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In 2020, an international expert panel proposed to replace nonalcoholic fatty liver disease with metabolic associated fatty liver disease (MAFLD). Recent studies have shown that there is a higher risk of chronic kidney disease (CKD) in the MAFLD population and that MAFLD is an independent risk factor for CKD. However, up to now, there are still no guidelines on the prevention and treatment of MAFLD-related CKD. Based on the Delphi method, the authors led a multidisciplinary team of 50 authoritative experts from 26 countries to reach a consensus on some open-ended research issues about the association between MAFLD and CKD, which can help to clarify the important clinical association between MAFLD and the risk of CKD and improve the understanding of the epidemiology, pathogenesis, management, and treatment of MAFLD and CKD, so as to establish a framework for the early prevention and management of these two common and interrelated diseases.
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BACKGROUND@#Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.@*METHODS@#Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).@*RESULTS@#A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal.@*CONCLUSION@#This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
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Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Keratin-18 , Biomarkers , Biopsy , Hepatocytes/pathology , Apoptosis , Liver/pathologyABSTRACT
Metabolic associated fatty liver disease (MAFLD) is a common chronic liver disease around the world, affecting more than a quarter of the adult population worldwide. MAFLD is characterized by the co-occurrence of hepatic steatosis and metabolic disturbance. As a metabolic disorder, MAFLD shares a similar pathogenesis with cardiovascular disease (CVD), and both diseases are closely associated with the well-established cardiovascular risk factors such as obesity, type 2 diabetes, and atherogenic dyslipidemia. An increasing amount of evidence has shown that MAFLD is closely associated with CVD; however, as a new risk factor for CVD, MAFLD differs from traditional risk factors for CVD, which requires further investigation. In this context, this consensus statement used the Delphi method to achieve a consensus on the association between MAFLD and the risk of CVD through two rounds of surveys and discussed the association between MAFLD and CVD in terms of epidemiological and clinical characteristics, as well as a range of topics including pathophysiological mechanisms, surveillance, and management.
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Metabolic associated fatty liver disease (MAFLD) is a hotspot in the field of fatty liver disease at present and it has become the most common chronic liver disease around the world. It is predicted that the incidence rates of MAFLD and related liver cirrhosis will continue to grow in the next 20 years and that they will become new global health issues. Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome of acute or subacute liver function decompensation within a short period of time in the presence of existing chronic liver diseases, with the main clinical manifestations of ascites, jaundice, coagulation disorder, and hepatic encephalopathy. Based on the existing data, this article discusses the epidemiology, pathogenesis, treatment and management strategies, and future prospects of MAFLD-ACLF.
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Objective To explore the effect and mechanism of sulfotanshinone sodium in lung fibrosis in ALI rats by intraperitoneal injection. Method The rats were divided into normal group,model group and sulfotan-shinone sodium group randomly.During the experiment,acute lung injury was induced by oleic acid in rats.Sulfo-tanshinone sodium group was treated by intraperitoneal injection of sulfotanshinone sodium for 14 days consecutively. The 12 rats were sacrificed at 7thand 14thday after last administration.The indexes of weight,arterial partial pres-sure of oxygen(PaO2),oxygenation index(PaO2/FiO2),lung index and wet/dry ratio,IL-1,TNF-α,PCⅢ,TGF-β1 and the lung histopathology of rats were observed. Results There was no difference in rat weight between the groups.The values of PaO2and PaO2/FiO2were increased.The lung index and wet/dry ratio,IL-1,TNF-α,PCⅢ, TGF-β1 and IQA were all reduced. The lung histopathology damage was significantly lightened.as compared with the model group. Conclusion It has treatment effect of sulfotanshinone sodium in lung fibrosis in the ALI rats, which may be related with the adjustment on inflammatory factor.
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Objective To explore the effect of apolipoprotein E (ApoE) on matrix metalloproteinases-9 (MMP-9) expression and its mechanism in astrocytes.Methods (1) Astrocytes in ApoE gene knock out (ApoE-/-) and wild type (WT) C57BL/6J suckling mice were cultured in vitro;glial fibrillary acidic protein antibodies were employed to identify the astrocytes;MMP-9.antibodies were employed to detect the MMP-9 expression in the astrocytes.(2) Astrocytes from the ApoE-/-and wild type WT C57BL/6J suckling mice were divided into activation group,antibody groups and control group randomly;cells in the control group did not give any treatment;cells in the activation group were given whooping cough toxin and thermal inactivation-mycobacterium tuberculosis H37Ra;cells in the antibody groups were given anti-interleukin-6 (IL-6),interferon gamma (IFN--γ),tumor necrosis factor-α (TNF-α) and IL-12,respectively,to inhibit their inflammatory factors.ELISA was performed to detect the concentrations of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1),and the inflammatory factors concentrations ofTNF-,IL-12,IL-6,and IFN-γ.Results These two kinds of rat astrocytes could both qualitatively express MMP-9;as compared with the control group,the activation group had significantly higher MMP-9 concentration (P<0.05);the activation group had significantly higher MMP-9 concentration as compared with the antibody groups (P<0.05);activation group from ApoE-/-C57BL/6J suckling mice had significantly higher MMP-9 concentration than that from wild type C57BL/6J suckling mice (P<0.05).The concentration of TIMP-1 was not significantly different among various groups (P>0.05).The concentrations of inflammatory factors in the activation groups from two kinds of mice were significantly higher than those in the control group (P<0.05);the concentrations of IL-6,IFN-γ TNF-α and IL-12 in each antibody group were significantly lower than those in the activated group (P<0.05);the concentrations of inflammatory factors in ApoE-/-rats were significantly higher than those in WT rats (P<0.05).Conclusion ApoE can regulate the MMP-9 expression by regulating the secretion of proinflammatory cytokines,which can affect the integrity of blood brain barrier.
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OBJECTIVE@#To analyze characteristics and curative effect of sudden sensorineural hearing loss (SSHL) inpatients with different audiometric curve and provide the reference for the diagnosis and treatment of SSHL.@*METHOD@#Retrospective analyze of 1033 cases of SSHL inpatients, compare the gender, the ears, the ages, with or without tinnitus and vertigo, hearing loss degree and the efficacy of distribution characteristics in different audiometric curves.@*RESULT@#Lnpatients with SSHL are mostly flat (27.24%), peak valley at least (5.94%); Gender distribution: male to female ratio was 1.3:1, audiometric curve for the rise type more than the decline type and flat type and completely deafness type (P < 0.01) in female. The ears distribution: the flat type more than increase type ( P < 0.01) in double eras SSHL. The age distribution: the flat type more than 60 years of age was significantly higher than that rising type (P < 0.01). Completely deafness type compared with the other types, the decline type compared with the rise type, the incidence of vertigo was significantly different (P < 0.01). Peak valley type with tinnitus was higher than the flat type. Degree of hearing loss distribution: completely deaf type in the very severe hearing loss was significantly higher than other types (< 0.01), flat type in severe hearing loss was significantly higher than other types (P < 0.01). The total effective rate was 51.01%. Rise type, peak valley type were more efficient than other types (P < 0.01); completely deafness type was less efficient than other types (P < 0.01).@*CONCLUSION@#The characteristics and curative effect are different in SSHL inpatients with different audiometric curves. Flat type was the most, peak valley type was the least. The curative effect of rise type and peak valley type are the best, completely deafness type is the worst. The degree of hearing loss and whether associated with vertigo is closely related in efficacy.
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Audiometry , Hearing Loss, Sudden , Therapeutics , Retrospective Studies , Treatment OutcomeABSTRACT
Objective To investigate the role of CD4+ CD25+ regulatory T lymphocyte(Tregs)in the immunological pathogenesis of liver fibrosis.Methods Twenty-six rats were divided into two groups:control group(6 rats)and model group(twenty rats).The rat model of liver fibrosis was induced bv subcutaneous injection of carbon tetrachloride(CCl4).The serums were collected for detection of hepatic function and fibrosis parameters.Hepatic tissue samples were used to observe the histopathological changes.The flow cytometry was used to detect the proportions of Tregs in both peripheral blood and spleen.The data were evaluated by t-test.The relationship between two variables was analyzed using Pearson linear correlation.Results The levels of serum alanine aminotransferase (ALT)and aspartate aminotransferase (AST) were significantly increased,but the level of serum albumin (Alb) was obviously decreased.The concentrations of serum hyaluronic acid (HA),procollagen type Ⅲ(PCⅢ),collagen type Ⅳ(CⅣ)of the model group increased to(177.42±61.25)μg/L,(34.86±7.47)μg/L and(7.32±3.71)μg/L,respectively,which were higher than those in the control group(t=-3.670,-5.661,-3.950,respectively;all P0.05).Conclusion These findings suggest that the reduction of CD4+ CD25+ Tregs probably play an important role in the immunological pathogenesis of liver fibrosis.
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ObjectiveTo investigate whether CD4+ CD25+ CD127dim/- regulatory T lymphocytes (Treg) can induce the proliferation of hepatic stellate cells (HSC) and expression of fibrosis-related factors on HSC in vitro and further to explore the mechanism of Treg inducing fibrogenesis. MethodsHSC LX-2 cells were subcultured.CD4+ CD25+ CD127dim/- cells were purified using magnetic cell separation. The HSC were co-cultured with Treg by direct contact or by Transwell system in vitro. The HSC cultured alone was used as control. Cell proliferation was measured by CCK-8 assay.The expression of transforming growth factor (TGF)-β1 was detected by enzyme-linked inmunosorbent assay (ELISA), and the expressions of hyaluronic acid (HA) and precollagen Ⅲ (PC Ⅲ ) were detected by radio immunoassay (RIA). The data were analyzed by LSD-t test. ResultsHSC proliferation was strongest when Treg∶ HSC= 1.5∶ 1. The absorbance in direct contact co-culture group and Transwell system co-culture group was (0. 713±0. 032) cpm and (0. 735±0. 028) cpm, respectively, both of which were higher than that in control group [(0. 677 ± 0. 029) cpm](t = 5. 4003 and 8. 7878,respectively; both P<0. 01). The concentrations of TGF-β1 in the supernatant were (781. 59 ±76.45) pg/mL and (813. 53±60. 62) pg/mL, respectively in direct contact co-culture group and Transwell system co-culture group, which were significantly higher than that in control group [(722.51±59. 66) pg/mL](t = 4.0014 and 6. 1653, respectively; both P<0.01).The concentrations of HA were (433. 575±27.90) ng/mL and (445.40±23.73) ng/mL, respectively in direct contact co-culture group and Transwell system co-culture group, which were higher compared to that in control group [-(415. 83±19.44) ng/mL](t =3. 3124 and 5. 5231, respectively; both P<0.01). Likewise, the concentrations of PCⅢ were (21. 93± 1.71) and (23. 125± 1.87) ng/mL in direct contact group and Transwell group, respectively compared to (20. 10± 1.49) ng/mL in control group (t = 4. 8082 and 7. 9436, respectively; both P < 0.01).Furthermore, the absorbance,concentrations of TGF-β1, HA and PC Ⅲ in Transwell co-culture group were all higher compared to direct contact group (t = 3. 3875, 2.1639, 2. 2107 and 3.1354, respectively; all P<0. 05).ConclusionsThe cell proliferation and the expressions of fibrosis-related factors in HSC increase greatly after co-cultured with CD4+ CD25+ CD127dim/-Treg. Therefore, Treg may play an important role in inducing liver fibrogenesis.
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Objective To investigate the roles of five scoring systems including model for endstage liver disease (MELD), Child-Turcotte-Pugh (CTP), Mayo, MESO and MELD-Na scoring systems, in predicting the prognosis of patients with chronic severe hepatitis. Methods The clinical data of 213 patients with chronic severe hepatitis were retrospectively studied. The five scoring systems were applied respectively to evaluate the scores in survival group and death group. The capability of these five scoring systems to predict the prognosis of severe hepatitis were compared by the receiver operating characteristic (ROC) curve, area under curve (AUC) and cut-off value.Measurement data were compared by group t test. The comparisons of AUC among scoring systems were done using MEDCLAC software. Results The scores of death group evaluated by MELD, CTP,Mayo, MESO or MELD-Na scoring systems (30.6 ± 9.5, 11.3 ± 1.5, 10.4 ± 1.3, 2.3 ± 0.8 and 39.0 ± 11.8, respectively) were consistently higher than those of survival group (21.1± 6.8, 10.6 ±1.6, 9.0±1.5, 1.6±0.5 and 22.6±8.2, respectively) (P<0.01). The values of AUC of these five systems were 0.810, 0.623, 0.749, 0.829 and 0.885, respectively. The Youden's indexes of these five systems were 0.507, 0.175, 0.389, 0.528 and 0.650, respectively. Conclusions The CTP scoring systems can not predict the prognosis of chronic severe hepatitis very well. The Mayo scoring systems can partially predict the prognosis. On the contrary, MELD, MESO and MELD-Na systems can successfully predict the disease prognosis, and the score of MELD-Na system shows the best correlation with the prognosis.
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Objective To identify hepatitis C virus(HCV)-specific cytotoxicity T lymphocytes (CTL)epitopes by the combination of T epitopes prediction software and in vitro assays.Methods HCVspecific CTL epitopes were predicted by T epitope prediction software Rankpep and then candidate HCV-specific CTL epitopes were selected.Candidate HCV-specific CTL epitopes were used to stimulate PBMC of HCV-infected patients and healthy volunteers.and then enzyme-linked immunospot(ELISPOT)and intracellular cytokine staining(ICS)were used to measure the frequencies of IFN-γ-producing cells in total PBMC and the percentages of IFN-γ+CD8+T cells in total CD8+T cells,respectively.Results Five candidate CTL epitopes[NS3 450(TVPQDAVSR),NS3 594(GPTLLYRL),Ns4b 78(sMMAFSAAL),NS5a 416(SEENVSVVF)and NS5a 367(TVSSALAEL)]were used to stimulate PBMC of ten HCV-infected patients and two healthy volunteers.PBMC of seven HCV-infected patients secreted IFN-γ while PBMC of healthy volunteers did not produce IFN-γ.The frequencies of peptide-specific IFN-γ-producing cells ranged from 5 to 36 SFC/105 PBMC and the percentages of peptide-specific IFN-γ+CD8+T cells ranged from 0.02%-0.25%.Conclusion Resuhs of ELISPOT assay and ICS assay confirm that these five peptides NS3 450,NS3 594,NS4b 78,NS5a 416 and NS5a 367 are identified as Hovel HCV-specific CTL epitopes.
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Objective To study the protective role of ulinastatin in acute liver failure (ALF) and the effect on the expression of hemeoxygenase-1 (HO-1).Methods Sixty-six S-D rats were divided into three groups:control group,ALF group (model group) and ulinastatin group (intervention group).The rat model of ALF was induced by intraperitoneal injection of D-galactosamine (D-Gal) and lipopolysaccharide (LPS). The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) were detected dynamically after 6,12,24,36 and 48 h injection.HO-1 mRNA expression in liver tissue was determined by reverse transcriptionpolymerase chain reaction (RT-PCR), and the expression of HO-1 protein was detected by immunohistochemistry.The differences among multiple groups were compared by univariate ANOVA and pairwise comparison was done by least significant difference (LSD). Results D-Gal/LPS injections successfully induced ALF rat model which presented with elevated levels of serum ALT,AST and liver MDA after 6 h injections (F=23.864,38.446,18.051,respectively,all P<0.01),and peaked at 12-24 h after injections.Twenty-four hours after D-Gal/LPS treatment,the levels of serum ALT,AST and MDA in model group and intervention group were (8 346.7±1 363.1) U/L vs(4 151.3±970.0) U/L,(9 766.7±1.274.1) U/L vs (4 696.7±1 476.9) U/L,(8.34±1.13)μmol/g vs (4.66±0.91 ) μmol/g,respectively,which were significantly higher than those e (24.0±2.0) U/L,(82.3±16.9) U/L,(2.55±0.22) μmol/g,respectively] in control group (F=55.684,55.501,47.843,respectively,all P<0.01);while those in intervention group were much lower than those in model group (P<0.01).The expressions of HO-1 mRNA and protein in model group were significantly increased than those in control group (P<0.01),while those in intervention group were even higher (P<0.01).Conclusion Ulinastain could up-regulate the expressions of HO-1 mRNA and protein,which indicates that ulinastain may play anti-oxidant and anti-inflammatory roles in ALF through HO-1 pathway.
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Objective To evaluate the treatment effect of acute liver failure(ALF) by xeno-transplantation of co-microencapsulated Sertoli cells and hepatocytes and the intraperitoneal immune privilege effects of Sertoli cells on hepatocytes. Methods ALF rats were induced by intraperitoneal injection of D-galactosamine and, thereafter, were treated with physical saline, free hepatocytes, microencapsulated hepatocytes, or co-microencapsulated Sertoli cells and hepatocytes (CMSH), respectively. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected in rats' blood samples from various groups. Expression of Smac/Diablo and caspase-3 were determined by reverse transcription-polymerase chain reaction (RT-PCR). Fifteen rats in each group were used for survival rate analysis. The intraperitoneal microencapsules were observed and lymphocytes in ascites were counted. The data were analyzed by multi-factor or single factor analysis of variance and the comparison between groups was done by t test. Results In CMSH treatment group, ALT level decreased to (533.7 ± 76.5) U/L, AST level decreased to (381.2 5± 46.7) U/L after 48 h. TBil level reduced to (7.36 ± 2.18) μmol/L after 72 h. Albumin level increased to (28.4±2.5) g/L after 48 h. All these values were significantly different from those in other groups (F=10.7,6.5,12.2,8.4;P<0.05). The expression levels of Smae/Diablo and caspase-3 mRNA at 48 h and 72 h were lower in CMSH group than in other groups (F=3.7,4.8,3.6,4.2; P<0.05). Survival rates in microencapsulated hepatocytes group and CMSH group were similar while both of them were higher than other groups. Microencapsules neither in microencapsulated hepatocytes group nor in CMSH group were adhered to intraperitoneal mucosa. Lymphocyte counts in ascites of CMSH group were lower than those in microencapsulated hepatocytes group (t= 4.21, P<0. 05). Conclusions Intraperitoneal transplantation with CMSH is a promising approach for ALF treatment. Furthermore, Sertoli cells can help reduce lymphocytes' aggregation caused by encapsulated hepatocytes in ascites.
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Objective To investigate the changes of fractalkine (FKN) in rat model of acute liver failure (ALF) and the role of FKN in liver inflammatory injury.Methods SD rats were divided into tWO groups:6 in normal group and 36 in model group.D-galactosamine(D-Gal) was used to induce ALF in model group.The sera and hepatic tissue samples were collected at 12,24,48,72,120 andl68 h.After D-Gal injection.FKN mRNA and nuclear factor(NF)-kB mRNA in hepatic tissue samples were detected by reverse transcription-polymerase chain reaction (RT-PCR).Results The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at 12 h were(208.3±43.5)U/L and (375.2±117.3)lJ/L,respectively,which were both significantly higher than those in normal group[(31.8±2.9)U/L and (90.8±3.1)U/L](t=-9.912 and-5.935,respectively,both P<0.01);the levels of ALT and AST peaked at 72 h after D-Gal injection.The levels of FKN mRNA(O.086±0.009)in model group at 12 h were significantly higher than those (O.044±0.009) in normal group(t=-7.999.P<0.01),and peaked at 72 h (O.333±0.033),then decreased obviously at 120 h. The levels of NF-KB mRNA in the liver of normal rats were very little;and the levels in model group were increased gradually over time,then peaked at 72 h (O.583±0.i01,t=-12.607,P<0.01).FKN mRNA and NF0kB mRNA were positively correlated (r=0.760,P<0.01).Conclusion The FKN expression may play all important role in liver inflammatory injury in rat model of acute liver failure, which could provide a new approach for ALF therapy.
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Objective To evaluate the nourishment and immune privilege effects of Sertoli cells on co-encapsulated hepatocytes. Methods The hepatocytes and Sertoli cells were encapsulated or co-encapsulated in various ratio of 100∶1、50∶1、20∶1、10∶1, and co-cultured for 21 days in vitro. The secretion of albumin and urea was analyzed, and the morphology of encapsulated cells was observed by microscopy, then to determine the best mixed ratio of hepatocytes to Sertoli cells. Splenocyte proliferation response was assessed to evaluate Sertoli cell’s immune privilege function to hepatocytes by CCK-8.Results Sertoli cells could elevate hepatocyte’s secretion of albumin and urea when they were co-encapsulated with each in appropriate ratio (P
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Objective To evaluate the effectiveness of PGE1 therapy for survival and incidence of complications in patients with liver failure.Methods MEDLINE,EMBASE.com,Cochrane Controlled Register and CBMdisc were searched.Randomized controlled trials of PGE1 therapy for liver failure were collected and reviewed.The quality of articles was evaluated and data was extracted from it.The odds ratio for death and complications among the patients with PGE1 therapy as well as the blank controls was calculated at the end of therapy.The results of meta-analysis were assessed according to sensitivity and bias.RevMan4.2 was applied to process the data.Results The results of meta-analysis showed that PGE1 reduced the case-fatality ratio of liver failure [OR=0.30,95%CI(0.23~0.37)] and the risk difference was decreased 29% in PGE1 patients compared with the blank controls.And there was statistical significance in PGE1 reducing the incidence of hepatorenal syndrome,but occurance of the complieations such as hepatic encephalopathy,bleeding,infection etc.These results were not reversed in the analysis of sensitivity,and the analysis of bias showed little bias of them.Conclusions PGE1 can reduce the case-fatality ratio of liver failure and the incidence of hepatorenal syndrome.The accuracy of the results are low due to the poor quality of the included trials.Thus, the effect of PGE1 on liver failure needs to be further evaluated through randomized controlled trials of high quality to be carried out in multicenter and large samples.
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Objective To analyze the etiology and the clinical characteristis of fever in older patients in Wenzhou.Methods Totolly 87 cases admitted to the First Affiliated Hospital of Wenzhou Medical College from January 2001 to April 2004 were retrospectively analyzed;all cases displayed fever as the major clinical manifestation and met the criteria of fever well.Results The etiology of fever which was infectious disease was in 44 of the 87 cases,accounting for 50.6%,collagen-vascular diseases 4.6%,neoplasms 10.3% and miscellaneous diseases 5.7%.In 28.7% of the cases the etiology could not be found.And in the infectious disease the tuberculosis accounted for 13.6%(6/44). Ultrasonography ,X-rays,CT scan,MRI,the marrow puncture and biopsy contributed to the final diagnosis in 21.1%,16.9%,63%,0,16.7% and 57.1% of the cases,respectively.Conclusion Because the symptoms of the older patients'febrile diseases are atypical,the diagnosis is more difficult.Infectious disease still remains a major cause of the fever in the elderly.A thorough history of disease,full physical examination of the patient and routine laboratory studies,especially erythrocyte sedimentation rate,are very important in determining the etiology of febrile disease.Early and reasonable use of non-invasive imaging techniques and the essential invasive methods are helpful to diagnosis.
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PURPOSE Anti-cancer drug treatment induces cell death by apoptosis, whether the gene p53 undergoes mutant changes is found to have a close relationship with anti-cancer drugs. The aim of this work is to investigate the role that p53 plays in the 5-FU-induced apoptosis of colorectal cancer cells in vitro. METHODS Thirty-nine col-orectal cancer samples from patients were treated with 5-FU (10?g/ml) and folinic acid (5?g/ml. 10?g/ml) in vitro, using the in situ Terminal Deoxynucleotidyl Transferase assay (TDT) to detect the chemosensitivity. p53 mutations from tumor DNA were detected, after amplication by PCR of exons 5 to 8. by non-radioactive single-strand conformation polymorphism(PCR-SSCP). RESULTS p53-gene mutations were observed in 43. 6% (17/39) of colorectal carcinomas. When TDT assay was used to detect the tumor apoptotic rate, cells with mutated p53 had less chemosensitivity than those without (16. 4% ?4. 89% vs 26. 6%? 6. 80% P