Induced pluripotent stem (iPS) cell based on recently developed stem cell reprogramming technique holds great hope for regenerative medicine,in vitro disease modeling and drug evaluation.Recent progress on clinical hematology includes in vitro generation of hematopoietic progenitors and mature blood cells from somatic cells,iPS cells derived from chronic myeloid leukemia cells for the better understanding of the resistance mechanisms of bcr-abl inhibitor imatinib,and moreover,correction the monogenic inherited disease using gene-targeted strategies.However,whether the iPS cells can fully replace human embryonic stem cells still needs further investigation.

AimTo evaluate the effects of different doses of valsartan on blood pressure and left ventricular hypertrophy in spontaneously hypertensive rats (SHR) . MethodsEighteen SHR(fourteenweek-old, male) were divided into three groups (six rats in each group ): SHR control group in which the rats were fed with normal saline; low dose valsartan group in which the rats were fed with valsartan 8 mg· kg-1 · d-1 and high dose valsartan group in which the rats were fed with valsartan 24 mg · kg -1 · d-1, all for 8 weeks. The rats in the WKY control group(n ＝ 6) were fed with normal saline for 8 weeks. Results SBP, LVM/ BW and TDM of SHR were remarkably lower than those of the control after drug intervention, and the effect on SBP, LVM/ BW and TDM was most remarkable in the high dose valsartan group. ConclusionDifferent doses of valsartan can decrease SBP of SHR and inhibit the progression of ventricular hypertrophy.

Objective To investigate the incidence and risk factors of adverse drug reactions in hematological system induced by linezolid.Methods In this retrospective study, 124 inpatients treated with linezolid (n=62) or vancomycin (n=62) for anti-infective therapy between January 2012 and December 2015 in clinical departments of the Second Affiliated Hospital of Anhui Medical University were included.The incidence hematological adverse drug reactions were observed, and the single factor and the multiple factor Logistic regression methods were used to analyze the risk factors of developing thrombocytopenia and decline of hemoglobin.Results Among the 62 inpatients treated with linezolid, thrombocytopenia occurred in 21 patients(33.87%), and decline of hemoglobin occurred in 17 patients (27.42%).No patient discontinued the use of linezolid for the reason of thrombocytopenia or decline of hemoglobin.In multiple stepwise regression analysis, linezolid use[OR=7.699,95%CI (1.408,42.090),P=0.019], treatment duration>14 d[OR=7.639,95%CI(1.162,50.226),P=0.034], baseline eGFR<80 mL·min-1[OR=6.150,95%CI(1.604,23.577),P=0.008], baseline ALB<25 g·L-1[OR=4.078,95%CI(1.017,16.351),P=0.047] and baseline platelet count<200×109·L-1[OR=6.148,95%CI(1.705,22.172),P=0.006] were independent risk factors for thrombocytopenia;linezolid use [OR=4.335,95%CI(1.308,14.365),P=0.016] and baseline ALB<25 g·L-1[OR=5.424,95%CI(1.824,16.129),P=0.002] were independent risk factors for the decline of hemoglobin.Conclusion The incidences of thrombocytopenia and anemia induced by linezolid are not rare, and most of them can be returned to normal.The risk factors of thrombocytopenia and anemia should be concerned and the routine blood test should be monitored during use.

Objective To explore the clinical manifestation, imaging examination, treatment and prognosis of Alagille syndrome in a child combined with hepatocellular carcinoma. Method The clinical manifestation, assistant examination and diagnosis of Alagille syndrome combined with hepatocellular carcinoma were analyzed in the child, and the pertinent literature were reviewed. Results The 6-year-old girl was admitted to hospital for repeated jaundice, and had a history of cardiac surgery. After admission, the patient was found to have a typical face look such as frontal bossing, sunken eyes, pointed chin and hypertrophy of nasal tip. Blood biochemistry showed intrahepatic cholestasis and increased alpha-fetoprotein. Abdominal ultrasonography revealed diffuse multiple solid lesions in the liver. And magnetic resonance imaging of the liver indicated that the liver was enlarged and multiple solid space occupying masses. Jagged 1 gene detection showed heterozygosis mutation of c.1205delC. Conclusion Alagllie syndrome complicated with hepatocellular carcinoma in childhood is extremely rare, and early diagnosis and long-term follow-up are of positive significance for its treatment and prognosis.

Objective To assess the efficacy and safety of different dosages of oxycodone plus acetaminophen for treating acute pain after oral surgery,in order to provide a reasonable dosage of combination in clinic. Methods Randomized controlled trials ( RCTs ) on effect of combination of oxycodone plus acetaminophen on pain relief after oral operation were searched from the following data-bases:PubMed,EMbase,MEDLINE ( Ovid) ,the Cochrane Library,CNKI,and WANFANG from the date of their establishment to January 2015. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods by two reviewers independently,and after the quality was evaluated and cross-checked,meta-analyses were conducted using RevMan 5.2 software. Results A total of 11 studies in 10 literatures involving 1 028 patients were included and were designated to 3 different dosage groups (5 mg/325 mg,10 mg/650 mg,10 mg/1 000 mg,respectively). The results of Meta-analyses showed that pain remission rate was significantly higher in the 3 different dosages of oxycodone plus acetaminophen groups than in the placebo group (RR5 mg/325 mg=3.35,95%CI [1.74,6.45],I2=38%,P=0.000 3;RR10 mg/650 mg=6.88,95%CI [4.00,11.83],I2=0%,P<0.000 01;RR10 mg/1 000 mg=4.94,95%CI [3.23,7.56],I2=81%,P=0.005). In additional,the RR of oxycodone 10 mg/acetaminophen 650 mg and placebo groups for pain remission rate was higher than that of the other 2 dosages groups,moreover,more studies were enrolled and its low heterogeneity led to high reliability. Usage rate of remedial painkillers was significally lower in oxycodone plus acetaminophen groups than in the placebo group (RR5mg/325mg=0.71,95%CI [0.60, 0.85],P<0.000 01;RR10mg/650mg=0.50,95%CI [0.41,0.61],P<0.000 01;RR10mg/1000mg=0.77,95%CI [0.66,0.90],P=0.001) ,In addition, the RRs of usage rate in oxycodone 10 mg/acetaminophen 650 mg and placebo groups were significantly lower than the other 2 dosages groups. Incidence rates of adverse effects were similar in the 3 different dosages groups and higher than that of the placebo group. However,the adverse events were generally described as mild to moderate in severity and rarely led to drug withdrawal according to all reports in the studies ( only one event ) . Conclusion The present study showed that combination of oxycodone plus acetaminophen can provide better analgesia in acute pain after oral surgery with high safety. In addition,combination of oxycodone 10 mg plus paracetamol 650 mg may be better for acute pain relief after oral surgery.

Objective To assess the effectivity and safety of oxycodone plus acetaminophen for postoperative acute pain re‐lief .Methods Randomized controlled trials (RCT ) on combination of oxycodone plus acetaminophen treating postoperative pain re‐lief were searched from the following data‐bases as PubMed ,EMbase ,MEDLINE(Ovid) ,the Cochrane Library ,CNKI and WAN‐FANG from the date of their establishment to September 2014 .The data of RCT meeting the inclusive criteria were extracted ac‐cording to Cochrane methods by two reviewers independently ,and after the quality was evaluated and cross checked ,meta analyses were conducted using RevMan 5 .2 sotware .Results A total of 18 studies involving 2 213 patients were included .The results of Meta‐analyses showed that compared with placebo group or the equal dosage oxycodone alone group ,the combinations of oxycodone plus acetaminophen were more effective in postoperative pain relief (P<0 .01) .However ,there are no significant difference in the effective between the combinations of oxycodone plus acetaminophen and the higher dosage oxycodone alone group or the acetamin‐ophen alone group for postoperative pain relief (P>0 .05) .Adverse events occurred more frequently with combination therapy than placebo or acetaminophen alone group ,but were generally described as mild to moderate in severity and rarely led to withdrawal . There are no significant difference in the adverse events between the combination of oxycodone plus acetaminophen and the oxyc‐odone alone group .Conclusion The present study showed that combination of oxycodone plus acetaminophen is effective and high safe in postoperative acute pain relief .

Objective To constitute a database of chronic wounds for characterizing the patients with chronic wounds.Methods Based on the guideline of chronic wounds defined by international wound healing society,86 outpatients with chronic wounds were selected between January and October in 2013 to set up a wound database using the wound information management system.The parameters including etiology,age distribution,mean time of fracture healing and wound healing time posterior to different treatments were analyzed.Results (1) Statistical difference existed for cause distribution (P ＜0.05).Top three causes were trauma (29％),varicosity (26％) and pressure sore (19％).(2) Age distribution varied significantly among the patients with various causes of chronic wounds (P ＜ 0.05).(3) Statistical difference was observed in healing time of various types of chronic wounds (P ＜ 0.05).Diabetic wound and varicose ulcer took the longest healing time,with average 116.36 days and 88.48 days respectively.(4) Patients treated with novel dressings had shorter healing time than those managed with traditional dressings (P ＜ 0.05).Conclusions Trauma,varicosity and pressure ulcer are relatively common among the outpatients.Etiology of chronic wounds is strongly related to age and novel dressings contributed to a shortened cause of the disorder.

Aim To investigate the effect of intrathecal injection of CCR2 antagonist on pain behaviours,spinal astrocytes activation in the spinal cord in a rat model of bone cancer pain. Methods Forty female SD rats weighing 150 ~180 g were randomly divided into five groups ( n=8 each ):(Ⅰ) sham group;(Ⅱ) sham +RS102895 group;(Ⅲ) bone cancer pain group;(Ⅳ) bone cancer pain + DMSO group;(Ⅴ) bone cancer pain+RS102895 group. Rats received i. t. injections of either RS102895 (3 g·L-1 ) 10 μl or 10%DMSO 10 μl at the time of 10-12 days after the operation. Bone cancer was induced by intra-tibial inoculation of 1 × 105 Walker 256 breast cancer cell. Mechanical hind paw withdrawal threshold test was performed one day before and at 3rd,6th,9th, 10th,11th and 12th days after surgery. Immunofluorescence was used to observe the activation of the spinal astrocytes. Results Compared with group Ⅰ, the rats in bone cancer pain group appeared obvious mechanical hyperalgesia (Ⅲ、Ⅳ、Ⅴ) ,the volume,shape and mean optical den-sity ( MOD) of spinal astrocytes could be seen obvious-ly increased,groupⅡhad no obvious statistical signifi-cance (P>0. 05). Compared with group Ⅳ ,i. t. in-jections of RS102895 increased the paw mechanical withdrawal threshold, suppressed the action of astro-cytes,reduced the MOD of spinal astrocytes. Conclu-sion CCR2 might participate in the formation of bone cancer pain via activating spinal astrocytes. CCR2 will be a potential target for the treatment of bone cancer pain.

With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.
Enzymes ; chemistry ; Humans ; Inactivation, Metabolic ; Mass Spectrometry ; Membrane Transport Proteins ; chemistry ; Pharmacokinetics ; Proteomics