Humans ; Intestinal Obstruction/complications* ; Ileus/etiology* ; Abdominal Injuries/complications*

Currently,the toxicity study of traditional Chinese medicine is faced with the following problems. Firstly,the evaluation in vitro cannot fully reflect the true state of the body. Secondly,the traditional method is not sensitive enough to the early toxicity. Lastly,the toxicity evaluation indexes cannot determine whether the compatibility of traditional Chinese medicine produces toxicity or increases toxicity systematically. The paper proposed a synthesized early evaluation research method for target organ toxicity induced by traditional Chinese medicine:screening,validation,optimization and application. This method mainly inoolves early target organ toxicity biomarkers in screening,optimi?zation,validation,biological significance explanation,and application to the traditional Chinese medicine incompatibility based on the metabolic dynamic fingerprint spectrum in order to obtain biomarkers of target organ toxicity that are sensitive and precede conventional biochemical indices for early evaluation . We attempted to analyze the pattern of chang of the biomarkers for animals acted by″18 incompatible medicaments″compatibility combination. We found that Radix Aconiti Lateralis Preparata with cardiotoxicity were compatible with Rhizoma Pinelliae,and that Trichosanthes kirilowii Maxim,Fritillaria,Ampelopsis Radix and Bletilla striata without non-cardiotoxicity produced and increased cardiotoxicity systematically.

Objective To investigate the protective effect of agmatine (AGM) against peritoneal inflammatory response and neutrophil (PMN) infiltration induced by zymosan (ZYM) in mice. Methods Thirty-six adult male C57BL/6 mice were randomly divided into sham group, model group, and AGM treatment group. Peritonitis model was reproduced by intra-peritoneal injection of 1 mg/mL ZYM (0.5 mL), while equivalent phosphate buffer saline (PBS) was given to sham group. 200 mg/kg AGM was injected into peritoneal cavity after ZYM challenge in AGM treatment group. Six mice in each group were sacrificed at 2 hours and 6 hours, respectively, after reproduction of the model. Blood sample and peritoneal lavage fluid (PLF) were collected. The levels of keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), tumor necrosis factor-α (TNF-α), interleukins-6 (IL-6) in serum and PLF were determined by enzyme linked immunosorbent assay (ELISA). The number of leukocytes and PMN in PLF were determined by hemocytometer and flow cytometry, respectively. Results Compared with sham group, all serum and PLF levels of KC, MIP-2, TNF-α and IL-6 were greatly elevated at 2 hours after ZYM injection in model group, while AGM treatment could dramatically reduce the levels of the above-mentioned cytokines in serum and PLF as compared with those of the model group [serum KC (ng/L): 990.7±137.9 vs. 2 053.2±262.7, MIP-2 (ng/L): 642.2±124.4 vs. 1 369.7±146.5, TNF-α (ng/L): 608.6±38.1 vs. 1 044.7±101.0, IL-6 (ng/L): 1 058.2±129.1 vs. 1 443.3±190.1; PLF KC (ng/L): 7 462.3±839.6 vs. 12 723.5±1 515.7, MIP-2 (ng/L): 1 570.8±193.4 vs. 3 471.4±384.7, TNF-α (ng/L): 1 115.8±156.7 vs. 1 499.2±231.2, IL-6 (ng/L): 2 646.5±223.2 vs. 3 126.7±291.4; all P < 0.05]. The expressions of KC, MIP-2 and TNF-α at 6 hours were significantly lower than those at 2 hours in model group and AGM treatment group, but IL-6 levels were further increased. The levels of KC and MIP-2 in serum and PLF at 6 hours were decreased to the levels of sham group. At 6 hours after the reproduction of the model, the number of total inflammatory cells and PMN of PLF in the model group was significantly higher than those of the sham group. In contrast, AGM notably lowered the number of inflammatory cells and PMN in peritoneal fluid after ZYM attack [total inflammatory cells (×109/L): 14.7±1.1 vs. 2.0±0.4, 10.1±1.2 vs. 14.7±1.1; PMN (×109/L): 11.37±1.22 vs. 0.18±0.05, 7.69±0.57 vs. 11.37±1.22, all P < 0.05]. Conclusion AGM can effectively alleviate acute peritoneal inflammatory injury induced by ZYM, mainly through reducing the secretion of inflammatory mediators and chemokines, and inhibiting the infiltration of leukocytes and neutrophils.

Objective To examine the role of p38MAPK in high glucose-induced apoptosis of osteoblast MC3T3-E1 cell line, and to investigate its effect on the expressions of apoptosis-related molecules including caspase3, bax, and bcl-2. Methods The lentiviral vector containing short hairpin RNA targeting p38MAPK was constructed. The cultured osteoblast MC3T3-E1 cell were divided into 5 groups:normal control group(A group), high glucose group(B group), p38MAPK-shRNA transfection group(C group), signal transduction inhibitor group(D group), and transfection with negative control siRNA group(E group). RT-PCR was used to determine the p38MAPK mRNA expression levels in MC3T3-E1 cells. Flow cytometry(FCM)was employed to detect the cell apoptotic percentage. The protein levels of apoptosis-related molecules p38MAPK, p-p38MAPK, caspase-3, bax, and bcl-2 were assayed by Western blot. Ultrastructural alternation of MC3T3-E1 cell was observed under transmission electron microscopy(TEM). Results The lentiviral vector containing short hairp in RNA targeting p38MAPK was successfully constructed and transfected into MC3T3-E1 cells. RT-PCR result suggested that the siRNA targeting p38MAPK could effectively reduce the p38MAPK mRNA expression level induced by high glucose in MC3T3-E1 cell line. FCM showed siRNA significantly decreased high glucose-induced apoptosis percentage of MC3T3-E1 cells(P＜0.01). Meanwhile, we also found the siRNA significantly attenuated the proteins levels of p38MAPK, p-p38MAPK, caspase-3, and gene bax induced by high glucose in MC3T3-E1 cells, whereas the protein level of gene bcl-2 was enhanced remarkably when compared with high glucose group and negative control siRNA group(P＜0.01, P＜0.05).Conclusion The iRNA targeting p38MAPK suppressed high glucose-induced MC3T3-E1 cell apoptosis via inhibiting the activation of p38MAPK signaling pathway, thereby reducing the expressions levels of p-p38MAPK, caspase-3 and gene bax, and up-regulating the level of gene bcl-2.

Objective To investigate the effect of chronic intermittent hypoxia(CIH)on the cardiovascular system in anesthetized rats. Methods A totally of 72 male SD rats were randomly divided into three groups(n=24),namely the ormoxia control group(control group), the normoxia anesthesia group(model group)and the chronic intermittent hypoxia group(CIH group).Rats of the control group breathe nor-mally.The model group was given intraperitoneal injection of 10%hydration with 0.3 mL/kg,and the CIH group was given chronic intermit-tent hypoxic stimulation with 8 h/d in addtion to the model group.The difference of ultrasonic echocardiography data,blood pressure,endothe-lin type-1,and endothelial nitric oxide synthase(eNOS)in rats of the three groups were compared.After 28 days,these rats were sacrificed to observe the changes of myocardial cell structure.Results In the control group,the myocardial morphology was normal,the cells arranged e-venly,and there was no swelling and inflammation.In the model group,the myocardial cells were evenly arranged without hypertrophy and in-flammatory changes.In the CIH group,the myocardial cells in the hypoxic group were not evenly arranged,and hypertrophy,swelling,deform-ation,hyperchromia,and obvious inflammatory changes of the myocardial tissue were observed.In the control group,myocardial cell nucleus and cytoplasm were uniformly arranged,and there was no obvious changes in the model group.On the contrary,myocardial cell morphology changed obviously in the CIH group,with the cell morphology and size of the inhomogeneity increased, and the color of the apoptosis cells changes from light to dark.The tail artery systolic pressure of rats in CIH group was significantly higher than that of the control group and the model group,and the LVEF of CIH group was significantly lower than that of the other two groups(P<0.05).Ultrasound detection value sug-gests that the LVID and left ventricular of rats in the CIH group were slightly larger,and the diastolic function was normal.The LVDs of the model group and the CIH group were both higher than that of the control group with statistically significant difference(P<0.05).The RBC, HCT,dp/dtmax,and -dp/dtmax in the CIH group were significantly higher than those of the control group and the model group(P<0.05). Serum levels of endothelin-1 in CIH group were significantly higher than that of control group and model group,while the summation of serum NO2-/NO3-and eNOS in CIH group were significantly lower than those of the control group and the model group(P<0.05).Conclusion Chronic intermittent hypoxia can cause cardiac dysfunction in anesthetized rats,which may lead to the imbalance of serum endothelin-1 and NO levels,leading to endothelial dysfunction and myocardial injury.

OBJECTIVE: MicroRNAs (miRNAs) play a vital role in pathogenesis and progression of many cancers, including cervical cancer. However, importance of serum level of miR-101 in cervical cancer has rarely been studied. In the present study, clinical significance and prognostic value of serum miR-101 for cervical cancer was investigated. METHODS: Association between miR-101 level in cervical cancer tissues and prognosis of patients was analyzed by using data retrieved from The Cancer Genome Atlas (TCGA) database, which was followed with our clinical study in which miR-101 serum level comparison between cervical cancer patients and healthy controls was conducted by real-time quantitative polymerase chain reaction (PCR). RESULTS: TCGA database demonstrated that miR-101 was down-regulated in cervical cancer tissues compared with normal cervical tissues, and univariate Cox regression analysis indicated that decreased miR-101 expression was a highly significant negative risk factor. Similar trend was found in the serum miR-101. Serum level of miR-101 was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4 (p=0.007). The overall survival time of cervical cancer patients with a higher level of serum miR-101 was significantly longer than that of patients with a lower level of serum miR-101. Moreover, multivariate Cox regression analysis indicated that the down-regulated serum level of miR-101 was an independent predictor for the unfavorable prognosis of cervical cancer. CONCLUSION: Serum level of miR-101 is closely associated with metastasis and prognosis of cervical cancer; and, hence could be a potential biomarker and prognostic predictor for cervical cancer.
Carcinoma, Squamous Cell ; Clinical Study ; Disease Progression ; Genome ; Gynecology ; Humans ; Lymph Nodes ; MicroRNAs ; Neoplasm Metastasis ; Obstetrics ; Polymerase Chain Reaction ; Prognosis* ; Risk Factors ; Uterine Cervical Neoplasms*

Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in Gardenia jasminoides Ellis. In the present study, geniposide, crocins, crocin-1 and crocetin were separated from gardenia chromatographically. Then, mice were orally administrated with geniposide (400 mg/kg b.w.), crocins (400 mg/kg b.w.), crocin-1 (400 mg/kg b.w.) and crocetin (140 mg/kg b.w.) once daily for 7 days with CCl4. Hepatoprotective properties were evaluated by biochemical parameters: Administration of geniposide, crocins, crocin-1and crocetin significantly lowered serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in CCl4-treated mice. The reduced glutathione (GSH) levels and antioxidant enzymes (SOD and CAT) activities were also increased by geniposide, crocins, crocin-1 and crocetin. Histopathological examination of livers showed that these components reduced deformability, irregular arrangement and rupture of hepatocyte in CCl4-treated mice. These biochemical results and liver histopathological assessment demonstrated that geniposide, crocetin derivatives and crocetin show comparative beneficial effects on CCl4-induced liver damage via induction of antioxidant defense. Therefore, contents of geniposide and crocetin derivatives should be both considered for hepatoprotective efficacy of Gardenia jasminoides Ellis.
Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Gardenia ; Glutathione ; Hepatocytes ; Iridoid Glycosides ; Liver* ; Mice* ; Rupture

Objective To study the changing trend of prevalence rates of healthcare-associated infection (HAI) and antimicrobial use in hospitalized patients in medical institutions of Hubei Province,and provide a scientific basis for improving HAI management.Methods The cross-sectional survey results of HAI in Hubei Province in 2010, 2012,and 2014 were analyzed.Results The prevalence rates of HAI in 2010,2012,and 2014 were 3.48%(1526/43909),3.03%(1919/63320),and 2.86%(2174/76145)respectively,which showed a downward trend,differ-ence was statistically significant(χ2 =36.44,P <0.01).Antimicrobial usage rate decreased from 54.29% (23838/43909)in 2010 to 41.02% (31238/76145)in 2014,difference was statistically significant(χ2 =2194.09,P <0.01).Among patients receiving therapeutic use of antimicrobial agents,the specimen detection rate increased from 30.49% (4297/14091)in 2010 to 52.13% (10556/20248)in 2014 (χ2 =1593.98,P <0.01).Conclusion The prevalence rate of HAI showed a downward trend in Hubei Province,cross-sectional survey on antimicrobial use showed a gradual decrease.

Objective: To determine the contribution of follow-up formula (FUF) to the nutrient intake of 7-24-month-old infants and young children. Methods: The cluster random sampling method and the convenience sampling method were used in combination, and geographic and economic factors were taken into consideration. Four areas of China (Beijing, Hebei, Guangxi, Guangdong) were selected, with 120 infants chosen from each of these areas (half of which were 7-12 months old, and half were 13-24 months old). A dietary survey was completed by a continuous 24-hour weighing method over two days. Questionnaires were completed by their caregivers which included weighing the FUF and supplementary food given to the infant, and recording the frequency of breast feeding and any supplementary nutrients. A total of 518 questionnaires were distributed, and 472 questionnaires qualified for inclusion. Nutrient intake was calculated using the China food composition, infant formula food nutrient content and infant nutrition supplement brand-label information databases, and then the nutrient intake proportion (the percentage of estimated energy requirement (EER%), recommended nutrient intake (RNI%) or adequate intake (AI%)), and the contribution rate of FUF were analyzed. Results: A total of 472 infants were investigated (227 infants aged 7-12 months old, 245 infants aged 13-24 months old). The findings revealed that the median energy intake of 7- 12-month-old and 13- 24-month-old infants were 2 530.08 kJ and 3 445.48 kJ, respectively, which accounted for 85.18% and 94.14% of EER, respectively; and the median intake of protein reached 91.50% and 105.88% of their RNI/AI, respectively. For micronutrients, the median intake of vitamin B₁, vitamin B₂, niacin, vitamin E, potassium, zinc and manganese in 7- 12-month-old infants and vitamin B₂, vitamin E, potassium, magnesium, iron and manganese in 13-24-month-old children accounted for 82.00% and 114.29% of RNI/AI (RNI%/AI%), respectively. The intake of vitamin B₆, iron and selenium in 7-12-month-old infants and vitamin B₁, vitamin B₆, vitamin C, calcium and selenium in 13-24-month-old children was less than 80% RNI/AI. Furthermore, some nutrients showed higher intake levels, such as vitamin A, calcium, phosphorus and magnesium in 7-12-month-old infants and vitamin A and phosphorus in 13-24-month-old children, which were higher than 130% RNI/AI. In total, 40.53% (92) of infants aged 7-12 months and 52.65% (129) of children aged 13- 24 months were fed FUF as part of their diet, and its contribution rate to macronutrients was 29.69% for carbohydrates and 51.77% for fats, and to micronutrients was 2.04% for manganese and 74.24% for vitamin C. Conclusion FUF contributes to the nutrient intake of infants and young children aged from 7-24 months old at different rates depending on the macronutrient or micronutrient analyzed.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a key process in determining distant metastasis and intra-hepatic dissemination of hepatocellular carcinoma (HCC). Follistatin (FST) family members are considered to be an attractive therapeutic targets and prognostic indicators in cancers. As a derivative of FST, Follistatin Like 5 (FSTL5) may play a similar role in HCC cells. This study aimed to investigate the expression and function of FSTL5 in HCC and its role in EMT. METHODS: FSTL5, E-cadherin and vimentin in HCC, and paracancerous tissues were detected by immunohistochemistry. Correlation of FSTL5 expression with overall survival was assessed. The proliferation and invasion of HCC cell lines SK-Hep1 and MHCC-LM3 were analyzed by cell counting kit-8 and Transwell assays. The expression of FSTL5, E-cadherin, and vimentin in HCC cells was examined by polymerase chain reaction and Western blot analysis. T-test was used to analyze the difference in proliferation and invasion ability between groups. The Spearman rank correlation test was used to detect the correlation between the expression of FSTL5 and E-cadherin or vimentin. RESULTS: The expression of FSTL5 in HCC was lower than that in paracancerous tissues (9.97% vs. 82.55%, χ = 340.15, P < 0.001). Patients with high FSTL5 expression had a better prognosis (χ = 8.22, P = 0.004) and smaller tumor diameter (χ = 45.52, P < 0.001), less lymph node metastasis (χ = 5.58, P = 0.02), earlier tumor node metastasis stage (χ = 11.29, P = 0.001), a reduced number of tumors (χ = 5.05, P = 0.02), lower alpha-fetoprotein value (χ = 24.36, P < 0.001), more probability of hepatitis carrying (χ = 40.9, P < 0.001), and better liver function grade (χ = 5.21, P = 0.02). Immunohistochemistry showed that FSTL5 expression in HCC tissues was positively correlated with E-cadherin expression (r = 0.38, P < 0.001) and negatively correlated with vimentin expression (r = -0.385, P < 0.001). Furthermore, over-expression of FSTL5 up-regulated the expression of E-cadherin and down-regulated the expression of vimentin in SK-Hep1 (negative control [NC] vs. FSTL5-interfering group [Lv-FSTL5]: E-cadherin [t = 45.03, P < 0.001], vimentin [t = 67, P < 0.001]) and MHCC-LM3 (NC vs. Lv-FSTL5: E-cadherin [t = 50, P < 0.001], vimentin [t = 72.75, P < 0.001]) cells at mRNA level. The same as protein level. In addition, the over-expression of FSTL5 inhibited the proliferation (NC vs. Lv-FSTL5: SK-Hep1, 3 d [t = 7.324, P = 0.018], 4 d [t = 6.23, P = 0.021], 5 d [t = 10.21, P = 0.003]; MHCC-LM3, 3 d [t = 4.32, P = 0.037], 4 d [t = 7.49, P = 0.012], 5 d [t = 9.3661, P = 0.009]) and invasion (NC vs. Lv-FSTL5: SK-Hep1, t = 21.57, P < 0.001; MHCC-LM3, t = 18.04, P < 0.001) of HCC cells. CONCLUSIONS Down-regulation of FSTL5 may contribute to EMT of HCC, and FSTL5 is a potential target in the treatment of HCC.