Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Low Serum Levels of Brain-Derived Neurotrophic Factor Were Associated with Poor Short-Term Functional Outcome and Mortality in Acute Ischemic Stroke.

Circulating brain-derived neurotrophic factor (BDNF) has been highlighted as being a key regulator of rehabilitation-induced recovery after stroke. The aim of this study was to evaluate the association between serum levels of BDNF and functional outcome and mortality events in a 3-month follow-up study in a cohort of patients with an acute ischemic stroke (AIS). From January 2015 to December 2015, consecutive first-ever AIS patients admitted to the Department of Emergency of our hospital were identified. Serum BDNF levels were measured at admission. Functional outcome was evaluated at 3 months using the modified Rankin scale (m-Rankin). We used logistic regression models to assess the relationship between BDNF levels and functional outcome or mortality. In this study, 204 patients were included. Patients with poor outcomes and non-survivors had significantly lower BDNF levels on admission (P < 0.0001 all). Multivariate logistic regression analysis adjusted for common risk factors showed that BDNF levels in the lowest interquartile (≤1st 9.2 ng/ml) was an independent predictor of functional outcome (odds ratios [OR] = 3.75; 95 % confidence interval [CI], 2.43-8.12) and mortality (OR = 4.04; 95 % CI, 2.07-9.14). The area under the receiver operating characteristic curve of BDNF was 0.77 (95 % CI, 0.70-0.84) for functional outcome and 0.79 (95 % CI, 0.71-0.86) for mortality. The findings indicated that low serum levels of BDNF at admission were significantly associated with poor short-term functional outcome and mortality, suggesting that BDNF may serve as a biomarker of poor function outcome after stroke.

Procalcitonin Is a Stronger Predictor of Long-Term Functional Outcome and Mortality than High-Sensitivity C-Reactive Protein in Patients with Ischemic Stroke.

Inflammatory markers have been associated with functional outcome and mortality of stroke. We investigated the changes in procalcitonin (PCT) and high-sensitivity C-reactive protein (Hs-CRP) levels during the acute period of ischemic stroke and evaluated the relationship between these levels and the long-term functional outcome and mortality. We prospectively studied 376 patients with acute ischemic stroke (AIS) who were admitted within 24 h after the onset of symptoms. PCT, Hs-CRP, and NIH Stroke Scale (NIHSS) were measured at the time of admission. Long-term functional outcome were measured by modified Rankin scale (mRS) at 1 year after admission. The correlations between the levels of PCT, Hs-CRP, and mortality at 1 year after stroke onset were analyzed. Patients with poor with functional outcome and non-survivors had significantly increased PCT and Hs-CRP levels on admission. Multivariate logistic regression analysis showed that PCT was an independent prognostic marker of 1-year functional outcome and death [odds ratio (OR) 2.33 (95% CI, 1.33-3.44) and 3.11 (2.02-4.43), respectively, P < 0.0001 for both, adjusted for age, NIHSS, other predictors, and vascular risk factors] in patients with AIS. The area under the receiver operating characteristic curve of PCT was 0.77 (95% CI, 0.72-0.83) for functional outcome and 0.88 (95% CI, 0.84-0.93) for mortality. PCT improved the area under the receiver operating characteristic curve of the NIHSS score for functional outcome from 0.74 (95% CI, 0.66-0.81) to 0.85 (95% CI, 0.76-0.92; P < 0.0001) and for mortality from 0.77 (95% CI, 0.70-0.83) to 0.94 (95% CI, 0.89-0.97; P < 0.0001). Serum level of PCT at admission was an independent predictor of long-term functional outcome and mortality after ischemic stroke in Chinese sample.

Profiles and removal efficiency of polybrominated diphenyl ethers by two different types of sewage treatment work in Hong Kong.

This study was to investigate removal efficiencies and profiles of 14 polybrominated diphenyl ether (PBDE) congeners by two different types of sewage treatment work (STW) in Hong Kong: Stonecutters Island STW (SCISTW) which uses chemically enhanced primary treatment (CEPT) process and Sha Tin STW (STSTW) which adopts biological treatment. The results indicated that both SCISTW and STSTW had a high total removal efficiency for BDE-47, BDE-99 BDE-209 and total PBDEs (SCISTW: 71.6 ± 15.8, 84.7 ± 12.3, 96.0 ± 2.62 and 87.4 ± 8.02%, respectively; STSTW: 74.8 ± 9.5, 90.7 ± 9.14, 96.2 ± 2.41 and 89.3 ± 2.62%, respectively) and PBDEs were chiefly removed by sorption. However, the profile of PBDEs demonstrated that the relative proportions of BDE-28 and BDE-47 in total PBDEs markedly increased, while that of BDE-209 decreased in the effluent samples of the two sewage treatment works, especially in STSTW. The percentage of BDE-209 in total PBDEs in effluent (49.3%) of SCISTW was 21.2% lower than that in influent (70.5%), and the percentage of BDE-209 in total PBDEs in effluent (13.8%) of STSTW was 34.1% reduced from influent (47.9%). Despite overall removal, the percentage of BDE-47 in total PBDEs in effluent (17.6%) of SCISTW was 6.85% higher than that in influent (10.7%), and the percentage of BDE-47 in total PBDEs in effluent (33.5%) of STSTW was 18.1% increased from influent (16.8%). The increase in proportion of BDE-47 in the effluent might raise environmental and public health concerns. Our study is a first attempt in reporting the PBDE congener profiles in different phases of sewage treatment.

Persistent toxic substances released from uncontrolled e-waste recycling and actions for the future.

The Basel Convention on the Control of Transboundary Movement of Hazardous Wastes and their Disposal was adopted on March 22, 1989 and enforced on May 5, 1992. Since then, the USA, one of the world's largest e-waste producers, has not ratified this Convention or the Basel Ban Amendment. Communities are still debating the legal loophole, which permits the export of whole products to other countries provided it is not for recycling. In January 2011, China's WEEE Directive was implemented, providing stricter control over e-waste imports to China, including Hong Kong, while emphasizing that e-waste recycling is the producers' responsibility. China is expected to supersede the USA as the principal e-waste producer, by 2020, according to the UNEP. Uncontrolled e-waste recycling activities generate and release heavy metals and POPs into the environment, which may be re-distributed, bioaccumulated and biomagnified, with potentially adverse human health effects. Greater efforts and scientific approaches are needed for future e-product designs of minimal toxic metal and compound use, reaping greater benefits than debating the definition and handling responsibilities of e-waste recycling.

Persistent toxic substances: sources, fates and effects.

Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

[Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumor-targeted drug carrier].

OBJECTIVE: To synthesize and characterize paclitaxel (PTX)-loaded folate-conjugated chitosan (FA-CTS/PTX) nanoparticles and evaluate its cytotoxicity in vitro. METHODS: CTS/PTX and FA-CTS/PTX nanoparticles were prepared using reductive amidation and ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size was determined by laser scattering and the morphology observed using transmission electron microscopy, and the PTX content in the nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated with FA-chitosan nanoparticles in the presence or absence of folic acid in the culture medium. RESULTS: PTX loading did not cause adhesion of the FA-CTS nanoparticles, which presented with uniform spherical morphology with an average diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater extent of intracellular uptake in the absence of folic acid, indicating that the cellular uptake of the nanoparticles occurred through endocytosis mediated by the folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX-loaded CTS nanoparticles. CONCLUSION: FA-CTS can be a promising drug carrier with high efficiency in condensing drug, good tumor-targeting ability and low cytotoxicity.

Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumor-targeted drug carrier / 南方医科大学学报

<p><b>OBJECTIVE</b>To synthesize and characterize paclitaxel (PTX)-loaded folate-conjugated chitosan (FA-CTS/PTX) nanoparticles and evaluate its cytotoxicity in vitro.</p><p><b>METHODS</b>CTS/PTX and FA-CTS/PTX nanoparticles were prepared using reductive amidation and ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size was determined by laser scattering and the morphology observed using transmission electron microscopy, and the PTX content in the nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated with FA-chitosan nanoparticles in the presence or absence of folic acid in the culture medium.</p><p><b>RESULTS</b>PTX loading did not cause adhesion of the FA-CTS nanoparticles, which presented with uniform spherical morphology with an average diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater extent of intracellular uptake in the absence of folic acid, indicating that the cellular uptake of the nanoparticles occurred through endocytosis mediated by the folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX-loaded CTS nanoparticles.</p><p><b>CONCLUSION</b>FA-CTS can be a promising drug carrier with high efficiency in condensing drug, good tumor-targeting ability and low cytotoxicity.</p>

Interindividual variability in the effect of atazanavir and saquinavir on the expression of lymphocyte P-glycoprotein.

OBJECTIVES: ABCB1 encodes the efflux transporter P-glycoprotein (P-gp), which regulates the intracellular concentration of many xenobiotics, including several HIV protease inhibitors (PIs). Exposure to some xenobiotics, such as the antibiotic rifampicin, increases P-gp expression. In the present study, we investigated the effect of the HIV PIs saquinavir and atazanavir on the expression and function of ABCB1 and P-gp in primary and cultured lymphocytes, as well as the molecular interactions between these drugs and P-gp. ABCB1 and P-gp expression and function were examined in lymphocyte samples from healthy subjects before and after atazanavir-boosted saquinavir treatment. Expression and function were also studied in CEM cells following exposure to atazanavir and saquinavir. The inhibitory effects of these drugs were investigated in ABCB1-transfected HEK293T cells. METHODS: P-gp expression and function were measured by flow cytometry. ABCB1 mRNA expression was evaluated using quantitative RT-PCR. RESULTS: There were no overall changes in ABCB1 or P-gp expression or function after saquinavir-atazanavir treatment in primary lymphocyte samples. However, there was considerable interindividual variability in baseline lymphocyte ABCB1 expression, as well as in the degree of change in ABCB1 expression after saquinavir-atazanavir administration. In cell culture, 5 microM saquinavir increased ABCB1 levels, although it did not affect P-gp expression. Atazanavir inhibited P-gp function at concentrations above therapeutic levels. CONCLUSIONS: Differences in lymphocyte ABCB1 expression, which may be caused by genetic polymorphisms in ABCB1 or its regulatory partners, are a likely cause of interindividual variation in the disposition and efficacy of clinically relevant P-gp substrates, including HIV PIs.

Pharmacokinetics of saquinavir with atazanavir or low-dose ritonavir administered once daily (ASPIRE I) or twice daily (ASPIRE II) in seronegative volunteers.

ASPIRE I and II were prospective, 3-way sequential crossover studies in healthy volunteers to compare the safety and pharmacokinetics of saquinavir/ritonavir (SQV/RTV) with saquinavir/atazanavir (SQV/ATV) administered either once daily (QD, ASPIRE I) or twice daily (BID, ASPIRE II). Treatments were separated by 10 days, and pharmacokinetic analyses were performed on days 11, 32, and 53. SQV pharmacokinetics were significantly higher when dosed with RTV compared to ATV (P < .05 for all comparisons). ATV pharmacokinetics were similar within treatment arms. ATV Cmin increased approximately 60%, and Cmax decreased approximately 35% with BID dosing compared with QD dosing. Women had higher exposure for all 3 protease inhibitors (PIs) compared with men after adjusting for weight. Adverse effects were primarily gastrointestinal-related with SQV/RTV and hyperbilirubinemia with SQV/ATV. Although SQV plasma concentrations were higher when coadministered with RTV, a combination of SQV/ATV administered BID may be a viable alternative in HIV-infected, PI-naive subjects intolerant to RTV.

[Correlation of antitumor drug sensitivity between marrow mesenchymal stem cells (MSCs) and hepatocarcinoma cells in rats].

BACKGROUND & OBJECTIVE: As hepatocarcinoma stem cells may originate from oval cells and oval cells are difficult to be separated and purified, MSCs (marrow mesenchymal stem cells), which are the progenitor cells of the hepatocarcinoma stem cells, were selected instead in our study to investigate the correlation of anticancer drug sensitivity between hepatocarcinoma cells and MSCs in rats. METHODS: The primary liver carcinoma modle of rats was induced by diethylnitrosamine. Tumor cells and MSCs from eight hepatocarcinoma rats were separated. The inhibitory effects of 3 anticancer drugs [adriacin (0.04 microg/ml), cisplatin (0.2 microg/ml) and fluorouracil (1 microg/ml)] to hepatocarcinoma cells and MSCs were measured by MTT assay. The weight of the tumor in nude mice which were injected with rat hepatocarcinoma cells was measured after 6 weeks. Then the correlation of the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and MSCs, and to the tumor weight of nude mice was analyzed. RESULTS: No correlation was revealed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was: 0.6307 (adriacin, P>0.05), 0.4358 (fuiorouracil, P>0.05) and 0.7080 (cisplatin, P>0.05). No correlation was observed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and to MSCs. The correlation coefficient was: 0.6316 (adriacin, P>0.05), 0.4214 (fluorouracil, P>0.05) and 0.5943 (cisplatin, P>0.05). However, significant reverse correlation was found between the inhibitory ratio of 3 anticancer drugs to MSCs and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was: -0.8308 (adriacin, P<0.05), -0.8991 (fluorouracil, P<0.01) and -0.8311 (cisplatin, P<0.05). CONCLUSIONS: Conventional anticancer drug sensitivity experiments could not reflect the chemoresistance of the hepatocarcinoma cells. However the inhibitory ratio of the anticancer drugs to MSCs in the hepatocarcinoma rats can reflect the chemoresistance of hepatocarcinoma cells accordingly.

[The biological behavior of hepatocarcinoma stem cells in rats].

OBJECTIVES: To study the biological behavior of hepatocarcinoma stem cells in rats. METHODS: Primary liver carcinomas were induced in rats using diethylnitrosamine. Tumor cells from 8 rats were separated according to rats oval cell (OVC) markers CD34, c-Kit, Thy-1, AFP, CK7, CK8, CK14, CK18, CK19 and GGT and then they were separately injected into the livers of nude mice. The tumors grown from the different subpopulation of OVC markers in the nude mice livers (10 OVC markers negative or positive cells) were weighted 1 month after the inoculations. The hepatocarcinoma cell subpopulations with higher ability in causing tumor growths were further studied in vitro. The cell cycles and DNA content of those subpopulation cells were investigated using flow cytometry. RESULTS: (1) Subpopulation cells with CK7(-), Thy-1(+) and AFP(+) markers had a higher ability in causing tumors in nude mice; (2) Subpopulation cells, exhibiting characters of TSC, had a low growth rate in vitro. CONCLUSIONS: (1) Different subpopulations of hepatocarcinoma cells had different abilities in causing tumors in rats. Some subpopulation cells, such as CK7(-), Thy-1(+) and AFP(+) cells, have characteristics of tumor stem cells. (2) The hepatocarcinoma stem cells may have a low growth rate in vitro.

The biological behavior of hepatocarcinoma stem cells in rats / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the biological behavior of hepatocarcinoma stem cells in rats.</p><p><b>METHODS</b>Primary liver carcinomas were induced in rats using diethylnitrosamine. Tumor cells from 8 rats were separated according to rats oval cell (OVC) markers CD34, c-Kit, Thy-1, AFP, CK7, CK8, CK14, CK18, CK19 and GGT and then they were separately injected into the livers of nude mice. The tumors grown from the different subpopulation of OVC markers in the nude mice livers (10 OVC markers negative or positive cells) were weighted 1 month after the inoculations. The hepatocarcinoma cell subpopulations with higher ability in causing tumor growths were further studied in vitro. The cell cycles and DNA content of those subpopulation cells were investigated using flow cytometry.</p><p><b>RESULTS</b>(1) Subpopulation cells with CK7(-), Thy-1(+) and AFP(+) markers had a higher ability in causing tumors in nude mice; (2) Subpopulation cells, exhibiting characters of TSC, had a low growth rate in vitro.</p><p><b>CONCLUSIONS</b>(1) Different subpopulations of hepatocarcinoma cells had different abilities in causing tumors in rats. Some subpopulation cells, such as CK7(-), Thy-1(+) and AFP(+) cells, have characteristics of tumor stem cells. (2) The hepatocarcinoma stem cells may have a low growth rate in vitro.</p>

[Expression of DNA transcription- and repair-related genes in cisplatin-resistant human ovarian carcinoma cell line COC1/DDP].

OBJECTIVE: To study the molecular mechanism underlying cisplatin resistance in ovarian carcinoma by detecting the expressions of DNA transcription- and repair-related genes in cisplatin-resistant human ovarian carcinoma COC1 cell line. METHODS: The differential expression of DNA transcription- and repair-related genes between the parental COC1 and cisplatin-resistant COC1/DDP cell line was determined using cDNA microarray. RESULTS AND CONCLUSION: Compared with COC1 cells, 143 genes in COC1/DDP cells showed significant differential expression, among which 20 were DNA transcription- and repair-related genes including 13 significantly up-regulated genes and 7 down-regulated ones. Abnormality of DNA transcription and repair might be involved in the development of cisplatin resistance in COC1/DDP cells.

Synthesis of targeted drug delivery system for fluorouracil using sulfadiazine as the carrier.

OBJECTIVE: To synthesize a targeted drug delivery system for 5-fluorouracil (5Fu) using sulfadiazine (SF) as a carrier with reduced side-effects and strong antitumor activity. METHODS: SF-poly (ethylene glycol) (PEG) conjugate was initially synthesized. 5Fu was subjected to reaction with trichloromethyl chloroformate to prepare chloroformyl 5Fu, which was linked to a spacer hydroxyl group of PEG that served as a macromolecular linking arm between SF and 5Fu. The content of 5Fu in the conjugate was determined by ultraviolet spectrophotometry. Spectrum of ultraviolet and infrared along with differential scanning calorimetry were employed to identify the structure of the conjugate of SFPEG-end capped 5Fu. RESULTS: The drug loading content of the conjugate was 3.2 %, and structural analysis confirmed the linkage between 5Fu and SF via PEG. CONCLUSION: Targeted drug delivery system for 5Fu using SF as a carrier has been successfully synthesized by this means.