Loading...
Online Office
Download CenterMore...
LinksMore...
WeChat
WeChat Code
Website Code
Subscribe Code

Journal of Practical Hepatology

2011 Vol. 14, No. 2 Published:10 April 2011
Effect of interfering RNA targeting β-Catenin on the proliferation and apoptosis of hepatic stellate cells in vitro
GE Wensong,WU Jiangxin,CHEN Yinwei,et al.
2011, 14(2):  91-94.  doi:10.3969/j.issn.1672-5069.2011.02.002
Abstract ( 122 )   PDF (1549KB) ( 245 )  
References | Related Articles | Metrics
Objective To investigate the effect of synthetic small interfering RNA(siRNA)targeting β-Catenin on the biological characters of hepatic stellate cells(HSCs)in vitro. Methods Synthetic siRNA targeting β-Catenin was transfected into HSC-T6 cells by lipofectamine package. Negative siRNA transfection and no transfection were used as negative and blank control,respectively. After incubation with siRNA,total RNA and protein of HSC-T6 cells were extracted. The expression of β-Catenin gene and protein was detected by reverse transcription-polymerase chain reaction and Western blotting. The proliferation of HSC-T6 was determined using MTT assay. HSC-T6 proliferation and apoptosis were measured by flow cytometry. Content of collagen type Ⅰand Ⅲin the supernatants were determined by Western blotting. Results After HSC-T6 cells transfected with different concentrations of β-Catenin SiRNA,the level of β-Catenin mRNA decreased significantly as compared to the negative and blank control;β-Catenin protein expression was inhibited by 56.43±2.88%(P<0.01),and Ⅰ and Ⅲ collagen expression were also inhibited by 46.58±3.46%(P<0.01)and 50.48±3.72%(P<0.01);the cell proliferation was significantly inhibited(P<0.01),while cell apoptosis rate was significantly higher than in the negative control(P<0.05). Conclusion Inhibition of β-Catenin by siRNA may have a potential effect on prevention and treatment of hepatic fibrosis by inhibiting proliferation of and promoting apoptosis of stellate cells.
Comparative study on two methods in isolating human marrow mesenchymal stem cells in vitro
WEI Kaipeng,PAN Xingnan,WANG Chongguo
2011, 14(2):  95-97.  doi:10.3969/j.issn.1672-5069.2011.02.003
Abstract ( 120 )   PDF (1028KB) ( 362 )  
References | Related Articles | Metrics
Objective To compare morphology,proliferation capacity and purity of human marrow mesenchymal stem cells by two isolation methods in vitro. Methods Human marrow mesenchymal stem cells were isolated by whole marrow culture and density gradient centrifugation. The appearance of the cells and growth curves of the third generation cells were observed. 1×105 of the third generation cells were cultured and counted continuously for 30 days. Surface antigens of the stem cells were detected with flow cytometry. Results The cells isolated by the two methods were both like long shuttle;the primary passage time of cells by whole marrow culture was 10d and the double time was 30±5.6h,while the primary passage time by density gradient centrifugation was 18d and double time was 38±7.2h;The total numbers of the former were 15 times more than the latter at 30th day. FACS showed that positive rates of CD73,CD105 and CD166 in the third generation cells isolated by whole marrow culture were less than that by density gradient centrifugation(P<0.05). Conclusion The two methods we used can successfully isolate human marrow mesenchymal stem cells. The former has a stronger proliferation ability and the latter has a higher purity of the stem cells.
Effects of Kezhi capsule on hepatic expression of heme oxygeanse-1 in mice with non-alcoholic steatohepatitis
WANG Rongqi,NAN Yuemin,ZHAO Suxian,et al.
2011, 14(2):  98-100.  doi:10.3969/j.issn.1672-5069.2011.02.004
Abstract ( 137 )   PDF (2676KB) ( 204 )  
References | Related Articles | Metrics
Objective To investigate the potential role of Kezhi capsule on the hepatic expression of heme oxygeanse-1(HO-1)in mice with non-alcoholic steatohepatitis(NASH). Methods Twenty male C57BL/6J mice were randomly divided into four groups:mice fed with methionine-choline adequate diet were controls;The NASH model group were fed with MCD diet;The Kezhi capsule treatment group were fed with MCD diet for four weeks, then plus chitosan and the spontaneous recovery group were fed with methionine-choline adequate diet after four weeks MCD feeding. 8 weeks later,blood samples were collected for the detection of serum transaminases and leptin. The histological changes were observed under light microscope and HO-1 mRNA was detected by real-time quantitative PCR. Results Compared with those in MCD group,the hepatic pathological changes were ameliorated,and the hepatic expressions of HO-1 and serum leptin were decreased in Kezhi capsule group(P<0.05). Conclusions Kezhi capsule can down-regulate the expressions of HO-1 and leptin,so it can attenuate hepatic steatosis and necroinflammation in mice with NASH.
Clinical curative effect of telbivudine in tuberculosis patients with hepatitis B viral carriers
MEI Mei,LU Wei
2011, 14(2):  101-102.  doi:10.3969/j.issn.1672-5069.2011.02.005
Abstract ( 140 )   PDF (484KB) ( 331 )  
References | Related Articles | Metrics
Objective To investigate the telbivudine’s protective effects of liver function in patients with hepatitis B viral carrier and pulmonary tuberculosis. Methods 82 patients with hepatitis B viral carrier and tuberculosis were randomly divided into two groups. Both groups were given(HRZE)2/(HRZ)4. 39 patients were given telbivudine for antiviral treatment and 43 didn’t. Results ALT,AST and TBil in the antiviral group(48.1±6.7U/L,39.1±5.6 U/L and 24.9±3.6μmol/L)were statistically significant lower than in control group(77.7±9.8 U/L),69.9±9.5 U/L and TBil 32.1±6.7μmol/L,P<0.01). Conclusion Telbivudine has obvious protective effect of liver function in patients with hepatitis B viral carrier and pulmonary tuberculosis.
The relationshiop of hepatitis B virus Pre-S1 antigen to HBV replication
ZHAN Guoqing,TAN Huabing,LI Fang,et al.
2011, 14(2):  103-105.  doi:10.3969/j.issn.1672-5069.2011.02.006
Abstract ( 145 )   PDF (494KB) ( 486 )  
References | Related Articles | Metrics
Objective To explore the clinical value of hepatitis B virus Pre-S1 antigen in the diagnosis of viral replication. Methods 450 HBsAg positive and 50 healthy control serum specimens were collected,and the Pre-S1 antigen and HBVM were detected by ELISA,HBV DNA levels by fluorescence quantitative polymerase chain reaction(FQ-PCR),and liver fuction by automatic biochemical analyzer respectively. Results The positive rates of HBeAg,Pre-S1 antigen and HBV DNA in all patients were 40.0%,57.3% and 61.6%,respectively;there were significant differences in the positive rates of Pre-S1 antigen and HBV DNA in HBeAg negative and positive group(x2=84.2,x2=110.7,P<0.01);Pre-S1 antigen were correlated with HBeAg and HBV DNA(x2=86.5,x2=272.1,P<0.01);AST,ALT,TBil and γ-GT in Pre-S1 antigen positive group were higher than those in negative group(P<0.01);When serum HBV DNA was more than 2.7lg copies/ml as the cut-off value for the HBV replication,the sensitivity,specificity,accuracy,positive predictive value,positive likelihood ratio and odds ratio of Pre-S1 were 87.7%,91.3%,89.1%,94.2%,10.1 and 75.3 respectively,while those of HBeAg were 59.2%,90.8%,71.3%,91.1%,6.43 and 14.2 respectively. Conclusions Pre-S1 antigen is correlated with HBeAg and HBV DNA for HBV replication.
Effect of adefovir dipivoxil and lamivudine combination therapy on hepatitis B patients with YMDD mutation
MA Hui,YU Wenlong,GAO Fan
2011, 14(2):  106-107.  doi:10.3969/j.issn.1672-5069.2011.02.007
Abstract ( 121 )   PDF (502KB) ( 302 )  
References | Related Articles | Metrics
Objective To evaluate the efficiency of lamivudine or/and adefovir dipivoxil for the treatment of chronic hepatitis B(CHB)patients with hepatitis B virus tyrosine-methionine-aspartate-aspartate(YMDD)mutations. Methods Fifty-six hepatitis B patients with YMDD mutation of lamivudine-resistant HBV were collected and randomly divided into two groups,both of the two groups were treated with Silibinin and Diammonium Glycyrrhizinate before. Patients were assigned to receive adefovir 10 mg/day and lamivudine 100 mg/day(Group A)or adefovir 10 mg once daily and lamivudine 100 mg once daily combination during first 12 weeks,and then stop lamivudine and continue adefovir(Group B). The efficiency was determined by comparison of viral loads,alanine aminotransferase(ALT)level and hepatitis B e antigen seroconversion pre-and post treatment after 96 weeks. Results The viral loads and ALT level of the two groups were decreased significantly. The negative rate of HBV DNA in group A was 96.4% on the 96 weeks,while in group B was 75.0%(P<0.05),the negative rate of HBeAg were 89.2% and 57.1% in the two groups,respectively(P<0.05). The ALT normalization rate were 96.4% and 85.7%(P>0.05),respectively. One patient had resistant mutation in group A and four patients in group B. No adverse reactions occurred in the study. Conclusion The present study confirmed that the combination of lamivudine with ADV was superior for the treatment of CHB patients with YMDD mutation.
The correlation of serum HBsAg to HBV DNA levels in patients with chronic hepatitis B
FANG Honglong,WU Jinming,JIANG Hongfeng,et al.
2011, 14(2):  108-109.  doi:10.3969/j.issn.1672-5069.2011.02.008
Abstract ( 136 )   PDF (484KB) ( 371 )  
References | Related Articles | Metrics
Objective To investigate the correlation of serum HBsAg to HBV DNA in patients with HBeAg positive and HBeAg negative chronic hepatitis B. Methods The HBsAg,ALT,AST and HBV DNA were detected in 55 patients with serum HBeAg(+)and 36 with HBeAg(-)chronic hepatitis B. Results The levels of HBV DNA,ALT and AST in HBeAg positive were higher than that in HBeAg negative patients(P<0.05);The levels of HBsAg in HBeAg positive were lower than that in HBeAg negative patients(P<0.05);There was a negative in HbeAg positive(r=-0.796,P<0.01),while there was no correlation(r=0.289,P>0.05)in HbeAg negative chronic hepatitis B patients between HBsAg and HBV DNA. Conclusion Detection of serum HbsAg might be useful in patients with chronic hepatitis B.
Clinical study on adefovir dipivoxil treatment on patients with chronic hepatitis B:65 case report
LI Yongnian,WU Weiqiang,ZHAI Peiren,et al.
2011, 14(2):  110-111.  doi:10.3969/j.issn.1672-5069.2011.02.009
Abstract ( 103 )   PDF (485KB) ( 373 )  
References | Related Articles | Metrics
Objective To evaluate the efficacy of adefovir dipivoxil treatment on patients with chronic hepatitis B. Methods Adefovir dipivoxil and lamivudine were given to 39 patients with HBeAg-positive,and adefovir dipivoxil was given to 12 with HBeAg-positive and to 14 with HBeAg-negative hepatitis B,respectively for 24 weeks. Results Serum HBV DNA undetectable rates at 3 mon,6 mon,12 mon and 24 mon both in HBeAg-positive patients with adefovir dipivoxil and lamivudine or in HBeAg-negative patients with adefovir dipivoxil alone were higher than in HBeAg-positive patients with adefovir dipivoxil alone;the normalization of ALT in the three groups were not significantly different. Conclusion We recommend combination of adefovir dipivoxil and lamivudine therapy for patients HBeAg-positive hepatitis B.
Analysis of pathological diagnosis of percutaneous liver biopsy in 71 patients with chronic hepatitis B
LI Xiaoling,LUO Xiaoke,LI Zhaoxin,et al.
2011, 14(2):  112-113.  doi:10.3969/j.issn.1672-5069.2011.02.010
Abstract ( 114 )   PDF (482KB) ( 302 )  
References | Related Articles | Metrics
Objective To explore the clinical significance of liver biopsy in patients with chronic hepatitis B. Methods The percutaneous liver biopsies were operated in 71 patients with CHB and the clinical diagnosis were assessed based on the pathological diagnosis. Results In the 71 patients with CHB,G1 to G4 were pathologically found in 9.9%,35%,24% and 31%,and S1 to S4 were 29%,25%,13% and 32%,respectively,while the sensitivity,specificity and accuracy of clinical diagnosis were relatively lower. Conclusion The percutaneous liver biopsy is vital to the diagnosis,treatment and prognosis of patients with chronic hepatitis B.
Observation upon curative effect of lamivudine and adefovir combination therapy on patients with chronic hepatitis B
CHENG Juan,CAI Wenhui,SHI Cuifen
2011, 14(2):  114-115.  doi:10.3969/j.issn.1672-5069.2011.02.011
Abstract ( 141 )   PDF (499KB) ( 403 )  
References | Related Articles | Metrics
Objective To observe the effect of lamivudine and adefovir combination therapy on patients with chronic hepatitis B. Methods 11 patients tolerated lamivudine switched to adefovir,6 tolerated to adefovir switched to lamivudine,and 28 tolerated lamivudine and 9 tolerated adefovir switched to lamivudine and adefovir combination therapy. Results At the end of 48 weeks therapy,the serum HBV DNA negative rate(76%)and ALT normalization rate(92%)in combination group were much higher than in adefovir(45%,73%)or lamivudine(50%,83%)groups. Conclusion The combination of lamivudine and adefovir therapy is an alternative option in hepatitis B patients tolerated to adefovir or lamivudine.
Imbalanced intrahepatic expression of interferon gamma,tumor necrosis factor alpha,and interleukin-10 in hepatitis B virus infection patients with acute-on-chronic liver failure
TIAN Hui,SUN Ying,TENG Guangju,et al.
2011, 14(2):  116-118.  doi:10.3969/j.issn.1672-5069.2011.02.012
Abstract ( 107 )   PDF (747KB) ( 341 )  
References | Related Articles | Metrics
Objectives This study attempted to determine intrahepatic expressions of proinflammatory and anti-inflammatory cytokines in patients with acute-on-chronic liver failure(ACLF)arosing from HBV infection. Methods In situ expressions of interferon(IFN-γ),tumor necrosis factor(TNF-α)and interleukin 10 (IL-10)were analyzed in the livers of patients with ACLF,chronic hepatitis B(CHB),and normal controls(NC)by using immunohistochemistry. Results Intrahepatic IFN-γ and TNF-α expressions were markedly up-regulated in patients with ACLF as compared to CHB and NC(both P<0.001);However,similar IL-10 expressions were observed in ACLF and CHB;IFN-γ over-expression was actively correlated with expression of TNF-α(r=0.886,P<0.001). Conclusions The imbalanced expression of proinflammatory and anti-inflammatory cytokines may contribute to immuno-pathogenesis in HBV-infected ACLF.
A comparative study of four prognostic systems for predicting the prognosis of patients with chronic severe hepatitis
ZHENG Sheng,YIN Fang,LIU Hai,et al.
2011, 14(2):  119-120.  doi:10.3969/j.issn.1672-5069.2011.02.013
Abstract ( 137 )   PDF (502KB) ( 701 )  
References | Related Articles | Metrics
Objective To compare the predictive values of four prognostic systems including model for end stage liver disease(MELD),Child-Turcotte-Pugh(CTP),MESO and MELD-Na scoring systems in predicting the prognosis of patients with chronic severe hepatitis. Methods A cohort of 156 patients with chronic severe hepatitis were retrospectively studied and followed-up for one year. MELD,CTP,MESO and MELD-Na scores were calculated at the day of admission. Receiver operating characteristics curves(ROC)and the area under ROC(AUC) were used to determine the ability of four systems for predicting the prognosis of patients with severe hepatitis. Results The sores in dead group evaluated by MELD,CTP,MESO and MELD-Na scoring systems(31.2±6.5,12.4±1.3,2.4±0.6,and 39.4±9.8,respectively) were higher than those in survival group(20.2±7.4,10.1±1.5,1.5±0.6,and 22.5±8.6,respectively,P<0.01);The values of AUC of these four systems were 0.824,0.675,0.826,and 0.898,respectively. Conclusion MELD-Na system is a useful prognostic indicator for patients with chronic severe hepatitis. The MELD-Na is superior to MELS,CTP and MESO systems.
Efficacy and safety of glucocorticoids on patients with severe viral hepatitis:A Meta-analysis
LI Jing,WANG Luwen,Gong Zuojiong
2011, 14(2):  121-123.  doi:10.3969/j.issn.1672-5069.2011.02.014
Abstract ( 144 )   PDF (633KB) ( 332 )  
References | Related Articles | Metrics
Objective To evaluate the efficacy and safety of glucocorticoids on severe viral hepatitis. Methods We searched Cochrane Central Register of Controlled Trials(The Cochrane Library,Issue 11,2010), PubMed,OVID,CNKI and Wanfang Data(2000 to 31 October 2010)to collect case-control trials of glucocorticoids for severe viral hepatitis. The language was confined to English and Chinese. We screened the retrieved studies according to the predefined inclusion and exclusion criteria,evaluated the quality of included studies,and performed Meta-analyses using the Cochrane Collaboration’s RevMan 5.0 software. Results Thirteen case-control trials involving 770 patients with severe viral hepatitis were included. All included trials were with average 1.6 of modified Jadad scores. Meta-analysis showed that the mortality of the patients in glucocorticoids group was significantly lower than in control group[RR=0.39,95%CI(0.30 to 0.49),P<0.00001]. Except for some controllable special adverse events found in some patients in glucocorticoids group,one trial showed that the incidence of major complications,such as infections,hemorrhage,hepatic encephalopathy and hepatorenal syndrome,was significantly lower in glucocorticoids group than in control group,which was not performed Meta-analysis because of too small sample size. Conclusion The patients treated with glucocorticoids in a timely and reasonable manner in the early stage of severe hepatitis could obtain better efficacy,lower mortality and no more incidence of complications. However,the accuracy of the results is weakened by the poor quality and quantity of the included trials. Thus,more randomized controlled trials of high quality are required to verify these conclusions.
The hepatic expression of HIF-1α and SDF-1α in patients with chronic liver failure
ZHU Yanfang,HUANG Xiaoping,FU Maoying,et al.
2011, 14(2):  124-126.  doi:10.3969/j.issn.1672-5069.2011.02.015
Abstract ( 132 )   PDF (3356KB) ( 272 )  
References | Related Articles | Metrics
Objective To investigate the hepatic expression of HIF-1α and SDF-1α in patients with chronic liver failure. Methods Liver tissues were obtained from 21 patients with chronic liver failure and 10 controls receiving liver resection for benign lesions,and HIF-1α and SDF-1α were stained immunohistochemically. Results HIF-1α and SDF-1α were overexpressed in livers of patients with chronic liver failure. The positive rates were 57.1% and 71.4%,respectively,much higher than in the normal liver tissues(P<0.05);There was an positive correlation between the expression of HIF-1α and SDF-1α in chronic liver failure(r=0.482,P<0.05). Conclusion HIF-1α and SDF-1α are highly expressed in chronic liver failure, which might promotes the repairment of injuried liver tissues.
The relationship of serum sodium levels to liver functional reserve in patients with liver cirrhosis
SUN Yuzhen,REN Min,DANG Xinyun,et al.
2011, 14(2):  127-128.  doi:10.3969/j.issn.1672-5069.2011.02.016
Abstract ( 154 )   PDF (485KB) ( 423 )  
References | Related Articles | Metrics
Objective To explore the relationship of serum sodium levels to liver functional reserve in patients with decompensated liver cirrhosis. Methods 150 decompensated liver cirrhosis patients with hyponatremia were analyzed retrospectively. The patients were divided into mild,moderate and severe hyponatremia groups according to their serum sodium levels. Results The more severe patients’serum hyponatremia,the higher their serum total bilirubin,urea nitrogen,creatinine,prothrombin time and Child-Pugh scores and the patients with severe hyponatremia had more major complications,and higher mortality. Conclusions The serum sodium levels in patients with decompensated liver cirrhosis reflect liver functional reserve.
The short-term prognostic value of the model for end-stage liver disease including serum sodium in liver cirrhosis patients with esophageal-gastric varices bleeding
FANG Nianfu,ZENG Jing,CHEN Fei,et al.
2011, 14(2):  129-131.  doi:10.3969/j.issn.1672-5069.2011.02.017
Abstract ( 126 )   PDF (519KB) ( 422 )  
References | Related Articles | Metrics
Objective To evaluate the clinical value of Child-Pugh,model of end-stage liver disease (MELD),and the MELD-Na model in the short-term predicting the rebleeding in patients of decompensated liver cirrhosis with esophageal-gastric varices bleeding(EGVB). Methods The patients were graded with MELD, Child-Pugh and MELD-Na and observed their rebleeding and mortality;The accuracy of the three models on predicting survival were analyzed using the area under the receiver operating characteristic(ROC)curve(AUC). Results 49 patients(52.13%)had re-bleeding within 3 months;the Child-Pugh,MELD and MELD-Na scores in patients with re-bleeding and non-bleeding were not significantly different;15 patients died within 3 months,whose MELD-Na score(26.6412.50)was higher than those of survivors(20.354.54,P<0.001);In determining the prognosis of patients with ROC curve AUC comparison,Child-Pugh classification(0.703)>MELD-Na score(0.661)>MELD score(0.627). Conclusion Child-Pugh score,MELD score and MELD-Na score can effectively predict the short-term prognosis of patients with decompensated liver cirrhosis,but can not predict the short-term rebleeding.
Clinical significance of serum anti-SP100 and anti-GP210 detection in diagnosis of patients with primary biliary cirrhosis
TANG Yingmei,BAO Weimin,YOU Liying,et al.
2011, 14(2):  132-134.  doi:10.3969/j.issn.1672-5069.2011.02.018
Abstract ( 130 )   PDF (545KB) ( 345 )  
References | Related Articles | Metrics
Objective To explore the clinical significance of serum anti-SP100 and anti-GP210 in diagnosis of patients with primary biliary cirrhosis. Methods Serum anti-GP210 and anti-SP100 were detected in 71 patients with PBC and 47 with autoimmune hepatitis,or AIH/PBC overlap syndrome. Results The positive rates in patients with PBC or with non-PBC were not significantly different;in patients with PBC,the specificities of anti-GP210,anti-SP100 and anti-GP210/anti-SP100 were 40.2%,76.6% and 82.4%,while the sensitivities were 26.8%,11.2% and 10.2%;there was no significant difference in the positive rates of the two antibodies or both in patients with different pathological stage of liver diseases. Conclusions The detection of serum anti-GP210 and anti-SP100 do not improve the diagnosis of patients with PBC.
Estimation of hepatic resection volume by SPECT in patients with primary liver cacer
SUN Yonggang,LI Jiansheng,JIA Weidong,et al.
2011, 14(2):  135-137.  doi:10.3969/j.issn.1672-5069.2011.02.019
Abstract ( 120 )   PDF (897KB) ( 370 )  
References | Related Articles | Metrics
Objective To investigate the evaulation of liver reserve by single-photon emission computed tomography(single photon emission computed tomography,SPECT). Method SPECT were conducted in 46 patients with primary liver cancer and the 5 min heart and liver-related index(5 minutes heart liver index,HLI),clearance index(blood clearance index,HH15),receptor index(receptor index,LHL15)and the peak value were measured. Results Preoperative HH15 in 31 patients with postoperative good liver function tests was much lower than that in 15 patients with liver failure(P<0.05),while ICGR15 and Child-Pugh scores were not significantly different in the two groups(P>0.05);when HH15≥0.533,the patients had much higher liver failure incidence as compared to those with HH15<0.533(P<0.05). Conclusion HH15 is a sensitive indicator of liver functional reserve.
The correlation between CT enhancement patterns and tumor angiogenesis in the edge of hepatocellular carcinoma
SHI Huiping,LIU Xiaoyu,LI Dongmei,et al.
2011, 14(2):  138-141.  doi:10.3969/j.issn.1672-5069.2011.02.020
Abstract ( 124 )   PDF (2878KB) ( 430 )  
References | Related Articles | Metrics
Objective To investigate the correlation between the enhancement characteristics and tumor angiogenesis in the edge of hepatocellular carcinoma. Methods The characteristics of CT enhancement confirmed by preoperative CT scan and contrast CT of hepatic arterial and portal phase were studied in 38 patients with hepatocellular carcinoma. CD34 was detected by immunohistochemistry in the tumor tissues. Results The tumors with clear edge shown on plain CT with thin or thick envelope were in the manner of expansive growth,while the tumors with unclear edge were in invasive growth;there was a higher probability of invasion for tumors with unclear and high-density,and a probable transfer for tumors with rich edge angiogenesis;relatively,there was lower transfer for tumors with low-density and fewer new blood vessels. Conclusion Dynamic enhanced CT scan can show the CT enhancement characteristics of the tumor,which might reflect the pathological changes and have great significance for clinical guidance.