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.

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

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

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.

Proprotein convertase subtilisin/kexin type 9(PCSK9)is a protein that is synthesized and secreted from hepato-cytes.It can reduce low-density lipoprotein(LDL)uptake by promoting degradation of LDL receptor(LDLR)on the surface of hepatocyte.Since application of PCSK9 inhibitors become more common,researchers have found that PCSK9 can regulate ather-osclerosis development,platelet activation and thrombosis,inflammation,and glycolipid metabolism.PCSK9 is also the main in-ducements of in-stent restenosis(ISR)after percutaneous coronary intervention(PCI).Therefore,this article reviews the research progress of mechanism of PCSK9 in ISR after PCI,and makes a preliminary prospect on the application of PCSK9 as a therapeu-tic target in coronary atherosclerotic heart disease.

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.

Respiratory syncytial virus(RSV)infection is a potential susceptibility factor for recurrent wheezing,which can affect the occurrence and development of asthma through immune damage,airway epithelial barrier damage,airway inflammatory infiltration,airway hyperresponsiveness,and high expression of induced susceptibility genes.Traditional Chinese medicine believes that asthma caused by RSV infection is mostly caused by the imbalance of the body's qi after infection and the retention of evil qi.By combing the mechanism of RSV infection in the occurrence and development of asthma and the research on traditional Chinese medicine intervention in recent years,it is hoped to provide ideas for the future application of combined Chinese and Western medicine to prevent and treat asthma.

Objective:To investigate the expression of PD-L1, CD4, CD8 and CXCL-13 in cervical carcinoma, and their clinicopathological significance was analyzed.Methods:A total of 77 patients with cervical carcinoma in the Seventh Medical Center, PLA General Hospital from January 2019 to December 2021 were included. All patients received radical surgical resection in the Seventh Medical Center of Chinese PLA General Hospital. The expression of PD-L1, CD4, CD8 and CXCL-13 was detected by immunohistochemical (IHC) method. The correlation between IHC markers and patients′ clinicopathological parameters was analyzed.Results:There were 59 cases of squamous cell carcinoma and 18 cases of adenocarcinoma (ranging from 29 to 69 years) with an average of (49.4±9.8) years. PD-L1 was expressed in different degrees in cervical squamous cell carcinoma and adenocarcinoma (χ2=4.975, P=0.026); CD4 +, CD8 +and CXCL-13 +tumor infiltrating lymphocytes (TIL) were observed in the carcinoma cell nests and peritumoral stroma. PD-L1 expression in cervical carcinoma was moderately correlated with the number of CD4 +TIL in the carcinoma nests, and the number of CD8 +, CXCL-13 +TIL infiltration in the carcinoma nests and stroma, but not to the patient′s age, histologic differentiation, presence or absence of vascular invasion, presence or absence of lymph node metastasis and FIGO stage ( P>0.05). Conclusions:The high expression of PD-L1 in cervical carcinoma tissues is closely related to the number of TIL in the carcinoma nests and peritumor stroma, suggesting that they may have important reference value for predicting the response to immunotherapy in patients with cervical carcinoma.