Mutation, translocation and loss of some genes have been known to contribute to chemoresistance, epigenetic mechanisms may also play an important role. About 29 000 CpG islands are primarily distributed in the promoter and the first exon regions of protein coding genes in normal cells. However, cancer cells exhibit significant changes in terms of DNA methylation, which can be summarized as global hypomethylation of the genome accompanied by focal hypermethylation. The relationship between aberrant methylation of gene in the promoter and chemoresistance was discussed in the review. A brief summary was also introduced with regard to the advances how in reversing aberrant methylation and overcoming chemoresistance.

Recent researches indicated that cyclooxygena se -2 (COX-2) expression was related not only to development of breast cancer but also to clinicopathological parameters and prognosis of advanced breast cancer. The preclinical and clinical studies on the use of selective COX-2 inhibitors f or the prevention and treatment of breast cancer have become the focus of invest igation.

Purpose:To investigate the prognostic factors for breast cancer patients with liver involvement.Methods:114 breast cancer patients with liver metastases,who were hospitalized in Fudan University Cancer Hospital between January,1996 and December,2003,were included in this study.Their survival data were analyzed.Results:The response rates with first-,second-,third-,fourth-line chemotherapy were 31.9%,27.8%,16.7% and 0%,respectively.Univariate analyses indicated that patients with impaired liver function and patients with a short interval between surgery and the first recurrence or metastasis had a poor prognosis.Multivariate analyses suggested that the presence of liver function impairment was an independent prognostic factor for overall survival.Conclusions:The response rates of chemotherapy drop with number of lines of chemotherapy.Breast cancer patients with liver involvement and impaired liver function have a poor prognosis.

ObjectiveTo observe the speech outcome of globle aphasia after rehabilitation.Methods9 patients with globle aphasia from Dec. 2008 to June. 2010 in our hospital were assessed with the Standard Aphasia Examination of Chinese(CRRCAE) and trained using the Schuell aphasic stimulation approach, promoting aphasics communication effectiveness (PACE) and functional communication therapy (FCP).Results9 patients were disabled with their faces, 8 cases were disabled with speech. 9 cases improved in understanding, retelling, naming, and copying after speech training(P<0.05). Boston Diagnostic Aphasia Examination (BDAE) showed 2 cases had obvious improvement, and 2 patients had mild improvement.ConclusionThe speech rehabilitation on globle aphasia is very difficult, but speech function can recover to a certain extent and the type of aphasia can tranffer after speech training, and it can raise the ability of daily exchange by combining nonspeech means.

Aim To explore the mechanisms of action (MOA) of synergistic anticancer function in the combination of berberine and evodiamine.Methods We first analyzed the action of suppression in the drug combination from the cell level and validated the dose scope as well as ratio of concentration in synergistic effects of drug combination.Then, the miRNA chip of liver cancer cell BEL-7402 under different treatment was analyzed.By building the miRNA-mRNA network, the MOA of the synergistic drug combination was illustrated.Results Berberine and evodiamine used in combination could significantly synergistically suppress the proliferative ability of liver cancer cells.The special differentially expressed miRNAs (DEmiRNAs) mainly participated in some cancer proliferation-related pathways and biological processes, such as MAPK signaling pathway, endocytosis pathway and insulin signaling pathway.The special target genes influenced by the drug combination not only covered three kinds of membrane receptors, but also took part in the regulation of downstream pathways.Conclusions From the regulation of miRNAs, it is clear that berberine may play a primary role in the synergistical suppression activity of the drug combination in cancer cells.The discovery of synergistic MOA in the combination of berberine and evodiamine from the miRNA level will provide a new guidance to explore more synergistic drug combinations in the future.

An efficient and sensitive analytical method for the simultaneous content determination of 18 amino acids in compound amino acid injection was developed using high performance liquid chromatography (HPLC) with pre-column derivatization. Phenyl isothiocyanate (PITC) was used as derivatization reagent. The target compounds were separated on a Unitary-C18 column (250 mm í 4.6 mm, 5 μm) in gradient elution mode using sodium acetate and the mixture of acetonitrile, methanol and water as mobile phases. The detection wavelength was 254 nm. The derivatization reagent dosage, derivatization time, salt concentration, the pH and the column temperature of mobile phase were investigated. Finally, 18 amino acids were separated within 40 minutes. The method showed that the good linearity (r2 ≥ 0.997 7) was at a range from 9 μg·mL-1 to 1 021 μg·mL-1. The recoveries ranged from 92.6% to 110.7%. And the relative standard deviations (RSD) ranged from 0.01% to 5.68%. The limits of quantification (LOQ, S/N = 10) ranged from 0.02 μg·mL-1 to 13.41 μg·mL-1. This method, which was simple, sensitive and accurate, can be applied for the content determination of amino acids in compound amino acid injections.

Objective To investigate the protection of agmatine on blood brain barrier (BBB) permeability and the effect on the expression of aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) in ischemic reperfusion injury rats.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into normal control group (NC),model group and agmatine group,and there were 20 rats in each group.Normal control group was treated with intraperitoneal injection of saline in 2 hours after incision and suture of skin.Model group was treated with intraperitoneal injection of saline in 2 hours after the establishment of middle cerebral artery occulation (MCAO) model.Agmatine group was treated with intraperitoneal injection of agmatine (AGM) in 2 hours after the establishment of MCAO model.The damage of blood brain barrier was detected by measuring the permeability of blood brain barrier.The infarct size of brain was observed with TTC staining.The morphological changes of neurons were observed with electron microscope.The expressions of AQP4 and MMP9 were detected using immunohistochemical method.Results The permeability of BBB of agmatine treatment group (0.31±0.10) decreased significantly compared with the model group (0.46±0.09) (P＜0.05),but was still significantly higher than the normal control group (0.24±0.12) (P＜0.05).There was no infarction area in normal control group and the infarction areas of agmatine group decreased obviously compared with the model group.Compared with model group,the number of neurons with morphological changes reduced significantly and the degree of pathological changes of neurons was obviously improved in agmatine group.Compared with normal control group,the expression of AQP4 and MMP9 in ischemic penumbra of left cerebral hemisphere parietal cortex in the rats of model group and agmatine group increased significantly(P＜0.05).And the expression of AQP4 and MMP9 in model group was significantly higher than that of agmatine group(P＜0.05).Conclusion Agmatine has a protective effect on BBB with ischemia-reperfusion injury due to its down-regulation the expression of AQP-4 and MMP-9.

Objective To explore the effect of CD40 small interfering RNA(siRNA)on the expressions of pe-ripheral blood interleukin(IL)-21 and IL -35 in rats with experimental autoimmune myocarditis (EAM)and its sig-nificance.Methods Twenty 6 -8 week male Lewis rats were divided into normal group,EAMgroup,CD40 siRNA group and siRNA group by using random number table,with 5 rats in each group.The normal rats were induced with phos-phate buffer saline in double foot pads on day 0 and day 7,while the rest 3 groups were induced with cardiac myosin protein to establish EAMmodels.The rats in CD40 siRNA group and siRNA group were respectively injected with CD40 siRNA and siRNA slow virus expression vector through the tail vein of rats on day 7.The rats were executed on 21 day after echocardiogram examination was made.The histopathologic changes were observed by using light microscope and the myocardial histopathology scores were calculated.Enzyme -linked immunosorbent assay was used to determine the levels of IL -21 and IL -35 in peripheral blood.Results (1)Except the normal group,the total incidence rate of rats of each group was 100%,and there was no rat death.(2)Compared with EAM group,the heart mass/body ratio and myocardial histopathology scores were lower in CD40 siRNA group,and the differences were significant (3.13 ±0.21 vs 3.80 ±0.29,2.22 ±0.43 vs 3.32 ±0.51,F =0.332,0.456,all P <0.05).(3)The echocardiogram showed that there was only 1 rat in EAM group with massive pericardial effusion,and there was no pericardial effusion in CD40 siRNA group.EAMgroup,CD40 siRNA group and siRNA group displayed hypertrophy of the ventricular septum and left ventricular wall,narrow heart cavity and weakening of ventricular wall motion.The left ventricular shortening rate in CD40 siRNA group was significantly higher than that in the EAMgroup[(63.34 ±11.06)% vs (38.56 ±6.98)%,F =16.080,P <0.05].(4)The peripheral blood level of IL -21 in CD40 siRNA group was lower than that in EAM group [(141.19 ±17.46)ng/L vs (157.81 ±17.58)ng/L,F =57.008,P <0.05],while its level of IL -35 was signifi-cantly higher than that in the EAMgroup [(195.96 ±18.26)ng/L vs (174.78 ±13.91 )ng/L,F =31.727,P <0.05].(5)The level of IL -21 in peripheral blood was positively correlated with myocardial histopathology scores in EAM group (r = 0.69,P < 0.05 ),but IL -35 was negatively correlated with myocardial histopathology scores (r =-0.64,P <0.05).Conclusions CD40 siRNA might relieve the myocardial inflammation and reduce the myocar-dial injury of EAMrats.The levels of IL -21 and IL -35 can partly reflect the degree of myocardial injury.The mecha-nism may be related to down -regulating the expression IL -21 and up -regulating the expression of IL -35.

Global Cancer Statistics for 2020 show that urinary system tumors account for approximately 13% of the total number of cancers. At present, the diagnostic methods of urinary system tumors are imaging, endoscopy, and pathological examination. As the gold standard of tumor diagnosis, pathological examination has problems such as lack of pathologists and long operation time. Artificial intelligence (AI), with a strong ability for pathology image recognition and feature analysis, can be used as an auxiliary diagnosis. It has realized automatic diagnosis, typing, staging, grading, and prognosis prediction in several urinary system tumors. However, AI still has many shortcomings, which limit its clinical application. This article will review the progress of AI and its application in the pathological study of urinary system tumors.

OBJECTIVETo separate and characterize aqueous extracts of Salvia miltiorrhiza and Carthamus tinctorius to efficient, high-throughput and strong polar components, to observe effects of their aqueous effective components compatibility on rat myocardial ischemic reperfusion injury.

METHODMyocardial ischemic reperfusion injury model were established on SD rats by 40 min ligation of the left anterior descending artery and 120 min reperfusion. The rats were injected experimental drugs intravenously from femoral vein after 10 min ischemia. Rats were randomly divided into sham group (the suture around the left anterior descending coronary artery was not tied), model group, Danhong injection group (content of protocatechualdehyde is 0.05 g x L(-1), injection dosage equivalent to 1.80 g x kg(-1)), aqueous effective component of S. miltiorrhiza group (content of salvianolic acid B is 49 g x L(-1), injection dosage equivalent to 30.68 g x kg(-1)), aqueous effective component of S. miltiorrhiza group (content of hydroxysafflor yellow A is 31.76 g x L(-1), injection dosage equivalent to 17.87 g x kg(-1)), aqueous effective components compatibility of S. miltiorrhizae and C. tinctorius group (injection dosage is respectively 24.28 g x kg(-1) and 48.55 g x kg(-1)), each group have ten rats. Drugs were diluted with an equal dose of normal saline. The rats of sham group and model group were injected equivalent dosage of saline. The myocardial infarction size and the contents of serum cTnT and CK-MB were detected. The level of TXB2, 6-keto-PGF(1alpha) and platelet aggregation in blood plasma were investigated.

RESULTCompared with sham group, serum cTnT and CK-MB contents in model group increased significantly (P < 0.01). Compared with model group, myocardial infarction size and serum cTnT and CK-MB contents in aqueous effective component of S. miltiorrhiza group, aqueous effective component of C. tinctorius group and aqueous effective components compatibility of S. miltiorrhiza and C. tinctorius groups decreased significantly. Aqueous effective component of S. miltiorrhiza increased the level of 6-ke-to-PGF(1alpha), as well as decreased content of TXB2 and inhibited platelet aggregation (P < 0.01). Aqueous effective component of C. tinctorius also decreased the content TXB2 (P < 0.01). Improved extent of some detected markers in aqueous effective components compatibility of S. miltiorrhiza and C. tinctorius groups were better than that of Danhong injection group.

CONCLUSIONEffective components compatibility of aqueous extracts from S. miltiorrhiza and C. tinctorius may reduce myocardial infarct size and leakage of myocardial enzyme, and increase the level of 6-keto-PGF1alpha, so as to inhibit platelet aggregation and prevent thrombosis, the result of which is to reduce myocardial ischemic reperfusion injury.

Animals ; Carthamus tinctorius ; chemistry ; Disease Models, Animal ; Drug Interactions ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Myocardial Reperfusion Injury ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry