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1.
试验旨在建立蛋鸡脂肪肝综合征病理模型。选取5日龄的海兰褐蛋鸡公雏280只，随机分为对照组（基础日粮组）和3个模型组（A、B、C组），试验第1~10天给模型组饲喂不同配比的高脂饲料，第11~20天饲喂常规基础日粮，每天观察并记录试验鸡精神状态、外观体征、饮水量和食欲情况，试验第0、10、20天从各组随机抽取15只鸡进行翅静脉采血并剖取肝脏和腹脂，测定肝脏系数、肝脂率、腹脂率，血清总胆固醇（TC）、甘油三酯（TG）、谷丙转氨酶（ALT）和谷草转氨酶（AST）水平。结果显示，试验第10天，3个模型组剖检时可见腹腔和肠系膜有大量的脂肪沉积，肝脏系数、肝脂率和腹脂率，以及血清中总胆固醇、甘油三酯、谷丙转氨酶和谷草转氨酶指标均符合鸡脂肪肝综合征模型的诊断标准；试验第20天，模型A、B组谷丙转氨酶和谷草转氨酶水平有所恢复，其他指标仍高于对照组，而模型C组的临床症状和各项检测指标仍符合鸡脂肪肝综合征模型的诊断标准。因此采用连续饲喂高脂饲料C（74.5%基础日粮、6%胆固醇、14%猪油、5%蔗糖、0.5%丙基硫氧嘧啶）可成功建立蛋鸡脂肪肝综合征模型。  相似文献   

2.
Progression of aflatoxicosis in growing barrows   总被引：5，自引：0，他引：5  
The progression of aflatoxicosis was evaluated in growing crossbred barrows given 0, 1, 2, 3, or 4 mg of aflatoxin (AF)/kg of feed for 28 days (6 to 10 weeks of age). On day 28, pigs were euthanatized and necropsied, and tissues were removed for histologic examination. Body weight gains were decreased in barrows fed 2 mg of AF/kg after 7 days and in barrows fed 1 mg of AF/Kg after 14 days. By 28 days, all barrows fed AF had decreased body weights and weight gains. Compared with decreased in all barrows fed AF. Neither liver weights nor bone ash values were altered, although liver lipid values were increased in barrows fed AF. Serum aspartate transaminase, gamma-glutamyl transferase, and alkaline phosphatase activities were increased in barrows fed AF, whereas creatine kinase activity was decreased. Aflatoxin diets resulted in decreases in serum concentrations of urea nitrogen, phosphorus, cholesterol, albumin, and total protein. Histologic alterations in liver included interlobular fibrosis, periportal lipidosis, bile duct hyperplasia, and periportal lymphocytic infiltration. Lymphocytes in the thymus were depleted, and numbers of granulocytic cells in the bone marrow were reduced. The frequency and severity of lesions increased with increased doses of AF.  相似文献   

3.
In order to investigate the effect of dietary soybean phospholipid supplement on hepatic and serum indexes relevant to fatty liver hemorrhagic syndrome (FLHS) in layers, 135 300‐day‐old Hyline Brown layers were randomly divided into three groups (control, pathology and prevention), and each group had 45 layers with three replicates. Birds in the three groups were respectively fed the control diet, high‐energy low‐protein diet and high‐energy high‐protein diet affixed with 3% soybean phospholipid instead of maize. Results showed in the 30th day, birds’ livers in the pathology group became yellowish, enlarged in size and had hemorrhagic spots, while the prevention and control groups’ layers did not have such pathological changes. Contents of triglyceride, total cholesterol, low‐density lipoprotein – cholesterol, non‐esterified fatty acid and malondialdehyde in serum or liver homogenate in prevention and control groups were remarkably lower than those in the pathology group (P < 0.05 or P < 0.01), as with the activities of glutamic oxalacetic transaminase and glutamic‐pyruvic transaminase (P < 0.01); high‐density lipoprotein – cholesterol value was strikingly higher than that of the pathology group (P < 0.01). It is suggested dietary soybean phospholipids supplement may effectively improve hepatic and blood indexes relevant to FLHS, which provides a new point for preventing FLHS occurrence rate in laying flocks and treating human non‐alcohol fatty liver disease.  相似文献   

4.
采用高脂日粮饲喂海兰褐蛋公雏,制作脂肪肝动物模型,再以柴胡舒肝汤进行干预。结果显示,试验组鸡只逐渐出现类似脂肪肝综合征的临床症状,实验室检验血清呈黄色稠膏凝脂状,血脂含量显著升高,剖检肝脏肿大呈土黄色泽,肝脏脂肪含量明显升高,表明以高脂日粮加丙基硫氧嘧啶人工造模成功。中药预防组在其饮水中加入4.5mL柴胡舒肝汤,结果较好地对抗了高脂日粮与丙基硫氧嘧啶的作用,试验鸡没有出现相应临床症状与实验室检验指标,表明柴胡舒肝汤对高脂日粮加丙基硫氧嘧啶所致脂肪肝有预防作用。对已发生脂肪肝病变的鸡以柴胡舒肝汤进行治疗,使相关临床症状逐步消失,肝脏病变与其他检验指标得到恢复,表明柴胡舒肝汤对高脂日粮加丙基硫氧嘧啶所致脂肪肝有治疗作用,可将在其饮水中加入4.5mL柴胡舒肝汤作为推荐剂量。试验中没有发现动物对柴胡舒肝汤呈现不良反应。  相似文献   

5.
本试验旨在建立急性应激致禽类肝损伤的试验动物模型.对麒麟鸡(卷羽鸡)进行持续高温应激后,检测血清中的肝损伤酶谷丙转氨酶(ALT)、天冬氨酸转氨酶(AST)、胆碱脂酶(CHE)和乳酸脱氢酶(LDH)活性的改变,观察肝脏病理组织学变化.结果显示,高温应激前期,麒麟鸡血清肝损伤酶AST和ALT活性极显著升高(P <0.01),高温应激后期,AST活性显著低于正常水平(P <0.05),而ALT活性极显著低于正常水平(P <0.01);持续高温应激期间,CHE的活性一直低于正常水平,高温应激后期,CHE活性极显著低于正常水平(P <0.01);在高温应激下LDH活性呈先下降后上升再下降的变化趋势,高温应激后期,LDH活性极显著高于正常水平(P <0.01).高温应激引起麒麟鸡肝细胞出现水泡变性、肝细胞核浓缩现象.结果表明,采用急性热应激可诱导麒麟鸡肝损伤试验模型,试验模型具备肝脏水泡变性和核浓缩病理特征.  相似文献   

6.
Experimental, subclinical acidosis was induced by oral administration of sacharose during the last 2 months of pregnancy in 15 cows. Seven cows and their newborn calves were used as a control group. The liver enzyme activities in the serum and the blood acid-base status were determined in the 15 calves from the cows in the experimental group. Mannitol was administered orally to 8 calves from the experimental group to induce osmotic diarrhoea. It was concluded that subclinical acidosis in pregnant cows alters the biochemical liver profile of their newborn calves, affecting the aspartate aminotransferase, alanine transaminase, beta glucuronidase, glutamate dehydrogenase and bilirubin activities in the serum, which are associated with oedematous changes to the hepatocytes. Diarrhoea was accompanied by an increase in the alkaline phosphatase and gammaglutamyl transferase activities and a decrease in the total protein concentration in the serum. These changes were apparently related to the numerous necrotic foci in the liver and the proliferation of the Kuppfer cells. It would appear from these results that the liver damage in the newborn calves was associated with the subclinical, metabolic acidosis in their dams and that osmotic diarrhoea occurring in the neonatal period additionally impaired the liver function.Abbreviations ALP alkaline phosphatase - ALT alanine transaminase - AST aspartate aminotransferase - GR betaglucuronidase - bw body weight - ELISA enzyme-linked immunosorbent assay - GD glutamate dehydrogenase - GGT gammaglutamyl transferase - IU international unit  相似文献   

7.
Male lambs of the pure breeds Texel, Flemish milk sheep, and Finnish landrace, and of the crossbrech Texel x Friesian milk sheep, Texel x Finnish landrace, Suffolk x Friesian milk sheep, and Finnish landrace x He de France were fed hay and concentrates, the latter differing only in the content of copper. At high (± 35 ppm) and at moderately low (± 10 ppm) copper levels in the concentrate, breed differences in the accumulation of copper in the liver were studied‐Hepatic Cu‐levels increased significantly in the case of the high Cu‐fed animals, but great differences in the metabolism of excessive amounts of dietary Cu exist between the particular breeds and crossbreds. The Texel breed was most susceptible to an excess of dietary Cu and the Finnish landrace was the least susceptible breed, while the Flemish milk sheep and the crossbreds were intermediate. In blood serum, the enzyme activities of sorbitol dehvdrogenase, lactate dehydroge‐nase, γ‐glutamyl transferase, and glutamic oxaloacetic transaminase were increased to a greater or less extent in the high Cu‐fed animals, but the correlation with hepatic Cu‐content was poor. For the most susceptible breeds, even a level of 10 ppm Cu in a ration with nearly equal amounts of hay and concentrate is insufficiently low for the prevention of Cu‐accumulation in the liver.  相似文献   

8.
选取50日龄左右健康短毛家猫20只,分为2组,每组10只,一组饲喂商品猫粮,另一组饲喂鸡肝,研究饲喂鸡肝对幼猫骨代谢的影响。结果表明:饲喂鸡肝可对幼猫的骨代谢产生明显影响,如显著降低血清钙(Ca)、骨钙素(BGP)和25OHD3含量;同时,血清碱性磷酸酶活性(AKP)和降钙素(CT)含量显著升高。鸡肝组幼猫在饲喂到50d时血清甲状旁腺激素(PTH)含量显著升高,但在饲喂到85d时显著降低。在饲喂到90d时,鸡肝组幼猫股骨长度极显著低于猫粮组(P<0.01)。  相似文献   

9.
OBJECTIVE: To evaluate postsurgical outcome in dairy cows with left-displaced abomasum (LDA) with regard to severity of fatty liver and assess the usefulness of preoperative determination of serum ornithine carbamoyl transferase (OCT) activity, bile acids concentration, and other variables for evaluating liver function during the postsurgical convalescence period. DESIGN: Prospective study. ANIMALS: 68 Holstein cows. PROCEDURES: Blood and liver biopsy specimens were obtained during standing LDA surgery. Liver tissue was examined histologically and classified by severity of fatty change. Serum activities of liver-derived enzymes and concentrations of total lipids, triglycerides, bile acids, glucose, beta-hydroxybutyric acid, bilirubin, and nonesterified fatty acids were determined. RESULTS: Most cows with LDA and cows with severe fatty liver were detected within the first month after calving. Postsurgical outcome was related to severity of fatty liver. All cows that died had severe fatty liver. Serum activities of OCT, aspartate aminotransferase, and glutamate dehydrogenase and serum total bilirubin concentration were sensitive indicators of fatty liver. Serum bile acids concentration was not an accurate indicator of fatty liver. CONCLUSIONS AND CLINICAL RELEVANCE: Postsurgical outcome of cows undergoing surgery to correct LDA was related to fatty liver severity. Assessment of serum activities of OCT, aspartate aminotransferase, and glutamate dehydrogenase and serum total bilirubin concentration is recommended for diagnosis of fatty liver in dairy cows with LDA, whereas determination of bile acids concentration is not. The strong correlation between OCT activity and degree of hepatocellular damage supports use of this enzyme for assessing severity of fatty liver and predicting postsurgical outcome in cows with LDA.  相似文献   

10.
Betulinic acid (BA), a pentacyclic lupane-type triterpene, has a wide range of bioactivities. The main objective of this work was to evaluate the hepatoprotective activity of BA and the potential mechanism underlying the ability of this compound to prevent liver damage induced by alcohol in vivo. Mice were given oral doses of BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and induced liver injury by feeding 50% alcohol orally at the dosage of 10 ml/kg after 1 h last administration of BA. BA pretreatment significantly reduced the serum levels of alanine transaminase, aspartate transaminase, total cholesterol, and triacylglycerides in a dose-dependent manner in the mice administered alcohol. Hepatic levels of glutathione, superoxide dismutase, glutathione peroxidase, and catalase were remarkably increased, while malondialdehyde contents and microvesicular steatosis in the liver were decreased by BA in a dose-dependent manner after alcohol-induced liver injury. These findings suggest that the mechanism underlying the hepatoprotective effects of BA might be due to increased antioxidant capacity, mainly through improvement of the tissue redox system, maintenance of the antioxidant system, and decreased lipid peroxidation in the liver.  相似文献   

11.
Reactive oxygen species (ROS) have been shown to have a role in inflammation. We investigated whether Forsythia suspensa extract (FSE) could exert its antioxidant potential against lipopolysaccharide (LPS)‐induced inflammatory liver injury in rats. Rats were orally fed FSE once daily for 7 consecutive days prior to LPS (Escherichia coli, serotype O55:B5) injection. LPS treatment caused liver dysfunction as evidenced by massive histopathological changes and increased serum alanine aminotransferase and aspartate aminotransferase activities which were ameliorated by FSE pretreatment. FSE attenuated LPS‐induced depletion of cytosolic nuclear factor‐erythroid 2‐related factor 2 (Nrf2) and suppression of Nrf2 nuclear translocation in liver, and the generation of ROS and malondialdehyde in serum and liver. FSE increased the Nrf2‐mediated induction of heme oxygenase‐1 in liver, as well as superoxide dismutase and glutathione peroxidase activities in serum and liver. Importantly, FSE attenuated LPS‐induced nuclear factor‐кB (NF‐кB) nuclear translocation in liver, and subsequently decreased tumor necrosis factor‐α, interleukin (IL)‐1β and IL‐6 levels in serum and liver, which were associated with FSE‐induced activation of Nrf2 in liver. These results indicate that the protective mechanisms of FSE may be involved in the attenuation of oxidative stress and the inhibition of the NF‐кB‐mediated inflammatory response by modulating the Nrf2‐mediated antioxidant response against LPS‐induced inflammatory liver injury.  相似文献   

12.
Geeldikkop was induced in sheep by the oral administration of crude steroidal saponins from Tribulus terrestris. Two of the sheep developed typical lesions of geeldikkop, including birefringent crystalloid material in bile ducts and concentric periductal lamellar fibrosis. The clinical pathological changes in these sheep were also consistent with those of geeldikkop: aspartate transaminase and gamma-glutamyl transferase activities in the sera of both were elevated, and one had bilirubinaemia. A third sheep became photosensitive without typical lesions of geeldikkop in the liver or changes in the activities of liver enzymes before euthanasia. The findings of these trials are consistent with reports from abroad that ovine hepatogenous photosensitization, caused by Agave lechuguilla and Narthecium ossifragum, can be induced with crude saponins from the respective plants.  相似文献   

13.
This study investigated the hypothesis that dietary supplementation of fish oil as a source of n‐3 polyunsaturated fatty acids (PUFA) influences the expression of target genes of sterol regulatory element‐binding proteins (SREBP)‐1 and (SREBP)‐2 involved in triacylglycerol (TAG) synthesis and fatty acid and cholesterol metabolism in the liver, and moreover activates the expression of target genes of peroxisome proliferation‐activated receptor (PPAR)‐α involved in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating sows were fed a control diet or a fish oil diet with either 50 g of a mixture of palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish oil group contained 19.1 g of n‐3 PUFA (mainly 20:5 n‐3 and 22:6 n‐3) per 100 g of total fatty acids, while the diet of the control group contained 2.4 g of n‐3 PUFA (mainly 18:3 n‐3) per 100 g of total fatty acids. The fish oil group had reduced relative mRNA concentrations of various target genes of SREBP‐1 involved in fatty acid and TAG synthesis in comparison with the control group (p < 0.05). Relative mRNA concentrations of target genes of PPARα involved in fatty acid catabolism in both liver and muscle, and mRNA concentrations of target genes of SREBP‐2 involved in cholesterol synthesis and uptake were not influenced by fish oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content of milk and weight gains of litters during the suckling period were not different between the two groups of sows. In conclusion, this study suggests that fish oil has only minor effects on hepatic lipid metabolism, which are non‐critical with respect to milk production in sows.  相似文献   

14.
We present the first reported study of Pearl millet (Pennisetum typhoides) goitrogenesis and enterohepatonephropathy in 5-9-month-old Nubian goats of either sex. The goats were fed 0.25 or 1 g millet per kg body weight per day for 62 days. The effects on thyroid follicles, intestines, liver and kidneys are described and correlated with clinical signs, changes in serum and tissue iodine and selenium concentrations and alterations in serum aspartate transaminase, gamma glutamyl transferase, total protein, total lipids and other constituents and haematological values.  相似文献   

15.
以小鼠为试验动物,研究柞蚕丝素粉与鸟氨酸的混合物对酒精性脂肪肝肝体比和脂类代谢的影响。结果表明,该混合物能明显降低小鼠的肝体比和血清甘油三酯、总胆固醇、低密度脂蛋白的浓度,能提高高密度脂蛋白浓度。因此认为柞蚕丝素粉与鸟氨酸的混合物可有效预防酒精性脂肪肝的发生。  相似文献   

16.
This study was conducted to evaluate the effect of Zingiber officinale and Thymus vulgaris aqueous extracts as a natural antioxidant on liver and kidney functions and antioxidant status of growing rabbits. A total of 24 V‐line male rabbits, 3 months old, 1.465 ± 0.12 kg average body weight (BW) were used in a complete randomized design. The rabbits were weighed individually and assigned randomly to four groups (6 animals/each). The first group (G1) was taken fresh water and served as control, rabbits of the second group (G2) were taken 100 mg/kg BW in drinking water of the Z. officinale aqueous extract daily. The third group (G3) was taken 50 mg/kg BW in drinking water of the T. vulgaris aqueous extract daily and the fourth group (G4) was taken 100 mg/kg BW of the Z. officinale aqueous extract plus 50 mg/kg BW of the T. vulgaris aqueous extract in drinking water daily. The oral administration of ginger and/or thyme aqueous extracts increased (p < .001) serum protein profile compared with control group. Moreover, results of group 2 showed significant (p < .001) decrease in cholesterol, triglyceride and very low‐density lipoprotein cholesterol compared with group 3 and 4. Serum urea, uric acid and creatinine levels were significantly (p < .001) decreased in treated groups compared with control group. Oral administration of ginger and/or thyme aqueous extracts to growing rabbits increased (p < .001) total antioxidant capacity and glutathione content and the activity of superoxide dismutase, catalase and glutathione‐S‐transferase compared with the control group. In conclusion, the current study showed that oral administration of ginger and thyme aqueous extracts to growing rabbits showed no adverse effects on liver and kidney function parameters, histological structures and improved antioxidant status.  相似文献   

17.
The aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)‐affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR‐affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80 mg/kg DHA (IUGR‐DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR‐affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non‐esterified fatty acids (NEFA), very‐low‐density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway‐related genes, whereas that of inflammatory factor‐related genes were downregulated. In conclusion, dietary inclusion of 80 mg/kg DHA can alleviate IUGR‐induced impairments in piglets.  相似文献   

18.
In the present study, 42 multiparous Holstein cows were used to investigate the relationship between fat accumulation in the liver and dry matter intake, milk yield and blood metabolites. Based on the percentage of fat in the liver cell at 2 weeks post‐parturition, the cows were classified into three groups. These groups were: (i) less than 10% of fat (normal group, n = 29); (ii) 10–20% of fat (mild group, n = 6); and (iii) more than 20% of fat (moderate group, n = 7). The bodyweight of the moderate group was high (771 kg) before calving. The sufficiency rates of total digestible nutrients (TDN) were remarkably decreased (approximately 65%) in early lactation. The milk fat yield and milk fat composition of the moderate group were higher (P < 0.05) than the other groups at 1 and 2 weeks post‐parturition. It was suggested that non‐esterified fatty acids (NEFA) mobilized from adipose tissues was directly used by the mammary gland for synthesis of milk fat. The percentage of bromsulfalein (BSP) retention of the moderate group was high (21.1%) at 30 min, and it showed that the BSP clearance function was significantly decreased. The concentrations of NEFA, β‐hydroxybutyric acid and glucose were appropriate indicators of energy status; however, aspartate aminotransferase, γ‐glutamyl transpeptidase and total bilirubin were not sensitive indicators of a moderate fatty liver. Thus, high‐yielding cows that calve in an overweight condition are more likely to develop excessive fat accumulation in the liver because of great mobilization from adipose tissues post‐parturition. In cows with a moderately fatty liver, a decrease in TDN sufficiency rates, an increase of milk fat yield and a reduction of liver function were observed in early lactation. The increase of serum NEFA and milk fat composition resulting from mobilization of adipose tissues helped to diagnose moderate fatty liver.  相似文献   

19.
Serum bile acids as an indicator of liver disease in dogs   总被引：1，自引：0，他引：1  
Total serum bile acids were determined in 62 dogs with different primary or secondary liver diseases, using 3α-hydroxysteroid dehydrogenase coupled to nitrobluetetrazolium in a centrifugal analyzer. A reaction time of 4 min was sufficient, yielding a within run coefficient of variation of 7% at 6 µmol/1 and 3% at 27 µmol/1. A reference range of 0–4.4 µmol/1 2 h post prandially was observed. The sensitivity of bile acids as a liver function test was superior to that of alanine and aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase and combinations of two of these. The bile acids test detected 36 of 39 patients with a morphological or clinical liver diagnosis. For dogs with heart failure the bile acids test was a markedly more sensitive indicator of secondary liver involvement than alanine aminotransferase or alkaline phosphatase. For secondary liver affections associated with pyometra or epilepsy medication the opposite was the case. Bile acid values in the pooled patient material was not correlated to any of the 4 enzymes measured. For cirrhosis there was positive correlation, however, with the amino transferase values.  相似文献   

20.
The effects of astaxanthin (ASTA) and esterified glucomannan (EMG) on hematological and serum parameters, and liver pathological changes in broilers fed on aflatoxin‐B1 (AFB1) contaminated diet were investigated. Two hundred and forty 10‐day‐old broilers were randomly assigned to one of five dietary treatments including: (i) control diet; (ii) AFB1‐contaminated diet; (iii) AFB1 + EGM diet; (iv) AFB1 + ASTA diet; and (v) AFB1 + EGM + ASTA diet. At 35 days old, blood and liver tissue samples were collected for analysis. Results indicated that total white blood cell (WBC) number, hemoglobin (Hgb) concentration, hematocrit (Hct) level, serum alanine amino transferase (AST) and γ‐glutamyl transferase (GGT) activities, red blood cell (RBC) number, serum globulin (GLB) and urea nitrogen (BUN) concentrations (P < 0.05) were increased by feeding AFB1‐contaminated diet. EMG and ASTA alleviated the alteration of RBC, WBC, Hgb and AST caused by AFB1‐contaminated diet. Liver superoxide dismutase (SOD) activity was reduced, while myeloperoxidase (MPO) activity was increased by AFB1‐contaminated diet (P < 0.05). Both EGM and ASTA restrained the increase of MPO activity (P < 0.05). Degeneration of the liver tissues was found in broilers fed AFB1‐contaminated diet. It suggested that feeding 0.4 mg/kg AFB1‐contaminated diet resulted in adverse effects on blood parameters and liver morphology. Dietary addition of EGM addition at 5 g/kg diet, ASTA at 10 mg/kg diet and especially their combination showed positive protection effects on alleviating the alteration of feeding AFB1. The results indicated that supplementation of 5 g EGM/kg diet, 10 mg ASTA/kg diet and their combination could partially or greatly alleviate the adverse effects caused by AFB1, with the EGM+ASTA group receiving the most effective treatment.  相似文献   

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