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.

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

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 investigate the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors.

METHODSA search of studies in PubMed and MedLine (from 1999 to 2008) was performed to assess the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors. The articles were retrieved with the entries of "gastrointestinal stromal tumors", "imatinib", "c-kit" and "mutation". A meta-analysis was performed to assess the data included.

RESULTSA total of 15 articles were collected in this analysis. No significant differences was found in incidence of mitoses (> 5/50 HPF) between the patients with wild type c-kit (wild type group) and the ones with mutated c-kit (mutation group) (P = 0.710); tumor recurrence and metastasis rate after surgery was significant higher in the mutation group than that in wild type group (P = 0.010); as for imatinib response with different c-kit mutation types, the results showed the incidence of clinical response (complete response + partial response) was significantly higher in mutation group than that in wild type group (P = 0.009), but the imatinib resistance rate was lower in mutation group (P = 0.000); three studies provided data for imatinib resistance with c-kit second mutations, the results showed the second mutations mainly focus on exon 13, 14, 17.

CONCLUSIONSC-kit mutation is related closely with the incidence of recurrence and metastasis in GIST after surgery. The mutations of c-kit influences the therapeutic effects of imatinib.

Antineoplastic Agents ; therapeutic use ; Benzamides ; Case-Control Studies ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; Humans ; Imatinib Mesylate ; Mutation ; Piperazines ; therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; Pyrimidines ; therapeutic use

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

OBJECTIVETo explore the possibility of treating solid tumor with siCD44.

METHODSHuman nasopharyngeal carcinoma cell CNE-2L2 with high expression of CD44 was used in this study. The malignant activities of cells were examined by colony formation test, tumorigenesis, and lung metastasis of the tumor in nude mice. Ad5-siCD44 was constructed and adenoviruses were produced in 293 cells. CNE-2L2 cells were subcutaneously inoculated into nude mice. When tumors grew to 50-100 mm3, Ad5-siCD44 was injected into tumors, and Ad5-egfp and PBS were also injected as controls. The size and weight of tumors were compared after 2 weeks.

RESULTSSuppression of CD44 expression profoundly inhibited the malignant activities of CNE-2L2 cell. The average sizes of the tumors were (3.139 +/- 0.850), (3.612 +/- 0.888), and (1.512 +/- 0.742) cm3 after the intra-tumor injection of PBS, Ad5-egfp, and Ad5-siCD44, respectively, after two weeks. Significant difference was found between Ad5-siCD44 group and control groups (P < 0.05). The average weights were (2.28 +/- 0.73), (1.83 +/- 0.26), and (1.20 +/- 0.64) g, respectively, and significant difference was also found between Ad5-siCD44 group and control groups (P < 0.05).

CONCLUSIONIntra-tumor injection of Ad5-siCD44 can exhibit the therapeutic effect on the tumor inoculated with CNE-2L2 cells with high expression of CD44 in nude mice.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Genetic Therapy ; Humans ; Hyaluronan Receptors ; biosynthesis ; genetics ; Injections, Intralesional ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; genetics ; pathology ; therapy ; Neoplasm Transplantation ; Transplantation, Heterologous

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

In order to build a protein expression system in a cold-adapted bacterium Acinetobacter sp. DWC6, a promoter probe vector was constructed based on the plasmid pBR322. A fragment containing the promoter of the beta-lactamase gene (the ampicillin resistance gene) in pBR322 was eliminated and replaced by a fragment comprizing a kanamycin resistance gene amplified from pJRD215. DNA fragment harboring in the Acinetobacter species specific ori was also inserted into the plasmid pBR322 to construct a promoter probe vector named pBAP1, which could replicate both in E. coli and in Acinetobacter sp. DWC6. The promoter selection library was constructed by randomly inserting genomic DNA fragment of Acinetobacter sp. DWC6 at upstream of reported gene, and target promoters were screened from genomic library on ampicillin selection plates. The function of pBAP1 and isolated promoters were determined by detection of the ampicillin sensitivity and the expression level of beta-lactamase in the host cell.
Acinetobacter ; genetics ; Adaptation, Physiological ; Bacterial Proteins ; genetics ; metabolism ; Cloning, Molecular ; Cold Temperature ; DNA, Bacterial ; genetics ; Electrophoresis, Polyacrylamide Gel ; Genetic Vectors ; genetics ; Models, Genetic ; Plasmids ; genetics ; Promoter Regions, Genetic ; genetics ; beta-Lactamases ; genetics ; metabolism