Research progress on the association between childhood obesity and pubertal timing / 中国学校卫生

Abstract@#With the increasing prevalence of overweight and obesity in children, the influence of overweight and obesity on pubertal timing has attracted the attention of scholars. This paper reviewed the correlation and mechanism between childhood obesity and pubertal timing, especially for earlier pubertal timing, and found that the regulation of hypothalamic-pituitary-gonadal axis function by nutrition and metabolic signals might under lie those associations. Obesity in girls was positively correlated with early pubertal timing, while the conclusions in boys were inconsistent. Overweight in boys was related to early pubertal timing, obesity in boys could lead to both earlier and later onset of puberty, which warrents further investigation.

Relationship between high blood pressure and body mass index, waist circumference, and waist-height ratio among children and adolescents in Suzhou / 中国学校卫生

@#To assess the relationship between high blood pressure (HBP) and body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR) among children and adolescents in Suzhou.@*Methods@#A total of 3 150 children and adolescents aged 7-17 years were enrolled through stratified cluster sampling from September to October, 2019. Questionnaire survey was conducted, and height, weight, WC and BP were measured to calculate BMI and WHtR, relationship of HBP and adiposity indicators were evaluated.@*Results@#The prevalence of HBP was 11.3%, overweight/obesity rate was 28.5%, and centrality obesity based on WC and WHtR was 20.6% and 23.7%, respectively. There were significant relationships between HBP and BMI, WC, and WHtR (χ2=157.80,105.87,124.17,P<0.01). As Logistic regression showed, compared to normal weight group, overweight/obesity based on BMI had positive relation with HBP (OR=3.89, 95%CI=3.09-4.90); compared to normal WC/WHtR, centrality obesity showed positive association with HBP (WC: OR=3.05, 95%CI=2.41-3.86; WHtR: OR=3.35, 95%CI=2.67-4.21). Meanwhile, BMI had joint effects on HBP with WC/WHtR. Specifically subjects with overweight/obesity and center obesity had higher risk of HBP, compared to normal BMI and WC subjects(OR=4.28, 95%CI=3.31-5.53).@*Conclusion@#Significant relationships between HBP and BMI, WC, and WHtR were found. BMI had joint effects on HBP with WC/WHtR. Keeping normal body weight and WC/ WHtR would have significant effects on HBP.

Effects of the Chinese herbal extract Songyou Yin on the residual hepatocellular carcinoma after chemotherapy in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of a Chinese herbal extract Songyou Yin on residual hepatocellular carcinoma after chemotherapy in nude mice and the relevant mechanisms.</p><p><b>METHODS</b>Orthotopic nude mouse models bearing residual hepatocellular carcinoma after chemotherapy was established using human liver carcinoma MHCC97L cells. Three different doses of Songyon Yin (2.1 g/kg, 4.2 g/kg and 8.4 g/kg) were administered to the mice in the trial groups by intragastric gavage, respectively. The mice in the control group were administered physiological saline. The tumor growth, metastasis and survival in the mice of each group were recorded. The corresponding mechanisms were studied.</p><p><b>RESULTS</b>The pulmonary metastasis rates of the control group and 2.1g/kg, 4.2g/kg, 8.4g/kg Songyou Yin treatment group were 86.7%, 73.3%, 40.0%, and 20.0%, respectively, and the survivals of these groups were 53.83 ± 4.71, 56.50 ± 6.09, 66.67 ± 5.61, 81.17 ± 7.36 days, respectively. Compared with the mice in the control group, mice in the 4.2 g/kg, 8.4 g/kg Songyou Yin treatment groups had a lower pulmonary metastasis rate (P = 0.021 and P = 0.001, respectively) and longer survival (P = 0.002 and P = 0.001, respectively). A restoration of E-cadherin expression and a concomitant reduction of N-cadherin expression were detected in the tumors of the 4.2 g/kg and 8.4 g/kg Songyou Yin treatment groups.</p><p><b>CONCLUSIONS</b>Songyou Yin effectively inhibits the invasion and metastasis of the residual hepatocellular carcinoma after chemotherapy in nude mice through attenuating the epithelia-mesenchymal transition and prolongs the survival. Songyon Yin may have potential to promote the efficacy of chemotherapy in hepatocellular carcinoma.</p>

Suppression of the growth of subcutaneous transplanted human liver cancer and lung metastasis in nude mice treated by sorafenib combined with fluorouracil / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to explore the inhibitory effect of sorafenib and 5-Fu on transplanted human liver cancer in nude mice, and to investigate the synergistic effect and mechanism between sorafenib and 5-Fu.</p><p><b>METHODS</b>The nude mouse model of human liver cancer was made by transplantation of human highly metastatic liver cancer cell line HCCLM3 cells, and the tumor-bearing nude mice were treated with sorafenib, 5-Fu or both, respectively, and mock-treated tumor-bearing nude mice as negative control. To assess the anti-tumor effect of sorafenib and the synergistic effect of sorafenib combined with 5-Fu by measuring the tumor weight and number of lung metastases. Moreover, the expressions of phosphorylated extracellular signal-regulated kinase (p-ERK), P-glycoprotein (P-gp) and topoisomerase 2-alpha (Topo IIa) in the nude mice were assayed by immunocytochemistry and Western blot.</p><p><b>RESULTS</b>The tumor weights and numbers of lung metastases were: (2.7 ± 0.825) g and 12.714 ± 6.317 in the negative control group, (0.933 ± 0.333) g and 4.333 ± 3.983 in the sorafenib group, (0.786 ± 0.212) g and 5.429 ± 4.315 in the Sorafenib + 5-Fu combination group, and (2.438 ± 0.793) g and 10.429 ± 6.241 in the 5-Fu group. Statistically, the tumor weights and numbers of lung metastases in the sorafenib group and combination group were significantly decreased, compared with that in the control group (P < 0.05). There was no significant difference in the tumor weight and number of lung metastases between the sorafenib group and the combination treatment group (P > 0.05). The expression levels of p-ERK, P-gp and Topo IIa proteins in the tumors after normalization were: negative control (0.017 ± 0.010, 0.085 ± 0.012, 0.103 ± 0.093), sorafenib group (0.010 ± 0.008, 0.044 ± 0.020, 0.020 ± 0.018), combination group (0.011 ± 0.007, 0.043 ± 0.023, 0.062 ± 0.026), and 5-Fu group (0.018 ± 0.009, 0.063 ± 0.032, 0.065 ± 0.034), respectively. Statistically, the expression of p-ERK, P-gp and Topo IIa in the Sorafenib group was significantly reduced compared with that of the control group (P < 0.05), and there was no significant difference in the expression of p-ERK, P-gp and Topo IIa between the sorafenib group and the combination treatment group (P > 0.05).</p><p><b>CONCLUSIONS</b>Sorafenib can inhibit not only the tumor growth and lung metastsis in the nude mouse models, but also reduce the expression of multidrug resistance proteins P-gp and Topo IIa as well. There is no significant advantage for the sorafenib + 5-Fu combination treatment than Sorafenib alone in inhibiting the expression of p-ERK, P-gp and Topo IIa.</p>

Anti-proliferation effect of sorafenib in combination with 5-FU for hepatocellular carcinoma in vitro: antagonistic performance and mechanism / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the anti-cancer efficacy and mechanism of sorafenib and 5-fluorouracil (5-FU) therapy in vitro using the HCC cell line MHCCLM3.</p><p><b>METHODS</b>The effects of sorafenib and 5-FU, alone or in combination, on the proliferation of MHCCLM3 cells were evaluated by cell viability assays. Combined-effects analyses were conducted according to the median-effect principle established by Chou and Talalay. Effects on cell cycle distributions were tested by flow cytometry and expression of proteins related to the RAF/MEK/ERK and STAT3 signaling pathways and cyclinD1 were tested by western blotting.</p><p><b>RESULTS</b>Sorafenib and 5-FU alone or in combination displayed significant efficacy in inhibiting proliferation of the MHCCLM3 cells, with the following inhibition rates: sorafenib: 46.16% +/- 2.52%, 5-FU: 28.67% +/- 6.16%, and sorafenib + 5-FU: 22.59% +/- 6.89%. The sorafenib + 5-FU combination did not provide better results than treatment with either drug alone. The combination index values of the sorafenib and 5-FU treatments were mainly greater than 1, indicating that the two agents induced antagonistic, instead of synergistic, effects on the MHCCLM3 cells. In addition, the MHCCLM3 cells were less sensitive to 5-FU when administrated in combination with sorafenib, as evidenced by the half inhibitory concentration (IC50) significantly increasing from (102.86 +/- 27.84) mg/L to (178.61 +/- 20.73) mg/L (P = 0.003). Sorafenib alone induced G1 phase arrest (increasing from 44.73% +/- 1.63% to 65.80% +/- 0.56%; P less than 0.001) and significantly decreased the proportion of cells in S phase (decreasing from 46.63% +/- 0.65% to 22.83% +/- 1.75%; P less than 0.01), as well as down-regulated cyclinD1 expression (0.57 +/- 0.03-fold change vs. untreated control group; P less than 0.01). 5-FU alone up-regulated cyclinD1 expression (1.45 +/- 0.12-fold change vs. untreated control group; P less than 0.01). Moreover, sorafenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways, with the fold-changes of p-C-RAF, p-ERK1/2 and p-STAT3 being 0.56 +/- 0.05, 0.54 +/- 0.02 and 0.36 +/- 0.02, respectively (all P less than 0.01); 5-FU alone produced no significant effects on these pathways.</p><p><b>CONCLUSION</b>Administered alone, both sorafenib and 5-FU exert anti-tumoral activity on in vitro cultured HCC cells. The sorafenib + 5-FU combination treatment produces antagonistic, rather than synergistic, effects. Sorafenib-inhibited RAF/MEK/ERK and STAT3 signaling and cyclinD1 expression may have induced the observed G1phase arrest and S phase reduction, thereby reducing the cells' sensitivity to 5-FU.</p>