Application value of donor liver autologous portal venous blood rinse in orthotopic liver trans-plantation / 中华消化外科杂志

Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.

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.

The Role of Power Arm by Combined Use of Clear Aligner and Miniscrew in En-Masse Retraction of Maxillary Anterior Teeth / 医用生物力学

Objective To investigate the role of Power Arm in en-masse retraction of maxillary anterior teeth using clear aligner (CA) and micro-implant anchorage (MIA). Methods The three-dimensional (3D) model of maxillary anterior teeth by combined use of CA and MIA was established, and the 6 mm-height Power Arm, was attached to the canine or appliance. The initial displacement and the maximum von Mises stress of periodontal ligament under three loading conditions were analyzed, namely the force was loaded by CA+150 g retraction force at canine, CA+150 g retraction force on Power Arm at appliance, CA+150 g retraction force on Power Arm at canine. Results In sagittal direction, the crown and root displacement difference of maxillary central incisor was 129, 129, 133 μm，respectively. The crown displacement of the maxillary first molar was -23.3, -23.5, -26.8 μm, respectively. The maximum von Mises stress of periodontal ligament in central incisor was 48.4, 72.6, 40.0 kPa, respectively, and that of the first molar was 5.3, 10.5, 5.8 kPa, respectively. Conclusions It can not be testified that retraction of the 6 mm-height Power Arm at canine or appliance with 5 mm-height mini-screw has more advantages than retraction of the canine directly for more favorably controlling the torque of incisors, saving anchorage of posterior teeth and decreasing von Mises stress of the periodontal ligament.

Effect of hydroxysafflor yellow A on COX-2/PGD2/DPs pathway in cortex of mice with cerebral ischemia-reperfusion injury / 中国药理学通报

Aim To observe the effect of hydroxysafflor yellow A (HSYA) on the COX-2/PGD/DPs pathway in the cortex of mice with cerebral ischemia-reperfusion injury. Methods C57BL/6 male mice were randomly divided into sham group, model group and HSYA group. Right middle cerebral artery occlusion/reperfusion model was established in mice by intraluminal suture method. HYSA (20 mg • kg"1) was injected into the tail vein for five consecutive days before the operation. The sham group and the model group were given the same volume of normal saline. The neurological function score and cerebral infarct volume were measured 24 hours after operation. The histopathological changes of mouse cortex were observed by HE staining. The protein and mRNA expression of COX-2, DP, and DP2 were detected by Western blot and qRT- PCR respectively. The levels of TNF-a, IL-1 (3 and PGD2 were detected by ELISA. Results Compared with sham group, the scores of neurological function, infarct volume, the expression of COX-2, DP, and DP2 protein and mRNA, and the contents of TNF-a, IL-1 (3 and PGD2 in the cortex of model group significantly increased. Compared with model group, the scores of neurological function and the infarct volume significantly decreased in HSYA-treated group, and the damage of cortical cells in ischemic area was significantly improved. The expressions of COX-2, DP, and DP2mRNA and protein were significantly down-regula- ted, and the levels of inflammatory factors such as TNF-a, IL-1 p and PGD2 were markedly down-regula- ted. Conclusions HSYA inhibits the activation of COX-2/PGD2/DPs pathway in mouse brain tissues, which may be involved in the protective mechanism of HSYA in cerebral ischemia-reperfusion injury.

Prevalence of anti- "Mia" in blood donors and patients, Zhongshan city / 中国输血杂志

【Objective】 To understand the frequency and significance of anti-" Mia" (anti-" Mia" mixtures of antibodies) in local population in Zhongshan, and the influence of different experimental conditions on the activity of human anti-" Mia" . 【Methods】 The microplate-based agglutination assay and polybrene method were used to screen anti-" Mia" in 3 587 blood samples from voluntary blood donors and patients using O type red blood cells with positive Mia antigen, then.rechecked by tube method and microcolumn gel card method. 【Results】 The frequency of anti-" Mia" was 1.06% (38/3 587), among which 60.5% (23/38) were IgM and 39.5% (15/38) were mixture of IgM and IgG; 0.61% (13/2 135) in local blood donors and 1.72% (25/1 452) in patients(P<0.01). 65.8% (25/38) of the population carrying anti-" Mia" had a history of immunity. 57.9% (22/38) were identified to be anti-" Mur" and 42.1% (16/38) anti-" Mia" using GP.Vw erythrocyte. The appropriate incubation time for anti-" Mia" test was 10 min. 【Conclusion】 The frequency of anti-" Mia" was relatively high among blood donors and patients in Zhongshan, and most of the anti-" Mia" carriers had a history of immunity. Most anti-Mia antibodies were active in saline, and some of them were mixture of IgM and IgG. It may be helpful to include Mia positive red blood cells in the irregular antibody screening cell panel to improve the safety of blood transfusion.

Preventive effect of water extract of danshen on degeneration of osteoarticular cartilage induced by monosodium iodocaetate in rats / 中国药理学通报

Aim: To explore the preventive effect of water extract of Danshen (DWE) on degeneration of osteoarticular cartilage induced by monosodium iodocaetate (MIA). Methods: Twenty-seven female SD ratswere randomly divided into sham group, MIA group and DWE group. Rats in sham group were injected a single intra-articular of saline in left knee, while rats in MIA and DWE group were injected a single intra-articular of MIA(60 g L-1). The rats were administered on the second day after the injection of MIA. The rats in sham group and MIA group were given 5 mL · kg-1 of saline, and the rats in DWE group received 5 mL · kg-1 of DWE every day for six weeks. At the end of the experiment, the serum was tested for MMP-13, IL- 6 and TNF-α by enzyme-linked immunosorbent assay (ELISA). The left knee femur of rats was taken for safranine O-fixed green staining and tibia was collected for Micro-CT assay. Results: Compared with sham group, the serum level of MMP-13 and the pathological score of the medial femoral articular cartilage in MIA group significantly increased (P < 0. 01), while cartilage thickness and cartilage volume of the medial tibial articular cartilage markedly decreased (P < 0. 01). Compared with MIA group, the serum level of MMP-13 and the pathological score of the medial femoral articular cartilage in DWE group significantly decreased (P <0. 05,P <0. 01), while cartilage thickness and cartilage volume of the medial tibial articular cartilage increased (P < 0. 01, P < 0. 05). Conclusion: DWE has a protective effect on degeneration of osteoarticular cartilage induced by monosodium iodocaetate.

Combined use of miniscrews and clear aligner for en-mass retraction of maxillary anterior teeth: A finite element analysis / 实用口腔医学杂志

Objective: To evaluate the biomechanical effects of combined use of miniscrew and clear aligner in different kinds of loading condition on the en-mass retraction of maxillary anterior teeth. Methods: 3 D finite element models of the maxillary bone with miniscrews and clear aligner were reconstructed using the method of reverse engineering with CBCT data of an adult patient who had maxillary first premolars extracted. The orthodontic force was loaded by (1) clear aligner, (2) clear aligner and 1. 47 N force of retraction at appliance and (3) clear aligner and 1. 47 N force of retraction at canine, respectively. Results: Under the working condition of (1), (2) and (3), in sagittal direction, the displacement difference of crown and root of the maxillary central incisor was 1. 12 E-02 mm, 1. 29 E-02 mm and 9. 62 E-03 mm respectively, the displacement of the first molar crown was-2. 49 E-02 mm, -2. 09 E-02 mm and-2. 00 E-02 mm respectively; in vertical direction, extrusion of the maxillary central incisor was 1. 77 E-03 mm, 2. 93 E-03 mm and 6. 53 E-04 mm respectively. Conclusion: The working condition (3) is more advantageous to control the torque of incisors and to save the anchorage of posterior teeth, and more effective to control the extrusion of the incisors.

Symptom load assessment of Ph chromosome/ BCR-ABL fusion gene negative myeloproliferative tumor patients at different efficacy evaluation periods / 国际肿瘤学杂志

Objective To observe the disease type and the changes of symptom load during treatment of patients with Ph chromosome/ BCR-ABL fusion gene negative myeloproliferative neoplasm (MPN). Methods A total of 84 patients with MPN diagnosed from May 2017 to January 2019 in People's Hospital of Longhua Dis-trict of Shenzhen were selected,and were divided into polycythemia vera (PV)group,essential thrombocy-hemia (ET)group,and myelofibrosis (PMF)group according to their subtypes,with 28 cases in each group. The scores of MPN-SAF-TSS were compared among the three groups. Besides,the scores of the scale (myelo-proliferative neoplasm symptom assessment form total symptom score,MPN-SAF-TSS)in different treatment periods (at the time of the visit,when the disease progressed,when the disease was stable,when the clinical improvement was made,when the partial remission was completed,at the time of remission and recurrence) were also compared. Results At the time of initial diagnosis,there were significant differences in the inci-dences of symptom burdens among the three groups of MPN patients with abdominal fullness (χ2 = 6. 095,P =0. 047),abdominal discomfort (χ2 = 7. 342,P = 0. 025),poor mobility (χ2 = 13. 029,P = 0. 001),inatten-tion (χ2 = 6. 099,P = 0. 047),pruritus (χ2 = 6. 956,P = 0. 031),bone pain (χ2 = 7. 807,P = 0. 020),fever (χ2 = 8. 000,P = 0. 018)and weight loss (χ2 = 27. 340,P < 0. 001). The incidences of poor mobility (85. 71％,24 / 28),inattention (67. 86％,19 / 28)and weight loss (82. 14％,23 / 28)in PMF group were significantly higher than those in PV group [42. 86％ (12 / 28),39. 29％ (11 / 28),35. 71％ (10 / 28)]and ET group [46. 43％ (13 / 28),39. 29％ (11 / 28),14. 29％ (4 / 28)](all P < 0. 05). The incidences of abdominal discomfort (75. 00％,21 / 28)and bone pain (60. 71％,17 / 28)in PMF group were higher than those in PV group [39. 29％ (11 / 28),25. 00％ (7 / 28)](both P < 0. 05). The incidences of abdominal fullness (89. 29％,25 / 28)and fever (42. 86％,12 / 28)in PMF group were higher than those in ET group [60. 71％ (17 / 28),10. 71％ (3 / 28)](both P < 0. 05). The incidence of pruritus in PV group (71. 43％, 20 / 28)was higher than that in ET group (42. 86％,12 / 28)and PMF group (39. 29％,11 / 28)(both P <0. 05). Symptom load scores of patients with fatigue (χ2 = 368. 594,P < 0. 001),abdominal fullness (χ2 =261. 312,P < 0. 001),abdominal discomfort (χ2 = 195. 629,P < 0. 001),poor mobility (χ2 = 217. 862,P <0. 001),lack of concentration (χ2 = 280. 664,P < 0. 001),night sweats (χ2 = 239. 650,P < 0. 001),pruri-tus (χ2 = 254. 418,P < 0. 001),bone pain (χ2 = 180. 291,P < 0. 001),fever (χ2 = 231. 613,P < 0. 001) and weight loss (χ2 = 227. 831,P < 0. 001)were significantly different during different therapeutic periods. The fatigue symptom load score was higher when the disease progressed than that at the time of the visit (P <0. 05),and the symptom score of abdominal fullness was lower than that at the time of visit (P < 0. 05). Symp-tom load scores of weakness and pruritus when the condition was stable was lower than those when the disease progressed (both P < 0. 05). When the clinical improvement was made,symptom load scores of weakness, abdominal discomfort,inattention,night sweats,weight loss were lower than those when the disease was stable (all P < 0. 05). Symptom load scores of abdominal fullness,poor mobility,inattention,night sweats and pruri-tus in partial remission period decreased compared to temporary improvement period (all P < 0. 05). Compared to the partial remission period,the symptom load scores of weakness,abdominal fullness,night sweats,pruri-tus,bone pain and weight loss in complete remission period were lower (all P < 0. 05). At last,symptom load scores of weakness,abdominal fullness,abdominal discomfort,poor mobility,inattention,night sweats,pruri-tus,bone pain,fever and weight loss in recurrence period were higher than those in complete remission period (all P < 0. 05). Conclusion There are several differences in the main clinical symptoms among patients with different MPN subtypes,and there are significant changes in the main clinical symptoms as the disease progresses or turns around.

The protective effect of salidroside on oxygen glucose deprivation/reoxygenation in human umbilical vein cells / 中国药理学通报

Aim To investigate the effects of salidro-side on oxygen glucose deprivation/reoxygenation ( OGD/R) injury in human umbilical vein cells ( HU-VECs ) and the possible mechanism. Methods OGD/R model was built after the density of cell growth reached 80％ ～85％. The OGD time point was deter-mined by MTT method to detect cell viability;LDH ac-tivity detection was used to explore the best dosage sol-ubility;NO content assay was applied to determine the best drug solubility, the degree of apoptosis was detec-ted by Annexin V/PI, and the expression of P-selectin was detected by immunohistochemistry. Results MTT detection determined that the time point of OGD was 16 h; LDH activity detection and NO content detection showed that the best efficacy of salidroside was 10μmol · L-1 . Compared with control group, Annexin V/PI detection showed that the apoptotic rate increased significantly ( P <0.01 ) after OGD/R, and the ex-pression of P-selectin in OGD/R group obviously in-creased ( P <0.01 ) . Compared with OGD/R group,the expression of P-selectin obviously declined ( P <0.05 ) , while the cell apoptotic rate increased ( P <0.05) after the administration. Conclusions Salidro-side may protect HUVEC cells from OGD/R injury and its mechanism may be related to related to the down-regulation of P-selectin and the inhibition of the pro-duction of inflammation.

The effects of secretory clusterin on oxidative damage in MIA PaCa-2 cells treated by gemcitabine and preliminary mechanism of resistance to gemcitabine / 中国癌症杂志

Background and purpose: Gemcitabine (GEM) is a first-line chemotherapy drug for pancreatic cancer. With the emergence of clinical drug resistance, the efficacy of chemotherapy has been greatly reduced, while the expression of secretory clusterin (sCLU) was closely related to chemotherapy resistance in multiple tumors. This study aimed to explore the effects of secretory clusterin on oxidative damage in MIA PaCa-2 cells treated by GEM and preliminary mechanism of resistance to GEM. Methods: MIA PaCa-2 was exposed to GEM and sCLU intervened groups with different concentrations (0, 0.63, 1.25, 2.50, 5.00 and 10.0 μg/mL) for 24 hours. The intervened concentration of GEM was 5.4 μmol/L. The inhibition rates of cell proliferation were determined by CCK-8. Cell reactive oxygen species (ROS) was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Superoxide dismutase (SOD) activity and catalase (CAT) activity were measured by their corresponding assay kits respectively. Results: Compared with the negative control group (0 μg/mL), the inhibition rates of the GEM groups and sCLU intervened groups were significantly increased (P＜0.05) in a distinct dose-effect manner. At a low concentration of 0.63 μg/mL, the inhibition rates of the GEM groups were higher than those of the sCLU intervened groups, while the trend was reversed in high concentration range. Compared with the negative control group (0 μg/mL), the intracellular ROS levels, SOD and CAT activity of the GEM and sCLU intervened groups significantly increased (P＜0.05). ROS levels presented a distinct dose-effect relationship while the SOD and CAT activities increased first and then decreased along with the increase of GEM concentrations. The ROS levels of the GEM group were lower than those of the sCLU intervened group at the same dose (P＜0.05). The SOD activities of the GEM group were higher than those of the sCLU intervened group, while the CAT activities were opposite at the concentrations of 5.00 and 10.00 μg/mL (P＜0.05). Conclusion: GEM exposure can inhibit the growth of MIA PaCa-2 cells. After GEM exposure, the ROS levels, SOD and CAT activity of MIA PaCa-2 cells can be changed by sCLU intervention. GEM resistance could be regulated by sCLU through oxidative damage effect.

Analysis on correlation between coronary lesion with serum Cys C and endothelial function in patients with coronary heart disease / 重庆医学

Objective To investigate the correlation between coronary lesions with serum cystatin C (Cys C)and vascular endothelial function(RHI)in the patients with coronary heart disease(CHD).Methods A total of 318 patients receiving coronary angiography(CAG)were selected as the research subjects and divided into the control group(65 cases)and CHD group;then the CHD group was divided into the single-vessel lesion group(77cases),double-vessel lesions group(70c ases),multiple-vessel lesions group(106 cases)according to CAG and the number of disease vessels;the CHD group was re-divided into the low score group(67 cases),middle score group(107 cases)and high score group(79 cases)according to the Gensini score of coronary artery lesions.The vascular endothelial function was evaluated by using peripheral arterial tension (PAT)measurement technique.The reactive hypere-mia index(RHI)was calculated;serum Cys C level was determined by immunoturbidimetry.Results The serum Cys C level was in-creased and RHI level was reduced as the number of lesion vessels increasing,the inter-group comparison showed the statistical difference (P 0.05);the serum Cys C level was increased as the Gensini score increasing,the difference between the groups had statistical significance (P <0.05);the vascular RHI value was reduced as the coronary Gensini score increasing(P <0.05);moreover the Cys C level was positively correlated with the Gensini score (r=0.375,P <0.01);RHI was negatively correlated with corornary Gensi-ni score (r=-0.587,P <0.01 );the serum Cys C was negatively correlated with RHI(r =-0.350,P <0.01 ).Conclusion The vascular endothelial dysfunction and serum Cysc C level increase are associated with coronary lesions in CAD patients,moreover Cys C is negatively correlated with vascular RHI,serum Cys increase may be a predictive index for vascular endothelial function damage in CHD patients.

Practice of Clinical Pharmacists Participating in Drug Treatment for a Leukemia Child with Neutrophil De-ficiency Complicated with Fever / 中国药房

OBJECTIVE:To explore the role of clinical pharmacists in the process of drug treatment for leukemia children with neutrophil deficiency complicated with fever (NDCF). METHODS:Clinical pharmacists participated in the treatment for a leuke-mia child with NDCF. Considering about continuous decrease of platelet accompanied by epistaxis,combined with age,clinical symptom,lab indexes and related guidelines,clinical pharmacists thought it was possibly associated with bone marrow induced by chemotherapy drugs and drug-induced hemorrhage induced by cefoperazone sodium and sulbactam sodium. It was suggested to stop using cefoperazone sodium and sulbactam sodium;use Meropenem for injection 1.0 g,ivgtt,q8 h instead for anti-infection;addi-tionally use Recombinant human thrombopoietin injection 15000 U,sc,qd for elevating platelet. During treatment,taking into ac-count the low levels of neutrophils(0.17×109 L-1)and platelets(11×109 L-1)in this child,it was recommended to continue anti-in-fection and elevating platelet treatment,and continue to use Lienal polypeptide injection to auxiliarily enhance hematopoietic func-tion. When the child's condition was stable and neutrophils returned to normal,it was successively recommended to stop elevating platelet and anti-infection treatment;at the same time,conduct pharmaceutical care as body temperature examination,related indi-cator examination (such as routine blood test) and ADR monitoring,etc. RESULTS:Physicians adopted the clinical pharmacist's suggestions. The body temperature of the child was decreased,the hemogram recovered gradually,no infection occurred,and the next round of chemotherapy was successfully carried out. CONCLUSIONS:The clinical pharmacists participate in drug treatment for leukemia children with NDCF,pay attention to the prevention,diagnosis and treatment of drug-induced disease,and make com-prehensive analysis by using their own professional advantage,taking the possible effects of drugs on blood system,pharmacody-namics and pharmacokinetic characteristics as the breakthrough point,combing with the specific situation of children's age and ill-ness;assist physicians to formulate and optimize drug therapy plan so as to guarantee safe and effective drug use.

2-Deoxyglucose improves sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin by blocking aerobic glycolysis / 中国药理学通报

Aim To investigate the effect of 2-deoxy-D-glucose(2-DG)on the sensitivity of leukemia multi-drug resistant K562/ADMcells to adriamycin by inhib-iting glycolytic pathway as well as its molecular mecha-nisms.Methods The leukemia drug-resistant K562/ADM cells and parental K562 cells were used as the target cell models.The cell proliferating activity was assessed with an MTT colorimetric assay,and the gly-colysis including glucose consumption,lactate export, and hexokinase activity was determined by glucose, lactic acid and hexokinase (HK)testing kits.The ex-pression and phosphorylation of mammalian target of rapamycin(mTOR)and glucose transporter-4 (GLUT-4)expression were analyzed by western blot.Results K562/ADM drug-resistant cells possessed higher HK activity,GLUT-4 expression level and aerobic glycolic ability than K562 sensitive cells. 2-DG treatment markedly inhibited HK activity,glucose consumption, and lactate export both in K562 cells and K562/ADM cells,and suppressed the proliferation of the two cells in a time-and concentration-dependent manner.Low concentration of 2-DG or adriamycin could increase the expression and phosphorylation of mTOR.However, the co-administration of 2-DG and adriamycin markedly counteracted adriamycin-mediated enhancement of mTOR expression and phosphorylation and down-regu-lated GLUT-4 expression in K562/ADM cells,and 2-DG dramatically improved the sensitivity of K562/ADM cells to cytotoxicity.Conclusion 2-DG inhibits the proliferation of drug-resistant K562/ADM cells and en-hances the sensitivity to adriamycin by blocking aerobic glycolysis pathway through inhibiting hexokinase activi-ty,counteracting adriamycin-stimulated increased ex-pression and phosphorylation of mTOR and downregu-lating GLUT-4 expression.

Cytotoxicity of Mycobacterium indicus pranii on Mia-Pa-Ca2 cells

Background: MIP is a cultivable, non-pathogenic organism, which shares several antigens with Mycobacterium tuberculosis and Mycobacterium leprae. It has several proposed clinical applications. However, its cytotoxic effect on pancreatic cancer has not been documented. Hence, the study was conducted to investigate MIP induced cytotoxicity on Mia-Pa-Ca2 cells. To determine the cytotoxic potential of heat killed Mycobacterium indicus pranii (MIP) on pancreatic cancer cells in vitro along with gemcitabine & 5-fluorouracil (5-FU). Mitogen-activated protein kinase (MAPK) level was also studied post MIP treatment. Methods: Cytotoxic effect of MIP, gemcitabine and 5-FU on Mia-Pa-Ca2 cells was determined. We have analyzed extent of apoptosis using flow cytometry and changes in p38 levels, c-Jun N-terminal kinases (JNK) and extracellular signal­regulated kinase (ERK) using ELISA. Results: MIP not only exhibits cell cytotoxicity in dose dependent manner, but also enhances efficacy of gemcitabine and 5-FU when used in combination. Flow cytometry analyses reveals apoptosis of Mia-Pa-Ca2 cells post MIP treatment compared to untreated cells. MAPK pathway study using ELISA shows that p38 and JNK levels are suppressed while there is no change in ERK level. Conclusion: With these results we conclude that MIP is a cytotoxic agent. Cytotoxicity is exhibited by apoptosis. Combining MIP with gemcitabine and 5-FU shows synergistic effect (AU)

Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

Frequency of Mia antigen: A pilot study among blood donors.

The Miltenberger (Mi) classes represent a group of phenotypes for red cells that carry low frequency antigens associated with the MNSs blood group system. This pilot study was aimed at determining the Mia antigen positivity in the blood donor population in a tertiary care hospital in New Delhi, India. The study was performed between June to August 2014 on eligible blood donors willing to participate. Antigen typing was performed using monoclonal anti-Mia antiserum by tube technique. Only one of the 1000 blood donors (0.1%) tested was found to be Mia antigen positive. The Mia antigen can, therefore, be considered as being rare in the Indian blood donor population.

Anti-inflammatory effect of egg white-chalcanthite and purple bamboo salts mixture on arthritis induced by monosodium iodoacetate in Sprague-Dawley rats / 한국실험동물학회지

The aim of this study is to investigate the potential of anti-osteoarthritis effects on egg white-chalcanthite (EC), purple bamboo salts (PBS), and a mixture of EC and PBS (EC+PBS). EC is a mixture of egg white and pulverized chalcanthite. PBS has been widely used as one of functional foods in Korea and shows unique features compared with common salt. Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA, 4mg/kg bw) in Sprague-Dawley (SD) rats. Test substances were administered once daily for 6 weeks at doses of 10 mg EC, EC+100 mg PBS, EC+200 mg PBS before and after MIA injection. Each substance was assessed by blood chemistry parameters, and by serum cytokines including IL-1β and IL-6, and nitric oxide (NO) and prostaglandin-E2 (PGE2). Structural changes of articular cartilage were also evaluated by histopathological examination. As a result, body weight and blood chemistry parameter were not different in all experimental groups. EC+PBS mixture reduced the production of PGE2, NO, IL-1β, and IL-6. In histological grade of osteoarthritis, EC+PBS mixture had a tendency to ameliorate damage of articular cartilage induced by MIA in a dose-dependent manner. In conclusion, EC+PBS mixture was demonstrated to have a potential for anti-inflammatory effect against osteoarthritis induced by MIA in a dose-dependent manner.

The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 microl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Effects of HSP70 inhibitor on expression of iNOS induced by IFN-γ / 中国药理学通报

Aim To research the effects of HSP70 in-hibitor ( PFTμ) on the expressions of iNOS induced by IFN-γ in RAW 264. 7 cells. Methods The NO con-centration was measured by Griess Kit. The expression of interest protein was measured by Western blot and iNOS mRNA was measured by RT-PCR. Mouse cardi-ac ischemia-reperfusion ( I/R ) model was established to set up the inflammatory response. These were divid-ed into control and treated groups. The infarct size was monitored on myocardial I/R mice. Results We found that PFTμsignificantly blocked the production of NO and the expression of iNOS protein and mRNA in RAW 264. 7 cells. The mechanism may be part of the inhibition of nuclear IRF-1 protein expression. We also found that PFTμ reduced the infarct size in myocardial I/R mice ( P <0. 05 ) . Conclusion These results suggest that PFTμ down-regulates the IFN-γ-induced iNOS transcription through decreasing translocated IRF-1 protein.

A short version of the questionnaire of metamemory in adulthood (MIA) in portuguese

The aim of this study was to develop a short version of the Metamemory in Adulthood Questionnaire (MIA) in Brazilian Portuguese. The original MIA is an instrument in english composed by 108 items, divided into seven dimensions of metamemory (Strategy, Task, Capacity, Change, Anxiety, Achievement and Locus). Despite of being widely used, the extension of the instrument makes its application impractical in many contexts, reinforcing the need for a short version. A total of 472 participants answered the original full version of the MIA. First, Item Response Theory (IRT) analyses revealed that nine items of the instrument could be excluded due to poor infit and outfit values. After exploratory factor analyses, the 99 items left were judged by five experts that chose the most appropriate items following previously established criteria (factor loading, repetitiveness, bad writing, and temporal/cultural inadequacy). A 39-items version (MIAr) was obtained, with the same factorial structure of the original MIA. The MIAr demonstrated satisfactory internal consistency indexes, as well as evidences of convergent validity and validity based on the response process. The results revealed that the MIAr achieved good psychometric properties, serving as a more parsimonious and practical option for metamemory assessment. (AU)