OBJECTIVETo evaluate the enhanced effect of gemcitabine by emodin and the possible mechanisms of the enhancement.

METHODBased on the model of SW1990 cell xenograft on athymic mouse, the mice were randomized to four groups with intraperitoneal (IP) injections of different drugs: group N (injecting 0.9% sodium chloride), group E (emodin, 40 mg x kg(-1)), group G (gemcitabine, 125 mg x kg(-1)), and group E + G (emodin 40 mg x kg(-1) and gemcitabine 80 mg x kg(-1) in combination). The tumor volume, tumor weight and body weight of mice were measured during the drug therapy. The mice were sacrificed one week after last injection of drug. Tunel assay were used used to detect the apoptosis of tumor cells. And immunohistochemistry (IHC) and Western blot (WB) were used to detect the variance of the apoptosis relative protein expression of Bax, Bcl-2, and Cytochrome C .

RESULTOne week after the last administration, the mean tumor volume and tumor weight in group E + G were significantly decreased compared to the other groups. Tunel assay showed group E + G presented apparently more apoptosis than the other groups. Immunohistochemistry (IHC) and Western blot (WB) analysis showed the expression of Cytochrome C in cytoplasmin and Bax in group E + G was apparently upregulated while the expression of Bcl-2 was apparently downregulated compared to the other groups. As a result, Bcl-2/Bax ratio was significantly decreased in group E + G.

CONCLUSIONEmodin can significantly improve the antitumor effect of gemcitabine on transplanted tumor of SW1990 cell line through apparently enhancing the tumor cell apoptosis by gemcitabine. Downregulation of Bcl-2/Bax ratio and promoting release of Cytochrome C from mitochondria is possibly one of the mechanisms of the augmented apoptosis.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Cytochromes c ; metabolism ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Drug Synergism ; Emodin ; pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein ; metabolism

Objective:To evaluate the efficacy and safety of the combination of conventional western medicine therapy and oral traditional Chinese medicine (TCM) compound in the prevention and treatment of radiotherapy-inducedoral mucositis (RTOM) of nasopharyngeal carcinoma patients treated with concurrent radiotherapy and chemotherapy.Methods:A randomized, single-center, and open-label controlled experiment was conducted. Software Stata was used to generate random numbers, and 100 subjects were randomly assigned to two groups ata 1∶1 ratio, namely the integrated Chinese and western medicine group(the integrated group) and the conventional western medicine group. This study focused on the incidence of level-ⅢRTOM, followed by these verity degree of RTOM, therisk of malnutrition, and safety.Results:The incidences of level-III RTOM in the integrated group and the conventional western medicine group were 18% and 46%, respectively, with a statistically significant difference ( χ2=9.007, P=0.003). Compared to the integrated group, the conventional western medicine group showed a significantly increase dseverity degree of RTOM ( OR=3.269, 95% CI: 1.627-6.567, P<0.001) and higher risk of malnutrition ( OR=3.021, 95% CI: 1.786-5.109, P<0.001). Moreover, compared to the integrated group, the conventional western medicine group showed decrease dincidence of thirst (48.97% and 72.00% respectively; χ2=5.493, P=0.019) and decreased incidence of neutrophilcount reduction(12.24% and 30.00%, respectively, χ2=4.668, P=0.031). The incidence of mild/moderate adverse events related to TCM compound was 4.08%(2/49), and no serious adverse events related to TCM compound were observed. Conclusions:Compared to the conventional western medicine regimen, the integrated Chinese and western medicine regimen IS more effective in the prevention and treatment of RTOM. Meanwhile, its clinical application is safe and reliable.

Objective To cxplore the optimal levels of serum calcium,phosphorus and intact parathyroid hormone (iPTH) in peritoneal dialysis (PD) patients.Methods This study is a single center,retrospective cohort study.The associations between serum calcium,phosphorus and iPTH and all-cause mortality in 217 PD patients were analyzed.All patients started PD between January 1,2008 and April 30,2016 were enrolled and followed up to December 31,2016.At baseline and every 3 months,biochemical and therapeutic information was collected.Cox proportional hazard regression models and cubic splines analysis were employed to assess the lowest mortality risk ranges in serum markers of bone metabolism.Results There was no significantly difference between patients within target ranges based on KDOQI or KDIGO guideline and those outside the target ranges by Kaplan-Meier survival analysis.The lowest mortality risk ranges were 2.17-2.40 mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH by using Cox models and cubic splines analysis.Moreover,cumulate survival had significant difference between patients within the descriptive ranges and those out of the descriptive ranges at time-averaged values but not at baseline values.Conclusions The optimal time-averaged ranges of PD patients are 2.17-2.40mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH.These ranges need further validation by large population studies to further conform.

Objective: To delineate the clinical and genetic features of two pedigrees affected with aromatic L-amino acid decarboxylase (AADC) deficiency. Methods: The clinical features, family history and results of genetic testing of 2 patients with AADC deficiency were retrospectively analyzed. Results: Both patients featured hypotension, developmental delay and oculogyric crisis during infancy.Genetic testing confirmed that they have respectively carried c. 714+ 4 (IVS6) A>T/c.175(exon2)G>A compound heterozygous variants and c. 714+ 4(IVS6)A>T homozygous variant. Conclusion The clinical manifestation of children with AADC deficiency may include hypotonia, developmental delay and paroxysmal oculogyric crisis. The combination of 3-O-methyldopa testing and variant analysis is not only very useful for early diagnosis, but also important for the evaluation of treatment effect and prognosis of the disease. Discovery of the novel variants has enriched the variant spectrum of AADC deficiency.