ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

ObjectiveTo investigate the different effects of Yunvjian with or without Achyranthis Bidentatae Radix on glucose and lipid metabolism and inflammatory response in diabetic rats with the syndrome of Yin deficiency and internal heat. MethodThe rat model of diabetes due to Yin deficiency and internal heat was established by feeding with a high-sugar and high-fat diet and injection of thyroxine and streptozotocin. The successfully modeled rats were randomized into model control， Yunvjian without Achyranthis Bidentatae Radix （11.8 g·kg^-1）， Yunvjian with Achyranthis Bidentatae Radix （12.8 g·kg^-1）， and Achyranthis Bidentatae Radix （1.0 g·kg^-1） groups （n=10）， and another 10 rats were taken as the normal control group. Each group was administrated with corresponding drugs or saline by gavage for 28 days. The fasting blood glucose （FBG）， fasting insulin （FINS）， total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in rats were measured. Enzyme-linked immunosorbent assay was employed to determine the levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， triiodothyronine （T₃）， thyroxine （T₄）， interleukin （IL）-1β， IL-6， tumor necrosis factor （TNF）-α， and C-reactive protein （CRP） in the serum. The histopathological changes of the liver were observed. The expression of lipoxygenase-2 （COX-2） was detected by immunofluorescence. The mRNA levels of nuclear transcription factors-κB （NF-κB）， monocyte chemotactic protein-1 （MCP-1）， and intercellular adhesion molecule-1 （ICAM-1） were determined by real-time polymerase chain reaction （Real-time PCR）.Western blot was employed to determine the protein levels of NF-κB in hibitory protein（IκB） kinase β （IKKβ）， IκBα， and phosphorylated IκBα （p-IκBα） in the liver and the protein levels of NF-κB in the cytoplasm and nucleus. ResultCompared with the normal group， the model group showed elevated levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T₃， T₄， IL-1β， IL-6， TNF-α， and CRP， up-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and up-regulated protein levels of COX-2， p-IκBα， and nuclear NF-κB （P<0.01）. Compared with the model group， Yunvjian without Achyranthis Bidentatae Radix lowered the levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T₃， T₄， IL-1β， IL-6， TNF-α， and CRP， down-regulated the mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated the protein levels of COX-2， p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. Compared with the Yunvjian without Achyranthis Bidentatae Radix， Yunvjian with Achyranthis Bidentatae Radix showed lowered levels of FBG， FINS， insulin resistance index， and inflammatory cytokines， down-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated protein levels of p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. ConclusionAchyranthis Bidentatae Radix can enhance the performance of Yunvjian in reducing blood glucose and inhibiting inflammation in diabetic rats with the syndrome of yin deficiency and internal heat by down-regulating the IKK/IκB/NF-κB signaling pathway.

ObjectiveTo understand the relative bioavailability （RBA） of cadmium in different aquatic products. Based on the consideration of the gender differences and the relative bioavailability of cadmium in different foods， the physiologically based toxicokinetic （PBTK） model of cadmium was further optimized and verified. The correlation between internal and external exposure in quantitative risk assessment of food safety was optimized， and the provisional tolerable daily intake （PTDI） value of cadmium was derived. MethodsThe relative bioavailability of cadmium in different aquatic products was determined in four-week-old Balb/c female mice. The PBTK model of cadmium metabolism was optimized by ABC-MCMC method using combined internal and external exposure data of cadmium in Shanghai residents， and the PTDI was calculated accordingly. ResultsExcept for scallops and squid， the RBA of aquatic samples was less than 1， indicating that the absorption rate of cadmium in aquatic products was lower than that of cadmium chloride. The higher RBA of squid and scallop may be due to the presence of cadmium in the visceral organs， which is conducive to cadmium absorption and its higher concentration of cadmium. Frying at the temperature less than 160 ℃ reduced cadmium absorption but may increase cadmium absorption at the temperature greater than 160 ℃. The optimized model parameters converged well and the model could reasonably estimate urinary cadmium level according to the external exposure of cadmium. The PTDI value was0.466 4 μg·（kg·day）^-1 according to the optimized single-chamber model. ConclusionThe relative bioavailability of cadmium in different foods varies greatly， except for squid and scallops， RBA is less than 1， and cooking processing will affect the RBA of food. The construction of the PBTK model did not only consider the effects of gender differences on cadmium metabolism， but also included the relative bioavailability data to optimize and adjust the correlation coefficient of absorption rate. Compared with the model without RBA adjustment， the adjusted model has enhanced the ability to predict urinary cadmium level， which provides a new， more accurate method for the risk assessment of food safety.

Objective:To explore the effect of a Chinese medicinal composition ( Xiadanqi) on the prevention of radon exposure induced injuries of lung in vitro and in vivo. Methods:Mice were randomly divided into three groups of blank control group, radon-exposed group alone and radon-exposed group intervened with Chinese medicinal composition. The pathological changes of lung tissues in each group after 120 WLM were observed by HE and Masson staining, and the expressions of α-SMA protein and Vimentin protein in lung tissues were detected by immunohistochemistry staining. The levels of oxidative stress in lung tissue of each group were detected with SOD and MDA kits. At the same time, a radon exposed cell model and a radon exposure + Xiadanqi intervention cell model were constructed using an ecological radon chamber. The cell adhesion abilities of different groups were detected by an adhesion kit. The cell migration ability of each group was determined by the transwell migration experiment. The expression of E-cadherin and Vimentin protein was detected by Western blot. Results:Compared with the radon exposure group, the concentration of MDA was decreased ( t=4.43, P<0.05), the activity of SOD was increased ( t=3.22, P<0.05), and α-SMA and Vimentin protein expressions were decreased ( t=3.08, 7.57, P<0.05) in lung tissue of mice intervened with 2 mg/g Xiadanqi. In vitro, compared with radon exposure group, the migration ability was reduced ( t=4.78, 13.01, P<0.05), the cell adhesion property was enhanced ( t=3.41, 12.55, P<0.05), the expression of E-cadherin protein was increased ( t=2.96, 19.57, P<0.05), and the expression of Vimentin protein was obviously reduced ( t=21.00, 33.32, P<0.05) in radon-exposed cells with the treatment of Chinese medicine (150 μg/ml and 200 μg/ml). Conclusions:The Chinese medicinal composition ( Xiadanqi) has a certain radioprotective effect on radon exposure induced injury by reducing oxidative stress, attenuating EMT and fibrosis, and thus it may be applied as a protective agent for radon induced injury.

Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high-throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways—the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion, 'whether to do it’, ten years ago, the question, 'how to do it’, has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi-disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.

The assay was used in HIV/AIDS surveillance sentinel sites to identify recent HIV-1 infection, to estimate HIV-1 incidence and understand the epidemic trends among men who have sex with men during 2011-2015. During 2011-2015, the HIV-1 incidence of men who have sex with men was 5.16%(95%CI: 4.65%-5.66%) in Sichuan Province. According to, a total of 9 cities had been divided into two type of regions: the first type(the proportion of live HIV/AIDS accounts for more than 0.1% of the permanent population, and the number of live HIV/AIDS has reached 500 cases and above) and the second type(the proportion of live HIV/AIDS accounts for 0.03% to 0.100% of the permanent population, and the number of live HIV/AIDS has reached 100-500 cases). During 2011-2015, the HIV-1 incidence of the second type was 4.24% (95%CI: 3.72%-4.76%). The HIV-1 incidence of men who have sex with men was at a high level. The spread of HIV-1 to the second region was possible.

The assay was used in HIV/AIDS surveillance sentinel sites to identify recent HIV?1 infection, to estimate HIV?1 incidence and understand the epidemic trends among men who have sex with men during 2011-2015.During 2011-2015, the HIV?1 incidence of men who have sex with men was 5.16%(95%CI: 4.65%-5.66%) in Sichuan Province. According to, a total of 9 cities had been divided into two type of regions: the first type(the proportion of live HIV/AIDS accounts for more than 0.1% of the permanent population, and the number of live HIV/AIDS has reached 500 cases and above) and the second type(the proportion of live HIV/AIDS accounts for 0.03% to 0.100% of the permanent population, and the number of live HIV/AIDS has reached 100-500 cases). During 2011-2015, the HIV?1 incidence of the second type was 4.24% (95%CI:3.72%-4.76%). The HIV?1 incidence of men who have sex with men was at a high level. The spread of HIV?1 to the second region was possible.

Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high?throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways—the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion,‘whether to do it’, ten years ago, the question,‘how to do it’, has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi?disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.

The assay was used in HIV/AIDS surveillance sentinel sites to identify recent HIV?1 infection, to estimate HIV?1 incidence and understand the epidemic trends among men who have sex with men during 2011-2015.During 2011-2015, the HIV?1 incidence of men who have sex with men was 5.16%(95%CI: 4.65%-5.66%) in Sichuan Province. According to, a total of 9 cities had been divided into two type of regions: the first type(the proportion of live HIV/AIDS accounts for more than 0.1% of the permanent population, and the number of live HIV/AIDS has reached 500 cases and above) and the second type(the proportion of live HIV/AIDS accounts for 0.03% to 0.100% of the permanent population, and the number of live HIV/AIDS has reached 100-500 cases). During 2011-2015, the HIV?1 incidence of the second type was 4.24% (95%CI:3.72%-4.76%). The HIV?1 incidence of men who have sex with men was at a high level. The spread of HIV?1 to the second region was possible.