Serum beta2-microglobulin in liver disease.

The concentration of beta 2-microglobulin in serum was determined in seventy-one patients with various liver disorders. Elevated values were found in most patients with chronic active or chronic persistent hepatitis and in over 80% of patients with alcohol-induced liver cirrhosis. In contrast, patients with alcohol-induced fatty liver, the serum beta 2-microglobulin concentrations were mostly within the normal range. Significant correlation (P less than 0.001) was noted between the elimination rate of galactose from blood and the serum beta 2-microglobulin concentration in patients with alcoholic liver damage but not in patients with chronic hepatitis. The reasons for the increased S-beta 2-microglobulin concentrations in liver diseases are unknown. Several explanations including a release of beta 2-microglobulin from necrotic liver cells or an increased synthesis of beta 2-microglobulin consequent to inflammation in the liver are possible. Alternatively, raised beta 2-microglobulin levels may reflect the hepatic synthesis during reparative growth.     

1-14C]Ethanol breath test in alcoholic liver disease

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.     

gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.     

Hepatitis B antigens and antibodies in asymptomatic carriers and in chronic liver diseases.

88% of asymptomatic hepatitis B surface antigen (HBsAg) carriers and 97% of HBsAg positive patients with chronic hepatitis or non-alcoholic liver cirrhosis showed high titers of antibody to hepatitis B core antigen (anti-HBc). A high titer of anti-HBc, thus suggested to be an indicator of persistent hepatitis B virus infection, was found rarely in seronegative patients with chronic hepatitis, non-alcoholic cirrhosis, or alcoholic liver diseases. It was not revealed in idiopathic portal hypertension or Budd-Chiari syndrome. In asymptomatic HBsAg carriers of 20--29 years of age, hepatitis B e-antigen (HBeAg) was significantly more frequently found in males than in females. There were differences in sex ratio, age, and history of blood transfusion between B type and non-B type of chronic hepatitis and non-alcoholic liver cirrhosis.     

Serum beta 2-microglobulin levels in chronic post-transfusion non A non B liver disease

Serum beta 2-microglobulin (beta 2 mu), a reliable marker of T-cell activation, was measured in 25 patients with chronic post-transfusion non A non B (NANB) liver disease and in 21 patients with HBsAg positive chronic liver disease. beta 2 mu levels were elevated in NANB patients when compared with controls but not in comparison with the HBsAg carriers. In NANB patients, beta 2 mu concentrations were significantly correlated with serum IgG (P less than 0.001) and with circulating immune complex activity, assessed by the 125IClq binding test (P less than 0.01). These findings suggest that, in addition to T-cells, the B-cells contributed also to the beta 2 mu production. Patients with "active disease" (chronic active hepatitis and active cirrhosis) had significantly higher beta 2 mu levels (P less than 0.001) than did those with "inactive disease" (chronic persistent hepatitis and inactive cirrhosis). This relation of serum beta 2 mu concentrations and histological activity was also observed in the HBsAg carriers and suggests that the course of post-transfusion NANB chronic hepatitis could be determined by host's immune response rather than by a direct effect of the virus.     

Localization of T and B cells and alpha fetoprotein in hepatic biopsies from patients with liver disease.

Peripheral blood and hepatic tissue T- and B-lymphocyte distributions, serum alpha fetoprotein (AFP) concentrations, and hepatic AFP were studied in 46 patients undergoing diagnostic percutaneous liver biopsy. The patients included 26 with alcoholic liver disease, 13 with nonalcoholic hepatitis or cirrhosis, and 7 with either normal histology or minor nonspecific changes. Serum AFP was determined by radioimmunoassay and hepatic tissue AFP by indirect immunofluorescence. Peripheral blood T lymphocytes were identified by the sheep red-cell rosette technique; and B lymphocytes by fluoresceinated anti-immunoglobulin antisera and IgG aggregates. Tissue identification of T lymphocytes was accomplished using an extensively absorbed rabbit antihuman thymocyte antiserum and indirect immunofluorescence; tissue B lymphocytes were identified using pepsin F (ab')2 fragments of rabbit IgG antibodies to human immunoglobulins. T lymphocytes predominanted in hepatic lymphoid infiltrates from patients with alcoholic liver disease (91+/-4%), whereas in patients with chronic active or chronic persistant hepatitis, viral hepatitis, or cryoptogenic cirrhosis proportions of T and B lymphocytic infiltrates were similar (50+/-15%). Hepatic tissue AFP was detected in 9 of 18 patients with alcoholic hepatitis; serum AFP concentration was increased in only 1 of these 9 patients. Tissue AFP was not observed in the remaining biopsy material nor were serum AFP concentrations increased. Peripheral blood T-cell numbers were significantly decreased in patients with alcoholic liver disease (P less than 0.01) and in nonalcoholic hepatitis or cirrhosis (P less than 0.025). A close relationship between peripheral blood T-lymphocytopenia and hepatic T-cell infiltrates was observed in patients with alcoholic liver disease; this relationship was less apparent in patients with nonalcoholic hepatitis or cirrhosis.     

Red blood cell status in alcoholic and non-alcoholic liver disease.

Macrocytosis is most commonly associated with vitamin B(12) and folic acid deficiency, followed by alcoholism, liver disease, and other pathologic conditions. We studied the red cell and vitamin status in 423 consecutive patients with various liver diseases, including 31 with acute viral hepatitis (AVH), 105 with chronic hepatitis (CH), and 134 with alcoholic liver disease (ALD), who consisted of 84 with non-cirrhotic alcoholic liver disease (NCALD) and 50 with alcoholic liver cirrhosis (ALC), 60 with non-alcoholic liver cirrhosis (NALC), and 93 with hepatocellular carcinoma (HCC). The mean corpuscular volume (MCV) and red cell distribution width (RDW) were significantly higher in patients with ALD and NALC, and among them macrocytosis occurred more frequently in patients with ALC. Macrocytic anemia was mostly found in cirrhotic patients, in which the Child-Pugh score was closely related to the development of macrocytic anemia. In ALD, the MCV was significantly correlated with the estimated alcohol consumption and inversely correlated with the serum folic acid level, which, however, was often maintained within the normal range in patients with macrocytic ALC. After abstinence from alcohol, the MCV and RDW were reduced significantly and were associated with an increasing serum folic acid level. This suggests that macrocytic anemia was a common feature of alcoholic and non-alcoholic liver cirrhosis and that alcohol abuse and folic acid deficiency play a secondary role in macrocytosis.     

Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性乙型肝炎、肝硬化患者血清瘦素测定及临床意义

目的：测定慢性乙型肝炎(CHB)、乙型肝炎后肝硬化(LC)患血清瘦素水平，并探讨其异常变化的临床意义。方法：采用酶联免疫吸附试验(ELISA)，测定79例CHB、77例LC患的血清瘦素水平，同时检测76名正常人血清瘦素水平作为对照。结果：与正常对照组比较，CHB和LC患，无论男女其血清瘦素水平均明显降低，且CHB患瘦素水平明显低于LC患。以上3组血清瘦素水平女性均高于男性。结论：CHB和LC患，不论肝功能异常程度如何，其血清瘦素水平均低于正常人，其原因与肝脏受病毒感染损伤、肝脏功能异常明显相关。     

肝脏疾病诊断中腺苷脱氨酶、前清蛋白、α-L-岩藻糖苷酶、胆碱脂酶和5'-NT价值的临床评价

目的 了解腺苷脱氨酶（ADA）、α-L-岩藻糖苷酶（AFU）、胆碱脂酶、前清蛋白和5＇-核苷酸酶（5＇-NT）在肝脏疾病诊断中的意义.方法 选择332例肝脏疾病患者,其中,急性肝炎150例,重型肝炎25例,肝硬化40例,酒精性肝炎35例,慢性肝炎82例;选择同期90例健康体检者作为对照.采用Bayer ADVIA 2400 全自动生化分析仪检测其血清ADA、AFU、前清蛋白、胆碱脂酶和5＇-NT,绘制受试者工作特征曲线（ROC）并计算曲线下面积（AUC）,评价5项指标在不同肝脏疾病中的诊断意义.结果 重型肝炎、肝硬化患者血清ADA、AFU、5＇-NT显著增高,前清蛋白、胆碱脂酶显著降低;ADA、AFU、5＇-NT的异常值比例分别超过80%、65%、90%.急性肝炎、酒精性肝炎患者血清ADA、AFU、5＇-NT轻度升高,前清蛋白、胆碱脂酶轻度下降;急性肝炎患者血清胆碱脂酶、5＇-NT的异常值比例分别为80.0%、54.67%.血清前清蛋白、胆碱脂酶的AUC在重型肝炎患者中分别为0.022、0.000,在肝硬化组患者中分别为0.019、0.000;上述两组患者血清ADA、5＇-NT的AUC均大于0.950,AFU的AU均大于0.800.在急性肝炎和酒精性肝炎组中,患者血清ADA、5＇-NT的AUC均大于0.800,AFU的AUC分别为0.814、0.637.332例患者血清前清蛋白、胆碱脂酶的AUC分别为0.175、0.181,血清ADA、AFU、5＇-NT的AUC分别为0.850、0.743、0.714.结论 血清ADA、AFU、前清蛋白、胆碱脂酶和5＇-NT检测对肝脏疾病的诊断具有重要价值.     

慢性乙型肝炎合并酒精性肝病患者血清瘦素测定的临床价值

目的测定慢性乙型肝炎合并酒精性肝病患者血清瘦素水平，并探讨与胰岛素抵抗的关系。方法选择慢性乙型肝炎合并酒精性肝病患者17例，肝硬化15例，慢性乙型肝炎19例与12例男性健康受试者为对照组，各组间在性别、年龄和体质量指数（BMI）均相匹配。采用酶联免疫吸附法（ELISA）测定血清瘦素，同时测定血糖、血脂、胰岛素和肝肾功能等指标，并测量身高、体质量，计算BMI。并进行结果分析。结果慢性乙型肝炎合并酒精性肝病、肝硬化组血清瘦素水平高于对照组（P〈0．05），慢性乙型肝炎组与对照组比较差异无统计学意义（P〉0．05），慢性乙型肝炎合并酒精性肝病组瘦素水平与BMI、FINS呈显著正相关（r值分别为0．169，0．267，P〈0．05）；瘦素与三酰甘油里明显负相关（r值为-0．249，P〈0．05）。结论慢性乙型肝炎合并酒精性肝病患者血清瘦素水平明显增高，与高胰岛素血症和胰岛素抵抗存在相关性，瘦素表达不能评价肝病严重程度。     

非酒精性脂肪肝与代谢综合征的关系探讨

目的 :探讨非酒精性脂肪肝与代谢综合征的关系。方法 :采用病例对照研究 ,女性脂肪肝组 4 0例 ,无脂肪肝组 4 0例作为对照 ;男性脂肪肝组 6 0例 ,无脂肪肝组 6 0例作为对照。检测四组的血脂、血尿酸、空腹血糖、空腹血胰岛素 ,采用稳态模式胰岛素抵抗指数 (HOMA -IR)评价胰岛素抵抗。结果 :男女脂肪肝组与对照组比较 ,甘油三酯 (TG)、空腹血糖 (FPG)、空腹血胰岛素 (FINS)、HOMA -IR均有极显著升高 (P <0 .0 0 1) ;男性脂肪肝组与对照组比较 ,胆固醇 (TC)极显著升高 (P <0 .0 0 1) ,尿酸 (UA)显著升高 (P <0 .0 5 ) ;女性脂肪肝组与对照组比较 ,胆固醇 (TC)显著升高 (P <0 .0 5 ) ,尿酸 (UA)无显著差异 (P >0 .0 5 )。结论 :非酒精性脂肪肝存在明显胰岛素抵抗 ,非酒精性脂肪肝可作为代谢综合征 (MS)的特征之一 ,高尿酸血症可作为男性MS的特征之一。     

酒精性肝病患者健康相关生存质量研究

目的研究酒精性肝病患者健康相关生存质量及其与疾病严重程度的关系以及对比酒精性肝病与慢性乙型肝炎患者健康相关生存质量的差别。方法 2010年12月至2011年10月收治的70例男性酒精性肝病患者(非肝硬化组45例,肝硬化组25例),56例男性慢性乙型肝炎患者(非肝硬化组24例,肝硬化组32例)以及42例男性健康对照组受试者参与试验。所有受试者回答SF-36V2(中文版)量表,通过SF-36V2软件计算出:生理功能、生理职能、躯体疼痛、总体健康、活力、社会功能、情感职能、精神健康共8个维度,以及躯体健康总评和精神健康总评。使用协方差分析对比健康对照组,酒精性肝病非肝硬化组,以及酒精性肝病肝硬化组健康相关生存质量;对比酒精性肝病与慢性乙型肝炎患者健康相关生存质量。结果和健康对照组相比,酒精性肝病患者随着疾病的加重,SF-36V2各维度评分明显降低(P<0.05)。酒精性肝病非肝硬化组患者较慢性乙型肝炎非肝硬化组患者仅生理功能、生理职能、活力、躯体健康总评四项评分轻度受损(P<0.05)。酒精性肝病肝硬化组与慢性乙型肝炎肝硬化组患者SF-36V2各维度评分相似(P>0.05)。结论酒精性肝病患者健康相关生存质量降低,且病情越重,健康相关生存质量越差。酒精性肝病患者健康相关生存质量与慢性乙型肝炎患者相似。     

酒精性肝病患者血清TGF-β、IL-6和IL-8水平及临床意义

目的探讨酒精性肝病患者血清转化生长因子（transforming growth factor-β,TGF-β）白细胞介素-6（inter-leukin-6,IL-6）和白细胞介素-8（interleukin-8,IL-8）在酒精性肝病中的作用。方法 60例酒精性肝病患者按酒精性脂肪肝（n=20）、酒精性肝炎（n=20）和酒精性肝硬化（n=20）分为3组。采用ELISA法检测20例健康对照组和60例各类酒精性肝病患者血清中TGF-β、IL-6和IL-8水平。结果血清TGF-β、IL-6和IL-8水平随着肝脏病变程度加重而递增,酒精性脂肪肝组、酒精性肝炎组和酒精性肝硬化组3项指标水平均高于正常对照组,差异显著（P〈0.01）,其中以酒精性肝硬化组3项指标水平为最高。结论 TGF-β、IL-6和IL-8在酒精性肝病中具有重要作用,酒精性肝病患者血清TGF-β、IL-6和IL-8水平的检测可作为酒精性肝病病情监测和预后判断的有效指标。     

Collagen biosynthesis in liver disease of the alcoholic.

Percutaneous liver biopsies obtained from patients with a history of chronic alcoholism and normal liver, fatty liver, alcoholic hepatitis, or active cirrhosis were incubated with tritiated proline to determine the pattern of collagen biosynthesis in these conditions. Incorporation of labeled proline and hydroxyproline into salt-soluble and insoluble fractions of collagen was evaluated by radiochemical analysis and tissue localization documented by autoradiography. Biopsy specimens of alcoholic hepatitis and cirrhosis exhibit a significant increase in the amount of radioactive proline and hydroxyproline in salt-soluble and insoluble collagen. Marked accumulation of radioactivity occurred over bile ducts, fibroblasts, and collagen fibers in the portal area and over hepatocytes, fibroblasts, and collagen fibers in the centrilobular area. Fatty liver is associated with an increase in uptake of proline and hydroxyproline in the salt-soluble fraction of collagem; silver grains appear in the periphery of fat-laden cells and in areas of focal inflammation. Digestion by collagenase indicates that labeling over fibroblasts and collagen reflects active synthesis, whereas, entry of proline into the cell protein pool is responsible for accumulation of radioactivity in other sites. In vitro ethanol causes a significant increase in the incorporation of proline and hydroxyproline into collagen in biopsy specimens of alcoholic hepatitis or active cirrhosis, but has no effect on collagen synthesis by normal or fatty liver.     

Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease

Abstract. Serum immunoreactive prolyl hydroxylase protein was measured in sixty-five patients with liver disease, and liver prolyl hydroxylase activity, immunoreactive prolyl hydroxylase protein and collagen hydroxyproline in forty of these patients. Serum immunoreactive prolyl hydroxylase protein was above the 95% confidence limit of the controls in most patients with primary biliary cirrhosis, portal cirrhosis, acute hepatitis and cancer with liver metastases, but below this in most patients with fatty liver, chronic active hepatitis, extrahepatic cholestasis, cholangitis, cancer without liver metastases and other malignant diseases. Elevated serum immunoreactive prolyl hydroxylase protein decreased rapidly with time in acute hepatitis but not in primary biliary cirrhosis. Liver prolyl hydroxylase activity and immunoreactive prolyl hydroxylase protein were elevated in the same diseases as serum immunoreactive prolyl hydroxylase protein, and correlated significantly with the latter whereas no correlation was found between serum immunoreactive prolyl hydroxylase protein and collagen hydroxyproline. Serum immunoreactive prolyl hydroxylase protein correlated highly significantly with serum alkaline phosphatase and weakly with serum aspartate aminotransferase in primary biliary cirrhosis, but not in any other disease. No correlation was found between serum immunoreactive prolyl hydroxylase protein and other tests of liver function. The results suggest that changes in serum immunoreactive prolyl hydroxylase protein in liver disease primarily reflect changes in this enzyme in the hepatic tissue, and that assays of serum immunoreactive prolyl hydroxylase in liver disease may give useful information on the actual hepatic collagen synthesis.     

肝纤维化指标检测在非酒精性脂肪性肝病中应用价值

目的探讨非酒精性脂肪性肝病各期与血清肝纤维化标志物的关系。方法 126例非酒精性脂肪性肝病患者依据病情分为单纯性脂肪肝组51例,非酒精性脂肪性肝炎组42例,与非酒精性脂肪性肝炎相关肝硬化组33例,不嗜酒的体检健康者64名为对照组,检测4组血清透明质酸、Ⅲ型前胶原氨端肽、Ⅳ型胶原、层黏蛋白水平。结果非酒精性脂肪性肝炎组与非酒精性脂肪性肝炎相关肝硬化组各指标水平较对照组增高（P〈0.01）;单纯性脂肪肝组透明质酸与对照组比较差异有统计学意义（P〈0.05）;非酒精性脂肪性肝炎相关肝硬化组各指标水平高于非酒精性脂肪性肝炎组和单纯性脂肪肝组（P〈0.05）。结论肝纤维化血清学指标有助于了解非酒精性脂肪肝病患者肝纤维化程度。     

A comparative study of serum alpha 1-microglobulin and beta 2-microglobulin levels in cancerous and other diseases

The levels of serum alpha 1-microglobulin in 60 normal persons and in 191 patients suffering from a variety of benign and malignant disorders were determined by an enzyme immunoassay, and these values were compared with the levels of beta 2-microglobulin. A discrepancy between the serum levels of these proteins was found in hepatobiliary disorders; that is, an increased serum level of beta 2-microglobulin was observed in 73.9%, while in only 4.3% was there an elevation of alpha 1-microglobulin. In particular, alpha 1-microglobulin levels in patients with liver cirrhosis were well below the normal range, while beta 2-microglobulin levels were elevated. Elevated levels of both proteins were noted in patients with some impairments of renal function, particularly in chronic renal failure, and in immunological diseases. In 81 patients with neoplastic diseases, a high alpha 1-microglobulin value was found in only 15 patients (16.4%), while a high beta 2-microglobulin value in 62 patients (76.5%). The serum levels of both alpha 1-microglobulin and beta 2-microglobulin were especially high in plasma cell dyscrasia with Bence Jones protein, but other neoplastic diseases were mostly associated with beta 2-microglobulin elevation alone.     

A study of the microheterogeneity of transferrin in cirrhotic patients

In order to assess the specificity of transferrin molecular changes, we compared concentrations of subfractions and total transferrin in cirrhotic patients, in patients having non-alcoholic hepatitis, in patients with liver cancer, and in controls. The study was carried out in 79 patients divided into four groups: 20 patients with biopsy-proven cirrhosis of alcoholic origin, 20 patients with non-alcoholic hepatitis, 19 patients with liver cancer and 20 controls. Subfractions of serum transferrin were separated by isoelectric focusing followed by direct immunofixation. Fractions pI 5.7 percentages (expressed as percentages of one fraction over total transferrin) were significantly higher in the cirrhotic group than in the control group (p less than 0.01). Fraction pI 5.9 percentages were significantly higher in the cirrhotic group than in the hepatitis or control groups (p less than 0.05), or liver cancer group (p less than 0.01). A quantitative increase of fraction pI 5.7 was found in the cirrhotic patients. However, in this study, this parameter did not discriminate between patients with parenchymal liver diseases of alcoholic or other origin. Therefore, the value of determining fraction pI 5.7 as a marker of chronic alcohol consumption seems questionable. The elevation of fraction pI 5.9 constantly found in the cirrhotic patients could not be explained and needs further investigations.     

肝病患者血清转化生长因子β1水平及其临床意义

目的了解急、慢性肝炎及肝硬化患者血清转化生长因子β