ObjectiveTo establish the reference intervals for ALT,AST,GGT and LDH among the Han nationality in Beijing.MethodsThe document C28-P3 issued by CLSI was a guideline about how to define,establish,and verify reference intervals in the clinical laboratory.IFCC had established multicenter enzymes reference intervals based on the guideline.Exclusion criteria were designed for screening candidate reference individual according to the document C28-P3 and the multicenter study's experience.Blood specimens were collected from 315 healthy individuals aged 20 to 60 years old,including 132 males and 183 females.Reference materials were used to ensure the accuracy of the test results of the four liver enzymes.The methods which used to test the four liver enzymes could be traced to the IFCC enzymes reference measure procedure,the reagent of ALT and AST included pyridoxal phosphate.Results There was statistically difference between males and females of the referenceranges forALT, ASTand GGT.Therefore,gender-specific reference intervals were established as ALT:8.2 -50.8 U/L (F),12.7 -71.8 U/L (M) ; AST:15.0 -36.7 U/L ( F),16.6 -51.1 U/L (M) ;GGT:9.0 -37.3 U/L (F),12.0 -50.9 U/L (M).For LDH,the reference interval was 127 -224 U/L,as no significant gender difference was found.ConclusionsThe reference intervals for the four liver enzymes based on the population of the Han nationality in Beijing are established.The upper reference limit for ALT in Beijing Han population is higher than that from other similar studies.

Objective To investigate the changes of plasma ghrelin,growth hormone (GH) and growth hormone releasing hormone (GHRH) and gastric ghrelin in patients with chronic obstructive pulmonary disease( COPD ) and to explore their clinical significances.Methods Plasma ghrelin,GH,GHRH,TNFα,IL-6 and C reactive protein (CRP) were measured in 40 COPD patients and 20 controls with chronic bronchitis. Correlated factors of plasma ghrelin,TNFα,IL-6,CRP were analyzed. Body composition was assessed with bioelectrical impedance analysis.The expression of gastric ghrelin in patients with COPD was detected.Results Plasma ghrelin was higher in the underweight patients than in the normal weight patients and in the controls [ ( 1.78 ± 0.46 ) ng/L,( 1.39 ± 0.46 ) ng/L,( 1.36 ± 0.39 ) ng/L,respectively].Plasma GH was lower in the underweight patients than in the normal weight patients and in the controls [(4.12 ±0.83) μg,/L,(5.17 ±0.72) μg/L,(6.49 ± 1.13) μg/L,respectively].Plasma GHRH was lower in the underweight patients than in the normal weight patients and in the controls [ (20.43 ± 4.41 ) ng/L,(23.47 ± 3.97) ng/L,( 27.48 ± 10.06) ng/L,respectively ].Plasma ghrelin was higher in the underweight patients than in the controls ( P ＜ 0.01 ).Plasma ghrelin was higher in the underweight patients than in the normal weight patients with COPD.Plasma ghrelin (log transformed) was negatively correlated with BMI and percentage of body fat in the COPD patients.Plasma GHRH was positively correlated with ghrelin in the underweight patients ( r =0.515,P ＜ 0.05 ),while no correlation was found between plasma G H and ghrelin in the underweight patients (r =0.415,P ＞ 0.05 ).Plasma ghrelin was positively correlated with TNFα and IL-6 in the underweight patients.The gastric expression of ghrelin showed no evident difference between the patients with COPD and the controls.Conclusions The plasma GH in COPD patients may not be correlated with ghrelin.The plasma ghrelin level may be a useful indicator for malnutrition in COPD patients.Plasma ghrelin might be involved in the pathogenesis of CODP by affecting the body energy metabolism.

OBJECTIVETo investigate the role of nuclear factor-κB (NF-κB) activation in bilirubin-induced apoptosis of rat hippocampal neurons and the effect of TAT-NBD intervention on bilirubin neurotoxicity.

METHODSPrimary-cultured rat hippocampal neurons were treated with TAT-NBD in the initial 6 or 24 h or in the latter 6 h during a 24-h bilirubin exposure of the cells (early, continuous and late intervention groups, respectively). Immunocytochemistry was performed to detect NF-κB p65 protein expression, and the cell survival and apoptosis were assessed with a modified MTT assay, Annexin V-FITC/PI and TUNEL assay. IL-1β concentration in the supernatant was determined with ELISA.

RESULTSCompared with the control cells, bilirubin-treated cells showed a significantly increased NF-κB p65 protein expression (P<0.01), which reached the peak level at 6 and 24 h (P<0.01). The cell survival rate in early TAT-NBD intervention group was (80.784∓9.767)%, significantly lower than that of the control group (P<0.01) but higher than that of bilirubin group (P<0.01); the apoptotic rate in early TAT-NBD intervention group was significantly higher than that of control group (P<0.01) but lower than that of bilirubin group (P<0.01). IL-1β concentration was significantly lower in early TAT-NBD intervention group (15.348∓0.812 pg/ml) than in bilirubin group (P<0.05). The continuous and late TAT-NBD intervention groups showed comparable cell survival rate, apoptotic rate and IL-1β concentration with bilirubin group (P>0.05).

CONCLUSIONNF-κB bidirectionally regulates bilirubin-induced apoptosis of rat hippocampal neurons. Selective inhibition of the early peak of NF-κB by TAT-NBD offers neuroprotective effect. TAT-NBD can be potentially used for prophylaxis of bilirubin-induced brain injury.

Animals ; Apoptosis ; drug effects ; Bilirubin ; toxicity ; Cell Survival ; Cells, Cultured ; Female ; Hippocampus ; cytology ; Interleukin-1beta ; metabolism ; Male ; Neurons ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism

Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a traditional Chinese herbal medicine. Some recent studies prove its distinguished neuroprotective effect. These neuroprotective mechanisms have become hot points and show closely correlated to activating adenosine A1 receptor, ameliorating the function of cholinergic nerve, regulating ion channel homeostasis, retarding oxidative stress and apoptosis of the neurocytes, promoting nerve growth, having an influence on astrocytes and being ableto penetrate though blood brain barrier. In this review, we present the neuroprotective mechanisms of paeoniflorin in the following eight aspects.
Animals ; Apoptosis ; drug effects ; Benzoates ; analysis ; pharmacology ; Bridged-Ring Compounds ; analysis ; pharmacology ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Glucosides ; analysis ; pharmacology ; Humans ; Monoterpenes ; Neurons ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; analysis ; pharmacology ; Oxidative Stress ; drug effects ; Paeonia ; chemistry

Objective To preliminarily evaluate the effect of glycyrrhetinic acid on the proliferation and apoptosis of keratinocytes in patients with psoriasis,and to explore its possible mechanisms.Methods Keratinocytes were isolated from patients with psoriasis,and subjected to a primary culture in vitro.After 2-3 passages,the keratinocytes were divided into several groups to be treated with glycyrrhetinic acid at final concentrations of 0 (control group),1,2,4,8 and 10 mg/L (glycyrrhetinic acid groups),respectively.After 24-72 hours of treatment,MTS assay was performed to evaluate the effect of glycyrrhetinic acid on the proliferation of keratinocytes,and flow cytometry was conducted to detect the apoptosis of keratinocytes after 24-hour treatment with glycyrrhetinic acid at different concentrations.Real-time fluorescence-based PCR was performed to determine the expression of miR-21 in keratinocytes.Results After 24-72 hours of treatment with 1-10 mg/L glycyrrhetinic acid,the proliferation activity of keratinocytes significantly decreased along with the increase in the treatment duration and concentrations of glycyrrhizinic acid.After 24-hour treatment with 1,2,4,8,10 mg/L glycyrrhetinic acid,the apoptosis rates of keratinocytes increased to (9.64 ± 0.86)％,(25.24 ± 2.93)％,(27.68 ± 3.70)％,(35.55 ± 4.23)％ and (38.89 ± 2.31)％ respectively.As LSD-t test showed,the apoptosis rates of keratinocytes were significantly higher in all the glycyrrhetinic acid groups than in the control group (10.09％ ± 0.69％,all P ＜ 0.01),except the 1 mg/L glycyrrhetinic acid group.After 24-hour treatment with 1,2 and 4 mg/L glycyrrhetinic acid,the miR-21 expression (2-△△Ct) significantly decreased (0.24 ± 0.04,0.22 ± 0.07,0.17 ± 0.05,respectively) compared with the control group (0.92 ± 0.12,F =213.10,P ＜ 0.05).After 18-,24-and 48-hour treatment with 2 mg/L glycyrrhetinic acid,the miR-21 expression significantly decreased (0.55 ± 0.02,0.22 ± 0.06 and 0.15 ± 0.06 respectively) compared with the control group (0.98 ± 0.02,F =238.10,P ＜ 0.05).Conclusion Glycyrrhetinic acid can inhibit the proliferation of keratinocytes from psoriatic patients,but promote the apoptosis,likely by down-regulation of miR-21 expression.

Objective To evaluate serum albumin (ALB) combined with hemoglobin (Hb) (ALB-Hb) in the prediction of prognosis of patients with proximal gastric cancer.Methods Clinial data of 311 patients with stage Ⅰ-Ⅲ proximal gastric cancer who underwent radical surgery were retrospectively analyzed in Harbin Medical University Cancer Hospital from Sep 2001 to Nov 2014.The preoperative ALB-Hb was calculated as following:patients with both elevated serum albumin (≥40.25 g/L) and hemoglobin (≥120 in male or ≥110 g/L infemale) were given a score of 0,and patients with only one or none were given a score of 1 or2,respectively.The ALB-HB scores of 0 points had 175 cases (56.2％),1 point had 87 cases (28.0％),and 2 points had 49 cases (15.8％).The optimal cut-off value of serum albumin,platelet count and maximum tumor diameter were defined by ROC curve;Pearson correlation was used to evaluate the correlation coefficient between serum albumin and HB;Survival analysis was analyzed by Kaplan-Meier method.The prognostic factors for patients with proximal gastric cancer was analyzed by COX proportional hazards model.The ROC curve was used to compare the prognostic value of serum albumin,hemoglobin,and ALB-Hb.Results Patients with ALB-Hb score of 2 were associated with age,serum platelet level,and maximum tumor diameter (all P ＜ 0.05).The median survival time was 41 months (3-134 months).233 cases (74.9％) died and 78 cases (25.1％) survived as of Jan 2018.There was a significant difference in overall survival (OS) among A1B-Hb scores of 0,1,and 2 (P =0.011).Univariate analysis demonstrated that platelet count,ALB-Hb score,maximum tumor diameter,and clinical stage were related to the prognosis of patients with proximal gastric cancer (all P ＜ 0.05).By multivariate analysis there were statistically significant differences in pathological parameters:ALB-Hb score (HR =1.249,95％ CI 1.047-1.489,P =0.013),maximum tumor diameter (HR =1.352,95％ CI 1.016-1.799,P=0.038) and TNM clinical stage (HR=1.667 95％ CI 1.266-2.194,P＜0.001) is an independent risk factor for prognosis.ALB-Hb score compared to serum albumin and hemoglobin alone,has a higher AUC value (P =0.019).Conclusions The preoperative ALB-Hb score is superior to serum albumin or hemoglobin alone in assessing the prognosis for patients with stage Ⅰ,Ⅱ,and Ⅲ proximal gastric cancer.

Objective:To investigate the relationship between the changes of serum lipoprotein associated phospholipase A2 (Lp-PLA2), human Parkinson′s protein 7 (PARK7), erythropoietin (EPO) and neurological deficit score (NIHSS) and carotid intima-media thickness (CIMT) in patients with acute ischemic stroke (AIS).Methods:150 patients with AIS diagnosed in our hospital from January 2016 to January 2018 (AIS group) and 80 healthy subjects were selected as the control group. The Lp-PLA2, PARK7, EPO levels were compared between the two groups according to NIHSS score (mild, moderate and severe), carotid atherosclerotic plaque (unstable plaque, stable plaque, no plaque).Results:The serum level of Lp-PLA2, PARK7, EPO and CIMT values in the AIS group were significantly higher than those in the control group ( P<0.05). The Lp-PLA2 and PARK7 levels in the mild, moderate and severe AIS patients were gradually increased among the three groups, with statistically significant difference ( P<0.05). There was no significant difference in EPO levels between the different NIHSS groups ( P>0.05); The levels of Lp-PLA2, PARK7 and EPO of AIS patients in non plaque group, stable plaque group and unstable plaque group were gradually increased among the groups, and the difference between the two groups was statistically significant ( P<0.05). The level of Lp-PLA2 and PARK7 in patients with AIS and the NIHSS scores showed a significant positive correlation ( P<0.05). There was a significant positive correlation between Lp-PLA2, PARK7, EPO and CIMT in patients with AIS ( P<0.05). Conclusions:The serum levels of Lp-PLA2, PARK7 and EPO were significantly increased in AIS patients. Lp-PLA2, PARK7 were related to the aggravation of neurological deficits in potential patients. Lp-PLA2, PARK7 and EPO were related to the increase of carotid intima-media thickness in potential patients.

Objective To discuss the role of teachers in the integrated PBL teaching of pediatrics in the light of the investigation of students after PBL teaching.Method The multidisciplinary integrated PBL course established by the Department of Pediatrics of Chongqing Medical University has been implemented for more than two years in the teaching of the five year program in the Department of clinical medicine (pediatric direction).From September 28,2016 to October 25th,the researchers conducted a survey of 26 undergraduate students in the college who received PBL teaching at the professional probation stage.After the end of each PBL class,the teaching evaluation questionnaire recommended by Fudan University and Qian Ruizhe was distributed through the network teaching platform of Chongqing Medical University.The questionnaire was retrieved by students without a name,and the survey was carried out 3 times.The data of the questionnaire were summarized with Excel 2007.Result 77 questionnaires were issued and 77 were recovered,with a recovery rate of 100％.In the multidisciplinary integrated PBL class,94.8％-97.4％ students gave high score evaluation,and all the evaluation of teachers reached "excellent" level.In response to open-ended questions,students believed that teachers in teaching could inspire students to think positively,encourage students to express different views,create a mutually trusted environment for students,and cultivate students' interpersonal communication,communication and cooperation ability.Conclusion In pediatric multidisciplinary integrated PBL teaching,teachers should teach students correct learning methods,judge each student's knowledge and thinking level,and individualize teaching for each student's problems and characteristics.

Objective To evaluate the prognostic value of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal metastasis.Methods 287 gastric cancer patients with peritoneal metastasis were enrolled from Jan 2010 to Dec 2016.Results Compared with PNI ＞ 45,patients in PNI≤45 group were elder [(59 ± 11) vs.(54 ± 11),t =3.734,P =0.000],lower albumin [(35 ± 4) g/L vs.(42 ± 4)g/L,t =15.988,P =0.003)],lower plasm hemoglobin concentration [(110 ± 22)g/L vs.(129 ±24) g/L,t =6.245,P =0.000),higher platelet count/lymphocyte count ratio [PLR,(210 ± 89) vs.(150 ± 66),t =6.547,P =0.000],higher neutrophil count/lymphocyte count ratio [NLR,(3.7 ± 2.9)vs.(2.4 ± 1.2),t =4.628,P =0.000],lower percentage of pallative gastrectomy (45.5％ to 58.5％,x2 =4.45,P =0.035).Logistic regression analysis showed that age ＞ 58-years,NLR ＞ 2.87,PLR ＞ 170,hemoglobin ≤ 130 g/L,local organ infiltration were risk factors leading to low-PNI (all P ＜ 0.05).The median survival time for all patients was 8.7 months.Univariate analysis revealed that,PNI ＞ 45,serum albumin ＞ 40 g/L,no ascites,lower-grade of peritoneal metastasis,pallative gastrectomy,postoperation chemotherapy were positively associated with better prognosis (all P ＜ 0.05).Multivariate analysis demonstarted that,PNI (HR =0.717,P =0.039).Grade of peritoneal metastasis (HR =1.206,P =0.044),pallative gastrectomy (HR =1.529,P =0.001) were independent prognostic risk factors for the patients with peritoneal metastasis.Conclusion PNI are both predictors of nutrition assessment and of prognosis for gastric cancer patients with peritoneal metastasis.

Objective:To compare the ability of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in evaluating the prognosis of patients with TNM stageⅠto Ⅲ gastric cancer.Methods:From May 2001 to December 2013, the clinicopathological data of 645 patients with gastric cancer treated at Harbin Medical University Cancer Hospital were retrospectively analyzed. Chi-square test was used to analyze the differences between NLR, and PLR and clinicopathological characteristics of patients. Kaplan-Meier method and log-rank test were performed to compare the overall survival of patients. Cox proportional hazards regression model was performed to analyze the prognosis of gastric cancer patients. The ability of NLR and PLR to evaluate the prognosis of gastric cancer was compared by receiver operating characteristic curve.Results:The cutoff values of PLR and NLR were 141.50 and 1.94, respectively. PLR was associated with gender, resection method, maximum diameter of tumor, whether chemotherapy, T-stage, N-stage, TNM stage, tumor location, white blood cell, hemoglobin, albumin, and whether total gastrectomy ( χ2=9.224, 10.577, 28.825, 6.831, 29.059, 28.637, 30.748, 18.023, 24.320, 77.274, 9.021 and 10.745, all P<0.05). NLR were associated with resection method, maximum diameter of tumor, T-stage, N-stage and TNM stage, white blood cell, hemoglobin and albumin ( χ2=14.563, 12.092, 22.697, 44.735, 34.151, 7.949, 9.611 and 7.498, all P<0.05). The results of multivariate analysis showed that resection method, whether chemotherapy, T-stage, N-stage, PLR and whether total gastrectomy were all independent risk factors for gastric cancer patients ( χ2=23.653, 22.023, 16.697, 24.038, 4.110 and 22.364, all P<0.05). The five-year cumulative survival rate of the patients with PLR<141.50 was higher than that of patients with PLR≥141.50 (55.4% vs. 30.5%), and the difference was statistically significant ( χ2=47.968, P<0.01). The AUC value of PLR in prognostic evaluation of gastric cancer was 0.629, which was higher than that of NLR (0.596, P<0.01). Conclusion:PLR is better than NLR in the prognostic evaluation of gastric cancer patients.