PURPOSE: To investigate the effect of ultra low molecular weight heparin (ULMWH) on glutamate induced apoptosis in rat cortical cells and to explore the possible mechanisms. MATERIALS AND METHODS: Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was first analyzed with Hoechst 33258 and then confirmed by DNA fragmentation. The concentration of free intracellular calcium ([Ca2+](i)) was determined with fura-2/AM fluorometry. The expression of Bcl-2 family protein and caspase-3 were evaluated with Western blot. RESULTS: Typical apoptotic morphological change in rat cortical cells treated with 100micromol/L glutamate for 24h was detected by Hoechst 33258 staining, which was then confirmed by the DNA ladder of agarose gel electrophoresis. The apoptotic rate of the glutamate treated cells was up to 33.21%, and 24 h of treatment with glutamate increased [Ca2+](i), down-regulated Bcl-2 expression, up-regulated Bax expression, and increased caspase-3 activation in rat cortical cells. Our research demonstrated that ULMWH pretreatment can prevent the glutamate- induced apoptosis, attenuate the increase of [Ca2+](i) not only in medium containing Ca2+ but also in Ca2+-free medium, up-regulate the expression of Bcl-2, down-regulate the expression of Bax, and decrease caspase-3 activation. CONCLUSION: ULMWH has neuroprotective capacity to antagonize glutamate-induced apoptosis in cortical cells, through decrease of Ca2+ release and modulation of apoptotic processes.
Animals ; Apoptosis/*drug effects ; Blotting, Western ; Calcium/metabolism ; Caspase 3/metabolism ; Cell Survival/drug effects ; Cells, Cultured ; Cerebral Cortex/cytology ; DNA Fragmentation/drug effects ; Glutamic Acid/*pharmacology ; Heparin, Low-Molecular-Weight/*pharmacology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein/metabolism

OBJECTIVEThis study was to clarify E-cadherin expressions in non-small cell lung cancer (NSCLC) and its correlation with patients' prognosis.

METHODSTissue microarrays (TMAs) containing specimens from 365 different NSCLC were constructed, covering all stages and almost all histological types of this disease. Slides were immunohistochemically stained with antibodies against E-cadherin. Expression pattern of the protein was analyzed with relation to the clinicopathological. Correlations of the results with patients' overall survival were also examined.

RESULTSImmunohistochemical staining revealed that E-cadherin protein was localized mainly on membranes and the cytoplasm of NSCLC tumors cells. Reduced E-cadherin expression was evident in 32.1%. Reduced E-cadherin expression significantly correlated with lymph nodes metastasis (chi(2) = 16.430, P = 0.001), histological dedifferentiation (chi(2) = 9.243, P = 0.010) and advanced clinical stage (chi(2) = 9.421, P = 0.024). There was no significant difference in E-cadherin expression between squamous cell carcinoma and adenocarcinoma. E-cadherin reduced expression correlated with a poor prognosis (P < 0.0001) in univariate analysis. Multivariate analysis showed a significantly lower survival probability for patients with reduced E-cadherin (P < 0.001), and E-cadherin was an independent prognostic factor for survival of NSCLC patients.

CONCLUSIONSIt suggests that dysfunction of E-cadherin has an important impact in the progression of lung cancer. As an independent prognostic factor, expression of E-cadherin can predict outcome of different group, together with conventional prognostic factors, and subsequently make appropriate management.

Adult ; Aged ; Aged, 80 and over ; Cadherins ; biosynthesis ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; secondary ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; mortality ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate

To explore the effects of crude toxins from Colletotrichum gloeosporioides(C. gloeosporioides)on the growth of Dendrobium officinale Kimura et Migo(D. officinale),and to provide early basis for thescreening and cultivation of the resistant variants of C. gloeosporioides. Methods Seedlings of D. officinal werecultivated in MS medium added with different concentrations of the crude toxins from C. gloeosporioides. Theeffects of the crude toxin on the growth of seedlings were observed, and the optimum resistance -selectionthreshold was preliminarily screened. Results In the concentration range of 5％ - 15％(volume fraction),crudetoxins from C. gloeosporioides increased the plant height,stem diameter,number of new bud,root number,and fresh mass of D. officinale,among which the effect of 5％(volume fraction)of crude toxins was the moststrongest. In the concentration range of 35％ - 40％(volume fraction),crude toxins suppressed the plant height,leaf number,number of new bud,root number,and the fresh mass of D. officinale. When cultured with 20％(volume fraction)crude toxins, D. officinale was blooming, and the flowers appeared variation phenomenon.Conclusion The crude toxins from C. gloeosporioides have biological activity and certain toxicity,which can beconsidered as a selection agent instead of pathogenin in vitro to screen the resistant variant of D. officinale,butthe optimum resistance-selection threshold still needs further research.

Aim To investigate the protective roles of sonic hedgehog( Shh) signaling pathway in hypoxia-in-duced DNA damage with the neonatal rat cardiomyo-cytes. Methods The hypoxia model on neonatal car-diomyocytes was established with one to two days old Sprague Dawley rats by deprivation of oxygen and glu-cose ( OGD) . After pretreated with Shh pathway ago-nist SAG1.3 or antagonist GANT61, the survival rates of cardiomyocytes were assayed by MTT after OGD 6 hours or 12 hours. The protein levels of Shh pathway, phosphorylated histone H2AX at serine 139 (γH2AX), phosphorylated ATM (p-ATM), phospho-rylated p53 ( p-p53 ) , cleaved-caspase-3, Bcl-2 and Bax were detected by Western blot. The γH2AX foci was detected by immunofluorescence. Results Com-pared to control group, the protein expression of γH2AX, p-ATM, cleaved-caspase-3, p-p53 in OGD cardiomyocytes significantly increased, and Bcl-2/Bax ratio proportionally decreased. Particularly, the ex-pression of γH2AX, p-ATM was highest at OGD 6 h, and then gradually declined after OGD 12 h. After SAG1.3 pretreatment, the expression of γH2AX, p-ATM, cleaved-caspase-3 and p-p53 dramatically de-creased and the Bcl2/Bax ratio increased in OGD 6 h or OGD 12 h cardiomyocytes. On the contrary, in GANT61 pretreatment group, the expression of γH2AX, p-ATM, cleaved-caspase-3 and p-p53 signifi-cantly increased and the Bcl-2/Bax ratio decreased compared to the OGD 6 h or OGD 12 h cardiomyo-cytes. Conclusion The activation of Shh pathway protects cardiomyocytes against hypoxia-induced apop-tosis through inhibition of DNA damage.

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

OBJECTIVETo explore the associations between sugar-sweetened beverage (SSB) consumption and obesity as well as obesity-related cardiometabolic disorders among children in China.

METHODSA total of 6974 (boys 3558, girls 3412) children aged 6-13 years participated in the study. Each participant's height, weight, waist circumference, fasting glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. The type of beverage consumption was determined using a self-administered questionnaire.

RESULTSSSBs were consumed regularly by 46.1% of the children. The prevalence [adjusted odds ratio (95% confidence internal (CI)] of obesity was 7.6% [as the reference group (ref.)], 10.1% [1.36(1.07, 1.74)], and 11.6% [1.46(1.21, 1.75)], among children who regularly drank milk, other beverages and SSBs, respectively. Regularly drinking SSBs elevated the likelihood of abdominal obesity [adjusted odds ratio (95% CI): 1.36 (1.17, 1.59)]. The prevalence [adjusted odds ratio (95% CI)] of obesity among children who regularly drank sports/caloric beverages, carbonated beverages, sweet tea, and plant protein beverages was 16.8% [2.00(1.31, 3.07)], 12.7% [1.52(1.23, 1.88)], 11.5% [1.52(1.18, 1.95)], and 10.4% [1.41(1.03, 1.94)], respectively, which was higher than that of regular milk drinkers [7.6 % (ref.)]. The prevalence [adjusted odds ratio (95% CI)] of abdominal obesity among children who regularly drank sweet tea, fruit/vegetable juices, and carbonated beverages was 17.7% [1.55(1.26, 1.90)], 16.2% [1.36(1.09, 1.70)], and 15.3% [1.24(1.03, 1.50)], respectively, which was much higher than that of regular milk drinkers [12.8% (ref.)].

CONCLUSIONSRegular SSB consumption was positively related to obesity and abdominal obesity. This relationship should be investigated further using a longitudinal study design.

Adolescent ; Anthropometry ; Beverages ; Blood Pressure ; Child ; China ; epidemiology ; Female ; Humans ; Male ; Obesity ; epidemiology ; Sweetening Agents

OBJECTIVETo explore a suitable model regarding community-based case management of hypertension in the urban areas.

METHODSBased on the guidelines set by the Chinese Hypertension League (CHL), the goal of case management of hypertension was set as: to maintain blood pressure at the normal range. Family doctors were guided to take care of case management. Hypertension patients who had been contracted to the family doctors were followed by a team of family doctors for half a year.

RESULTSAfter the 6-month intervention, the rate of hypertension under control had increased from 50.44% to 69.84% (P < 0.0001) while the means of systolic blood pressure decreased by 3.72 mm Hg and diastolic blood pressure decreased by 2.67 mm Hg (P < 0.0001) respectively. The means of SBP decreased by 8.59 mm Hg and diastolic blood pressure decreased by 5.26 mm Hg in patients whose baseline blood pressure were not under control. The rates of smoking, higher salt intake and no physical exercise had significantly decreased (P < 0.05). The mean number of hospital visits in the six-month follow-up period was 7.69 +/- 2.37. The "rate of control" among those who had followed schedule was higher than that of those who were not on schedule (P < 0.0001). The rate among those who had followed the schedule tended to have increased with aging and the level of education (P < 0.001).

CONCLUSIONThe community-based case management program on hypertension played an important and effective role in the control of hypertension in urban areas. Patients received great benefit when following the guidance from their doctors.

Aged ; Case Management ; organization & administration ; China ; epidemiology ; Community Health Services ; organization & administration ; Evaluation Studies as Topic ; Female ; Humans ; Hypertension ; epidemiology ; Male ; Middle Aged ; Urban Health

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Objective:To investigate whether the therapeutic effect of Dahuang Mudan Tang on septic acute intestinal dysfunction in sepsis ratsis related to the regulation of expression of triggering receptor expressed on myeloid cells-1(TREM-1). Method:Totally 100 male SD rats were injected intraperitoneally with lipopolysaccharide (LPS) at a dose of 4.5 mg·kg^-1 to build sepsis model. The sepsis model rats were randomly divided into five groups:model group, glutamine group (3.75 g·kg^-1),low,medium, high-dose Dahuang Mudan Tang group(7.5,15,30 g·kg^-1),and another 10 normal rats were selected as normal group. Seven days later,2 mL suspension (100 mg lactulose and 50 mg mannitol) was orally administrated by gavage, and 24 h urinewas collected. The ratio of lactulose to mannitol in urine (L/M) was detected by HPLC with pulsed electrochemical detection (HPLC-PED).Serum citrulline concentrationsin blood and ileum were determined by HPLC.Enzyme linked immunesorbent assay (ELISA) was used to detect the concentrations of triggering receptor expressed on myeloid cells-1(TREM-1),tumor necrosis factor-α(TNF-α),intestinal fatty acid binding protein(iFABP) and D-lactic acid.Real-time PCR was used to detect the mRNA expressions of TREM-1,Toll-like receptors2(TLR2),Toll-like receptors 4(TLR4),myeloid cell differentiation protein(MyD88),nuclear transcription factor-κB(NF-κB).Electron microscopy was used to observe the pathological changes of intestinal mucosa injury. Result:Compared with normal group, the serum concentrations of TREM-1,TNF-α,iFABP, D-lactate; the ratio of lactulose to mannitol in urine (L/M)and the expressions of TREM-1,TLR2,TLR4,MyD88,NF-κB mRNA in model group were increased obviously(P<0.05,P<0.01); citrulline concentration was decreased obviously(P<0.05);the lengths of the villus and thicknesses of the mucosal layer were decreased obviously(P<0.05);the Chiu score was increased obviously(P<0.01).Compared with model group,the expressions of TREM-1,TLR2,TLR4,MyD88,NF-κB mRNA,and the serum concentrations of TREM-1 and TNF-α in all medication administration groups were decreased obviously(P<0.05), with no difference between these groups.Compared with model group, the serum concentrations of iFABP, D-lactate, L/M, the Chiu scorein glutamine group, medium-dose Dahuang Mudan Tang group and high-dose Dahuang Mudan Tang group were decreased obviously(P<0.05), lengths of villus and thicknesses of mucosal layers were increased obviously(P<0.05); and the citrulline concentrations were increased obviously(P<0.05). There was no difference between the three groups. Conclusion:Dahuang Mudan Tang can effectively treat SAID in rats, and its mechanism may be realized by regulating the expression of TREM-1 and relieving intestinal inflammation of intestinal tract.

OBJECTIVE: To explore the expression and clinical significance of chemokine CXCL10 and CXCR3 in hepatocellular carcinoma (HCC). METHODS: The expression and prognostic of CXCL10 and CXCR3 in HCC tumor tissues and non-tumor tissues were analyzed in two different publicly available databases the Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI). In addition, quantitative real-time PCR (qPCR) was used to detect the mRNA expression of CXCL10 and CXCR3 in 45 HCC clinical samples with HBV infection background. Pearson correlation and Spearman rank correlation were used to determine the correlation between the expression level of CXCL10 and CXCR3 in tumor and non-tumor tissues. RESULTS: In TCGA database, the expression of CXCL10 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: 3.379±2.081 vs. 2.213±2.274, P<0.001; paired samples: 3.159±2.267 vs. 2.213±2.274, P=0.018). Similarly in LCI datebase (7.625±1.683 vs. 7.287±1.328, P=0.009). And higher CXCL10 expression was significantly associated with a better prognosis in the patients with HCC both in TCGA and LCI database (P=0.107, P=0.002). In TCGA database, the expression of CXCR3 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: -0.906±1.697 vs. -1.978±1.629, P<0.001; paired samples: -1.329±1.732 vs. -1.978±1.629, P=0.037), while lower in LCI database (3.989±0.339 vs. 4.074±0.309, P=0.003). In both databases, higher CXCR3 expression was significantly associated with a better prognosis in the HCC patients (P=0.004, P=0.014). Furthermore, in TCGA database, the expression level of CXCL10 and CXCR3 was positively correlated both in HCC tumor tissues and matched non-tumor tissues (r=0.584, P<0.001; r=0.776, P<0.001). The qPCR assay showed that the expression of CXCL10 in HBV-related HCC tumor tissues was significantly higher than those in normal liver tissues [0.479(0.223, 1.094) vs. 0.131(0.106, 0.159), P=0.010], and the expression in HBV-related non-tumor tissues was also significantly higher than those in normal liver tissues [0.484(0.241, 0.846) vs. 0.131(0.106, 0.159), P<0.001]. The same was true as CXCR3 [0.011(0.006, 0.019) vs. 0.002(0.001, 0.004), P=0.004; 0.016(0.011, 0.021) vs. 0.002(0.001, 0.004), P<0.001]. However there was no significant difference of CXCL10 and CXCR3 between tumor tissues and matched non-tumor tissues (P=1.000, P=0.374). CONCLUSION Expression of CXCL10 was up-regulated in HCC tissues, expression of CXCR3 was down-regulated in HBV-related HCC tissues, and the higher expression of both genes was correlated with better overall survival in HCC patients.
Adult ; Carcinoma, Hepatocellular/metabolism* ; Chemokine CXCL10/metabolism* ; Humans ; Liver Neoplasms/metabolism* ; Prognosis ; Receptors, CXCR3/metabolism*