Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; drug therapy ; Male ; Practice Guidelines as Topic ; Prognosis

The experience of bug's growing and accumulated temperatures were important ways for determination of postmortem interval in forensic science. Here we used reverse accumulated temperature methods to estimate postmortem interval and made accordant result with their true time.
Adult ; Animals ; Cadaver ; Cause of Death ; Entomology ; Female ; Forensic Pathology/methods* ; Humans ; Larva/growth & development* ; Life Cycle Stages ; Muscidae/physiology* ; Postmortem Changes ; Temperature ; Time Factors

OBJECTIVE： To investigate estrogen-like effect of tetrahydroxy stilbene glucoside （TSG） and its effects on the expression of estrogen receptor （ER） in uterus of sexually immature mice. METHODS： Totally 60 sexually immature Kunming mice were randomly divided into normal group， positive control group （estradiol valerate， 0.18 mg/kg）， TSG low-dose and high-dose groups （50， 150 mg/kg）， TSG low-dose and high-dose groups+estradiol valerate groups （same dose as medication alone group）. Normal group was given constant volume of water intragastrically， and administration groups were given relevant medicine 0.2    mL/10 g， once morning and night， for consecutive 5 d. The uterus index and body weight increase of mice in each group were determined and calculated the next day after the last administration. The contents of serum estrogen （E2， LH， FSH） were determined by ELISA. HE staining was used to observe the morphology characteristics of uterus， and uterine tube diameter and endometrial thickness were detected. The expression of ER（ER-α and ER-β） in uterus was detected by immunohistochemical staining. RESULTS： The myometrium of the mice in normal group was parallel and compact， the epithelium of the uterus was columnar， and the expression of ER-α and ER-β was low. The uterine tube diameter， endometrium and epithelium of mice in each administration group increased， thickened or proliferated in varying degrees， and the expression of ER-α and ER-β changed. Compared with normal group， uterus indexes （positive control group， TSG high-dose group， TSG+estradiol valerate groups）， the increase of body weight （positive control group， TSG high-dose groups， TSG low-dose+estradiol valerate group）， uterine tube diameter and endometrial thickness （positive control group， TSG low-dose group， TSG+estradiol valerate groups）， the expression of ER-α （positive control group， TSG+estradiol valerate groups） and the expression of ER-β （postive control group， TSG high-dose+estradiol valerate group）were increased significantly， while serum contents of LH （positive control group， TSG high-dose group） and FSH （TSG low-dose+estradiol valerate group） were decreased significantly （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression in ER-α and ER-β of TSG+estradiol valerate groups， the increase of body weight and serum content of E2 in TSG low-dose+estradiol valerate group were significantly higher than same TSG dose alone groups （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression of ER-α and ER-β in TSG groups， uterine tube diameter and the expression of ER-β in TSG+estradiol valerate groups， body weight increase of mice in TSG low-dose group were significantly lower than positive control group， while serum content of LH in TSG+estradiol valerate groups were significantly higher than positive control group （P＜0.05 or P＜0.01）. CONCLUSIONS： TSG can increase uterus indexes and body weight of sexually immature mice to certain extent， regulate estrogen level， increase the diameter of uterine tube and endometrial thickness and up-regulate the expression of ER in the uterus， showing certain estrogen-like effect， which is weaker than that of estradiol valerate. Combined use of them may antagonize the effect of estradiol valerate.

This paper aimed to investigate the effects of Jinwu Jiangu recipe total extract on the IL-17/STAT3 signals in rheumatoid arthritis synovial fibroblasts(RASF). The primary RASFs were cultured by tissue piece method ， and divided into blank control group， Jinwu Jiangu recipe low dose group， Jinwu Jiangu recipe middle dose group， Jinwu Jiangu recipe high dose group， and tripterygium glycosides control group. They were then treated with corresponding serum free medium， different doses of Jinwu Jiangu recipe total extract(0.06， 0.6， 6.0 g·L⁻¹)， and tripterygium glycosides(0.03 g·L⁻¹) respectively for 24 hours. The gene expression levels of RORα， RORγt， and STAT3 mRNA were detected by polymerase chain reaction(PCR)， and the protein activity of IL-17R and pSTAT3 were measured by Western blot assay. The results showed that as compared with blank control group， the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA in RASF were significantly declined(<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe total extract middle dose group and high dose group can down-regulate the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA(<0.05)， and the effect was more obvious in high dose group(<0.01). As compared with blank control group， the protein expression levels of IL-17R and pSTAT3 in each treatment group were obviously decreased(<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe high dose group had more obvious effect in down-regulating the protein expression of pSTAT3(<0.01). Therefore， Miao medicine Jinwu Jiangu recipe total extract can down-regulate the expressions of RORα， RORγt， and STAT3 mRNA， and inhibit the protein activity of IL-17R and pSTAT3 in RASF.
Arthritis, Rheumatoid ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Fibroblasts ; Gene Expression Regulation ; Humans ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; Receptors, Interleukin-17 ; metabolism ; STAT3 Transcription Factor ; metabolism ; Synovial Membrane ; Synoviocytes ; drug effects

OBJECTIVETo study the expression of connective tissue growth factor (CTGF) mRNA and transforming growth factor beta 1 (TGFbeta1) mRNA in immunity-induced liver fibrosis rats and the effect of HanDanGanLe on them.

METHODSMale wistar rats were given intraperitoneal injection of porcine serum twice a week. At the beginning, the rats in HanDanGanLe-treatment group were feed with HanDanGanLe for precaution. The rats were killed after twelve weeks, then CTGF mRNA and TGFbeta1 mRNA were detected in liver samples with in situ hybridization, and the formation of liver fibrosis was observed with HE stain. The semi-quantitative

RESULTSof the two genes expression were analysed along with the stages of hepatic fibrosis.

RESULTSTypical liver fibrosis developed in the model group rats, and the positive stain of CTGF mRNA and TGFbeta1 mRNA increased, which was distributed in the areas where fibrosis occurred. There was obvious correlation between the expression strength of CTGF mRNA and TGFbeta1 mRNA (r = 0.799, P < 0.05). In the rats receiving HanDanGanLe, CTGF mRNA expression index decreased markedly (12.5+/-2.3 vs 28.8+/-1.4, t = 5.208, P < 0.01), so did TGFbeta1 mRNA expression index (25.4+/-3.2 vs 37.3+/-5.4, t = 5.655, P < 0.01). There was also significant correlation between the scores of CTGF mRNA expression and the stages of hepatic fibrosis (rs = 0.822, 0.808 in the model group and HanDanGanLe-treatment group, P < 0.05).

CONCLUSIONSThe expression of CTGF mRNA and TGFbeta1 mRNA is correlated closely with hepatic fibrosis degree. HanDanGanLe can effectively prevent the expression of CTGF and TGFbeta1. One of the mechanisms of the intervention may be its blocking the intracellular signalling pathways involved in liver fibrogenesis.

Animals ; Connective Tissue Growth Factor ; Drugs, Chinese Herbal ; pharmacology ; Immediate-Early Proteins ; biosynthesis ; genetics ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; genetics ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; metabolism ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Transforming Growth Factor beta1

OBJECTIVETo investigate the relationship between serum sex hormone levels, liver function, and pathogenic mechanisms related to cutaneous lesions involving the facial skin in male patients with liver cirrhosis.

METHODSFifty male cirrhotic patients with facial skin lesions, including spider angiomas, angiotelectasis and special type rash, (mean age: 48.1 +/- 12.2 years) were randomly selected for study and enrolled as the case group. Thirty cirrhotic male patients without facial skin lesions (mean age: 44.5 +/- 11.7 years) were enrolled as the control group. Serum levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), prolactin (PRL), estradiol (E2), progesterone (PRGE), and testosterone (T) were detected and compared between cases and controls by the t-test. All patients were sub-categorized according to severity of cirrhosis (Child-Pugh classification) and comparisons between cases and controls were carried out by single factor analysis of variance. Logistic regression modeling was used to evaluate whether the presence of skin lesions is related to changes in markers of liver impairment, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), serum albumin (Alb), prothrombin time (PT-SEC), creatinine (CREA), platelet count (PLT), and alcoholism.

RESULTSIn the cases with spider veins, LH level was significantly elevated (t = 2.01) and T level was significantly decreased (t = -2.20) (both, P less than 0.05 vs. controls). In the cases with telangiectasia, the LH level (t = 3.76, E2 (t = 2.08) and E2/T ratio (t = 2.98) were significantly elevated and T level was significantly decreased (t = -3.77) (all, P less than 0.05 vs. controls). In the cases with special type rash, FSH level was significantly elevated (t = 2.03) and T level was significantly decreased (t = -2.01) (both, P less than 0.05 vs. controls). In the case group, E2 levels decreased as severity of liver damage increased, while in the control group, E2 levels increased as severity of liver damage increased; however, the difference in average E2 values of the two groups did not reach statistical significance (P more than 0.05). In both cases and controls, the T levels were decreased as the severity of liver damage increased (F = 3.70, P less than 0.05). Multivariate logistic regression analysis showed that increased incidence of facial skin lesions is associated with alcoholism (odds ratio (OR) = 4.46, 95% confidence interval (CI) = 1.45-13.7, P less than 0.05) and elevated serum levels of AST (OR = 11.87, 95% CI = 1.24-113.1, P less than 0.05).

CONCLUSIONAlcoholism, impaired liver function, and perturbed levels of circulating sex hormones are associated with cirrhosis-related facial lesions and may play important roles in the pathogenesis of cutaneous lesions in patients with cirrhosis.

Adult ; Alcoholism ; physiopathology ; Case-Control Studies ; Face ; pathology ; Gonadal Steroid Hormones ; blood ; Humans ; Liver Cirrhosis ; blood ; pathology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Skin ; pathology

OBJECTIVETo investigate the expression of STK15 and P53 proteins in oral precancerous lesions and oral squamous cell carcinoma (OSCC) and elucidate the possible role of P53/STK15 switch activation-independent pathway in oral carcinogenesis.

METHODSFormalin-fixed, paraffin-embedded tissues of 8 cases of normal oral epithelium, 27 cases of dysplasia with different degree epithelium dysplasia and 43 cases of OSCC with different differentiation were investigated for the expression of STK15 and P53 proteins by using immunohistochemistry. The clinical and pathological significance of STK15 over-expression in oral carcinogenesis were statistically analyzed by SPSS 12.0.

RESULTSSTK15 protein was not detectable in normal oral epithelium and significantly altered from mild-dysplasia to OSCC. The percentage of STK15 over-expression were 40.74% (11/27) in dysplasia and 67.44% (29/43) in OSCC (P < 0.05). The percentage of STK15 over-expression in OSCC with positive P53 staining was significantly higher than that in OSCC with negative P53 staining (P < 0.05). STK15 over-expression was significantly associated with regional lymph node involvement (P < 0.05), while no correlation was found for STK15 over-expression and tumor differentiation, as well as TNM stages.

CONCLUSIONSTK15 up-regulation was an early event in oral carcinogenesis. The up-regulation of STK15 protein in OSCC may partly result from p53 mutations, which probably contribute a role in lymph node metastasis of OSCC as well. P53/STK15 switch activation-independent pathway may play some roles in oral carcinogenesis.

Aurora Kinase A ; Carcinogenesis ; Carcinoma, Squamous Cell ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Mouth Neoplasms ; Serine ; Tumor Suppressor Protein p53

OBJECTIVETo elucidate the possible role of p53-p21(waf1) pathway for centrosome amplification in oral squamous cell carcinoma (OSCC).

METHODSFormalin-fixed, paraffin-embedded tissues of 8 cases of normal oral epithelium tissues and 27 cases of OSCC tissues were examined for the expression of p21(waf1) and mutated p53 proteins by flow cytometry and immunohistochemistry, and centrosome status was investigated by indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The correlation between p21(waf1), p53 and centrosome amplification in OSCC was statistically analyzed by SPSS 12.0.

RESULTSAll normal oral epithelium tissues showed normal centrosomes (1-2 centrosomes per cell)in epithelium cells, while 21 out of 27 cases (78%) of OSCC showed the evidence of centrosome amplification characterized by supernumerary centrosomes ( >2 centrosomes per cell) in a fraction of tumor cells. The quantity of p21(waf1) protein was lower in OSCC with centrosome amplification [(0.878 +/- 0.081)] than that in OSCC without centrosome amplification [(0.952 +/- 0.018), t = 3.838, P < 0.01], and negative correlations were found between the quantity of p21(waf1) protein and the degree of centrosome amplification (r = -0.472, P < 0.05), as well as the positive staining of p53 (r = -0.491, P < 0.01).

CONCLUSIONSp53-p21(waf1) pathway might involve in centrosome duplication cycle in OSCC. Down-regulated p21(waf1) protein, via p53 transactivation-dependent mechanism, was likely a contributing factor towards centrosome amplification in OSCC.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Centrosome ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Humans ; Mouth Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVETo study the protective effects of blueberry against rat immune hepatic fibrosis, specifically through the expression of hepatic cytochrome P450 2E1.

METHODFifty Wistar rats were randomly divided into five study groups (n = 10 each): Group A: normal control group, Group B: hepatic fibrosis model group, Group C: preventive group administered blueberry juice, Group D: preventive group administered Fu-Fang-Bie-Jia-Ruan-Gan tablet, and Group E: preventive group administered a combination of blueberry juice and Fu-Fang-Bie-Jia-Ruan-Gan tablet. The hepatic fibrosis model was established by intraperitoneal injection of porcine serum once daily for 12 weeks. Simultaneously, rats in preventive groups (Groups C-E) were perfused with blueberry juice or Fu-Fang-Bie-Jia-Ruan-Gan tablet or combinations of blueberry juice and Fu-Fang-Bie-Jia-Ruan-Gan tablet, respectively, for 12 weeks. The normal control group was perfused with saline for 12 weeks. All animals were sacrificed at the end of the 12 weeks, and serum levels of alanine aminotransferase (ALT) were measured and activities of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (Hyp) in liver homogenates were determined. Pathology of hepatic fibrosis was evaluated by hematoxylin-eosin (HE) and Masson staining. Expression of CYP2E1 was detected by real-time RT-PCR, immunohistochemical techniques, and Western blotting.

RESULTSSerum ALT levels were not significantly different in the control and treatment groups (F=4.056, P more than 0.05): A: 37.87+/-4.53 U/L, B: 49.23+/-9.81 U/L, C: 39.94+/-6.32 U/L, D: 40.50+/-5.70 U/L, and E: 38.24+/-8.43 U/L. Compared with Group B, the pathological stages of hepatic fibrosis were significantly reduced in the prevention groups (C-E) (F=95.097, P less than 0.05). Hyp and MDA in liver homogenates of groups C-E were significantly lower than those of Group B (Hyp: C: 472.68+/-44.14 mug/g, D: 416.12+/-39.38 mug/g, E: 429.51+/-55.14 mug/g vs. B: 603.16+/-68.92 mug/g, F=39.315, P less than 0.05; MDA: C: 0.83+/-0.06 nmol/mg, D: 0.96+/-0.08 nmol/mg, E: 0.85+/-0.06 nmol/mg vs. B: 1.24+/-0.15 nmol/mg, F=46.376, P less than 0.05). In contrast, SOD activities in Group C-E were significantly higher than those in Group B (C: 2.47+/-0.38 U/mg, D: 1.95+/-0.45 U/mg, E: 2.16+/-0.23 U/mg vs. B: 1.56+/-0.41 U/mg, F=25.557, P less than 0.05). Compared with Group A, the mRNA and protein expressions of CYP2E1 were increased in groups B-E, however the differences did not reach statistical significance (mRNA: F=0.897, protein: F=0.492, both P more than 0.05). The mRNA and protein expressions of CYP2E1 in groups C-E were lower than those of Group B, however the differences did not reach statistical significance (mRNA: F=0.897, protein: F=0.492, P more than 0.05).

CONCLUSIONBlueberry exhibits certain protective effects against porcine serum-induced hepatic fibrosis in rats. The expression of hepatic cytochrome P450 2E1 in rats with immune hepatic fibrosis is not significantly different from the normal rats. Blueberry has no effect on the expression of hepatic cytochrome P4502E1.

Animals ; Blueberry Plants ; Cytochrome P-450 CYP2E1 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fruit ; Immune System Diseases ; metabolism ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

Objective: To investigate the inhibitory effect of leonurine on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and its effect on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and miRNA-1.Method: Cardiomyocyte hypertrophy was induced by Ang Ⅱ (0.1 μmol·L^-1) in primary neonatal cardiomyocytes. Experiments were designed in 6 groups as following:normal group, model group, p38 MAPK inhibitor group (SB203580, 10 μmol·L^-1), low-dose(5 μmol·L^-1), middle-dose(10 μmol·L^-1) and high-dose(20 μmol·L^-1) group. The cardiomyocyte surface area was measured by image software, and the protein contents were detected by Lowry. The concentrations of ANP in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The expression level of miRNA-1 was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expression levels of endothelin-1 (ET-1), p38 MAPK, p-p38 MAPK, myocyte enhancer factor 2 (MEF2), β-myosin heavy chain (β-MHC), α-myosin heavy chain (α-MHC) were detected by Western blot.Result: Compared with normal group, the surface area of cardiomyocyte, the protein contents, the concentrations of ANP, and the protein expression levels of ET-1, p38 MAPK, p-p38 MAPK, MEF2, β-MHC in model group were higher (P<0.05), but the protein expression levels of α-MHC and miRNA-1 were lower than those in normal group (P<0.05). Compared with model group, the surface area of cardiomyocyte, the protein contents, the concentrations of ANP, and the protein expression levels of ET-1, p38 MAPK, p-p38 MAPK, MEF2, β-MHC in high-dose group were lower (P<0.05), but the protein expression levels of α-MHC and miRNA-1 were higher than those in model group (P<0.05).Conclusion: Leonurine (20 μmol·L^-1) could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and the mechanism is related to the inhibition of activation of p38 MAPK signaling pathway and up-regulation the expression of miRNA-1.