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.

Objective To explore the diagnosis and management of functional pancreatic endocrine tumor.Methods Clinical data of 19 cases of functional pancreatic endocrine tumor were retrospectively analyzed.Results 15 cases of insulinoma,2 cases of gastrinoma and 2 cases of glucagonoma were qualitatively diagnosed.The positive rate of preoperative diagosis for type B ultrasonic inspection,CT,MRI,EUS,selective portovenous sampling and intraoperative type B ultrasonic inspection was 15.8％ (3/19),67.5％ (10/16),71.4％ (5/7),87.5％ (7/8),100％(2/2) and 85.7％(6/7) respectively.Of the total 19 cases,7 cases underwent open surgery,11 cases unde rwent laparoscopic surgery,and one case didn't undergo any surgery as liver metastasis had occurred when glucagonoma was diagnosed.The operation methods included tumor enucleation (n=13),distal pancreatic resection (n=3),distal pancreatic resection plus splenectomy (n=1),and pancreatic head resection with duodenum preserved (n=1).Conclusions The measurement of serum insulin,gastrin and glucagon is the main basis for qualitative diagonosis of pancreatic endocrine tumor.Two stage spinal CT thin scanning is the main method for tumor location.Intraoperative type B ultrasonic inspection is the supplement to preoperative location.Tumor enucleation is the main choice of treatment.

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

Objective To study the Effect of acute peripancreatitc fluid collection and pancreatic necrosis to the prognosis of acute pancreatitis.Methods Retrospectively analyzing the prognostic effect of acute peripancreatitc fluid collection and pancreatic necrosis according to the early Computed-Tomograghy of 323 consecutive acute pancreatitis patients from Jan 2003 to Dec 2007,the end points are systemic inflammation response syndrome ( SIRS),pancreatic infection,and mortality.Results Within 5d after onset,97 of 323 cases (30%) presented with SIRS and lasted more than 2d,12 cases (3.7%) occurred pancreatic infection during middle or late phase,14 cases died,the mortality is 4.3%.141 of 323 cases (43.7%) who had acute peripancreatic fluid collection presented with SIRS,acute peripancreatic fluid collection correlated significantly with the occurrence of SIRS,P ＜ 0.05.227 cases (277/323,85.8%) had no pancreatic necrosis,no pancreatic infection occurred,46 cases (46/323,14.2% )had pancreatic necrosis,pancreatic necrosis correlated significantly with pancreatic infection,P ＜ 0.05.Conclusions Acute poripancreafic fluid collection and pancreatic necrosis had different prognostic effect to acute pancreatitis.Acute peripancreatic fluid collection correlated well with the occurrence of SIRS during the early phase;Pancreatic necrosis may be infected during middle or late phase of acute pancreatitis,more extent of pancreatic necrosis,more possible that pancreatic infection will occur.

Objective: To evaluate left atrial (LA) function and synchrony in lone atrial fibrillation (LAF) patients by two-dimensional speckle tracking echocardiography (2D-STE) and to explore the predictive value of 2D-STE parameters for AF recurrence after ablation procedure. Methods: Our research included in 2 groups: LAF group,n=50 patients diagnosed in our hospital from 2013-06 to 2015-05; it was further divided into 2 subgroups as Non-LA enlargement subgroup,n=34 and LA enlargement subgroup,n=16 and Control group,n=35 healthy subjects. With sinus rhythm, 2D-STE was conducted to obtain LA peak ventricular systolic longitudinal strain (PALS), strain rate (SRs) and atrial contraction longitudinal strain (ACLS), strain rate (SRa). Standard deviation for the time to peak (TPSD) of regional strain was calculated. TPSD during ventricular systole was named as SDs and TPSD during ventriculardiastole was named asSDa. Results: Compared with Control group, LAF group had reduced PALS (28.34±8.57) vs (38.73±6.13), SRs (1.17±0.31) vs (1.57±0.25), ACLS (14.11±4.91) vs (18.86±3.57 ) and SRa (-1.41±0.58) vs (-1.90±0.30), allP<0.05; while elevated SDs (8.11±3.00) % vs (4.67±1.48) % and SDa (5.57±2.26) % vs (3.11±1.13) %, bothP<0.05. Furthermore, Compared with Control group, Non-LA enlargement subgroup had decreased PALS, SRs, ACLS and SRa, allP<0.05; while increased SDs and SDa, bothP<0.05. Logistic regression analysis indicated that compared with traditional parameters, SDs and SDa could more effectively distinguish LAF patients from normal subjects (SDs with the sensitivity 83%, speciifcity 72% and SDa with the sensitivity 81%, speciifcity 76%). Elevated SDa and SDs were the best predictors for post-operative AF recurrence (SDs with the sensitivity 80%, speciifcity 71% and SDa with the sensitivity 86%, speciifcity 79%). Conclusion: 2D-STE may detect LA dysfunction and dyssynchrony in LAF patients, abnormal parameters could be found in LAF patients without LA enlargement. SDs and SDa were the best predictors for post-operative AF recurrence.

Objectives To study the age and gender distribution of clinical and non-clinical depressive symptoms in chil-dren, and the potential link between non-clinical and clinical depressive symptoms. Methods 4520 children aged 8-15 years old were screened for mental disorders by Strength and Dififculties Questionnaire (SDQ) and the Development and Well Being Assessment (DAWBA), and further assessed by the Depression Self-Rating Scale for Children (DSSC). Fifty-three children diagnosed as depressive disorder were included in clinical group and 1504 children without depression disorders whose DSSC scores≥14 were included in non-clinical group. The relationship between gender, age and DSSC scores was analyzed. Results Interaction effect on DSSC scores between gender and age was found in clinical group (F=4.40, P=0.049), but not found in non-clinical group (F=1.04, P=0.409). DSSC scores of girls were higher than that of boys in clinical group (t=2.16, P=0.048). There was no statistically signiifcant main effect of gender in non-clinical group (F=0.21, P=0.646). No signiifcant difference in DSSC scores existed among different age groups in clinical group (F=0.82, P=0.573). There was signiifcant main effect of age in non-clinical group (F=1.96, P=0.048). Conclusions There were different age and gender distribution of clinical and non-clinical depressive symptoms in children.

AIM: To investigate the binding characteristics of cholecystokinin receptors in rat pulmonary interstitial macrophages (PIMs). METHODS: The PIMs were isolated from rat lung tissues, purified using the collagenase digestion method combined with alveolar lavage and pulmonary vessel perfusion. The PIM membrane was obtained by supercentrifuge. Receptors for CCK in PIMs were examined using [~3H] labeled CCK-8S as ligand. The specificity of [~3H]-CCK-8S binding to PIMs membrane and the subtypes of CCK receptors were determined by competitive inhibition experiments with CCK-8S, CCK-A and CCK-B receptors selective antagonists (CR1409 and CR2945). The effects of time and incubation temperature on the specific binding were also observed. RESULTS: The specific binding of [~3H]-CCK-8S was not detected in normal rat PIMs, but was detected in the rat administrated with LPS for 48 h. The capacity of ligand-receptor binding was dependent on the incubation temperature and time. Scatchard analysis of the saturation curves suggested that the presence of CCK receptors with high affinity [Kd=(0.68?0.28)mmol/L] and low binding capacity [Bmax=(32.50?2.70) pmol?g~(-1) protein] in PIMs. By means of competitive inhibition studies, the specific binding of [~3H]-CCK-8S to rat PIMs was inhibited by unlabelled CCK-8S [IC_(50)=(3.20?1.13) nmol/L], CCK-AR specific antagonist CR 1 409 [IC_(50)=(0.19?0.06)?mol/L] and CCK-BR specific antagonist CR 2945[IC_(50)=(2.30?0.80)nmol/L]. CONCLUSION: These results suggest the presence of two subtypes of CCK-AR and CCK-BR and provide a structural basis for CCK to play a pivotal role in PIMs.

OBJECTIVETo transfect a short hairpin RNA (shRNA) against survivin gene into human T lymphoblastic leukemia cell line Jurkat, and to explore the effects on apoptosis and proliferation of transfected cells.

METHODSThe survivin-shRNA expression vector were constructed and transfected into Jurkat cells. Expression of survivin mRNA and protein were assessed by RT-PCR and Western blot analysis respectively. Apoptosis index of transfected Jurkat cells was quantified by flow cytometry. The potential of cell proliferation was described by cell growth curves.

RESULTSIn survivin-shRNA transfected Jurkat cells, survivin mRNA levels were significantly reduced by 66.67% ( transient transfection) and 60.69% ( stable transfection) respectively, compared with that in control-shRNA treated group and PBS treated group (P < 0.05); and the levels of survivin protein were significantly reduced by 63.41% (transient transfection) and 60.18% (stable transfection), compared with that in the two control groups (P < 0.05). Apoptosis index was significantly increased during both transient and stable transfection, respectively [(22. 41 +/- 2.83)% and (20.73 +/- 2.56)% (P < 0.05)]. Survivin-shRNA also inhibited the proliferation of Jurkat cells.

CONCLUSIONSVector-based survivin-shRNA can effectively reduce the expression of survivin gene, induce apoptosis

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Gene Expression ; Gene Silencing ; Humans ; Inhibitor of Apoptosis Proteins ; Jurkat Cells ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA Interference ; RNA, Messenger ; biosynthesis ; RNA, Small Interfering ; pharmacology

OBJECTIVETo investigate the dynamic activity of NF-kappaB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain.

METHODSFrom January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment), ulinastain group (25 cases of multiple injury with ulinastain treatment), and mild injury group (20 cases) for basic control. The inclusion criteria for mild injury group were AIS-2005 less than or equal to 3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-kappaB activity in monocytes and the level of TNF-alpha,IL-1, IL-6 in serum on admission (day 0), day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups.

RESULTSNF-kappaB activity in monocytes and TNF-alpha,IL-1 and IL-6 of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-kappaB activity and levels of TNF-alpha,IL-1 and IL-6 were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d+/-3.1 d and 10 d+/-3.5 d in ulinastain group and control group respectively, and showed a significant difference.

CONCLUSIONSNF-kappaB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory response syndrome and multiple organ dysfunction syndrome, but does not show the ability to decrease the activity of NF-kappaB .

Cytokines ; Humans ; Interleukin-6 ; blood ; Multiple Trauma ; NF-kappa B ; Tumor Necrosis Factor-alpha

OBJECTIVETo study the emergency care effect of in-hospital severe trauma patients with the injury severity score (ISS) larger than or equal to 16 after medical staff received advanced trauma life support (ATLS) training.

METHODSATLS training was implemented by lectures, scenarios, field practices, and examinations. The clinical effect of in-hospital severe trauma care was compared 2 years before and after ATLS training.

RESULTSDuring 2 years (from January 1, 2004, to December 31, 2005) before ATLS training, 438 cases of severe trauma were admitted and treated emergently in our department. Among them, ISS score was 28.6+/-7.8 on average, and 87 cases died with the mortality of 19.9%. The duration in emergency department and from admission to operation were 69.5 min+/-11.5 min and 89.6 min+/-9.3 min respectively. Two years (from January 1, 2007, to December 31, 2008) after ATLS training, 382 cases of severe trauma were admitted and treated. The ISS was 25.3+/-6.1 on average and 62 cases died with the mortality of 15.1%. The duration in emergency department and from admission to operation were 47.8 min+/-10.7 min and 61.5 min+/-9.9 min respectively. The ISS score showed no significant difference between the two groups (P > 0.05), but the mortality, the duration in emergency department and from admission to operation were markedly decreased after ATLS training and showed significant difference between the two groups (P <0.05).

CONCLUSIONATLS course training can improve the emergency care effect of in-hospital severe trauma patients, and should be put into practice as soon as possible in China.

Adult ; Emergency Medical Services ; Female ; Humans ; Life Support Care ; Male ; Middle Aged ; Time Factors ; Wounds and Injuries ; mortality ; therapy