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ObjectiveTo investigate the value of aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in diagnosis of liver inflammation grade in patients with chronic hepatitis B (CHB). MethodsA total of 545 patients with CHB who underwent percutaneous liver biopsy and routine laboratory examinations during hospitalization in Shanghai Public Health Clinical Center Affiliated to Fudan University from October 2016 to October 2019 were enrolled. Inflammation grade (G) was determined according to the Scheuer scoring system, and APRI, FIB-4, and GPR were calculated based on related clinical indicators. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between two variables. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the three serum noninvasive diagnostic models in determining liver inflammation grade, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsAmong the 545 patients, 224 had grade G0-1 liver inflammation, 209 had grade G2 liver inflammation, and 112 had grade G3 liver inflammation. The Spearman correlation analysis showed that APRI, FIB-4, and GPR were positively correlated with liver inflammation grade (r=0.611, 0.470, and 0.563, all P＜0.001). APRI, FIB-4, and GPR had an AUC of 0.820, 0.719, and 0782, respectively, in the diagnosis of G≥2 liver inflammation, with optimal cut-off values of 0.53, 1.48, and 0.20, respectively; for the diagnosis of G≥2 liver inflammation, GPR had a better performance than FIB-4 (P=0.01) and a slightly lower performance than APRI (P=0.048). The stratified analysis based on alanine aminotransferase (ALT) level showed that in the ≤1×upper limit of normal (ULN) group, the (1-2)×ULN group, and the (2-5)×ULN group, APRI had an AUC of 0.847, 0.786, and 0.724, respectively, in the diagnosis of G≥2 liver inflammation, FIB-4 had an AUC of 0.777, 0.729, and 0.626, respectively, and GPR had an AUC of 0.801, 0.781, and 0.607, respectively; the subgroup analysis showed that GPR had a similar diagnostic performance to APRI and FIB-4 in all ALT stratification groups except the (2-5)×ULN group, in which GPR had a lower diagnostic performance than APRI (P=0.042). APRI, FIB-4, and GPR had an AUC of 0.791, 0.725, and 0.801, respectively, in the diagnosis of G≥3 liver inflammation, with optimal cut-off values of 0.66, 1.49, and 0.25, respectively; in the diagnosis of G≥3 liver inflammation, GPR had a similar diagnostic performance to APRI and a better diagnostic performance than FIB-4 (P=0.006). The stratified analysis based on ALT level showed that in the ≤1×ULN group, the (1-2)×ULN group, and the (2-5)×ULN group, APRI had an AUC of 0.900, 0.742, and 0.693, respectively, in the diagnosis of G≥3 liver inflammation, FIB-4 had an AUC of 0.874, 0.683, and 0.644, respectively, and GPR had an AUC of 0.890, 0.805, and 0.668, respectively. The subgroup analysis showed that GPR had a similar diagnostic performance to APRI and FIB-4 in all ALT stratification groups except the (1-2)×ULN group, in which GPR had a better diagnostic performance than FIB-4(P=0.015). ConclusionAPRI, FIB-4, and GPR may accurately diagnose liver inflammation grade in CHB patients, which helps to monitor the progression of CHB and determine the timing of antiviral therapy.
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Objective To assess the diagnostic performance of liver stiffness measurement(LSM)and serum markers on hepatic fibrosis in chronic hepatitis B(CHB)patients with alanine aminotransferase(ALT)less than or equal to two times the upper limit of normal(≤2×ULN).Methods A total of 284 CHB patients with ALT≤2×ULN who were treated in Department of Hepatobiliary Medicine,Public Health Clinical Center,Shanghai from October 2015 to December 2017 were analyzed.FibroScan,routine blood tests and serum fibrosis markers were conducted on the day or one day before liver biopsy.The Scheuer scoring system was used for liver histologic assessment.Aspartate aminotransferase to platelet ration index(APRI)and FIB-4 were calculated.Based on the results of liver pathology,the area under receiver operating characteristic curve(AUROC)was used to evaluate the value of LSM and serum markers in the diagnosis of liver fibrosis stage.Non-normal distribution variables were expressed as M(QR)as appropriate,and compared by analysis of Kruskal-Wallis test as appropriate.The correlation between two variables was analyzed by Spearman correlation analysis.Results Of 284 CHB patients,175 were male and 109 were female.For inflammatory grading,175 cases were G1 grade,88 cases were G2,and 21 cases were G3.For fibrosis grading,153 cases were S1,53 cases were S2,34 cases were S3,and 44 cases were S4.Spearman correlation analysis showed that LSM,APRI and FIB-4 were positively correlated with hepatic fibrosis stage(r=0.650,0.484,and 0.317,respectively,all P<0.01).The AUC of LSM for predicting fibrosis≥S2,≥S3,and S4 were 0.840,0.902,and 0.942,respectively.The cut-off of LSM values were 6.10,8.40,and 10.10 kPa,respectively.The values of AUC of APRI and FIB-4 for predicting fibrosis≥S2 were 0.755 and 0.638,respectively,those for predicting fibrosis≥S3 were 0.737 and 0.657,respectively,and those for S4 were 0.804 and 0.694,respectively.The AUCs of LSM for predicting fibrosis≥S2 in patients with ALT≤1×ULN and those with ALT>1 -≤2×ULN were 0.857 and 0.813,respectively,those for fibrosis≥S3 were 0.890 and 0.892,respectively,and those for S4 were 0.925 and 0.908,respectively.The cut-off of LSM were 5.90 and 7.80 kPa,8.10 and 9.50 kPa,8.40 and 10.40 kPa,respectively.Conclusions LSM could accurately assess the degree of liver fibrosis in CHB patients with ALT≤2×ULN,which is superior to serum markers for predicting liver fibrosis stage.
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Objective To assess the clinical diagnostic performance of liver stiffness measurement (LSM) and aspartate transaminase (AST)-to-platelet (PLT) ratio index (APRI) for liver fibrosis in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) less than or equal to five times of the upper limit of normal (≤5×upper limit of normal [ULN]).Methods FibroScan,blood routine and liver function test were conducted at the day or one day before liver biopsy in 383 CHB patients with ALT≤5 × ULN.The Scheuer scoring system was used for liver histologic assessment.APRI was calculated.Based on the results of liver pathology,the areas under receiver operating characteristic curve (AUC) of LSM and APRI for diagnosis of liver fibrosis stage were compared.Results The median LSM were 5.10 kPa for S0 fibrosis stage,5.20 kPa for S1,6.60 kPa for S2,10.10 kPa for S3,and 18.80 kPa for S4.The median APRI values were 0.36,0.38,0.63,0.61 and 1.27,respectively.The AUC of LSM were 0.817 for ≥S2,0.891 for ≥S3 and 0.913 for ≥S4.And the AUC of APRI were 0.717 for ≥S2,0.711 for ≥S3 and 0.746 for ≥S4.The cut-offs of LSM values were 6.8 kPa for ≥S2,8.7 kPa for ≥S3,and 10.9 kPa for ≥S4.Conclusion LSM can accurately assess the degree of liver fibrosis in CHB patients with ALT ≤5 × ULN,which is superior to APRI in clinical utility.
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OBJECTIVE To observe the regulation effect of chidamide on energy metabolism in HCT-8 and HT-29 cells. METHODS HCT-8 and HT-29 cells were treated with chidamide 5,10 and 20 μmol · L-1. Morphological changes of these cells were observed under an ordinary optical microscope. Cell proliferation was detected by MTT. ATP production was determined by CellTiter-Glo? assay kit. Metabolic changes were tested by glycolytic stress kit. The mRNA level of lactate dehydrogenase A (LDH-A)was analyzed by real-time quantitative PCR,whereas the protein level of LDH-A was analyzed by Western blotting. RESULTS Compared with control group,cell morphology of HCT-8 and HT-29 cells in chidamide treated group was irregular,accompanied by deformation,shrinkage and cell debris, and the inhibitory rate of proliferation increased(P<0.05). There was no significant difference in ATP total content between chidamide 5 and 10 μmol · L-1 16 h treatment groups,but in chidamide 20 μmol · L-1 treatment group it was decreased(P<0.05). Chidamide 20μmol · L-1 had no effect on oxygen consumption rate, but glycolysis ATP generation rate was reduced by 30.7% and 37.9%(P<0.05),respectively. Chidamide 20μmol · L-1 had no effect on LDH-A mRNA level,but it decreased the protein level of LDH-A(P<0.01). CONCLUSION Chidamide can abate the respiratory metabolic ability of HCT-8 and HT-29 cells. The mechanism may be related to the down-regulation of LDH-A.
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Objective To verify enzyme activity inhibition of a novel histone deacetylase inhibitor ( HDACi ) JZ005 using an HDACi chemiluminescence detection kit and a cell-based screening model .Methods The plasmid with p21 gene promoter elements and luciferase reporter gene was transfected into human embryonic kidney cells 293 , and the stable transfectants were established by G418 screening.Enzyme activity inhibition of JZ005 on histone deacetylases (HDACs) was verified by the HDACi chemiluminescence detection kit and the cell-based screening model .A well-known HDACi , tri-chostatin A ( TSA) was used as the positive control .MTT assay was used to detect the protection of rat H 9c2 myocardial cells suffering from CoCl 2-induced hypoxia and treated with different concentrations of JZ 005 .The expression of acetylated histone H3 protein of normal and CoCl 2-induced hypoxia H9c2 cells before and after JZ005 treatment was assayed by West-ern blotting while the effect of drug administration on apoptosis was detected by flow cytometry ( FCM) .Results An HDA-Ci cell-based screening system targeting the p21 gene promoter was ranging established .The JZ005, a HDACi, markedly suppressed the activity of HDACs by more than 50%with the concentration ranging from 50 to 400 μmol/L.JZ005 signifi-cantly protected H9c2 cells from hypoxia injury .Cell viability was increased by 38.33%,56.00% and 35.20% compared with control,accompanied by an enhanced acetylation level of histone H 3.JZ005(25,50 and 100 μmol/L) treatment sig-nificantly decreased the number of apoptotic cells (6.63%,10.56% and 8.89%) compared to control group (12.89%). Conclusion An HDACi cell-based screening system is successfully established .JZ005 effectively protects myocardial cells against hypoxia injury while enhancing the acetylation level of histone H 3.Our results indicate that JZ005 might be developed as a potential drug for hypoxia treatment .
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Objective To examine the anticancer effect of a novel histone deacetylase inhibitor (HDACi), JZ004, on colon cancer cells HCT-8 and HT-29, and to investigate the molecular mechanisms of proliferation inhibition and apoptosis induction of cancer cells treated by JZ 004.Methods Colon cancer cells were treated with a series of concentrations of JZ004 .MTT assay was used to detect the proliferation of cancer cells .The cell cycle distribution and apoptosis were deter-mined by flow cytometry .Rhodamine 123 and DCFH-DA were applied to detect the mitochondrial membrane potential (ΔΨm) and reactive oxygen species ( ROS) production.The protein expressions of acetyl-histone H3, p21, cyclin-dependent kinase(CDK)4, Bcl-2, Mcl-1 and Bax were assayed by Western blotting .Results JZ004 was found to inhibit proliferation and induce apoptosis of colon cancer cells in a time-and dose-dependent manner , accompanied by a dose-dependent hyperacetylation of histone H3.JZ004 induced the cancer cell arrest in G 0/G1 phase by increasing the expres-sion level of p21 while CDK4 was downregulated .JZ004 also increased cellular ROS production and reduced ΔΨm by regu-lating the expressions of Bcl-2 family proteins .Conclusion As a novel HDACi , JZ004 effectively inhibits proliferation and increases ROS production to induce apoptosis of colon cancer cells .The results indicate that JZ004 is a potential compound to be developed as an anti-colon cancer agent for clinic application .
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Objective To investigate effect of dexmedetomidine sedation anesthesia on perioperative hemo-dynamics and heart rate variability in patients with hypertension .Methods 50 cases with selective laparoscopic chol-ecystectomy were randomly divided into Group A ( dexmedetomidine sedation ) and Group B ( saline control ) ,25 cases each group .Low-frequency ( LFnu ) , high-frequency ( HFnu ) , LF/HF, LFnu ( LF/TP ×100%) , HFnu ( HF/TP × 100%)and total-power(TP)were recorded at the time points of baseline (T0),immediately after administration(T1), immediately after anesthesia induction (T2),1 min after anesthesia induction (T3),5 min after anesthesia induction (T4)and 10 min after anesthesia induction (T5).NIBP and HR were recorded at the points of T0 ~T5.Results Compared with T0 or Group A,there was an increase in SBP and HR at T2~T4(P<0.05)in Group B.Heart rate variability changes showed that Lfnu [(66.3 ±7.8),(64.5 ±6.0),(65.3 ±6.5)],LF/HF[(1.9 ±0.7),(1.7 ± 0.5),(1.7 ±0.8)],TP[(2 283 ±472),(2 197 ±310),(2 108 ±256)]decreased significantly at T2-T4(tLFnu=5.16,4.15,4.40,tLF/HF=4.55,4.24,3.49,tTP=3.27,1.71,0.96,P<0.05) in Group A,while there was no significant change in Group A .Conclusion Dexmedetomidine sedation may have less influence on hemodynamics and automomic nerve ,which be an useful analgesic adjuvanct for the patients undergoing selective laparoscopic chole -cystectom.
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ObjectiveTo investigate the clinical value of serum complement C3 and C4 levels for predicting the severity of hepatic fibrosis in patients with chronic hepatitis B.MethodsHistopathological diagnosis was confirmed in 442 patients with chronic hepatitis B.Serum complement C3 and C4 levels were determined by Beckman-Coulter Immage 800 immunochemistry system.ROC curve was used to analyze the value of serum complement C3 and C4 levels in predicting the severity of hepatic fibrosis.ResultsThe areas under ROC curve of complement C3 and C4 for predicting significant fibrosis ( ≥ S2),severe fibrosis ( ≥ S3) and cirrhosis (S4) were all significantly larger than the area under diagonal reference line ( P =0.009,0.000,0.000 and P =0.005,0.000,0.000,respectively).According to ROC curves,the optimal cut-offs of serum complement G3 for predicting severe fibrosis and cirrhosis were ≤0.74 g/L and ≤0.64 g/L,and the corresponding sensitivity,specificity,positive predictive value,negative predictive value,accuracy were 0.585,0.681,0.617,0.650,0.636 and 0.509,0.775,0.423,0.830,0.710,respectively.The optimal cut-offs of serum complement C4 for predicting severe fibrosis and cirrhosis were ≤0.14 g/L and ≤0.12 g/L,and the corresponding sensitivity,specificity,positive predictive value,negative predictive value,accuracy were 0.565,0.634,0.576,0.623,0.602 and 0.463,0.781,0.407,0.818,0.704,respectively.ConclusionSerum complement C3 and C4 may be used for predicting severe fibrosis and cirrhosis in patients with chronic hepatitis B,but its stability and reliability need to be improved.
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Objective To investigate the value in MR spectrum of diagnosis and grading of gliomas.Methods 36 cases of patient with gliomas who confirmed by histopathologic findings or clinical follow-up were collected. Using a GE Signa EXCITE HD 3.0T super conduct MR unit, all the cases of patients were performed conventional MR scan and multi-voxel with 2-D multi-voxel PRESS 144 ms. Functool software was used for post-processing of spectrum. The ratios of NAA/Cr, NAA/Cho, Cho/Cr were measured in the solid part of masses, circum of tumors and contralateral parenchyma respectively. The result was processed by the statistical method. Results The statistical analysis was exacted by SAS 8.2 software. In the solid part of masses, there were significant differences between low-grade gliomas and high-grade gliomas in the ratios of Cho/Cr, Cho/NAA、NAA/Cr and MI (P ＜0.05), but in peritumoral edema, there were significant differences in the ratios of Cho/Cr, NAA/Cr (P ＜0.05), and no significant differences in the ratios of MI (P ＜0.05).Conclusion 1H-MRS is very important and useful in the evaluation of gliomas. It has made it possible to exactly evaluate the grade of gliomas combined with other imagings.
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With cDNA from Phellodendron amurense seedlings treated with drought stress as tester and cDNA from this plant in normal growth as driver, we construct cDNA subtracted library using suppression subtractive hybridization (SSH). In the library, the rate of recombination was 95%, the size of inserts was 300-800 bp. Two hundred and sixty-five new genes were obtained by DNA sequencing 816 positive clones picked randomly, and partitioned to 16 classes after nucleotide Blast and BlastX homological analysis against NT, NR, SWISSPROT, KEGG database. Forty-four drought stress associated genes, such as heat shock protein cognate 70, dehydration responsive protein 22, universal stress protein, metallothionein II, late embryogenesis abundant protein, were obtained, which made 16.6% of the overall genes. These genes included osmotic regulator, signal component regulatory protein and antioxidant enzyme. The research had established a basis for cloning stress resistance genes and further studying genes expression in P. amurense seedlings under drought stress.