Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area / 中国实验血液学杂志

OBJECTIVE@#To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area.@*METHODS@#The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes.@*RESULTS@#Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05).@*CONCLUSION@#The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.

Study on mechanism of Trillium tschonoskii Maxim in treatment of myocardial ischemia based on network pharmacology and molecular docking / 中国药理学通报

Aim To reveal the aetion mechanism of Trillium tschonoskii Maxim (TTM) in the treatment of myoeardial ischemia ( MI) by using network pharma¬cology combined with molecular docking.Methods Compounds of TTM were detected and fished out from TCMID, TCM@TAIWAN , BATMAN-TCM database, and the literature data from PubMed , CNK1, and WAN- FANGD database.PharmMapper database was used to find the targets related to compounds, and DISGeNET, GeneCards, DrugBank and OMIM databases were used to find the targets related to Ml.The predictive targets of TTM in the treatment of Ml were obtained.Cytosca- ope 3.1.2 Software and String database were used to build compound-target network and PP1 network.Gene ontology ( GO ) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes ( KEGG ) pathway enrichment analysis were performed by utili¬zing the CludterProfiler Software package of RStudio software.The molecular docking was used for verifying the results of network analysis.Results The 10 active compounds of TTM were screened , and 13 core targets of Ml were predicted, such as ALB, EGFR, MAPK1 , CASP3,ESR1 ,etc.A total of 28 Ml-related signaling pathways were fished out.The results of molecular docking showed that the core active ingredients had good binding activity with the key targets.Conclusion TTM may play a role in the treatment of Ml through regulating multiple ingredients, multiple pathways, and multiple targets.

Relationship between the muscle mass index and the aggregation of cardiovascular risk factors in children and adolescents aged 12-17 years in Yinchuan City / 中国学校卫生

Objective@#To explore the relationship between the muscle mass index (MMI) and the aggregation of cardiovascular risk factors (CVRFs) in children and adolescents, and to provide a scientific basis for the prevention and treatment of cardiovascular diseases in children and adolescents.@*Methods@#The current situation study design was adopted, and 1 622 children and adolescents aged 12-17 years old in Yinchuan City were selected by a cluster random sampling method. All subjects were subjected to questionnaire survey, physical examination, body composition determination and laboratory index testing.@*Results@#When other variables were not adjusted, MMI was a risk factor for the aggregation of cardiovascular risk factors ( P <0.01). After adjusting for age, gender and BMI, MMI became a protective factor for CVRFs≥1 ( OR =0.74, 95% CI =0.62-0.89), compared with insufficient MMI, the risk of developing CVRFs≥1 with good MMI and sufficient MMI was 0.60(95% CI =0.46-0.79), 0.56(95% CI =0.37- 0.85 ) times. The risk of CVRFs≥2 was 0.54(95% CI =0.37-0.79), 0.51(95% CI =0.30-0.87) times, and similar results were found in boys ( P <0.05). @*Conclusion@#Under the same BMI level, muscle mass index is a protective factor for cardiovascular risk factor aggregation in children and adolescents. Physical exercise of children and adolescents should be emphasized to maintain the best muscle mass and weight.

Relationship between hypertriglyceridemic waist phenotype and abnormal blood pressure in children and adolescents in Yinchuan City / 中国学校卫生

Objective@#To investigate the relationship between hypertriglyceridemic waist (HTW) phenotype and abnormal blood pressure in children and adolescents in Yinchuan City, Ningxia, and to provide scientific basis for early identification and prevention of hypertension.@*Methods@#A cluster sampling method was adopted to select 1 566 children and adolescents in Yinchuan. All participants completed questionnaire survey, physical measurement and biochemical examination.@*Results@#In general, after adjusting for age, smoking, drinking, and family history of hypertension, compared with the normal triglyceride normal waist (NWNT) phenotype, the enlarged waist (EW) and HTW phenotypes both increased the risk of abnormal blood pressure ( OR EW =2.62, 95% CI =1.87-3.67; OR HTW =3.97, 95% CI =2.30-6.86); the risk of abnormal blood pressure in boys with EW and HTW phenotypes was that of boys with NTNW phenotype, respectively 3.80 times (95% CI =2.35-6.15) and 3.32 times (95% CI =1.59-6.92) of girls EW and HTW phenotypes. The risk of abnormal blood pressure in girls with EW and HTW phenotypes was that of girls with NTNW phenotype, respectively 1.72 times (95% CI =1.06-2.82) and 4.62 times(95% CI =1.97-10.85).@*Conclusion@#The hypertriglyceridemic waist phenotypes among children and adolescents in Yinchuan is significantly correlated with increased risk of abnormal blood pressure. More attention should be paid to triglyceride level and waist circumference among children and adolescents.

Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation / 中华心血管病杂志

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

Interaction between fat mass and fat free mass on the aggregation of cardiovascular disease risk factors among children and adolescents / 中国学校卫生

Objective@#To analyze the interaction of fat mass (FM) and fat free mass (FFM) on the aggregation of cardiovascular disease risk factors (CVRFs) among children and adolescents in Yinchuan City, China, so as to provide scientific basis for the prevention of CVRFs and cardiovascular disease in children and adolescents.@*Methods@#A total of 1 822 children and adolescents aged 12 to 18 years in Yinchuan City were randomly selected for questionnaire survey, physical examination, body composition assessment and laboratory tests, through a cluster sampling method from 2017 to 2020. Binary Logistic regression was used to analyze the relationship between FM, FFM and the aggregation of CVRFs, and their interaction was analyzed.@*Results@#After adjusting for sex and age, the risk of having CVRFs aggregation ≥1 in high FM and low FFM group and high FM and high FFM group was 2.01(95% CI =1.46-2.77) and 3.64(95% CI =2.66-4.98) times higher than that in low FM and low FFM group, and the risk of having CVRFs aggregation ≥2 was 1.67(95% CI =1.06-2.63) and 4.20 (95% CI =2.76-6.38) times, respectively( P <0.05). There was a multiplicative interaction between FM and FFM, which increased the risk of CVRFs aggregration ≥1 and ≥2. The adjusted OR and 95% CI were 1.58(1.04-2.40) and 1.95(1.12-3.42), respectively( P <0.05).@*Conclusion@#The results indicated the additive and multiplicative interactions between high levels of fat mass and fat free mass on the aggregation of cardiovascular risk factors, which increased the risk of aggregation of cardiovascular risk factors.

Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway

BACKGROUND: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. METHODS: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔψM) measurement. RESULTS: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney (ΔψM). CONCLUSION: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.

Systemic disseminated Mycobacterium fortuitum infection:one case report and literature review / 中国感染控制杂志

Objective To explore the clinical characteristics of systemic disseminated infection caused by Mycobacterium fortuitum (M.fortuitum), and improve the diagnostic rate and understanding of the disease.Methods One case of systemic disseminated M.fortuituminfection was reported, and analyzed in combination with relevant literatures.Results Patient was with multiple systemic involvement (including lung, lymph node, skin, joint), lymph node tissue culture was positive for M.fortuitum, patient was given clarithromycin+levofloxacin+linezolid for treatment, disease was remitted.Conclusion Systemic disseminated M.fortuituminfection is rare, and patient with GATA2 deletion and IFN-γautoantibody may be a potential mechanism, diagnosis is mainly based on pathological morphology and microbiological detection, but positive rate is low, diagnosis is difficult.

Clinical effects of Safflor Yellow Sodium Chloride Injection combined with Compound Anisodine Injection on patients with NPDR / 中成药

AIM To observe the therapeutic effects of Safflor Yellow Sodium Chloride Injection and Compound Anisodine Injection on patients with non-proliferative diabetic retinopathy (NPDR).METHODS Sixty-eight pa-tients (102 eyes) were randomly divided into control group (32 cases,48 eyes) and observation group (36 cases,54 eyes).The observation group was given Safflor Yellow Sodium Chloride Injection and Compound Anisodine Injection in addition to conventional therapy administered to the control group,and yet patients of both groups had their changes of vision,fundus hemorrhage,effusion,microaneurysm and central macular thickness checked and compared before and after the treatment.RESULTS The observation group displayed better post-treatment vision recovery,fundus improvement and central macular thickness control than the control group (P ＜ 0.05,P ＜ 0.01).CONCLUSION The combination therapy of Safflor Yellow Sodium Chloride Injection and Compound Anisodine Injection can be an appropriate option for NPDR patients to improve vision and slow progression.

Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation in ventilator-induced lung injury / 中华医学杂志(英文版)

<p><b>Background</b>Ventilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.</p><p><b>Methods</b>For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.</p><p><b>Results</b>In vivo, compared with Group C, total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = -28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-α (t = -19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P < 0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = -14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = -21.111, P < 0.01) and TNF-α (t = -15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = -3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.</p><p><b>Conclusions</b>High tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.</p>

The research progress of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors / 药学学报

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme of L-tryptophan metabolic oxidation pathway, in which the L-tryptophan is transformed into N-formyl kynurenine by oxidative cleavage. IDO1 is considered as a potential target for the development of cancer immunotherapeutic molecules. Up to now, at least 10 drug candidates have been advanced into clinical research. In this review, the binding mode and structure-activity relationships of the representative IDO1 small molecule inhibitors were summarized according the characteristics of chemical structures. Hopefully, this review could provide some insights for further development of novel IDO1 inhibitors.

Antitumor activity of a novel PARP1/2 inhibitor YHP-743 / 药学学报

Poly(ADP-ribose) polymerase (PARP)-1 and PARP2 function as ADP-ribosylases involved in DNA repair. PARP1/2 is highly expressed in cancers and emerged as an attractive target for antitumor drug. In this study, we investigated the antitumor activity of a novel PARP1/2 inhibitor YHP-743 in vitro and in vivo. The results showed that YHP-743 had potent enzymatic inhibitory activity against PARP1 and PARP2 to down-regulate the PAR level. YHP-743 not only inhibited breast cancer cells with genes deficiency of homologous recombination repair, but also potentiated chemotherapy agent's cytotoxicity, such as temozolomide, topotecan, cisplatin and doxorubicin. YHP-743 elicited good antitumor activity in combination with temo-zolomide in vivo.

Optimization of the experimental condition on separating lipoproteins by self-constructed asymmetrical flow field-flow fractionation / 北京大学学报(医学版)

OBJECTIVE@#To analyze and characterize the separation effectiveness of self-constructed asymmetrical flow field-flow fractionation system on proteins and lipoproteins, to achieve the optimization of the experimental conditions when separating lipoproteins by orthogonal design test and to investigate the carrier viscosity's influence on separation effectiveness.@*METHODS@#The evaluation of asymmetrical flow field-flow fractionation separation capacity was conducted by using two standard proteins (carbonic anhydrase and thyroglobulin). Under the optimized separation conditions of carbonic anhydrase and thyroglobulin, the channel actual thickness (after assembling, the actual thickness of separation channel was less than initial thickness) was calculated by the analytes' elution time based on the hydrokinetic theory. With orthogonal design test the optimized experimental conditions were studied and statistical analysis was carried on to find out the factors with statistical significance which needed further exploration.@*RESULTS@#According to the hydrodynamics principle and Stoke's function, the channel actual thickness was measured to be 164 μm by separating the two standard proteins, carbonic anhydrase and thyroglobulin, under proper experimental conditions. By the optimization based on orthogonal design test, base-line separation (the resolution had to be higher than 1.50) was achieved. The resolutions of the two experiments were 1.61 and 1.58. According to previous study/ pre-study and supporting theory, in the orthogonal design test, the total 5 factors were integrated for comprehensive investigation: the total flow rate (3.00, 3.50, 4.00, 4.50 mL/min), focus time (3.00, 3.50, 4.00, 4.50 min), transition time (0.5, 1.0, 1.5, 2.0 min), pH of the carrier fluid(6.8, 7.00, 7.20, 7.40) and viscosity of the carrier fluid hydroxypropylmethylcellulose concentration: 0.00%, 0.03%, 0.06%, 1.00%). Among the 5 factors, viscosity was found to have the statistical significance on separation effectiveness which was further investigated. The resolution of high density lipoprotein and low density lipoprotein was increased by the increasing viscosity which also caused more obvious negative spikes.@*CONCLUSION@#The separating capacities of self-constructed asymmetrical flow field-flow fractionation system on lipoproteins were verified to be effective and an optimized experimental condition was found to achieve the base-line separation of high density lipoprotein and low density lipoprotein. Viscosity of the carrier fluid was proved to have the statistical significance on lipoprotein separation.

Death caused by ST19 Klebsiella oxytoca with wcaG virulence gene in leukemic patient / 中国人兽共患病学报

We investigated the cause of a leukemia patient induced by infect in a strain of Klebsiella oxytoca with hypermucoviscosity (HMV) phenotype.Identification and drug susceptibility of the isolate were carried out with VITEK-2 compact system.HMV phenotype was detected by string-test.The major high virulence capsular serotypes (K1,K2,K5,K20,K54 and K57) and virulence factors (rmpA,wcaG,allS,kfu,aerobactin,fimH,uge,wabG and cf29a) were detected by polymerase chain reaction and DNA sequencing.Molecular typing was performed by multilocus sequence typing (MLST).Results showed that the isolates of blood and lung tissue were Klebsiella oxytoca belonged to ST 19,which were sensitive to the antibiotics used in test,expressing the HMV phenotype.The virulence gene wcaG was found,while other virulence genes and the major high virulence capsular serotypes were negative.It indicates that ST19 Klebsiella oxytoca with wcaG virulence gene is the main reason causing leukemic patient death.

2,3-Dihydro-1H-pyrrolo3,2-cquinoline and 2,3,5,9b-tetrahydro-1Hpyrrolo3,2-c-quinoline derivatives: synthesis and their inhibitory activity against Kv2.1 / 药学学报

Fourteen new compounds with 2,3-dihydro-1H-pyrrolo[3,2-c]-quinoline or 2,3,5,9b-tetrahydro- 1H-pyrrolo[3,2-c]quinoline scaffold were designed and synthesized, and their inhibitory activities against Kv2.1 were evaluated. As a result, 2,3-dihydro-1H-pyrrolo[3,2-c]quinoline derivatives 3a and 5a were identified as potent inhibitors of Kv2.1 with IC50 values of 10.2 and 9.0 μmol·L-1, respectively.

Practice and Experience of the Application of Automatic Pharmacy System in Outpatient Pharmacy of Our Hospital / 中国药房

OBJECTIVE:To provide reference for the construction and development of hospital modernization pharmacy in Chi-na,and to promote the application of pharmacy automation system in hospital. METHODS:By introducing the change of pharma-cy management due to the debugging and application of outpatient pharmacy automation system(rapid dispensing machine,intelli-gent access machine)in our hospital,the problems of automation system and countermeasures were put forward,and the effects of automation system in our hospital were evaluated. RESULTS:With the application of automation system,the pharmacy layout was adjusted,the drugs in the machine was debugged and optimized,the procedure on adding drugs and stocktaking drugs were im-proved,the reasonable scheduling work in outpatient pharmacy was worked,the complete management plan on validity of drugs was established;referring to the problems of automation system,the procedures of adding drugs by rapid dispensing machine and intelligent access machine were formulated as well as related working guide. The adding and delivering drug failure emergency han-dling procedure of rapid dispensing machine,intelligent access machine failure emergency handling procedure were formulated ac-cording to the possible fault of automation system. Related index evaluation showed that automation system was applied and continu-ously improved,which reduced labor intensity(step count of pharmacists adding drug decreased from 5 634.6 steps/day to 4 087.8 steps/day);the work efficiency was improved greatly(the number of prescriptions increased from 226.55 sheets/h to 311.55 sheets/h during rush hours);the work error was reduced(the number of dispensing internal error decreased from 54.75 items/week to 21.50 items/week). CONCLUSIONS:After appling the automation system in outpatient pharmacy,the drug dispensing and staff manage-ment has been standardized,and it become the hospital pharmacy development inevitable trend. But it is suggested to adjust and op-timize the automation system continuously so as to exert its maximal efficacy.

Purification of Puerarin from Pueraria lobata by FCPC versus HSCCC Using Small-volume Columns / 中草药·英文版

Objective: To develop an efficient method for separating and purifying puerarin from the roots of Pueraria lobata. Methods: Separation by fast centrifugal partition chromatography (FCPC) was processed with a biphasic solvent system composed of ethyl acetate- n-butanol-water (2:1:3). The separation conditions were determined as follows: sample loading of 10 mg, flow rate of 2 mL/min, rotation speed of 2200 r/min, ascending mode, and detection wavelength of 254 nm. High speed countercurrent chromatography (HSCCC) was used as a comparative method with the rotation speed of 800 r/min, flow rate of 2.0 mL/min, and sample loading of 10 mg in tail-to-head mode. Results: Puerarin was obtained by FCPC with a resolution of 0.90 and a purity above 99%, while a resolution below 0.50 and a purity below 90% by HSCCC. Compared with HSCCC, FCPC has the advantages with higher purity and better resolution. Conclusion: FCPC is a powerful method to separate and purify puerarin. © 2014 Tianjin Press of Chinese Herbal Medicines.

Design, synthesis and biological evaluation of novel 3-(2-oxo-2-substituted acetamido)benzamides as PARP-1 inhibitors / 药学学报

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.

Design, synthesis and biological evaluation of novel para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones as human PARP-1 inhibitors / 药学学报

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.

Effect of small interfering RNA targeting ΔNp63α gene on the biological characteristics of human esophageal squamous carcinoma cells / 第二军医大学学报

Objective To construct a small interfering RNA (siRNA) vector targeting ΔNp63α and investigate ΔNp63α gene interference on the proliferation and apoptosis of human esophageal squamous carcinoma Eca109 cell line. Methods Adeno-associated virus (AAV)-ΔNp63αshRNA driven by H1 promoter was constructed and was used to infect Eca109 cells. AAV-Null and normal cell lines were utilized in the control group and blank control group, respectively. The influence of siRNA interference of ΔNp6α expression on the growth, proliferation, tumorigenic efficiency and apoptosis of Eca109 cells were analyzed in vitro and in vivo. Results Compared with the two control groups, the specific siRNA targeting ΔNp63α gene significantly down-regulated the expression of ΔNp63α protein levels in Eca109 cells (all P<0.05). The growth of Eca109 cells infected with AAV-ΔNp63αshRNA was significantly lower than those in the two control groups (all P<0.05). Cell cycle analysis showed the proliferation index (PI) of AAV-ΔNp63αshRNA infected cell line was significantly lower compared with the two control groups (all P<0.01). In vivo experiment exhibited that AAV-ΔNp63αshRNA infected cells resulted in a lower tumor weight in nude mice compared with the cells in the two control groups (all P<0.05). In addition, the apoptosis index (AI) of AAV-ΔNp63αshRNA infected cells were significantly higher than those of the other cell lines (P<0.05). Conclusion AAV- mediated expression of shRNA can significantly reduce ΔNp63α expression in Eca109 cells, slowing down the proliferation, promoting the apoptosis, and subsequently inhibiting the growth of tumor.