BACKGROUNDPreeclampsia, especially early onset of preeclampsia (PE), is a common and serious disorder with high maternal and perinatal morbidity and mortality. Dietary factor is one of the most important factors which may affect the occurrence and development of the disease. The aim of this study is to investigate the effects of dietary factors on pathological changes of liver and placenta in preeclampsia-like mouse model by establishing the model at multiple stages of gestation.

METHODSWild-type (WT) mice were injected subcutaneously with nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME, 50 mg×kg(-1)×d(-1)) to establish PE-like model (L-NAME group) at early-, mid-, and late-pregnant periods respectively; simultaneously, the control mice were injected with normal saline (NS group). All the groups were divided into subgroups, standard chow group (SC), and high-fat diet group (HF). ApoE(-/-) pregnant mice served as a control group. Systolic blood pressure (SBP), urine protein, and histopathologic changes of placenta and liver in all groups were observed and statistically analyzed.

RESULTSIn WT and apoE(-/-) L-NAME subgroups, blood pressure and urine protein were significantly higher than those in all the gestational age matched NS groups (P < 0.05). Compared to other groups, remarkable liver fatty infiltration and lipid storage in placenta were found in early- and mid-L-NAME subgroups in apoE(-/-) mice (P < 0.05), especially in the early- and mid-HF+L-NAME subgroups in apoE(-/-) mice (P < 0.05). More lipid storage droplets both in liver and placenta were found in ApoE(-/-) mice than that of WT groups (P < 0.05). Morphology histopathologic examination of placentas showed varying degrees of fibrinoid necrosis and villous interstitial edema in early- and mid-L-NAME both in HF and SC of apoE(-/-) and WT subgroups compared to NS controls (P < 0.05). But there was no significant difference between HF and SC subgroups (P > 0.05), and no difference between apoE(-/-) and WT groups (P > 0.05).

CONCLUSIONSPreeclampsia-like conditions could be induced by L-NAME in mice at different gestational stages. Both WT and apoE(-/-) genotype mice with preeclampsia-like symptoms in early and mid stages of pregnancy presented lipid deposition in the placenta and hepatic fatty infiltration. To alter the environmental condition by feeding high-fat diet was harmful to the mother and the fetus. High-fat diet aggravated the impact of liver fatty infiltration at early and mid gestational stages especially in the apoE(-/-) mouse model. These results further revealed the association between early-onset preeclampsia and the dysoxidation of fatty acids.

Animals ; Apolipoproteins E ; deficiency ; genetics ; Diet, High-Fat ; Female ; Genotype ; Liver ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; NG-Nitroarginine Methyl Ester ; pharmacology ; Placenta ; drug effects ; metabolism ; Pregnancy

BACKGROUNDEarly and late-onset preeclampsia is thought to be different disease entities. This study aimed to determine the effects of early-onset preeclampsia-like symptoms on feto-placental outcomes and the adverse impacts of various factors on placental and fetal growth and development at different gestational stages in a mouse model.

METHODSPregnant C57BL/6J mice were divided into control and preeclampsia (PE) groups, and injected subcutaneously with the nitric oxide synthase inhibitor L-arginine methyl ester (L-NAME) 50 mgxkg(-1)d(-1). The PE group was divided into early-, mid- and late-PE groups with L-NAME injections starting on days 7, 11 and 16 of pregnancy, respectively. Corresponding control groups were injected with saline at the same time points. Blood pressure was measured until days 14 and 18, when the fetuses and placentas were removed under anesthesia. Blood pressure, urinary protein, and fetal and placental conditions were analyzed.

RESULTSBlood pressure and urinary protein increased following L-NAME injection. The fetal survival rate and fetal weight were reduced and the fetal absorption rate was increased in the early-PE group on days 14 and 18 of pregnancy, compared with the control group. There were no significant differences in these parameters between the late-PE group and the respective control group. Placental weights in the early- and mid-PE groups were significantly reduced at days 14 and 18 of pregnancy compared with the control groups, but there was no significant difference in placental weight between the late-PE group and the respective control group. Morphologic examination of placentas from the early- and mid-PE groups showed varying degrees of fibrinoid necrosis and villous interstitial edema, but no significant pathologic changes were found in the placentas from the late-PE or control groups.

CONCLUSIONPreeclampsia-like symptoms occurring during the early stage of pregnancy are more likely to affect placental and fetal development, whereas late onset preeclampsia-like symptoms have a direct impact on the mothers.

Animals ; Blood Pressure ; Disease Models, Animal ; Female ; Fetal Development ; Fetal Resorption ; etiology ; Fetal Weight ; Mice ; Mice, Inbred C57BL ; Organ Size ; Placenta ; pathology ; Pre-Eclampsia ; pathology ; physiopathology ; Pregnancy

BACKGROUNDPreeclampsia is one of hypertensive disorders in pregnancy. It is associated with abnormal lipid metabolism, including fatty acid oxidation metabolism. Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) plays an indispensable role in the oxidation of fatty acids. It has been reported that nitric oxide (NO) is one of the regulatory factors of the fatty acid oxidation pathway. The aim of this research was to investigate whether the nitric oxide synthase (NOS) inhibitor L-NAME may cause down-regulation of LCHAD in the pathogenesis of preeclampsia.

METHODSPregnant wild-type (WT) mice were treated with L-NAME or normal saline (NS) during gestation days 7 - 18 (early group), days 11 - 18 (mid group) and days 16 - 18 (late group), and apoE-/- mice served as a control. Systolic blood pressure (SBP), urine protein, feto-placental outcome, plasma lipid levels and NO concentrations were measured, and the expression of mRNA and protein for LCHAD in placental tissue were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively.

RESULTSIn WT and apoE-/- mice, SBP and urinary protein increased following L-NAME injection. Fetal and placental weights and NO concentrations were reduced and total cholesterol, triglycerides and free fatty acid levels were increased in early and mid L-NAME groups in WT and apoE-/- mice, compared with the NS group. There was no significant difference between the late L-NAME group and NS group. RT-PCR and Western blotting analysis showed that the mRNA and protein levels of LCHAD expression were significantly down-regulated in the early and mid L-NAME groups but not in the late L-NAME group in the WT and apoE-/- mice compared with the corresponding NS groups.

CONCLUSIONSInhibition of NO in early and mid gestation in mice may cause hyperlipidemia and suppression of fatty acid oxidation, whereas preeclampsia-like conditions in late gestation may be a maternal vascular response to inhibition of NO.

Animals ; Disease Models, Animal ; Enzyme Inhibitors ; pharmacology ; Fatty Acids ; metabolism ; Female ; Mice ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; antagonists & inhibitors ; Oxidation-Reduction ; Pre-Eclampsia ; chemically induced ; etiology ; Pregnancy

A single dose of 3H-norcantharidin solution was intragastrically given, blood, tissues, urine and feces were collected as scheduled, and radioactivity in these samples was determined by tritium tracing method to investigate the pharmacokinetics, tissue distribution and excretion of norcantharidin in Kunming mice. The pharmacokinetic characteristics of norcantharidin were evaluated by DAS version 2.0. The blood concentration reached to maximum 0. 5 h after intragastric administration. The radioactivity in tissues was high in small intestine, gallbladder, stomach, adrenal gland, kidney, heart and uterus 15 minutes after administration, descending with time, and high in gallbladder, adrenal gland and uterus 3 hours post dosing. The 24 h accumulative excretion ratio of urine and feces were 65.40% and 1.33% respectively. 3H-norcantharidin was easily absorbed after orally given to mice, the radioactivity was high and existed for a long-time in gallbladder, adrenal gland and uterus, and low but also existed for a long-time in large intestine, thymus and fat tissue. 3H-norcantharidin was declined quickly in small intestine, stomach, kidney and heart, and occurred rarely in brain. Norcantharidin was excreted mainly by urinary route and seldom in feces, which may be the cause of the urinary stimulation side effects observed. Because the radioactivity measured were the sum of 3H labeled norcantharidin and its metabolites, further studies on the disposition of norcantharidin in mammal animals, on the separation or identification of metabolites and, if any, on their activities, are fairly needed.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; pharmacokinetics ; urine ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; chemistry ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tissue Distribution ; Tritium

OBJECTIVETo investigate the changes of the goblet cells in the intestine during the restitution process of the gut barrier after hemorrhagic shock.

METHODSForty-nine Sprague-Dawley rats with body weight of 250-300 g were divided into control group (n=7) and experimental group (n=42). Rats in the experimental group was further divided into 6 groups (n=7 each) according to different time point at 1, 3, 6, 12, 24, and 36 hours after hemorrhagic shock resuscitation. The specimens from ileum tissue were taken to observe the morphological chan ges of the intestinal mucosa. The number of goblet cells was determined by light microscope and/or electron microscope. The contents of trefoil factor family 3 (TFF3) of goblet cells were examined using GC-9A gas chromatographic instrument.

RESULTSAfter hemorrhagic shock, mucosal epithelial injury was obvious in the small intestine. Tissue restitution was found after 3 hours, and mostly established after 12 hours. Following tissue restitution,the denuded mucosal surface was covered intensively by goblet cells. The number of goblet cells on the intestinal mucosa was reduced significantly from 243+/- 13 at 1 h to 157+/- 9 at 24 h (r=- 0.910, P< 0.01), and returned to normal level at 36 h. In the experimental group, the content of TFF3 in the intestinal mucosa increased significantly at 12 hours, decreased, but was still higher at 24 hours (t=3.24, P< 0.05).

CONCLUSIONSThe goblet cells play a key role in the restitution of intestinal mucosa. High expression of TFF3 may facilitate the intestinal mucosal restitution in the early phase.

Animals ; Goblet Cells ; metabolism ; Ileum ; cytology ; Intestinal Mucosa ; cytology ; metabolism ; pathology ; Neuropeptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; metabolism ; Trefoil Factor-3

AIM To determine effective components of Ampelopsis grossedentata (Hand.-Mazz.) W.T.Wang under different breeding modes and to analyze the antioxidant enzyme activities.METHODS Single factor and orthogonal tests were adopted in screening the optimal extraction process of antioxidant enzymes and analyzing antioxidant enzyme activities of A.grossedentata under common cutting,two-phase cutting and tissue culture.Solvent extraction method was adopted in extracting the effective components of three breeding modes in stem leaves of A.grossedentata,whose contents were determined.RESULTS In three breeding modes,the content of polysaccharides in tissue culture seedling was the highest,while the contents of flavonoids and polyphenols in the two stage cutting seedlings were the highest.The optimal extraction process of antioxidant enzymes was determined to be 6.0 for pH,20 ℃ for processing temperature and 20 min for processing time.Antioxidant enzyme activities were in sequence of two stage cutting seedlings ＞ common cutting seedling ＞ tissue culture seedling.CONCLUSION Considering the contents of effective components and antioxidant enzyme activities,two stage cutting method is the best among 3 breeding modes.

Objective To clarify the seasonal and geographical difference and pathogen patterns so as to provide reference of prevention and control of the disease through analyzing the epidemical characteristics of reported hand-foot-mouth disease(HFMD)cases in China,2008-2009.Methods We analysed the epidemiological data of HFMD from the Chinese national notifiable infectious diseases reporting system in 2008 and 2009.Results There were 488 955 and 1155525 reported HFMD cases in 2008 and 2009,in China,of which 1165 and 13810 were severe and 126 and 353 were fatal,respectively.The notification rates were 50.09/10 million,68.47/10 million and 59.04/10 million in high,medium and low latitudes areas,respectively.The epidemic periods in Medium and Low latitude were from 12 to 24 weeks in 2009,and in high latitude it was from 23 to 35 weeks.HFMD cases were concentrated mainly in 5 year-old or even younger children,accounted for 92.23% of the total cases.The incidence rate of two years old appeared to be the highest.The features of severe and death case concentrated in lower age groups were more evident,and the proportion of severe case and case fatality rate under 1 vears old was higher than that in other age groups.We also noticed that with the increasing of age,the proportion of severe case and case fatality rate had a decreasing trend.There was a difference between the pathogens seen.The relative risk(RR)for an human enterovirus 71(HEV71)isolate was higher among severe case than in common cases(RR=1.82),whereas the RR for an EV71 isolate was higher among the death cases than in common cases (RR=2.11).There was seasonal variation of pathogen composition.There were 477 clusters of cases from 2008 to 2009,of which 389 found in preschools,47 in rural villages,outbreaks of clusters were mainly from April to July. Conclusion The HFMD epidemics was increasing in 2009.The epidemic of HFMD in different latitudes area and seasons was different.Children of five year old or under were the major population groups at risk,of HFMD.The younger ones had higher risk of becoming severe and death cases.HEV71 and coxsackievirus A16 were both the major etiologic agents of HFMD.The preschool and rural villages were the main senings of clusters of cases.

How to use traditional medicine to play the role of primary health care to achieve strategic objectives of universal health coverage and health for all is an important issue for traditional medical development. World Health Organization (WHO) called out that the health system should return to primary health system which was officially launched 30 years ago. "Universal Health Coverage" was list as one of the overall objectives of WHO overall program in 2014-2019. WHO advocated incorporating traditional medicine into primary health care system to promote universal health coverage. At the same time, under the new situation of returning to the "basic health care", China has accumulated rich experience in incorporating TCM into basic health care system. Chinese medicine service has been successfully incorporated into the national basic public health services in grassroots medical institutions, and Chinese medicine service capacity has also been significantly improved under the guidance of good policy.

The changes of microRNA expression in rat hippocampus after traumatic brain injury (TBI) were explored. Adult SD rats received a single controlled cortical impact injury, and the ipsilateral hippocampus was harvested for the subsequent microarray assay at three time points after TBI: 1st day, 3rd day and 5th day, respectively. We characterized the microRNA expression profile in rat hippocampus using the microRNA microarray analysis, and further verified microarray results of miR-142-3p and miR-221 using quantitative real-time PCR. Totally 205 microRNAs were identified and up-/down-regulated more than 1.5 times. There were significant changes in 17 microRNAs at all three time points post-TBI. The quantitative real-time PCR results of miR-142-3p and miR-221 indicated good consistency with the results of the microarray method. MicroRNAs altered at different time points post-TBI. MiR-142-3p and miR-221 may be used as potentially biological markers for TBI assessment in forensic practice.

Objective: To analyze the change in community first diagnosis and two-way referral rate under the condition of the regional longitudinal medical consortium implementation in the country at large. According to the simulation results,some suggestions for hierarchical medical system were put forward. Methods : The community first diagnosis and two-way referral rates were determined using the literature meta-analysis, and were simulated under different conditions by means of the system dynamics. Results :The analysis results confirmed that simply increasing the financial subsidies can increase the community first diagnosis rate within a range from 0.08％ to 0. 17％. For in case increases are made by the government in technical financial input to enhance the technical level of the community health service centers and in compensatory financial input to reduce the higher hospitals dependence on the light disease, results showed that the lower conversion rate increased within the range of 0.33％～0.45％ in terms of the two-way referral rating. On the contrary, when technical financial input is increased to improve the technical level of community health service centers, the rate of change was in the range of 7.52％ '- 12.61％ - Conclusions : Firstly, the diversified strategy should be used to promote the achievement of graded diagnosis and treatment. Secondly, the Health Commission plays a key role in the promotion of themedical consortiumconstruction. Thirdly, medical insurance reimbursement differential strategy should be implemented and the supply-side reform should be strengthened. At last,attention should be paid to the rational development of existing referrals, especially the upper and lower ones.