Application of targeted therapy combined with chemotherapy in advanced gastric cancer / 医学研究生学报

Gastric cancer is one of the most common malignant tumors in the world. Due to its high recurrence rate, gastric cancer is the second leading cause of cancer death. Up to now, surgical treatment is the only method of cure for patients with early disease, and with the development of endoscopy, neoadjuvant radiotherapy and chemotherapy, 5-year survival rate of patients with early gastric cancer could reach more than 95%. However, no specific symptoms were reported in the early stage of gastric cancer, most patients were diagnosed with middle and late stage when they were symptomatic, and no longer candidates for surgical treatment. In recent years, treatment for gastric cancer has evolved rapidly regarding neoadjuvant chemotherapy, molecular targeted therapy and immunotherapy as well as new chemotherapeutic regimens. The representative in the first-line chemotherapy includes platinum and fluorouracil, or a combination of these two agents. Meanwhile, targeted therapy is also widely used in this setting due to its specificity. Thus, it is necessary to summarize the therapeutic effects of current targeted therapy combined with chemotherapy in treating patients with advanced gastric cancer.

Mitochondrial DNA hydroxymethylation level in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To study the methylation level and dynamic change of 5-hydroxymethylcytosine (5hmC) in mitochondrial DNA (mtDNA) in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage.@*METHODS@#A total of 24 male Sprague-Dawley rats aged 7 days were randomly divided into control group, 24-hour model group and 48-hour model group (n=8 each). Common carotid artery ligation combined with hypoxic treatment was performed to establish an animal model of hypoxic-ischemic brain damage. The rats in the control group were not given ligation or hypoxic treatment. Oxidative bisulfite sequencing was used to measure the level of 5hmC in the cerebral cortex. Western blot was used to measure the expression of 5hmC-related enzymes TET1, TET2 and DNMT1.@*RESULTS@#The 24- and 48-hour model groups had a significantly higher level of 5hmC than the control group (P<0.05). Western blot showed a significant increase in the expression of DNMT1 in the 24- and 48-hour model groups (P<0.05). Compared with the control group, the 24- and 48-hour model groups had significant differences in the 5hmC level at multiple mitochondrial genetic loci (P<0.05).@*CONCLUSIONS@#The level of DNMT1, a key enzyme for 5hmC modification in mtDNA, in the cerebral cortex increases in neonatal rats with hypoxic-ischemic brain damage, suggesting that there is an abnormal methylation level of 5hmC after hypoxic-ischemic brain damage, which might be associated with the regulation of hypoxic-ischemic brain damage.

Simultaneous determination of five constituents in Shanzhuyu Formulated Granules by QAMS / 中成药

AIM To establish a quantitative analysis of multi-components by single mark (QAMS) method for the simultaneous content determination of five constituents in Shanzhuyu Formulated Granules (Corni Fructus).METHODS The analysis of 80％ methanol extract of this drug was performed on a 30 ℃ thermostatic Wondasil C18column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.3％ phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 335 nm.With morroniside as an internal standard,the relative correction factors of gallic acid,5-hydroxymethylfurfural,loganin and cornuside were established,followed by the determination of their contents.RESULTS Gallic acid,5-hydroxymethylfurfural,morroniside,loganin and cornuside showed good linear relationships within the ranges of 0.0120-0.120,0.026 8-0.268,0.074 4-0.744,0.058 6-0.586 and 0.0086-0.086 μg (r≥ 0.9999),whose average recoveries (RSDs) were 103.43％ (1.45％),103.36％ (1.50％),104.47％ (0.30％),102.08％(1.74％) and 104.01％ (0.62％),respectively.The results obtained by QAMS approximated those obtained by external standard method.CONCLUSION This stable and reliable method can be used for the quality control of Shanzhuyu Formulated Granules.

Simultaneous determination of five constituents in Shanzhuyu Formulated Granules by QAMS / 中成药

AIM To establish a quantitative analysis of multi-components by single mark (QAMS) method for the simultaneous content determination of five constituents in Shanzhuyu Formulated Granules (Corni Fructus).METHODS The analysis of 80％ methanol extract of this drug was performed on a 30 ℃ thermostatic Wondasil C18column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.3％ phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 335 nm.With morroniside as an internal standard,the relative correction factors of gallic acid,5-hydroxymethylfurfural,loganin and cornuside were established,followed by the determination of their contents.RESULTS Gallic acid,5-hydroxymethylfurfural,morroniside,loganin and cornuside showed good linear relationships within the ranges of 0.0120-0.120,0.026 8-0.268,0.074 4-0.744,0.058 6-0.586 and 0.0086-0.086 μg (r≥ 0.9999),whose average recoveries (RSDs) were 103.43％ (1.45％),103.36％ (1.50％),104.47％ (0.30％),102.08％(1.74％) and 104.01％ (0.62％),respectively.The results obtained by QAMS approximated those obtained by external standard method.CONCLUSION This stable and reliable method can be used for the quality control of Shanzhuyu Formulated Granules.

Exploration on technical difficulties of multipath system in tissue cross-reactivity studies / 药物评价研究

Tissue cross-reactivity (TCR) studies play an important role in the preclinical safety evaluation of monoclonal antibody (mAb) drugs.The objective of TCR studies is to find out off-target binding sites of mAbs,and provide valuable predictions for the toxicological evaluation and safety medication in vivo.According to the new drug application requirements of FDA,EMA and CFDA,TCR studies need to be carried out before Phase I clinic trails.As the origin of mAb drugs was transferred from murine antibodies to fully humanized antibodies in current years,immunohistochemical methods used in TCR studies were confronted with some new problems and challenges.Taking our own experiences and recent progress on TCR studies at home and abroad together,the authors summarized the recent exploration on technical difficulties of multipath system in TCR studies.This may provide valuable insight for further improving the quality of TCR studies and increase the predictive value of TCR studies for in vivo toxicological evaluation in China.