Aging and Oral Health: Biological and Sociobehavioral Perspectives.

As the life expectancy and growth of the aging population increase globally, efforts to promote healthy longevity become more important. Holistic policy guidelines and actions have been designed to advocate and fortify healthy aging at multiple levels. Oral health, a fundamental contributor of overall health and well-being, forms a core part of the noncommunicable disease agenda within the sustainable development goals set by the World Health Organization. Aging significantly heightens the risk of myriad oral disorders and other noncommunicable diseases. As of 2019, oral disorders accounted for 8.9 million disability-adjusted life-years in individuals older than 60 y. In addition to the development of multidisciplinary aging-friendly policies to promote healthy aging, basic biology and translational research has been encouraged that focuses on deciphering the underlying mechanisms involved in age-related physical and cognitive decline or dysregulation of oral tissues. Given the relevance of oral health aging as a critical component of the One Health Initiative, this special issue encompasses a collection of articles dedicated to recent advances in the behavioral and social implications of age-related oral diseases and tooth loss on several aspects of the quality of life of adults as they age. Furthermore, it includes articles detailing molecular mechanisms associated with cellular aging and their implications for oral tissue health, periodontal disease severity, and the regenerative potential of stem cells.

[Association between cognitive impairment and main metals among oldest old aged 80 years and over in China].

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 µg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

Effects of Selenium Supplementation on the Ion Homeostasis in the Reproductive Organs and Eggs of Laying Hens Fed With the Diet Contaminated With Cadmium, Lead, Mercury, and Chromium.

The objective of this study was to explore the toxic effects of different heavy metals in combination with their deposition and ion homeostasis in the reproductive organs and eggs of laying hens, as well as the alleviating action of selenized yeast. A total of 160 Lohmann pink-shell laying hens (63-week-old) were randomly allocated into four treatments with 10 replicates of four hens each. The four dietary treatments were the corn-soybean meal basal dietary (control; CON); the CON dietary supplemented with 0.4 mg/kg selenium from selenized yeast (Se); the CON dietary supplemented with 5 mg/kg Cd + 50 mg/kg Pb +3 mg/kg Hg + 5 mg/kg Cr (HEM), and the HEM dietary supplemented with 0.4 mg/kg selenium from selenized yeast (HEM+Se). The dietary HEM significantly increased Cd, Pb, and Hg deposition in the egg yolk and ovary, and Cd and Hg deposition in the oviduct and in the follicular wall (p < 0.05). The HEM elevated Fe concentration in the egg yolk, ovary, and oviduct (p < 0.05). The HEM decreased Mn concentration in the egg yolk, Fe, Mn, and Zn concentrations in the egg white, Cu concentration in the ovary, Mg concentration in the oviduct, as well as Ca, Cu, Zn, and Mg concentrations in the follicular walls (p < 0.05). Dietary Se addition elevated Se concentration in the egg yolk, oviduct, and follicular walls and Mg concentration (p < 0.05) in the oviduct, whereas it reduced Fe concentration in the oviduct compared with the HEM-treated hens. Some positive or negative correlations among these elements were observed. Canonical Correlation Analysis showed that the concentrations of Pb and Hg in the egg yolk were positively correlated with those in the ovary. The concentration of Cd in the egg white was positively correlated with that in the oviduct. In summary, dietary Cd, Pb, Hg, and Cr in combination caused ion loss and deposition of HEM in reproductive organs of laying hens. Dietary Se addition at 0.4 mg/kg from selenized yeast alleviated the negative effects of HEM on Fe and Mg ion disorder in the oviduct and follicle wall of hens.

[Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years].

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Fertilizer P-derived uranium continues to accumulate at Rothamsted long-term experiments.

The application of phosphorus (P) fertilizers inevitably contributes to the accumulation of trace elements, such as uranium (U), in agricultural soils. The fertilizer-derived U accumulation was first reported in Rothamsted Research in 1979. In the present study, we expand this early key research by evaluating the fertilizer-derived U accumulation in topsoil (0-23 cm) from 1876 to the 2010s. We found that total U accumulation rates ranged from 2.8 to 6.1 µg U kg-1 yr-1 at the Broadbalk and Park Grass, respectively, being similar to those observed 40 years ago. This highlights that U accumulation is still an ongoing process in Rothamsted. Fortunately, the proportion of fertilizer-derived U did not significantly increase in the ammonium acetate extractable ('proxy' of plant-available) fraction over 130 years. In addition, we compiled an overview of the global rate of mineral P fertilizer-derived U accumulation in agricultural systems using existing literature (36 experimental trials, from 11 countries). The resulting dataset predicts an estimated mean U accumulation of 0.85 µg U kg-1 soil for an annual application of 1 kg P ha-1 in the topsoil of agricultural systems (0.26 µg U kg-1 per kg P ha-1 for arable land and 1.34 µg U kg-1 per kg P ha-1 for grassland). The annual U accumulation per applied kg P ha-1 being 0.08 (Broadbalk) and 0.17 µg U (Park Grass) corresponds to around one-third and one-eighth of the worldwide mean U accumulation for their respective agricultural systems, suggesting 'relatively' low U contents of the applied P fertilizers. Our study underscores that fertilizer-derived U accumulation is a persistent problem on the global scale, even if at different rates, and therewith suggests an evaluation of current regulatory limits and acceptable U input levels from P fertilization.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

[Analysis of influencing factors on occupational pressure of medical staff in a third-level first-class hospital of traditional Chinese medicine in Tianjin].

Objective: To explore the status and influencing factors of occupational pressure among medical staff in a third-level first-class hospital of traditional Chinese medicine in Tianjin, and to provide reference for formulating relevant policies. Methods: From September to October in 2019, doctors, nurses, pharmacists laboratory, radiology and management personnel were randomly selected as the research objects. A total of 191 questionnaires were distributed and recovered, and 189 valid questionnaires were recovered, with an effective recovery rate of 98.95%. The Scale for Occupational Stressor on Clinician was used for investigation. The influence of different characteristics on the occupational pressure of medical staff was analyzed. Results: The average total score of occupational pressure was (94.8±15.4) . There were significant differences in occupational pressure among different age groups (P<0.05) . There were significant differences in total pressure score, organization management, occupational interest, workload, external environment, doctor-patient relationship and other dimensions (P<0.05) . The average total score of occupational pressure of doctors was (101.7±13.3) , which was significantly higher than that of nurses, pharmacists, laboratory, rodiology and managers (P<0.05) . Conclusion: The occupational pressure of doctors is relatively serious, and the occupational pressure should be alleviated from the external environment, doctor-patient relationship and workload.

Heavy metal pollution improves allelopathic effects of Canada goldenrod on lettuce germination.

Large amounts of heavy metals have been released into the environment. Thus, the allelopathic effects of invasive alien species on the germination performance of co-occurring indigenous species may be altered or even heightened with the rapid growth in heavy metal pollution. This study evaluated the impacts of Canada goldenrod (Solidago canadensis L.) leaf extracts at concentrations of 0, 10 or 20 gl 1 on the germination of lettuce under different forms of heavy metal pollution (Cu2+ , Pb2+ or a combination of Cu2+ and Pb2+ ; 35 mgl 1) during incubation in Petri dishes for 10 days. Goldenrod leaf extracts (high concentration) reduced growth of aboveground and belowground parts of lettuce as well as competition for light and soil nutrients. However, low concentrations of goldenrod leaf extracts dramatically improved growth of lettuce roots, competition for light, soil nutrient availability, leaf photosynthetic area and growth competitiveness. The combination of goldenrod leaf extracts and heavy metal pollution was synergistic on most lettuce germination parameters, probably because high concentrations of goldenrod leaf extracts together with heavy metal pollution had a synergistic negative impact on lettuce germination. Consequently, increased levels of heavy metal pollution may favour invasion of invasive alien species while largely suppressing germination of indigenous species.

[The status analysis of diagnosis and treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China: a report of 1 003 cases in 16 domestic medical centers].

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

Mechanisms of vasorelaxation induced by total flavonoids of Euphorbia humifusa in rat aorta.

Euphorbia humifusa Willd. (EH), rich in flavonoids, has long been used for the treatment of bacillary dysentery and enteritis in China, and is known to have antioxidant, hypotensive and hypolipidemic properties. However, the vasorelaxant effect of total flavonoids of EH (TFEH) and action mechanisms are not clearly defined yet. The aim of the present study was to investigate the effects of TFEH on the vascular tension and its underlying mechanisms. Experiments were performed in rat thoracic aorta using the organ bath system. TFEH (0.01 - 100 µg/ml) caused a concentration-dependent vasorelaxation, which was dependent on a functional endothelium, and were significantly attenuated by inhibitors of endothelial NO synthase, its upstream signaling pathway, PI3K/Akt, and soluble guanylate cyclase, but not by blockade of KCa channel, KATP channel, cyclooxygenase, muscarinic and ß-adrenergic receptors. Extracellular Ca2+ depletion, and pre-treatment with modulators of the store-operated Ca2+ entry channels, Gd3+ and 2-aminoethyl diphenylborinate, significantly attenuated the TFEH-induced vasorelaxation. Our findings suggest that TFEH elicit vasorelaxation via endothelium-dependent NO-cGMP pathway through activation of PI3K/Akt- and Ca2+-eNOS-NO signaling. Further, it is suggested that TFEH-induced activation of the NO-soluble guanylate cyclase-cGMP-protein kinase G signaling relaxes vascular smooth muscle cells through an inhibition of the L-type Ca2+ channel activity.

[Coenzyme Q(10) treatment for one child with COQ6 gene mutation induced nephrotic syndrome and literature review].

Objective: To summarize the clinical manifestation and molecular characteristics of COQ6 mutation induced nephrotic syndrome, and to evaluate efficacy of CoQ(10) therapy. Method: Clinical data of the case with infantile nephrotic syndrome was summarized, including clinical manifestations, laboratory findings and family investigation. The patient received CoQ(10) 30 mg/(kg·d) therapy. Urine protein/creatinine ratio, serum albumin and creatinine were detected to assess the efficacy of the therapy. Result: (1) The 10 months old boy was presented with nephrotic level proteinuria and hypoalbuminemia. Extra-renal manifestations included cardiovascular abnormality, motor and mental retardation and unilateral ptosis. The patient had no consanguinity. A novel homozygous p. R360W mutation in COQ6 gene was identified and confirmed by next-generation sequencing and Sanger sequencing, respectively. Family analysis showed that homozygous p. R360W mutation in COQ6 gene was inherited from his parents. Missense p. R360W mutation was damaging by prediction online PolyPhen and SIFT software. After 2 months of CoQ(10) complementary therapy, the patient's urine protein/creatinine ratio declined from 7.2 to 1.3, and decreased further to 0.01 mg/mg with normal albumin level and renal function within 3 months. Nephropathy remission was maintained and growth retardation improved significantly during the last follow-up. Nevertheless, the patient manifested with sensorineural deafness at the age of 2 years. (2) There were 6 different mutations in coenzyme Q(10) biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping in the whole world. Each mutation was linked to early-onset SRNS with sensorineural deafness. Renal biopsy revealed FSGS in 7 cases and DMS in 1 case. Other manifestations included ataxia, seizures, facial dysmorphism, nephrolithiasis and growth retardation. Four patients received CoQ(10) supplementation and responded to the treatment. Conclusion: Renal disease caused by recessive COQ6 gene mutation was nephrotic syndrome. The patient benefited from early CoQ(10) complement and reached nephropathy remission.

Transcriptional profiles of emasculated flowers of black locust (Robinia pseudoacacia) determined using the cDNA-AFLP technique.

Black locust (Robinia pseudoacacia) is a tree in the subfamily Faboideae, native to North America, that has been naturalized and widely planted in temperate Europe and Asia. Black locust has important ecological and economic value, but its quality needs improvement. Hybridization programs are important for black locust breeding, but the low rate of fruit set after controlled pollination limits both its breeding and that of other monoclinous plant species that share this problem. In this study, we investigated gene expression in emasculated black locust flowers using the cDNA-amplified fragment length polymorphism technique to determine why the rate of fruit set is low after controlled pollination. Flowers that were emasculated after being frozen in liquid nitrogen were used as controls. Changes in the flower transcriptome were more dramatic at 5 h after emasculation than at 48 h. Injury caused by emasculation decreased the expression levels of genes associated with metabolism, growth regulation, signal transduction, and photosynthesis, and it increased the expression of genes related to stress-response metabolism, signal transduction, and promotion of senescence. The changes in the expression levels of these genes had negative effects on sugar metabolism, protein metabolism, lipid metabolism, energy metabolism, matter transport, signal transduction, osmotic regulation, pH regulation, and photosynthesis. Thus, emasculation accelerated flower senescence, resulting in low fruit set.

Effect of Saccharomyces boulardii and Bacillus subtilis B10 on intestinal ultrastructure modulation and mucosal immunity development mechanism in broiler chickens.

The recent ban on the use of antibiotics as a feed additive has led to the search for alternative sources of antibiotics in the feed industry. Presently, probiotics are considered as a potential substitute for antibiotic as a live biotherapeutic agent to improve animal health and performance. Accordingly, study was focused on evaluating the effect of Saccharomyces boulardii (Sb) and Bacillus subtilis B10 (Bs) on ultrastructure modulation and mucosal immunity development in broiler chickens. A total of three hundred 1-d-old Sanhuang broilers (a Chinese cross breed) were randomized into 3 groups, each group with 5 replications (n = 20). The control group (Ctr) was fed a basal diet containing an antibiotic (virginiamycin, 20 mg/kg). Meanwhile, broilers in experimental groups received Sb and Bs (1 × 10(8) cfu/kg of feed) in addition to the basal diet for 72 d. The results of the experimental groups revealed a significant improvement in live BW and relative weight of bursa of Fabricius and thymus. Also, intestinal villus height, width, and number of goblet cells increased in the Sb and Bs groups. Meanwhile, modulation in the intestinal ultrastructure and increased mRNA expression levels of occluding, cloudin2, and cloudin3 (P < 0.05) were observed in the Sb and Bs groups. Moreover, IgA-positive cells significantly increased in the jejunum of Sb- and Bs-supplemented groups (P < 0.05). Intestinal cytokines interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-ß, and secretory IgA concentrations were (P < 0.05) improved in the probiotic groups; however, Sb induced inflammatory and antiinflammatory cytokines (P < 0.05) in comparison with the Ctr group. The present findings conclusively revealed that Sb and Bs increased IgA-positive cells in the lumen of the intestinal villus and revealed that Sb and Bs could modulate intestinal ultrastructure through increasing occluding, cloudin2, and cloudin3 mRNA expression levels in broiler intestine.

CT-guided percutaneous chemoablation using an ethanol-ethiodol-doxorubicin emulsion for the treatment of metastatic lymph node carcinoma: a comparative study.

Current therapies for metastatic lymph node (LN) are a major burden on health-care systems. Alternative such as percutaneous chemoablation using interstitial injection of ethanol or ethanol-ethiodol-drug(s) mixture (EEM) has been successfully applied to solid tumor ablation of the liver, adrenal glands, lymph nodes and others. However, EEM chemoablation efficacy on two most frequent clinical lymph node presentation, isolated or confluent, has not yet been determined. This study was designed to compare the therapeutic effects of CT-guided percutaneous EEM injection (PEEMI) on patients presenting with single or multiple confluent metastatic LN localizations from various carcinoma. Thirty six patients with metastatic LN carcinoma at various anatomical regions were enrolled from 2009 to 2010 over a nine month period. They were separated into two groups: group A includes 24 single isolated metastatic lymph nodes and group B includes 12 multiple and confluent nodes. The primary end point was the ablative efficacy of PEEMI. The intratumoral (IT) EEM distribution and the occurrence of reflux were recorded. Adjuvant systemic chemotherapy was administered after the procedure. Contrast-enhanced CT scans were performed during procedure and follow-up. Six patients were tested for Fluorodeoxyglucose (FDG) fixation before and after the procedure. For group A the EEM IT distribution-to-tumor ratio was 100% vs. 50% to 80% for group B (t = 11.5, p < 0.05). The reflux frequency was 80% for group A versus 30% for group B. For group A, a complete response (CR) rates of 45.8%, 70.8%, 91.7% and a partial response (PR) rates of 54.2%, 29.2%, 8.3% were obtained at 3, 6 and 12 months after therapy. Regarding group B, a CR rate of 0%, 0%, 0% and PR rate of 16.7%, 50%, 58.3% were observed at similar period of time. Standardized rate by direct method was performed and the CR rate (74.5%) for group A was higher than for group B. The tumor FDG uptake was lower 6 months after PEEMII compared with the preoperative images. Five patients presenting with concomitant lung metastasis, had a good local response-node size reduction on postoperative CT scanning, but no response on lung nodules that were progressing. No serious adverse events were observed. A few patients had mild pain during the procedure, which resolved with peritumor injection of local anesthetic. No needle tract seeding or infection occurred. CT-guided PEEMI treatment is a simple, fast and predictable procedure that has better effectiveness on single, well circumscribed metastatic lymph node than on multiple and confluent ones. Technical improvements are expected to bring better results on large nodes that should be confirmed on larger group of patients.

Combination of differentiation and T stage can predict unresponsiveness to neoadjuvant therapy for rectal cancer.

AIM: The study aimed to identify the factors predictive for extreme unresponsiveness to neoadjuvant therapy for rectal cancer. METHOD: Ninety-six patients with rectal cancer received neoadjuvant therapy (41 were treated with radiotherapy and 55 with chemoradiotherapy) before surgery. Tumour response, downstaging, pathological complete response (pCR) and disease-free survival were evaluated. RESULTS: Tumour response, downstaging and pCR occurred in 70 (72.9%), 47 (49.0%) and 14 (14.6%) patients, respectively. Univariate analyses showed that a large tumour size, T4 stage, elevated serum tumour markers, poor differentiation, radiotherapy alone and mucinous tumour were indicators of poor tumour response and/or downstaging. On multivariate analysis, chemoradiotherapy was found to be predictive for tumour response and downstaging, whereas mucinous type and T4 stage negatively affected tumour response. No variable was found to be associated with pCR, but poor differentiation and T4 stage together predicted extreme unresponsiveness with a high specificity and a high positive predictive value. Very poor disease-free survival was also observed in patients simultaneously carrying these phenotypes. CONCLUSION: Neoadjuvant chemoradiotherapy is superior to radiotherapy alone in producing a response of rectal cancer. Unresponsiveness was most likely to occur in patients with poor differentiation and T4 disease.

Pharmacokinetic/pharmacodynamic model-based combination therapy approach to target antibiotic resistant populations emerged from ciprofloxacin exposure.

BACKGROUND: Despite decades of antimicrobial usage, the relationship between antimicrobial drugs and the development of drug resistance has not been fully delineated. This has led to increased frequency of resistance with increased usage of antimicrobials. In recent years, new insights into the mechanisms of antibiotic resistance have been proposed, leading to a re-evaluation of novel pharmacokinetic/pharmacodynamic (PK/PD) models. We have developed a semi-mechanistic PK/PD model to describe drug-bacteria kill curve relationships using the compensatory mutation hypothesis. In addition, we explored the model-based combination therapy approach to combat the resistance population. METHODS: In vitro kill-curves of E. coli 204 up to 48 h following initial ciprofloxacin (CIP) treatment at 0.0, 0.1, 0.2, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 and 125 times the minimum inhibitory concentration (MIC) totaling 193 data points were obtained with an in vitro system with a simulated CIP half-life of 4 h. The proposed antibiotic resistant mechanism mimics the sequential compensatory mutation hypothesis, in which mutations that acquire drug resistant traits are associated with fitness costs. Subsequent restoration of bacterial fitness is necessary for the population to be clinically relevant. Model parameters were estimated from simultaneous fitting of eleven dose groups using Adapt II software. Standard goodness of fit criteria used to obtain the final model included model convergence, Schwartz Criterion, Akaike Information Criterion, residuals versus predicted concentrations and time, and visual inspection. RESULTS/CONCLUSIONS: The eleven E. coli kill curves after CIP treatment were well described simultaneously by the compensatory mutation model. The emergence of bacterial population with drug resistance characteristics and bacterial fitness restored appears to dominate shortly following CIP treatment. The model suggests a subsequent dose of a different mechanisms of action should be considered for the emerged resistant population.

Fine mapping of a gene for non-pollen type thermosensitive genic male sterility in rice (Oryza sativa L.).

The thermo-sensitive genic male sterility (TGMS) lines play a crucial role in two-line hybrid rice production. For a practical TGMS line, the stability of male sterility is one of the most important technical indicators. In this study, XianS, a spontaneous mutant with stable male sterility from an indica rice cultivar Xianhuangzhan, was classified as a non-pollen type TGMS line. The critical non-pollen sterility point temperature of XianS was determined as 27 degrees C. Genetic analysis demonstrated that the non-pollen sterility in XianS was controlled by a single recessive gene. Using SSR markers and bulked segregant analysis, the TGMS gene in XianS was fine mapped to a 183 kb interval between RMAN81 and RMX21 on chromosome 2. Two markers, 4039-1 and RMX14 completely cosegregated with this gene. Allelism test indicated that the non-pollen phenotype in seven non-pollen type TGMS lines from different sources, XianS, AnnongS-1, Q523S, Q524S, N28S, G421S, and Q527S is caused by the same TGMS gene. Although the location of TGMS gene in XianS is close to the gene OsNAC6, a previously identified candidate gene of tms5 in AnnongS-1, the sequence of OsNAC6 and its promoter region was identical in TGMS line XianS, AnnongS-1, and wild-type Xianhuangzhan. These results suggest that the non-pollen type TGMS trait probably be controlled by the same TGMS gene in different TGMS rice lines, but its real candidate gene still need to be further studied and identified.

Brazilein inhibits survivin protein and mRNA expression and induces apoptosis in hepatocellular carcinoma HepG2 cells.

Hepatocellular carcinomas represent the third leading cause of cancer-related deaths worldwide. Survivin, a structurally unique member of the inhibitor of apoptosis protein (IAP) family, is overexpressed in a wide range of malignancies, including hepatocellular carcinoma. Due to its involvement in cancer progression and treatment resistance, survivin is currently undergoing extensive investigation as a novel intervention target to induce apoptosis in cancer cells by phytochemicals or synthetic agents. Brazilein, a compound obtained in a large amount from the dried heartwood of Caesalpinia sappan Linn., which has long been used in traditional medicine in China, has some pharmacological activities. Human hepatocellular carcinoma HepG2 cells were treated with brazilein and analyzed for survivin protein and mRNA levels by Western blotting and real-time RT-PCR, respectively. Brazilein treatment of cells for 48 h at 5 and 10 microg/ml doses resulted in significantly decrease in survivin protein expression. We also observed that brazilein caused a strong decrease in survivin mRNA expression. In other studies, down-regulation of survivin by brazilein was associated with a strong and prominent caspases-9 and -3 activation as well as PARP cleavage. It was also shown that brazilein induced a strong apoptotic cell death, as shown by DNA ladder assay, and growth inhibition of HepG2 cells. Further studies are needed to investigate in vivo effect of brazilein on survivin expression and associated biological effects in hepatocellular carcinoma that could provide useful information for brazilein efficacy in the prevention/intervention of human hepatocellular carcinoma.

Recycling of waste tyre rubber into oil absorbent.

The abundant and indiscriminant disposal of waste tyres has caused both health and environmental problems. In this work, we provide a new way to dispose off waste tyres by reusing the waste tyre rubber (WTR) for oil absorptive material production. To investigate this feasibility, a series of absorbents were prepared by graft copolymerization-blending method, using waste tyre rubber and 4-tert-butylstyrene (tBS) as monomers. Divinylbenzene (DVB) and benzoyl peroxide (BPO) were employed as crosslinker and initiator, respectively. The existence of graft-blends (WTR-g-tBS) was determined by FTIR spectrometry and verified using thin-layer chromatography (TLC). In addition, the thermal properties of WTR-g-tBS were confirmed by a thermogravimetric analyzer (TGA). Oil absorbency of the grafted-blends increased with increases in either feed ratio of WTR to tBS or DVB concentration. This absorbency reached a maximum of 24.0gg(-1) as the feed ratio and DVB concentration were 60/40 and 1wt%, respectively, after which it decreased. At other ratios and concentrations the absorbency decreased. The gel fraction of grafted-blends increased with increasing concentration of DVB. Oil-absorption processes in pure toluene and crude oil diluted with toluene were found to adhere to first-order absorption kinetics. Furthermore, the oil-absorption rate in diluted crude oil was observed to be lower than pure toluene.

Puerarin for acute ischaemic stroke.

BACKGROUND: Puerarin, a form of herbal medicine, is widely used in the treatment of acute ischaemic stroke in China. OBJECTIVES: To assess the efficacy and safety of puerarin in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched August 2006), the Trials Register of the Cochrane Complementary Medicine Field (last searched June 2006) and the Chinese Stroke Trials Register (last searched June 2006). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to August 2006), EMBASE (1980 to June 2006), AMED (1985 to June 2006) and the China Biological Medicine Database (CBM-disc, 1979 to June 2006). We searched reference lists, relevant clinical trials and research registers and contacted pharmaceutical companies and researchers in an effort to identify further published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled clinical trials comparing puerarin with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: One trial, involving 98 participants, was included. No significant difference in death or dependency was shown between the treatment and control groups (odds ratio (OR) 0.81; 95% confidence interval (CI) 0.35 to 1.87). No serious adverse effects were reported. AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the effect of puerarin on survival or dependency of patients with acute ischaemic stroke. High-quality and large-scale randomised controlled trials are needed to assess its efficacy.