Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia, characterized by the reciprocal chromosomal translocation of t (15;17)(q22;q21), which generates PML-RARαfusion protein. All-trans-retinoic acid (ATRA) and As2O3 could induce APL cells to differentiation and apoptosis, respectively, making APL become the first curable leukemia. Autophagy is one of metabolic mechanisms to maintain cell homeostasis. Recent studies have showed that autophagy plays an important role in the differentiation of APL cells induced by ATRA/As2O3. Meanwhile, autophagy may affect the sensitivity of APL cells to the pro-apoptotic effect of drugs. Therefore, targeting and regulating autophagy might be a new therapeutic approach of APL and even other leukemia in the future. This article will briefly review the advance of autophagy in APL in recent years.

AIM:To establish the quality specification of Yinzhihuang Injection (extract of Herba Artemisiae scopariae,extract of Fructus Gardeniae,extract of Radix Scutellariae,extract of Flos Lonicerae Japonicae); METHODS:Extractum Artemisiae Scopariae、 Extractum Fructus gardeniae、 Extractum Flos lonicerae and Extractum Radix scutellariae were identified by TLC and were determined by HPLC. RESULTS:The average recoveries of chlorogenil、gardenoside、baicalin and p-hydroxyacetophenone were 99.8%,99.2%,100.1% and 99.9%,respectively.RSD were 0.81%,1.20%,1.90% and 0.55%,respectively.The TLC sports developed were fairly clear,and the blank test showed no interference. CONCLUSION:The method developed is simple and accurate with good reproducibility,and the method can be used for quality control of Yinzhihuang Injection.

Objective:To investigate the correlation between lumbar bone mineral density (BMD), musculoskeletal perfusion andmuscle mass.Methods:From May 2019 to August 2020, totally 91 patients who applied for CT perfusion (CTP) examination of abdomen (the scan range included the vertebral body of L1－L3) in Shanghai Tenth People′s Hospital of Tongji University were retrospectively analyzed. The mean BMD of L1－L3 vertebral body was measured by quantitative CT (QCT) at the same time of CT plain scan. According to BMD, the subjects were divided into normal BMD group ( n=33), osteopenia group ( n=41) and osteoporosis (OP) group ( n=17). The L3 level perivertebral muscle mass index and fat fraction were calculated based on QCT examination. The lumbar vertebral and perivertebral muscle perfusion parameters were measured based on CTP images. The parameters of QCT and CTP among three groups were analyzed by Kruskal-Wallis H test or one-way ANOVA. The correlation analysis was conducted between these parameters using Pearson or Spearman analysis. Results:The differences of the perivertebral muscle mass index and fat fraction among three groups were statistically significant ( P<0.05). The differences of the lumbar vertebral perfusion parameters including blood flow (BF), blood volume (BV) and flow extraction product (FE) among three groups were statistically significant ( P<0.05), and BF, BV and FE were positively correlated with BMD ( r=0.444, 0.312 and 0.266 respectively, all P<0.05; adjusted for age and gender r=0.437, 0.340 and 0.337 respectively, all P<0.05). There was no statistically significant difference in perivertebral muscle perfusion parameters among three groups ( P>0.05). Perivertebral muscle mass index was negatively correlated with fat fraction ( r=-0.599, P<0.001; adjusted for age and gender r=-0.404, P<0.001), and there was no correlation between perivertebral muscle mass index and muscle perfusion parameters, as well as perivertebral muscle fat fraction and muscle perfusion parameters. Conclusions:With the changes of BMD, bone mass and perivertebral muscle mass at L3 level are synchronous. Decreased vertebral bone mass is accompanied with reduced perivertebral muscle mass, increased muscle fat and decreased bone perfusion. The changes of vertebral perfusion and perivertebral muscle perfusion at L3 level are asynchronous, which implies that reduced perfusion in OP patients may be confined to the bone.

An extremely thermoacidophilic isolate K4-1 was obtained from an acidic hot spring in Teng- chong Rehai, Yunnan province. Morphology, growth characteristics, utilization of carbon compounds, en- ergy sources and 16S rRNA gene sequence of K4-1 were studied. Cells of K4-1 are irregular cocci with monotrichous flagella. The strain grew aerobically in either a lithotrophic or a heterotrophic mode. Growth on elemental sulfur occurred through oxidation of sulfur. It grew optimally at 75?C and pH 3.5. On the basis of 16S rRNA gene sequence similarity, strain K4-1 was shown to belong to genus Sulfolobus, being related to the type strains of genus Sulfolobus (86.6%~94.3% similarity), and being most closely related to strain Sulfolobus tengchongensis RT8-4 (98.9% similarity). The GenBank accession number of strain K4-1 16S rRNA gene sequence is EU729124.

OBJECTIVETo observe the inhibiting effect of acupuncture on blood lipid, myocardial hypertrophy and fibrosis in mice with hyperlipemia, and explore its possible action mechanism.

METHODSTen inbred mice (C57) were applied. Forty ApoE(-/-) mice who removed gene of apolipoprotein E were randomly divided into a control group, a non-acupoint group, an acupoint group and a medication group. The points 0. 5 cm and 1 cm next to the end of mice tail were respectively punctured in the non-acupoint group; "Neiguan" (PC 6) and "Fenglong" (ST 40) were punctured in the acupoint group; intragastric administration of simvastatin was applied in the medication group. After 8 weeks of treatment, the changes of total cholesterol (TC) and ratio of heart to body mass in each group were measured; changes of cardiac muscle fiber and ventricular wall thickness were observed; enzyme linked immunosorbent assay (ELISA) was used to test the level of angiotensin II (Ang I ) in plasma, and western blotting method was used to test protein content of angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) in the heart.

RESULTSAfter 8 weeks of intervention, compared with the control group, rising range of blood lipid was obviously decreased (P<0.01) in the acupoint group and medication group, ratio of P<0.01), myocardial heart to body mass was decreased (P<0.05), thickness of ventricular wall was reduced (P fibrosis was relieved, levels of Ang II and ET-1 in plasma were decreased (P<0. 05), content of NO was increased (P<0. 05), and protein content of AT1R and ETAR was decreased in the heart (P<0. 05).

CONCLUSION40) could inhibit the rising of blood lipid in ApoE(-/-) mice, lower the levels of Ang II and ET-1 in peripheral blood, increase the content of NO and inhibit the expression of AT1R and ETAR in heart tissue, which could relieve myocardial hypertrophy and fibrosis to play a protective role on heart.

Acupuncture Points ; Acupuncture Therapy ; Angiotensin II ; metabolism ; Animals ; Blood Pressure ; Disease Models, Animal ; Heart ; physiopathology ; Heart Diseases ; etiology ; metabolism ; physiopathology ; prevention & control ; Humans ; Hyperlipidemias ; complications ; physiopathology ; therapy ; Male ; Mice ; Mice, Inbred C57BL ; Myocardium ; metabolism

OBJECTIVETo evaluate the pharmacokinetic profile of telbivudine in healthy Chinese subjects after oral administration of single and multiple doses.

METHODSForty-two healthy adult male and female subjects 18-40 years of age were randomized into four telbivudine dosing groups of 200 mg, 400 mg, 600 mg and 800 mg. Subjects in the 600 mg group received both a single dose and once daily multiple doses for 8 consecutive days. Telbivudine concentrations in plasma and urine samples collected at different time points before and after the drug administration were measured using HPLC-MS/MS. Pharmacokinetic parameters were calculated by using the non-compartmental approach.

RESULTSAfter a single dose of 200 mg, 400 mg, 600 mg and 800 mg, tmax (median) were 2.50, 2.00, 2.00 and 2.50 hours respectively; t1/2 were (43.3 +/- 15.2) h, (49.1 +/- 14.4) h, (39.4 +/- 12.1) h and (46.7 +/- 20.8) h respectively; Cmax were (1,753.2 +/- 389.0) ng/ml, (2,586.7 +/- 871.4) ng/ml, (3,703.6 +/- 1,219.0) ng/ml and (3454.6 +/- 953.9) ng/ml respectively; AUC(0-infinity) were (12,843.2 +/- 2,925.6) ng.h(-1).ml(-1), (22,948.9 +/- 5,721.0) ng.h(-1)/ml(-1), (26,440.5 +/- 8,938.1) ng.h(-1).ml(-1) and (28, 820.9 +/- 7 912.9) ng.h(-1).ml(-1) respectively, and CL(R) (600 mg) was (6,545.6 +/- 1 504.4) ml/h. The AUCss from multiple doses was (1,088.5 +/- 299.8) ng/ml; Cmax and AUC accumulation ratio were 1.02 +/- 0.21 and 1.23 +/- 0.26 respectively, which implicated moderated accumulation.

CONCLUSIONPharmacokinetic parameters of telbivudine in Chinese healthy subjects were determined.

Adolescent ; Adult ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Nucleosides ; pharmacokinetics ; Pyrimidinones ; pharmacokinetics ; Thymidine ; analogs & derivatives ; Young Adult

OBJECTIVETo investigate the expression of chemokine receptor CXCR4 in colorectal carcinoma and its relationship with the clinicopathological parameters, and to reveal the role of CXCL12/CXCR4 in the invasion and metastasis of colorectal carcinoma.

METHODSCXCR4 expression was studied in 53 colorectal cancer tissues and 27 normal tissues by immunohistochemistry. Its relationship with clinicopathological characteristics of colorectal cancer patients were analyzed. The CXCR4 expression in tumor and normal specimens and its metastatic sites were assessed by RT-PCR and Western blot.

RESULTSFifty-three colorectal cancer patients,collected from July 2005 to February 2007 in our hospital,were enrolled in this study. CXCR4 was positive in 39 cancer tissue specimens(73.6%) and its high expression rate (in > 50% of cells) was 45.3%. High CXCR4 expression rate was significantly higher in patients with lymph node metastases (N(1)+N(2): 65.4%) than that in those without metastases(N(0) 25.9%). There were also associations between the high CXCR4 expression and the vascular and lymphatic vessel invasions (P<0.01). Meanwhile, there was a rising trend of high expression rate according to American Joint Committee on Cancer (AJCC) stage and pathologic grade,but no significant difference was found(P>0.05). There were no significant correlation of CXCR4 expression with clinicopathological parameters such as tumor location, tumor size, depth of tumor invasion(P>0.05). In addition, the CXCR4 mRNA expression in primary tumor specimens (n=27) from AJCC stage IIII( patients was significantly higher than that in normal tissues. CXCR4 mRNA expression of liver metastasis specimens(n=5) was significantly higher as compared with the primary colorectal cancer specimens(P<0.01).

CONCLUSIONSChemokine receptor CXCR4 is associated with the progression of colorectal carcinoma. High CXCR4 expression is associated with metastasis. The CXCL12-CXCR4 signaling pathway may be a potential novel target of therapy for patients with colorectal cancer.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; genetics ; Receptors, CXCR4 ; metabolism

OBJECTIVETo analyze the relationships among the aberrant methylation of Runx3 gene promoter, the Runx3 protein expression and clinicopathological features in gastric cancer.

METHODSMethylation specific PCR was used to measure the promoter methylation status of Runx3 gene in tumor and the adjacent normal mucosal tissues from 40 patients with gastric cancer. Protein expression of Runx3 was measured by immunohistochemistry.

RESULTSThe frequency of promoter methylation of Runx3 gene in gastric cancer tissue(55.0%) was significantly higher compared to the adjacent normal tissues (12.5%)(P<0.01). The positive rate of protein expression of Runx3 in gastric cancer tissue(37.5%) was significantly lower compared to the adjacent normal tissues (100%). There was marked association between hypermethylation and negative protein expression (P<0.05). The frequency of Runx3 promoter methylation was associated with histological type, N grade, and tumor stage.

CONCLUSIONThe promoter hypermethylation is a main mechanism of reduced or loss expression of Runx3 gene, which may provide molecular diagnosis and stage evaluation of gastric cancer.

Adult ; Aged ; Core Binding Factor Alpha 3 Subunit ; genetics ; metabolism ; CpG Islands ; DNA Methylation ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; Stomach Neoplasms ; diagnosis ; metabolism ; pathology

BACKGROUNDLumiracoxib is a highly selective cyclooxygenase-2 (COX-2) inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.

METHODSThe antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Drug-drug interactions were analyzed using the coefficient of drug interaction (CDI) to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry.

RESULTSLumiracoxib (15 - 240 micromol/L) has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the IC50 values of 2597 micromol/L and 833 micromol/L, respectively. The synergistic effect was prominent when lumiracoxib (15 - 240 micromol/L) was combined with docetaxol (0.2 - 2 micromol/L) (CDI < 1). Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.

CONCLUSIONSLumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.

Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Diclofenac ; analogs & derivatives ; pharmacology ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Taxoids ; pharmacology

Laser-induced breakdown spectroscopy (LIBS) was used for analysis of the distribution of S,Mn,Fe,Cr,Mo,Si,Al in a 34CrNiMo6 steel sample cut from a main shaft of wind driven generator.The MnS inclusion area in each ablation craters cover zone was extracted in the way of comparing the metallograph captured by optical microscopy before and after LIBS scanning ablation.The statistic relation between MnS inclusion area and signal intensity of S and Mn was analyzed.The result showed that the abnormal signal of S and Mn occurred at the same position with the existence of MnS inclusion,and their signal intensity showed linear relationship.The abnormal signal of S and Mn were triggered mainly by MnS inclusion.The statistic result also showed linear relationship between signal intensity and MnS inclusion area both for S and Mn.It was possible to determine the inclusion type,size and distribution by analyzing abnormal signal.A simplified ablation model was established to calculate the relation of S and Mn content to MnS inclusion area.The arithmetic result showed a linear relation between the content and MnS inclusion area both for S and Mn.The calculation confirmed the linear relationship between signal intensity and inclusion area observed in experiment.The linear relationship could be interfered by macro-segregation,micro-segregation,deviation in measuring inclusion area,and inclusion spatter in pre-ablation.