A new indolizinium alkaloid from marine-derived Streptomyces sp. HNA39.

A new indolizinium alkaloid, named as cyclizidine J (1), was identified from Gause's liquid fermentation of marine-derived Streptomyces sp. HNA39. Its structure was elucidated by extensive NMR spectroscopic methods, HRESIMS data, and ECD calculations. To our best knowledge, compound 1 was a unique cyclizidine-type alkaloid that contain a chlorine atom substituted at position C-8. Unfortunately, biological evaluation of 1 exhibited no active against PC-3 cancer cell line, BRD4, and ROCK2 protein kinase.

Incidence trends and age distribution of colorectal cancer by subsite in Guangzhou, 2000-2011.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in China. The incidence of CRC has been increasing in recent years. The aim of this study was to explore the incidence trends and the age distribution of CRC by subsite in Guangzhou between 2000 and 2011. METHODS: A total of 22,432 incident cases of CRC between 2000 and 2011 from Guangzhou Cancer Registry were identified. Crude incidence and age-standardized rates (ASRs), using the Segi's world standard population, were calculated for CRC and CRC subsites. The incidence trend was analyzed and the annual percentage change (APC) in incidence was calculated by using JoinPoint software. RESULTS: The crude incidence increased significantly from 23.4/10(5) in 2000 to 37.4/10(5) in 2011 for males and from 20.9/10(5) to 30.5/10(5) for females. The ASRs of CRC incidence stabilized during the period of 2000-2011 for both males and females. The ages at the onset of CRC for both males and females during 2010-2011 were significantly higher compared with those during 2000-2002 (males: t = 1.95, P = 0.05; females: t = 6.03, P < 0.01). For males aged 50-64 years, the CRC incidence increased by 8.50% annually (P = 0.04) during 2000-2004 and by 1.68% annually (P = 0.03) during 2005-2011. For females aged 65 years and older, the CRC incidence increased by 5.77% annually (P = 0.03) during 2000-2004. There were no significant changes for the CRC incidences in males aged 49 and younger and 65 years and older and females aged 64 years and younger during 2000-2004, or for those in all females as well as males aged 49 years and younger and 65 years and older during 2005-2011. The percentage of colon cancer in all CRCs increased significantly for both males and females between the periods of 2000-2002 and 2010-2011. The ASRs of descending colon and sigmoid colon cancer incidences increased significantly for females during 2005-2011 (APC, 5.51% and 1.08%, respectively, both P < 0.05). CONCLUSIONS: The crude incidence of CRC increased significantly between 2000 and 2011 because of the aging, whereas the ASRs kept stable. The percentage of colon cancer in all CRCs increased significantly. Further surveillance, research, and intervention are needed to identify the causes of these changes and to reduce the incidence and mortality of CRC.

The impact of relative humidity and atmospheric pressure on mortality in Guangzhou, China.

OBJECTIVE: Although many studies have examined the effects of ambient temperatures on mortality, little evidence is on health impacts of atmospheric pressure and relative humidity. This study aimed to assess the impacts of atmospheric pressure and relative humidity on mortality in Guangzhou, China. METHODS: This study included 213,737 registered deaths during 2003-2011 in Guangzhou, China. A quasi-Poisson regression with a distributed lag non-linear model was used to assess the effects of atmospheric pressure/relative humidity. RESULTS: We found significant effect of low atmospheric pressure/relative humidity on mortality. There was a 1.79% (95% confidence interval: 0.38%-3.22%) increase in non-accidental mortality and a 2.27% (0.07%-4.51%) increase in cardiovascular mortality comparing the 5th and 25th percentile of atmospheric pressure. A 3.97% (0.67%-7.39%) increase in cardiovascular mortality was also observed comparing the 5th and 25th percentile of relative humidity. Women were more vulnerable to decrease in atmospheric pressure and relative humidity than men. Age and education attainment were also potential effect modifiers. Furthermore, low atmospheric pressure and relative humidity increased temperature-related mortality. CONCLUSION: Both low atmospheric pressure and relative humidity are important risk factors of mortality. Our findings would be helpful to develop health risk assessment and climate policy interventions that would better protect vulnerable subgroups of the population.

Impact of heat wave in 2005 on mortality in Guangzhou, China.

OBJECTIVE: To assess the impact of the heat wave in 2005 on mortality among the residents in Guangzhou and to identify susceptible subpopulations in Guangzhou, China. METHODS: The data of daily number of deaths and meteorological measures from 2003 to 2006 in Guangzhou were used in this study. Heat wave was defined as ⋝7 consecutive days with daily maximum temperature above 35.0 °C and daily mean temperature above the 97th percentile during the study period. The excess deaths and rate ratio (RR) of mortality in the case period compared with the reference period in the same summer were calculated. RESULTS: During the study period, only one heat wave in 2005 was identified and the total number of excess deaths was 145 with an average of 12 deaths per day. The effect of the heat wave on non-accidental mortality (RR=1.23, 95% CI: 1.11-1.37) was found with statistically significant difference. Also, greater effects were observed for cardiovascular mortality (RR=1.34, 95% CI: 1.13-1.59) and respiratory mortality (RR=1.31, 95% CI: 1.02-1.69). Females, the elderly and people with lower socioeconomic status were at significantly higher risk of heat wave-associated mortality. CONCLUSION: The 2005 heat wave had a substantial impact on mortality among the residents in Guangzhou, particularly among some susceptible subpopulations. The findings from the present study may provide scientific evidences to develop relevant public health policies and prevention measures aimed at reduction of preventable mortality from heat waves.

A functional variant of NEDD4L is associated with obesity and related phenotypes in a Han population of Southern China.

NEDD4L is a candidate gene for hypertension, both functionally and genetically. Recently, studies showed evidence for the association of NEDD4L with obesity, a key intermediate phenotype in hypertension. To further investigate the relationship between NEDD4L and body mass-related phenotypes, we genotyped three common variants (rs2288774, rs3865418 and rs4149601) in a population-based study of 892 unrelated Han Cantonese using the Sequenom MALDI-TOF-MS platform. Allele frequencies and genotype distribution were calculated in lean controls and overweight/obese cases and analyzed for association by the Chi-squared test and Logistic regression. Linear regression analysis was used to analyze the effect of individual genotypes on quantitative traits. Multivariate analyses demonstrated that the minor allele of rs4149601(A = 20.9%) was associated with a 2.60 kg, 2.78 cm and 0.97 kg/m2 decrease per allele copy in weight, waist and BMI, respectively. Carriers of this allele also had a significant lower risk of overweight/obesity (p < 0.0001, OR = 0.52, 95% CI: 0.37-0.74) as compared to non-carriers. However, no significant association between genotypes at rs2288774 and rs3865418 and covariate-adjusted overweight/obesity or any related phenotypes was observed. These results suggested that the functional variant of NEDD4L, rs4149601, may be associated with obesity and related phenotypes, and further genetic and functional studies are required to understand its role in the manifestation of obesity.

A Retrospective Study of Recurrent Bacterial Meningitis in Children: Etiology, Clinical Course, and Treatment.

Objectives: Recurrent bacterial meningitis (RBM) is a rare but life-threatening disease. This study aims to analyze the clinical features, potential causes, and therapeutic outcomes of RBM in children. Methods: This article retrospectively reviews the clinical characteristics, etiologies, and treatments in children with RBM hospitalized in Hebei children's hospital from 2012 to 2020. Results: A total of 10 children with RBM, five males and five females, were included in this study. The age of RBM in children spans from the neonatal stage to the childhood stage. The underlying illnesses were identified and classified as cerebrospinal fluid rhinorrhea (1 case), humoral immunodeficiency with Mondini dysplasia (1 case), common cavity deformity with cerebrospinal fluid ear leakage (1 case), Mondini malformations (2 cases), incomplete cochlear separation type I with a vestibular enlargement (2 cases), local inflammation of the sphenoid bone caused by cellulitis (1 case), congenital skull base defects (1 case), and congenital dermal sinus with intraspinal abscess (1 case). 6 patients chose targeted therapy for potential reasons. Conclusions: Congenital abnormalities or acquired injuries lead to intracranial communication with the outside world, which can quickly become a portal for bacterial invasion of the central nervous system, resulting in repeated infections.

Cost-effectiveness analysis of different screening strategies for colorectal cancer in Guangzhou, southern China: a Markov simulation analysis based on natural community screening results.

OBJECTIVES: To evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer (CRC) screening compared with no screening using the Markov model. METHODS: Treeage Pro V.2011 software was used to simulate the Markov model. The incremental cost-effectiveness ratio, which was compared with the willingness-to-pay (WTP) threshold, was used to reflect the cost-effectiveness of the CRC screening method. One-way sensitivity analysis and probabilistic sensitivity analysis were used for parameter uncertainty. RESULTS: All strategies had greater effectiveness because they had more quality-adjusted life years (QALYs) than no screening. When the WTP was ¥435 762/QALY, all screening strategies were cost-effective compared with no screening. The double iFOBT strategy was the best-buy option compared with all other strategies because it had the most QALYs and the least cost. One-way sensitivity analysis showed that the sensitivity of low-risk adenoma, compliance with colonoscopy and primary screening cost were the main influencing factors comparing single iFOBT, double iFOBT and HRFQ+double iFOBT with no screening. However, within the scope of this study, there was no fundamental impact on cost-effectiveness. Probabilistic sensitivity analysis showed that when the WTP was ¥435 762/QALY, the probabilities of the cost-effectiveness acceptability curve with HRFQ alone, single iFOBT, double iFOBT and HRFQ+double iFOBT were 0.0%, 5.3%, 69.3% and 25.4%, respectively. CONCLUSIONS: All screening strategies for CRC were cost-effective compared with no screening strategy. Double iFOBT was the best-buy option compared with all other strategies. The significant influencing factors were the sensitivity of low-risk polyps, compliance with colonoscopy and cost of primary screening.

Synthesis and anticancer evaluation of alpha-lipoic acid derivatives.

alpha-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 microg/mL. Compound 17 m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which had 24.7% tumor-weight inhibition through intragastric administration of 200mg/kg of body weight. Moreover, the LD(50) in mice for 17 m through ig exceeded 1000 mg/kg of body weight.

High prevalence of hyperuricaemia and its impact on non-valvular atrial fibrillation: the cross-sectional Guangzhou (China) Heart Study.

OBJECTIVES: There are country and regional variations in the prevalence of hyperuricaemia (HUA). The prevalence of HUA and non-valvular atrial fibrillation (NVAF) in southern China is unknown. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 11 488 permanent residents aged 35 or older from urban and rural areas of Guangzhou, China were enrolled. A questionnaire was used to compile each participant's demographic information and relevant epidemiological factors for HUA and NVAF. All participants were assessed using a panel of blood tests and single-lead 24-hour ECG. MAIN OUTCOME MEASURES: HUA was defined as serum uric acid level >420 µmol/L in men and >360 µmol/L in women. NVAF was diagnosed as per guidelines. RESULTS: The prevalence of HUA was 39.6% (44.8% in men and 36.7% in women), and 144 residents (1.25%) had NVAF. Prevalence of HUA increased with age in women but remained stably high in men. After adjusting for potential confounders, age, living in urban areas, alcohol consumption, central obesity, elevated fasting plasma glucose level, elevated blood pressure, lower high-density lipoprotein cholesterol level and elevated triglycerides level were associated with increased risk of HUA. Residents with HUA were at higher risk for NVAF. Serum uric acid level had a modest predictive value for NVAF in women but not men. CONCLUSIONS: HUA was highly prevalent among citizens of southern China and was a predictor of NVAF among women.

Separation of cytidine 5'-triphosphate biosynthesized from cytidine 5'-monophosphate on ion-exchange resin and HPLC analysis of cytidine compounds.

Conditions were studied in the biosynthesis of cytidine 5'-triphosphate (CTP) from cytidine 5'-monophosphate (CMP). A 201 x 7 anion ion-exchange resin was applied for the separation of CTP from CMP. Adsorption isotherm and elution conditions (eluant, eluant concentration, flow rate, sample volume loaded) were investigated. At the same time, a new high-performance liquid chromatography on an anion ion-exchange column WAX-1 with UV detector at 260 nm was developed to measure CMP, cytidine 5'-diphosphate (CDP), and CTP. The retention time for CMP, CDP, and CTP are 0.723, 1.448, and 4.432 min, respectively. This new rapid high-performance liquid chromatography (HPLC) method for the analysis of cytidine compounds in biological sample has a wide linear range with high precision and repeatability.

Willingness to pay for colorectal cancer screening in Guangzhou.

AIM: To measure the willingness to pay for colorectal cancer screening in Guangzhou, and to identify those factors associated with it. METHODS: A face-to-face questionnaire survey for pre-screening population from free and non-free colonoscopy districts was used to collect information on demographic characteristics, health behaviours, the intention of the cancer screenings and willingness to pay for colorectal cancer screening. A total of 1243 participants who took part in the pre-screening for colorectal cancer in Guangzhou were collected in the study. Categorical data were compared using the χ2 test to analyse significant differences. Non-conditional logistic regression and multi-class logistic regression were also performed for multivariate analysis and to estimate the odds ratios. RESULTS: The percentage of participants willing to pay for colorectal cancer screening was 91.7%. "Unnecessary" was the dominant reason that participants gave for their unwillingness, accounting for 63.1%. Of those who were willing to pay, 29.2%, 20.7%, 14.8%, 13.0% and 22.4% of participants were willing to pay less than \100, \100-\199, \200-299, \300-\399 and more than \400, respectively. Non-logistic regression analysis showed that respondents who were male, had a high level of education, were from the family with more children/older to raise, and accepted colorectal cancer screening were willing to pay for this screening. Multi-class logistic regression analysis showed that respondents with higher annual household income per capita, from government and private enterprises, government agency/institution and peasants, and less family medical expenditure were willing to pay more. CONCLUSION: Willingness to pay for colorectal cancer screening in Guangzhou is high, but the amount of willing to pay is not much.

Spatio-temporal analysis of the incidence of colorectal cancer in Guangzhou, 2010-2014.

INTRODUCTION: Colorectal cancer (CRC) is a common type of neoplasm. This study examined the spatio-temporal distribution of the CRC incidence in Guangzhou during 2010-2014. METHODS: Colorectal cancer incidence data were obtained from the Guangzhou Cancer Registry System. Spatial autocorrelation analysis and a retrospective spatio-temporal scan were used to assess the spatio-temporal cluster distribution of CRC cases. RESULTS: A total of 14,618 CRC cases were registered in Guangzhou during 2010-2014, with a crude incidence of 35.56/100,000 and an age-standardized rate of incidence by the world standard population (ASRIW) of 23.58/100,000. The crude incidence increased by 19.70% from 2010 (32.88/100,000) to 2014 (39.36/100,000) with an average annual percentage change (AAPC) of 4.33%. The AAPC of ASRIW was not statistically significant. The spatial autocorrelation analysis revealed a CRC incidence hot spot in central urban areas in Guangzhou City, which included 25 streets in southwestern Baiyun District, northwestern Haizhu District, and the border region between Liwan and Yuexiu Districts. Three high- and five low-incidence clusters were identified according to spatio-temporal scan of CRC incidence clusters. The high-incidence clusters were located in central urban areas including the border regions between Baiyun, Haizhu, Liwan, and Yuexiu Districts. CONCLUSIONS: This study revealed the spatio-temporal cluster pattern of the incidence of CRC in Guangzhou. This information can inform allocation of health resources for CRC screening.

Knowledge, Attitudes, Preventive Practices and Screening Intention about Colorectal Cancer and the Related Factors among Residents in Guangzhou, China

Background: In Guangzhou, China, colorectal cancer (CRC) is the second most commonly diagnosed cancer. The government initiated a CRC screening program in 2015, and investigating the knowledge, attitudes, and practices toward CRC would help facilitate the participation of the program. Methods: A cross-sectional survey was conducted from October 2014 to September 2015. Questionnaires were passed out with a cluster sample in 15 randomly selected primary schools of Guangzhou China, and one of each student's family members aged between 20 to 65 years old were included. Results: A total of 6839 questionnaires were obtained and the successful response rate was 78.5%. The majority (88.3%) of them were under 46 years old and female subjects accounted for 65.8%. Over 80% of the respondents knew that CRC was able to be cured by early diagnosis and treatment and that tobacco use, alcohol abuse, and dietary without enough fruits or vegetables may increase the risk of CRC, although a few knowledge scores were relatively low, such as physical exercise as a protective factor and bowel habits change as a symptom suggestive of CRC. In contrast, only 52.2% of the subjects were sure to participate in a future CRC screening provided by local government. We further found that the higher level of knowledge about CRC risk and positive cancer preventive attitude and practice were associated with higher education level, female gender, and positive family history. Conclusion: These results suggested that the priority may be laid on improving the conversion from knowledge to practice to implement screening program in Guangzhou, while efforts should also be made to improve public awareness about CRC.

Can the Air Pollution Index be used to communicate the health risks of air pollution?

The validity of using the Air Pollution Index (API) to assess health impacts of air pollution and potential modification by individual characteristics on air pollution effects remain uncertain. We applied distributed lag non-linear models (DLNMs) to assess associations of daily API, specific pollution indices for PM10, SO2, NO2 and the weighted combined API (APIw) with mortality during 2003-2011 in Guangzhou, China. An increase of 10 in API was associated with a 0.88% (95% confidence interval (CI): 0.50, 1.27%) increase of non-accidental mortality at lag 0-2 days. Harvesting effects appeared after 2 days' exposure. The effect estimate of API over lag 0-15 days was statistically significant and similar with those of pollutant-specific indices and APIw. Stronger associations between API and mortality were observed in the elderly, females and residents with low educational attainment. In conclusion, the API can be used to communicate health risks of air pollution.

3'3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling.

Late stage hepatocellular carcinoma (HCC) usually has a low survival rate because it has high potential of metastases and there is no effective cure. 3'3-Diindolylmethane (DIM) is the major product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables. DIM has been proved to exhibit anticancer properties. In this study, we explored the effects and molecular mechanisms of anti-metastasis of DIM on HCC cells both in vitro and in vivo. We chose two HCC cell lines SMMC-7721 and MHCC-97H that have high potential of invasion. The results showed that DIM inhibited the proliferation, migration and invasion of these two cell lines in vitro. In addition, in vivo study demonstrated that DIM significantly decreased the volumes of SMMC-7721 orthotopic liver tumor and suppressed lung metastasis in nude mice. Focal Adhesion Kinase (FAK) is found over activated in HCC cells. We found that DIM decreased the level of phospho-FAK (Tyr397) both in vitro and in vivo. DIM inhibition of phospho-FAK (Tyr397) led to down-regulation of MMP2/9 and decreased potential of metastasis. DIM also repressed the migration and invasion induced by vitronectin through inactivation of FAK pathway and down-regulation of MMP2/9 in vitro. We also found that pTEN plays a role in down-regulation of FAK by DIM. These results demonstrated that DIM blocks HCC cell metastasis by suppressing tumor cell migration and invasion. The anti-metastasis effect of DIM could be explained to be its down-regulated expression and activation of MMP2/9 partly induced by up-regulation of pTEN and inhibition of phospho-FAK (Tyr397).

Global climate change: impact of diurnal temperature range on mortality in Guangzhou, China.

Diurnal temperature range (DTR) is an important meteorological indicator associated with global climate change, but little is known about the effects of DTR on mortality. We examined the effects of DTR on cause-/age-/education-specific mortality in Guangzhou, a subtropical city in China during 2003-2010. A quasi-Poisson regression model combined with distributed lag non-linear model was used to examine the effects of DTR, after controlling for daily mean temperature, air pollutants, season and day of the week. A 1 °C increase in DTR at lag 0-4 days was associated with a 0.47% (95% confidence interval: 0.01%-0.93%) increase in non-accidental mortality. Stroke mortality was most sensitive to DTR. Female, the elderly and those with low education were more susceptible to DTR than male, the youth and those with high education, respectively. Our findings suggest that vulnerable subpopulations should pay more attention to protect themselves from unstable daily weather.

Thimerosal-induced apoptosis in mouse C2C12 myoblast cells occurs through suppression of the PI3K/Akt/survivin pathway.

BACKGROUND: Thimerosal, a mercury-containing preservative, is one of the most widely used preservatives and found in a variety of biological products. Concerns over its possible toxicity have reemerged recently due to its use in vaccines. Thimerosal has also been reported to be markedly cytotoxic to neural tissue. However, little is known regarding thimerosal-induced toxicity in muscle tissue. Therefore, we investigated the cytotoxic effect of thimerosal and its possible mechanisms on mouse C2C12 myoblast cells. METHODOLOGY/PRINCIPAL FINDINGS: The study showed that C2C12 myoblast cells underwent inhibition of proliferation and apoptosis after exposure to thimerosal (125-500 nM) for 24, 48 and 72 h. Thimerosal caused S phase arrest and induced apoptosis as assessed by flow cytometric analysis, Hoechst staining and immunoblotting. The data revealed that thimerosal could trigger the leakage of cytochrome c from mitochondria, followed by cleavage of caspase-9 and caspase-3, and that an inhibitor of caspase could suppress thimerosal-induced apoptosis. Thimerosal inhibited the phosphorylation of Akt(ser473) and survivin expression. Wortmannin, a PI3K inhibitor, inhibited Akt activity and decreased survivin expression, resulting in increased thimerosal-induced apoptosis in C2C12 cells, while the activation of PI3K/Akt pathway by mIGF-I (50 ng/ml) increased the expression of survivin and attenuated apoptosis. Furthermore, the inhibition of survivin expression by siRNA enhanced thimerosal-induced cell apoptosis, while overexpression of survivin prevented thimerosal-induced apoptosis. Taken together, the data show that the PI3K/Akt/survivin pathway plays an important role in the thimerosal-induced apoptosis in C2C12 cells. CONCLUSIONS/SIGNIFICANCE: Our results suggest that in C2C12 myoblast cells, thimerosal induces S phase arrest and finally causes apoptosis via inhibition of PI3K/Akt/survivin signaling followed by activation of the mitochondrial apoptotic pathway.

Selective carboxypropionylation of chitosan: synthesis, characterization, blood compatibility, and degradation.

Two water-soluble chitosan (WSC) derivatives of N-succinyl-chitosan (NSCS) and N,O-succinyl-chitosan (NOSCS) with a degree of substitution (DS) that ranged form 0.28 to 0.61 were selectively synthesized by varying the molar ration of succinic anhydride and chitosan. The chemical structure and physical properties of the chitosan derivatives were characterized by FT-IR, 1H NMR, and XRD. XRD analysis showed that the derivatives were amorphous. The lysozyme enzymatic degradation results revealed that the NSCS was of higher susceptibility to lysozyme. The degradation rate and the solubility of the chitosan derivatives were strongly determined by the degree of substitution and the position of the substitution. The results of antithrombotic properties, hemolytic properties and anticoagulant properties of WSCs indicated that the blood compatibility was dramatically improved, and the carboxyl group introduced on the C-6 or C-2 hydroxyl group appeared to impact anticoagulant activity in different ways.