hg2+-Au0/Au+ interaction. Based on this finding, quantitative determinations of Hg(II) via visual observation and absorption spectra were achieved. The proposed strategy displays high selectivity that arises from the strong aurophilic interaction of mercury towards gold. Moreover, the developed method is highly sensitive with a wide linear range and low detection limit of 1.16 nM. This strategy is not only helpful to develop effective nanomaterials-based artificial enzyme mimics but also irradiative to discover new applications of artificial mimic enzymes in bio-detection, medical diagnostics, and biotechnology. Graphical abstract Protamine-gold nanoclusters (PRT-AuNCs) synthesized by one-pot method exhibit peroxidase-like activity. Hg(II) can stimulate the peroxidase-like activity of PRT-AuNCs selectively, enhancing their ability to catalyze the chromogenic reaction of TMB by H2O2.

Protamine-stabilized gold nanoclusters as a fluorescent nanoprobe for lead(II) via Pb(II)-Au(I) interaction.

The authors report on a one-pot approach for synthesizing highly fluorescent protamine-stabilized gold nanoclusters. These are shown to be a viable nanoprobe for selective and sensitive fluorometric determination of lead(II) via quenching of fluorescence via Pb(II)-Au(I) interaction. Under optimized conditions, fluorescence measured at excitation/emission peaks of 300/599 nm drops in the 80 nM-15 µM lead(II) concentration range. The detection limit is 24 nM, and relative standard deviations (for n = 11) at concentrations of 0.10, 4.0 and 15 µM are 1.6, 2.5 and 1.9%, respectively. The relative recoveries of added lead(II) in the water samples ranged from 97.9 ± 2.29% to 101.2 ± 1.83%. Graphical abstract Lead(II) ions are found to be able to selectively and sensitively quench the fluorescence of the protamine-gold nanoclusters (PRT-AuNCs). Thereby, an inexpensive, selective and sensitive lead(II) assay was established.

A multifunctional fluorescent aptamer probe for highly sensitive and selective detection of cadmium(II).

We report a highly sensitive and selective strategy for Cd(II) assay using a singly labeled multifunctional probe consisting of a Cd(II)-specific aptamer (CAP), which acted as a recognition element for Cd(II) and a signal reporter. The presence of Cd(II) can induce the conformational switching of the CAP, accompanied by a change in fluorescence intensity. Thereby, a fluorescence strategy for Cd(II) assay was established. The proposed method has a detection limit of 2.15 nM, which is much lower than the detection limits reported in related literature. This strategy involves only an aptamer probe, and the use of such a G4-based quencher avoids the dual labeling of the CAP with fluorophore/quencher units. It is obviously more convenient and economical than the other aptamer-based biosensors for Cd(II) detection. The mechanism by which Cd(II) induces the CAP to change from a random coil sequence to a stem-loop structure was studied in a series of control experiments. This strategy would be helpful in the design of a sensitive analytical platform for various target assays in environmental and biomedical fields. Graphical Abstract The presence of Cd2+ leads to the conformational change of CAP from a random coil sequence to a stem-loop structure, resulting in a quenching in the fluorescence.

[Effect of Crude Antigens from Ascaris lumbricoides on the Apoptosis and Secretion of IL-6 and TGF-ß of Human Lung Adenocarcinoma Cells].

OBJECTIVE: To investigate the effect of crude antigens of Ascaris lumbricoides on the secretion of IL-6 and TGF-ß of human lung adenocarcinoma cells (A549 cells), and the apoptosis of A549 cells. METHODS: Crude antigens of A. lumbricoides were prepared. A549 cells were co-cultured with 25, 125, and 500 µg/ml crude antigens of A. lumbricoides for 1, 18, and 24 h, named as low concentration group, medium concentration group, and high concentration group, respectively. Meanwhile, A549 cells were co-cultured with culture medium (negative control) and 12.5 µg/ml adriamycin (positive control). The apoptosis rate was detected by using Annexin V-FITC apoptosis detection kit. The cell changes were determined by flow cytometry. The levels of mRNA expression of IL-6 and TGF-ß were detected by ELISA and real time PCR, respectively. RESULTS: The apoptosis rate of A549 cells induced by crude antigens for 1, 18, and 24 h was significantly higher than that of negative control (P < 0.01). The apoptosis rate in medium concentration group (treated for 18 h) was highest [(47.10 ± 3.68)%]. After co-culture with 125 µg/ml crude antigens for 18 h, the proportion of G0/G1 phase cells increased and that of S phase cells decreased, and there was a significant difference between medium concentration group and negative control group. At the same time, the level of IL-6 increased with the increasing concentration of crude antigens. However, no significant difference was found in the level of TGF-ß among the groups. In the medium concentration group, mRNA expression levels of IL-6 (5.95 ± 0.31) and TGF-ß (3.43 ± 0.35) of A549 cells reached peak on the 18th hour, and were significantly higher than that of the control (P < 0.01). CONCLUSION: The cell cycle of A549 cells is blocked in G0/G1 phase induced by crude antigens of A. lumbricoides. And the apoptosis may be related to the changes in the level of TGF-ß and IL-6.

[Comparison between application of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening].

OBJECTIVE: To compare the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening. METHODS: A representative random population of 9000 subjects aging between 40 and 74 years old were selected from Xuxiang, Haining city, Zhejiang province, by random cluster sampling method in year 2011. The fecal samples from each subject were separately detected by the two methods, namely fecal occult blood quantitive testing instrument and colloidal gold strip method. The positive result was standardized by hemoglobin concentration (HGB) ≥ 100 ng/ml under the application of quantitive testing instrument, or color-developing by colloidal gold strip method. The positive subjects from either method would be provided a further colonoscopy examination for pathological diagnosis. The positive rate and consistency of the two methods were compared, as well as the positive predictive value and population detecting rate of the colorectal cancer and adenoma. RESULTS: A total of 6475 (71.9%) subjects submitted their two fecal samples according to our requirement in 9000 subjects. There were separately 319 positive cases (4.9%) and 146 positive cases (2.3%) by the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method, including 45 positive in both tests (Kappa = 0.168, 95%CI:0.119-0.217).184 out of the 319 positive cases (57.7%) in the test by quantitive testing instrument and 89 out of 146 positive cases (61.0%) in the test by colloidal gold strip method received the colonoscopy examination. There were no significant statistical differences between the two methods in the positive predictive value of colorectal cancer (P > 0.05) , developing adenoma and non-developing adenoma.However, the population detecting rate of the colorectal cancer and developing adenoma were higher in the test by quantitive testing instrument (26 cases, 0.402%) than it in the test by colloidal gold strip method (10 cases, 0.154%). The difference showed statistical significance (χ(2) = 7.131, P < 0.01). CONCLUSION: The performances of fecal occult blood quantitive testing instrument might be better than colloidal gold strip method in colorectal cancer screening. However, the results need to be further verified.

[Anti-tumor effect of the whole worm extract of Ascaris lumbricoides on Lewis lung carcinoma in mice].

Forty-five C57BL/6 mice were randomly divided into five groups (A-E). Group B and D served as the control group of A and C. Each mouse of group A was intraperitoneally injected with 0.1 ml whole worm extract of Ascaris lumbricoides every other day, and 10 days later injected with 0.1 ml Lewis lung carcinoma (LLC) cells at right axillary subcutaneously region. Mice of group B were injected with normal saline and then developed tumor model. Each mouse of group C was injected with 0.1 ml LLC cells, and two days later, injected with 0.1 ml whole worm extract of A. lumbricoides every other day for 5 times. After the tumor model developed, mice in group D were injected with normal saline. Group E was the negative control group. Time intervals between implantation and active growth and tumor weight were recorded. Tumor inhibition rate was calculated. The average time interval between tumor implantation and measurable tumor growth for groups A, B, C and D was (7.0 +/-1.1), (6.0 +/- 0.7), (9.0 +/- 1.2) and (7.0 +/- 0.9) days. Tumor weight of [(338.9 +/- 282.2) mg] (P < 0.05). The tumor inhibition rate group A [(722.2 +/- 413.5) mg] was heavier than that of group B was the highest in group C (33.3%). Tumor weight of group C [(237.8 +/- 101.8) mg] was lighter than that of group D [(356.7 +/- 176.9) mg] (P < 0.05). The results indicated that the tumor formation is affected by the whole worm extract of A. lumbricoides which may have an inhibitory effect on tumour growth.

A large perturbation on geometry structures, excited state properties, charge-injection and -transporting abilities of Ir(III) complexes by different substituents on ligands: a DFT/TDDFT study.

The molecular geometries, electronic structures, photophysical properties, charge-injection and -transporting abilities of a series of Ir(III) complexes with different carrier-transporting substituents, such as carbazole, oxadiazole and dimesitylboryl groups, are investigated theoretically using density functional theory (DFT) and time-dependent DFT (TDDFT) calculations to understand the influence of these substituents on the optical and electronic properties of Ir(III) complexes and to explore how to improve the optoelectronic properties of the complexes. It is found that the introduction of substituents can stabilize both HOMOs and LUMOs and induce variations in the energy gap between HOMO and LUMO. The introduction of hole-transporting carbazole substituent induces the blue-shift of absorption spectrum and improves the hole-injection and -transporting performances of complex. The introduction of electron-transporting oxadiazole substituent and electron-accepting dimesitylboryl substituent induces the red-shift in absorption spectra of complexes, improves their charge transfer abilities and leads to the better balance between the hole- and electron-transporting abilities. Through Lewis acid/base interactions between B atom and F(-), the electronic properties of 4 show dramatic changes in the presence of F(-) and thus 4 can also be used as selective phosphorescent F(-) probe.

[Primary evaluation of a mass screening program for colorectal tumor in China].

OBJECTIVE: To evaluate a colorectal cancer screening program by tumor detection rate and discussing its application values. METHOD: In total, 43 713 subjects were recruited in the screening program who were the registered people aged 40 - 74 in Xiacheng and Jiashan during year 2007 - 2009. The first screening involved questionnaire survey of colorectal cancer related risk factors and fecal occult blood test (FOBT), colonoscopy was performed when a positive result was observed in the first screening. If polyps were found during colonoscopy, biopsy and pathological diagnosis were carried out. The screening data were analyzed and the tumor detection rate was calculated according to age or sex. RESULTS: 6489 subjects (14.85%) belonged to the high risk group of colorectal cancer in the first screening, in which 4701 subjects finished complete colonoscopy. Finally, 569 colorectal neoplasm were diagnosed, the detection rate was 12.10% (95%CI: 11.17% - 13.04%). It included 52 colorectal cancer (1.11%, 95%CI: 0.81% - 1.41%), 183 advanced adenoma (3.89%, 95%CI: 3.34% - 4.45%), 334 non-advanced adenoma (7.10%, 95%CI: 6.37% - 7.84%). The highest detective rate was observed in male group that aged 70 - 74 (22.81%, 95%CI: 16.98% - 28.70%), the lowest detective rate was observed in female group aged 40 - 44 (2.49%, 95%CI: 0.79% - 4.20%). CONCLUSION: The current colorectal cancer screening program in China works well, but the revision of the program is necessary.

Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis.

BACKGROUND: Multiagent chemotherapy is the primary treatment for acute lymphoblastic leukemia (ALL), of which asparaginases including Escherichia coli L-asparaginase (E. coli L-Asp) and pegylated-asparaginase (PEG-Asp), are cornerstone components. The study aimed to conduct a meta-analysis to compare the efficacy and safety of PEG-Asp with E. coli L-Asp in Chinese children with ALL. METHODS: A systematic literature search was conducted to collect randomized controlled trials (RCTs) on PEG-Asp versus E. coli L-Asp in Chinese children with ALL. Two reviewers independently selected articles and extracted data. Risk-of-bias assessment was conducted with Cochrane recommendation tool. Pooled estimates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for all outcomes in Review Manager 5.3. RESULTS: Out of the 470 publications screened, 15 studies were included, involving 1,194 patients. Pooled estimates showed that there were no significant differences in complete responses (CR), overall response rate (ORR), gastrointestinal symptoms, and coagulation abnormalities rate between the PEG-Asp and E. coli L-Asp groups (all P>0.05). Hypersensitivity (RR =0.63; 95% CI, 0.40-1.01; Ρ=0.05) and hepatic injury rate (RR =0.45; 95% CI, 0.27-0.75; Ρ=0.002) were lower in the PEG-Asp group. The frequency of administration and length of hospital stay of patients in the PEG-Asp group were less than those in the E. coli L-Asp group (both Ρ<0.0001). CONCLUSIONS: Current evidence pointed out a similar efficacy in the two groups. The PEG-Asp group showed a lower hypersensitivity and hepatic injury rate. In addition, using PEG-Asp decreased the frequency of administration and the length of hospital stay, which, to some extent, might reduce patients' burden caused by medical resource consumption.

Infection with severe fever with thrombocytopenia virus in healthy population: a cohort study in a high endemic region, China.

BACKGROUND: Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region. METHODS: A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates. RESULTS: Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334-4.461 compared to the group of < 50 years old, P = 0.004], recent contact with cats (adjusted OR = 2.195, 95% CI: 1.261-3.818, P = 0.005), and working in tea garden (adjusted OR = 1.698, 95% CI: 1.002-2.880, P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjusted OR = 2.691, 95% CI: 1.271-5.695 compared to the group of < 50 years old, P = 0.010), and recent contact with cats (OR = 2.648, 95% CI: 1.419-4.941, P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced. CONCLUSIONS: Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.

Solvent- and pH-induced self-assembly of cationic meta-linked poly(phenylene ethynylene): effects of helix formation on amplified fluorescence quenching and Förster resonance energy transfer.

We reported here the synthesis and characterization of a novel water-soluble, meta-linked poly(phenylene ethynylene) (m-PPE-NEt(2)Me(+)) featuring quaternized side groups. We studied the solvent-induced self-assembly of m-PPE-NEt(2)Me(+) in MeOH/H(2)O solvent mixtures by using UV-vis absorption and fluorescence spectroscopies. The results showed that the polymer folded into a helical conformation and that the extent of helical folding increased with the volume % water in the solvent. This cationic polymer also exhibited unique pH-induced helix formation, which was attributed to the partial neutralization of quaternized side groups at high pH and the meta-links in the main chain of the polymer. Studies on the fluorescence quenching of m-PPE-NEt(2)Me(+) by anthraquinone-2,6-disulfonate (AQS) and Fe(CN)(6)(4-), two small-molecule anionic quenchers with different typical structures, revealed more efficient quenching of helical conformation by AQS than by Fe(CN)(6)(4-). We proposed that the two quenchers most likely interacted with the polymer helix in two different modes; that was, AQS featuring large planar aromatic ring could intercalate within adjacent π-stacked phenylene ethynylene units in the polymer helix, whereas Fe(CN)(6)(4-) mainly bound to the periphery of polymer helix through ion-pair formation. Finally, the results of FRET from the helical polymer to the fluorescein (C*)-labeled polyanions, ssDNA-C* (ssDNA: single-stranded DNA) and dsDNA-C* (dsDNA: double-stranded DNA) also suggested two different modes of interactions. As compared with the FRET to dsDNA-C*, the FRET to ssDNA-C* was slightly more efficient, which was believed to arise from the additional binding of ssDNA-C* with the polymer via intercalation of its exposed hydrophobic bases into the π stack of adjacent phenylene ethynylene units in the polymer helix.

[Effect of hydroxycamptothecin (HCPT) on proliferation and apoptosis of rat hepatic stellate cells].

OBJECTIVE: To investigate the effects of hydroxycamptothecin (HCPT) on proliferation and apoptosis of rat hepatic stellate cells (HSC). METHODS: Rat HSC line (HSC-T6) and rat hepatocyte line (BRL-3A) were treated with different concentrations of HCPT (0, 0.008, 0.016, 0.031, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32 mg/L respectively) for 24 h. Cell proliferation was assessed by MTT colorimetric assay, apoptosis was detected with PI staging followed by flow cytometry, and by DNA ladder assay. The morphological change of apoptosis was observed under transmission electron microscopy (TEM). RESULTS: MTT assay indicated that HCPT significantly inhibited the proliferation of HSC-T6 and BRL-3A in a dose-dependent manner. 24 h after the treatment with different concentrations of HCPT (0.25, 0.5, 1 mg/L), the apoptosis rate (13.46%+/-2.42%, 26.25%+/-5.65%, 47.05%+/-8.76%, respectively) in HSC-T6 was significantly higher than that in control cells (4.89%+/-1.80%, F = 34.24, P less than 0.01). 24 h after 0.5 mg/L HCPT treatment, cell shrinkage, nucleoli disappearance, chromatin condensation were found under TEM, and DNA ladder was demonstrated by agarose gel electrophoresis. CONCLUSION: HCPT could significantly inhibit proliferation and induce apoptosis of HSC-T6 in a dose-dependent manner.

Sensitive and selective assay of uranyl based on the aggregation induced fluorescent quenching of protamine capped gold nanoclusters.

The protamine capped gold nanoclusters (AuNCs@PRT) were synthesized by an one-pot approach, and utilized as a nanoprobe for highly sensitive and selective assay of U(VI) ions. The method is based on the aggregation induced fluorescent quenching of AuNCs@PRT by U(VI) ions. Under optimum conditions, the decrease of fluorescence intensity displayed a good linear correlation with the concentration of U(VI) ions ranging from 20.4 nM to 9.74 µM, with a detection limit of 6.1 nM. The relative standard deviations were 3.86%, 1.41% and 1.71% via 11 detections at concentrations of 40 nM, 0.40 µM and 4.0 µM of U(VI), respectively. The quenching mechanism was demonstrated to be due to the binding of U(VI) towards PRT to cause the aggregation of AuNCs@PRT rather than metal-metal interaction. The results suggest the potential application of this approach for monitoring the level of U(VI) in environmental samples.

Correlation between thrombocytopenia and host response in severe fever with thrombocytopenia syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.

Hyaluronic Acid Nanoparticles Based on a Conjugated Oligomer Photosensitizer: Target-Specific Two-Photon Imaging, Redox-Sensitive Drug Delivery, and Synergistic Chemo-Photodynamic Therapy.

Self-assembled hyaluronic acid (HA) nanoparticles have been extensively investigated as anticancer therapeutic agents due to the biocompatibility, biodegradability, and active targeting characteristics of HA. However, many HA nanoparticles are restricted to the applications in drug delivery for chemotherapy or lack effective imaging agents. Hence, we developed the camptothecin (CPT)-loaded HA-SS-BFVPBT nanoparticles (HSBNPs) as a multifunctional platform for two-photon imaging and synergistic chemo-photodynamic therapy at the same time. A novel conjugated oligomer photosensitizer, BFVPBT, which was conjugated onto HA through the redox-responsive disulfide linkage (SS), could not only provide a hydrophobic domain for the formation of nanoparticles and drug entrapment but also act as a two-photon photosensitizer that can be directly excited and simultaneously used in two-photon imaging and photodynamic therapy (PDT). HeLa cells overexpressing the HA receptor (CD44) were used for in vitro studies, which proved the specific cellular uptake of CPT-loaded HSBNPs and excellent two-photon PDT/chemotherapy synergistic effect. The nanoparticles have also been shown to realize tumor-targeting in vivo imaging in HeLa-tumor-bearing mice. Moreover, the fluorescence of CPT-loaded HSBNPs could be activated due to the degradation by the reductive glutathione (GSH) and overexpressed hyaluronidases (Hyal-1) in cancer cells, and the intracellular drug release rate was quickened, thus improving the probability of precise cancer diagnosis and therapy. Accordingly, this HSBNPs system is also anticipated to be a precise nanocarrier for other imaging and therapeutic agents besides CPT, offering a promising new avenue for imaging-guided efficient cancer therapy.

[Comparison of clinical and genetic phenotypes between Chinese and Korean hereditary nonpolyposis colorectal cancer families].

OBJECTIVE: To compare the clinical and genetic features between Chinese and Korean hereditary nonpolyposis colorectal cancer (HNPCC) families. METHODS: Thirty-one Chinese HNPCC families and 63 HNPCC Korean families were involved in this study. The clinical data of the probands and families were collected. Genomic DNAs were prepared from peripheral blood samples of probands for DNA test. PCR and DHPLC were employed to screen the mutations. Sequencing analysis was followed to find out the exact mutation site and feature in samples showing abnormalities in SSCP or DHPLC analysis. RESULTS: In a total, there were 136 malignant neoplasms diagnosed in the 31 Chinese families, about 77.9% of them were colorectal cancer. The mean age of colorectal cancer at diagnosis was (48.6+/- 29.0) years. Gastric cancer was the second most common cancer in these familiesîSeven pathogenic mutations (3 in hMLH1 gene and 4 in hMSH2 gene) were detected in the 31 probands, including 2 missense mutations, 2 nonsense mutations, 2 frameshift mutations and 1 large-fragment deletion. The total mutation rate was 22.6%. In the 63 Korean families, 293 malignant neoplasms were documented, 82.6% of them were diagnosed as colorectal cancer. The mean age of colorectal cancer at diagnosis was (45.9+/- 11.0) years. Gastric cancer was also the most common extracolonic cancer in these Korean families. Nineteen pathogenic mutations (17 in hMLH1 gene and 2 in hMSH2 genes) were detected in the 63 probands, including 12 frameshift mutations, 5 missense mutations, 1 nonsense mutation and 1 base-change at the splicing site. The total mutation rate was 30.2%. CONCLUSION: (1) Chinese and Korean HNPCC families had many similar clinical features, such as early-onset of colorectal cancer, predominance in distal colon and rectum, lower incidence of synchronous or metachronous colorectal cancers as compared with Western countries, and a frequent occurrence of gastric cancer in the families. (2) The total mutation rate of hMLH1 and hMSH2 gene in Chinese and Korean HNPCC families was similar and lower than that reported in Western countries. But the mutation characteristics, such as predominant gene, mutation type and mutation distribution, were different in the two populations.

Ultrasensitive detection of Ag(I) based on the conformational switching of a multifunctional aptamer probe induced by silver(I).

We for the first time confirmed that the low concentrations of Ag(I) could induce a silver specific aptamer probe (SAP) from a random coil sequence form to G-quadruplex structure. Thereby, a novel highly sensitive fluorescence strategy for silver(I) assay was established. The designed multifunctional SAP could act as a recognition element for Ag(I) and a signal reporter. The use of such a SAP can ultrasensitively and selectively detect Ag(I), giving a detection limit down to 0.64nM. This is much lower than those reported by related literatures. This strategy has been applied successfully for the detection of Ag(I) in real samples, further proving its reliability. Taken together, the designed SAP is not only a useful recognition and signal probe for silver, but also gives a platform to study the interaction of monovalent cations with DNA.

An effective strategy to tune supramolecular interaction via a spiro-bridged spacer in oligothiophene-S,S-dioxides and their anomalous photoluminescent behavior.

[structure: see text] We demonstrate that incorporating nonplanar spiro-bridged structures is an effective strategy for tuning supramolecular interactions of optoelectronic functional moieties. In the model compounds spiro-bridged oligothiophene-S,S-dioxides (BSiSDTFO), unusual dimers constructed by spiro-bridged spacers do not form excimers, which is confirmed by crystallographic data and fluorescent emission spectra.