Probabilistic risk assessment for determining nonessential metals in commercial infant formula products in Taiwan.

During the early months of life, infant formula plays a crucial role as a primary source of both food and essential nutrients for infants, serving as a replacement for or supplement to breast milk. However, nonessential metals in infant formulas are a concern because infants are highly vulnerable to chemical exposure. The aim of this study was to investigate infant exposure to nonessential metals in infant formula products in Taiwan and assess the associated health risks. In this study, concentrations of arsenic (As), barium (Ba), cadmium (Cd), manganese (Mn), lead (Pb), and vanadium (V) in 45 formula products for 0-1-year-old infants were determined by inductively coupled plasma mass spectrometry. The mean As, Ba, Cd, Mn, Pb, and V concentrations were 6.42, 280, 3.72, 1425, 20.4, and 21.9 µg/kg, respectively. According to our probabilistic simulation of the estimated daily intake of metals, the proportion of hazard quotients exceeding one was 7.69% for As and 3.29% for Mn, and that of hazard index (HI) values exceeding 1 was >17% for metals. Arsenic had the largest HI contribution (46.9%), followed by Mn (22.3%) and Pb (12.7%). The nonessential metals content in infant formula raises potential noncarcinogenic health concerns for infants in Taiwan. Therefore, regulations for nonessential metals must be imposed on related food products in Taiwan, with a particular focus on As and Mn.

Puerarin prevents sepsis-associated encephalopathy by regulating the AKT1 pathway in microglia.

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.

Antenatal steroid as an independent risk factor for vitamin K2 deficiency in newborns: A Chinese single-center, retrospective study.

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.

The dose-response association between LEAP 1000 and birthweight - no clear mechanisms: a structural equation modeling approach.

BACKGROUND: Birthweight is an important indicator of maternal and fetal health globally. The multifactorial origins of birthweight suggest holistic programs that target biological and social risk factors have great potential to improve birthweight. In this study, we examine the dose-response association of exposure to an unconditional cash transfer program before delivery with birthweight and explore the potential mediators of the association. METHODS: Data for this study come from the Livelihood Empowerment Against Poverty (LEAP) 1000 impact evaluation conducted between 2015 and 2017 among a panel sample of 2,331 pregnant and lactating women living in rural households of Northern Ghana. The LEAP 1000 program provided bi-monthly cash transfers and premium fee waivers to enroll in the National Health Insurance Scheme (NHIS). We used adjusted and unadjusted linear and logistic regression models to estimate the associations of months of LEAP 1000 exposure before delivery with birthweight and low birthweight, respectively. We used covariate-adjusted structural equation models (SEM) to examine mediation of the LEAP 1000 dose-response association with birthweight by household food insecurity and maternal-level (agency, NHIS enrollment, and antenatal care) factors. RESULTS: Our study included a sample of 1,439 infants with complete information on birthweight and date of birth. Nine percent of infants (N = 129) were exposed to LEAP 1000 before delivery. A 1-month increase in exposure to LEAP 1000 before delivery was associated with a 9-gram increase in birthweight and 7% reduced odds of low birthweight, on average, in adjusted models. We found no mediation effect by household food insecurity, NHIS enrollment, women's agency, or antenatal care visits. CONCLUSIONS: LEAP 1000 cash transfer exposure before delivery was positively associated with birthweight, though we did not find any mediation by household- or maternal-level factors. The results of our mediation analyses may serve to inform program operations and improve targeting and programming to optimize health and well-being among this population. TRIAL REGISTRATION: The evaluation is registered in the International Initiative for Impact Evaluation's (3ie) Registry for International Development Impact Evaluations (RIDIESTUDY- ID-55942496d53af) and in the Pan African Clinical Trial Registry (PACTR202110669615387).

[Characteristics of Soil Carbon, Nitrogen, Phosphorus, and Ecological Stoichiometry in Vegetable Fields and Orchard in the Coastal Area of Fuzhou].

The soil ecological stoichiometric characteristics of different agricultural land use types have a certain indicator function for characterizing the level of soil nutrient supply and are of great significance to the management of nutrient resources in farmland ecosystems. In order to reveal the soil carbon (C), nitrogen (N), and phosphorus (P) contents and their ecological stoichiometric characteristics in different vegetable fields and orchard agricultural land use types, this study took vegetable fields (taro field and jicama field) and orchards (citrus tree orchard, watermelon field, and pear tree orchard) as the research objects in the coastal area of Fuzhou City. The contents of soil C, N, and P and their ecological stoichiometric characteristics in different vegetable fields and orchard agricultural land uses were measured and analyzed. The soil C and N contents were in the order of orchard>vegetable field (P<0.05). The C content in the citrus tree orchard was the highest (4.44 g·kg-1), and the N content in the watermelon field was the highest (1.46 g·kg-1). The soil P content was vegetable field>orchard (P<0.05), and the jicama field had the highest P content (0.19 g·kg-1). The soil carbon and nitrogen ratio (C/N), carbon and phosphorus ratio (C/P), and nitrogen and phosphorus ratio (N/P) were orchard>vegetable field (P<0.05). Among them, the citrus tree orchard had the highest C/N (7.40) and C/P (61.43), and the watermelon field had the highest N/P (10.27). Soil N content was significantly and negatively correlated with bulk density and conductivity (r=-0.49, r=-0.28, P<0.05), and there was a significant and positive correlation with soil water content (r=0.61, P<0.05). C/P and C/N were significantly and positively correlated with SOM (r=0.71, r=0.64, P<0.01). In the process of crop planting and management in the coastal area of Fuzhou City, it is necessary to reasonably add nitrogen fertilizer to compensate for the N limitation, and slow-release nitrogen fertilizer is better for promoting the sustainable supply of nitrogen nutrients in the growth and development of crops.

Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1.

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION: CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification.

BACKGROUND: Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise. METHODS: Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments. RESULTS: In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain. CONCLUSION: The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

First-Trimester Maternal Folic Acid Supplementation Modifies the Effects of Risk Factors Exposures on Congenital Heart Disease in Offspring.

This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004-2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.

Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring.

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment <12 years, household individual income <3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study.

BACKGROUND: As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important. OBJECTIVE: To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level and COVID-19 infection, its severity, and its clinical case characteristics. METHODS: This case-control study compared serum 25(OH)D levels and rates of vitamin D deficiency (VDD) between 80 healthy controls and 62 patients diagnosed with COVID-19 and admitted to Guangxi People's Hospital, China, 2/16/2020-3/16/2020. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. Logistic regression analysis was conducted to examine the associations between 25(OH)D level, or VDD, and case status/severity of COVID-19 while controlling for demographics and comorbidities. A threshold level of vitamin D for conveying COVID-19 risk was estimated. RESULTS: Severe/critical COVID-19 cases were significantly older and had higher percentages of comorbidity (renal failure) compared to mild cases. The serum 25(OH)D concentration in COVID-19 patient was much lower than that in healthy control. And 25(OH)D level was the lowest in severe/critical cases, compared with mild cases. In further, significantly higher rates of VDD were found in COVID-19 cases (41.9%) compared to healthy controls (11.1%). And VDD was the greatest in severe/critical cases (80%), compared with mild cases (36%). These statistically significant associations remained even after controlling for demographics and comorbidities. A potential threshold of 25(OH)D (41.19 nmol/L) to protect against COVID-19 was identified. CONCLUSION: Elderly and people with comorbidities were susceptible to severe COVID-19 infection. VDD was a risk factor for COVID-19, especially for severe/critical cases. While further confirmation is needed, vitamin D supplementation may have prevention or treatment potential for COVID-19 disease.

First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first-trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case-control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong Province, China. Adjusted odds ratios (aORs) of FAS and multivitamin use between CHD cases (overall and specific CHD phenotypes) and controls were calculated by controlling for parental confounders. The multiplicative interaction effect of FAS and multivitamin use on CHDs was estimated. A significantly protective association was detected between first-trimester maternal FAS and CHDs among offspring (aOR, 0.69; 95% CI, 0.62-0.76), but not for multivitamin use alone (aOR, 1.42; 95% CI, 0.73-2.78). There was no interaction between FAS and multivitamin use on CHDs (P=0.292). Most CHD phenotypes benefited from FAS (aORs ranged from 0.03-0.85), especially the most severe categories (ie, multiple critical CHDs [aOR, 0.16; 95% CI, 0.12-0.22]) and phenotypes (ie, single ventricle [aOR, 0.03; 95% CI, 0.004-0.21]). Conclusions First-trimester maternal FAS, but not multivitamin use, was substantially associated with lower risk of CHDs, and the association was strongest for the most severe CHD phenotypes. We recommend that women of childbearing age should supplement with folic acid as early as possible, ensuring coverage of the critical window for fetal heart development to prevent CHDs.

Electrochemical Assessment of Anticancer Compounds on the Human Tongue Squamous Carcinoma Cells.

The most common oral cancer is squamous cell carcinoma (SCC) and its highest occurrence is in the tongue. Almost 30% of patients with one primary head and neck tumor will have a second primary malignancy. In recent studies, two novel plant extracts, andrographolide and cannabidiol (CBD), have been exploited for their anticancer effects. Here, we investigated the cytotoxic effects of these two compounds on SCC-25 cells, a human tongue squamous carcinoma cell line, and compared the outcomes with two chemotherapeutic drugs, cisplatin and fluorouracil. Electric cell substrate impedance sensing (ECIS) system was applied to measure frequency- and time-dependent impedance of SCC-25 cell-covered electrodes and to further assess subtle changes in cell morphology and micromotion in response to different concentrations (0, 10, 30, 100, and 300 µM) of these compounds. AlamarBlue and Annexin V/7-AAD binding assays were used to measure the concentration dependent changes in viability and apoptosis of SCC-25 cells. Our results demonstrate that 24 hours after exposure to 30 µM CBD can significantly decrease the micromotion rate, damage the integrity of cell morphology, reduce cell viability, and induce higher apoptosis in treated SCC-25 cells, while the other three drugs attain similar effects at the concentration of 100 µM or higher. The apoptosis-induced changes in cell morphology and micromotion monitored by ECIS correlate well with biochemical assays. Thus, both frequency- and time-dependent impedance measurements using ECIS can be used to real-time follow cancer cell activities in response to anticancer drugs with different temporal cytotoxicity profiles.

Weather effects on hand, foot, and mouth disease at individual level: a case-crossover study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) raises an urgent public health issue in the Asia-Pacific region, especially in China. The associations between weather factors and HFMD have been widely studied but with inconsistent results. Moreover, previous studies utilizing ecological design could not rule out the bias of exposure misclassification and unobserved confounders. METHODS: We used case-crossover analysis to assess the associations of weather factors on HFMD. Individual HFMD cases from 2009 to 2012 in Guangdong were collected and cases located within 10 km of the meteorological monitoring sites were included. Lag effects were examined through the previous 7 days. In addition, we explored the variability by changing the distance within 20 km and 30 km. RESULTS: We observed associations between HFMD and weather factors, including temperature and relative humidity. An approximately U-shaped relationship was observed for the associations of temperature on HFMD across the same day and the previous 7 days, while an approximately exponential-shaped was seen for relative humidity. Statistically significant increases in rates of HFMD were associated with each 10-unit increases in temperature [Excess rate (ER): 7.7%; 95% Confidence Interval (CI): 3.9, 11.7%] and relative humidity (ER: 1.9%; 95% CI: 0.7, 3.0%) on lag days 0-6, when assessing within 10 km of the monitoring sites. Potential thresholds for temperature (30.0 °C) and relative humidity (70.3%) detected showed associations with HFMD. The associations remained robust for 20 km and 30 km. CONCLUSIONS: Our study found that temperature and relative humidity are significantly associated with the increased rates of HFMD. Thresholds and lag effects were observed between weather factors and HFMD. Our findings are useful for planning on targeted prevention and control of HFMD.

Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain.

Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine-an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.-has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI) neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR) were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

The global regulator of pathogenesis PnCon7 positively regulates Tox3 effector gene expression through direct interaction in the wheat pathogen Parastagonospora nodorum.

To investigate effector gene regulation in the wheat pathogenic fungus Parastagonospora nodorum, the promoter and expression of Tox3 was characterised through a series of complementary approaches. Promoter deletion and DNase I footprinting experiments identified a 25 bp region in the Tox3 promoter as being required for transcription. Subsequent yeast one-hybrid analysis using the DNA sequence as bait identified that interacting partner as the C2H2 zinc finger transcription factor PnCon7, a putative master regulator of pathogenesis. Silencing of PnCon7 resulted in the down-regulation of Tox3 demonstrating that the transcription factor has a positive regulatory role on gene expression. Analysis of Tox3 expression in the PnCon7 silenced strains revealed a strong correlation with PnCon7 transcript levels, supportive of a direct regulatory role. Subsequent pathogenicity assays using PnCon7-silenced isolates revealed that the transcription factor was required for Tox3-mediated disease. The expression of two other necrotrophic effectors (ToxA and Tox1) was also affected but in a non-dose dependent manner suggesting that the regulatory role of PnCon7 on these genes was indirect. Collectively, these data have advanced our fundamental understanding of the Con7 master regulator of pathogenesis by demonstrating its positive regulatory role on the Tox3 effector in P. nodorum through direct interaction.

[Effect of Taohong Qinlian Decoction on HMGB1 in Septic Rat Cardiac Muscle].

OBJECTIVE: To observe the levels of high mobility group box-1 protein (HMGB1), tumor necrosis factor-alpha (TNF-α), IL-6, troponin I (Tn I) release in septic rats, and to explore themechanism of Taohong Qinlian Decoction (TQD) in the treatment of septic myocardial injury. METHODS: A total of 48 healthy male Wistar rats of clean grade were randomly divided into the sham-operation group (Sham), the sepsis model group (CLP), and the TQD treatment group (ZY), 16 in each group. Concen-trations of TNF-α, IL-6, Tn I, and HMGB1 expression were detected in each group at 24 and 48 h after operation. Pathological changes of cardiac muscle were observed under light microscope. RESULTS: Concentrations of TNF-α, IL-6, Tn I and HMGB1 at 24 and 48 h after operation were significantly higher in the CLP group than in the Sham group (P < 0.01). Concentrations of TNF-α, IL-6, Tn I, and HMGB1 at 24 and 48 h after operation were significantly lower in the ZY group than in the CLP group (P < 0.05). Myocardial injury occurred in the CLP and the ZY group under light microscope. And this injury was more severe in the CLP group than in the ZY group. CONCLUSION: TQL could reduce the level of sepsis-related inflammatory cytokines and protect myocardium in septic rats.

[Evaluation and cumulative characteristics of heavy metals in soil-Uncaria rhynchophylla system of different functional areas].

Soil and Uncaria rhynchophylla in different functional areas were selected for the study,the content of heavy metals such as As, Cd, Cu, Cr, Pb, and Hg in soil and U. rhynchophylla was discussed, the characteristics of their accumulation in the U.rhynchophylla was analyzed, the contamination levels of heavy metals in soil in different functional areas was evaluated. The results showed that content of Cu, As, Pb and Cr in soil was being cropland>woodland>wasteland, content of Cd was being woodland>cropland>wasteland, content of Hg was being cropland>woodland>wasteland. According to quality standard of soil environment, soil Cd in woodland, cropland and wasteland all exceeded the state-level standards, soil Cd in woodland exceeded the secondary standard, soil Hg in cropland and wasteland all exceeded the state-level standards. According to technical conditions of green food producing area, soil Cd in woodland exceeded the limit value of standard. According to Green Trade Standards of Importing Exporting Medicinal Plants Preparations,the content of heavy metals of U.rhynchophylla in cropland,woodland and wasteland were correspond to the specification. From the single factor pollution index, the soil in woodland was polluted by Cd. From the comprehensive pollution index, the soils in different functional areas were not contaminated by heavy metals. The enrichment coefficient of heavy metals such as As, Cu, Cr, and Pb in hook of U.rhynchophylla was being wasteland>woodland>cropland, the enrichment coefficient of Cu in hook of U. rhynchophylla in wasteland was more than 1. Except Cu, the enrichment coefficient of other heavy metals was low.

[Determination of Six Ingredients in Gardenia jaminoides Fruits with Quantitative Analysis of Muti-components by Single Marker].

OBJECTIVE: To establish a method of quantitative analysis of multi-components, by single marker(QAMS)for simultaneously determining six ingredients in Gardenia jasminoides fruits. METHODS: A multi-wavelength segmentation detection method was used. A methodological mode was found to analysis six ingredients in Gardenia jasminoides fruits by quantitative analysis of QAMS. Taken geniposide as reference to create RCF with gardenia acid, chlorogenic acid, crocin I, crocin II and crocin III. RESULTS: The good reproducibility and acceptable durability of method was validated between two HPLC systems and three columns. 20 batches of Gardenia jaminoides fruits was analysis, and the results showed good linear correlation compared to external standard method (r > 0. 999). CONCLUSION: QAMS can be used as quality evaluation method of multi-component Gardenia jaminoides fruits.

Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats.

Madecassoside, a triterpenoid derivative isolated from Centella asiatica, exhibits anti-inflammatory and antioxidant activities. We investigated its neuroprotective effect against ischemia-reperfusion (I/R) injury in cerebral neurons in male Sprague-Dawley rats. Madecassoside (6, 12, or 24mg/kg, i.v.) was administered 1h after the start of reperfusion, and neurological deficit score and infarct volume were evaluated 24h later. Neuronal apoptosis was assessed by performing terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, and pathological brain damage was estimated by performing hematoxylin and eosin staining. Serum levels of malondialdehyde, superoxide dismutase activity, reduced glutathione levels, and nitric oxide levels were also determined. mRNA and protein expression of pro-inflammatory cytokines (Interleukin-1ß/6, and tumor necrosis factor-α) were measured by real-time RT-PCR and ELISA, respectively; NF-κB p65 expression was determined by western blotting. Madecassoside significantly reduced brain infarct area, resolved neurological deficit, and ameliorated neuronal apoptosis. It also significantly reduced the levels of malondialdehyde and nitric oxide, and augmented the antioxidant activity in rats subjected to cerebral I/R. Moreover, the levels of pro-inflammatory cytokines and NF-κB p65 significantly reduced after madecassoside treatment. These results indicate that madecassoside is neuroprotective and may be useful in reducing the damage caused by stroke.

Routine defunctioning stoma after chemoradiation and total mesorectal excision: a single-surgeon experience.

AIM: To investigate the 10-year results of treating low rectal cancer by a single surgeon in one institution. METHODS: From Oct 1998 to Feb 2009, we prospectively followed a total of 62 patients with cT2-4 low rectal cancer with lower tumor margins measuring at 3 to 6 cm above the anal verge. All patients received neoadjuvant chemoradiation (CRT) for 6 wk. Among them, 85% of the patients received 225 mg/m(2)/d 5-fluorouracil using a portable infusion pump. The whole pelvis received a total dose of 45 Gy of irradiation in 25 fractions over 5 wk. The interval from CRT completion to surgical intervention was planned to be approximately 6-8 wk. Total mesorectal excision (TME) and routine defunctioning stoma construction were performed by one surgeon. The distal resection margin, circumferential resection margin, tumor regression grade (TRG) and other parameters were recorded. We used TRG to evaluate the tumor response after neoadjuvant CRT. We evaluated anal function outcomes using the Memorial Sloan-Kettering Cancer Center anal function scores after closure of the defunctioning stoma. RESULTS: The median distance from the lower margin of rectal cancer to the anal verge was 5 cm: 6 cm in 9 patients, 5 cm in 32 patients, 4 cm in 10 patients, and 3 cm in 11 patients. Before receiving neoadjuvant CRT, 45 patients (72.6%) had a cT3-4 tumor, and 21 (33.9%) patients had a cN1-2 lymph node status. After CRT, 30 patients (48.4%) had a greater than 50% clinical reduction in tumor size. The final pathology reports revealed that 33 patients (53.2%) had a ypT3-4 tumor and 12 (19.4%) patients had ypN1-2 lymph node involvement. All patients completed the entire course of neoadjuvant CRT. Most patients developed only Grade 1-2 toxicities during CRT. Thirteen patients (21%) achieved a pathologic complete response. Few post-operative complications occurred. Nearly 90% of the defunctioning stomas were closed within 6 mo. The local recurrence rate was 3.2%. Pathologic lymph node involvement was the only prognostic factor predicting disease recurrence (36.5% vs 76.5%, P = 0.006). Nearly 90% of patients recovered sphincter function within 2 year after closure of the defunctioning stoma. CONCLUSION: Neoadjuvant CRT followed by TME, combined with routine defunctioning stoma construction and high-volume surgeon experience, can provide excellent surgical quality and good local disease control.