It is increasingly recognized that cirrhotic or cholestatic buy NVP-LDE225 patients show abnormal renal histology with glomerular and tubulointerstitial lesions that may not be noted by routine renal function tests. Microscopic urinanalysis is readily available, inexpensive and noninvasive, and currently considered to be a well-suited surrogate parameter for structural kidney damage. We hypothesized that cirrhotic or cholestatic patients with

preserved renal function (eGFR >60 ml/min) upon routine laboratory evaluation frequently show structural renal injury reflected by a pathologic urine cytology. This may represent a herald of subsequent impaired renal function. Aim: To find a useful non-invasive clinical test to identify early structural kidney injury EX 527 nmr in liver patients. Material and Methods: We collected blood and urine samples from a total of 150 patients [liver cirrhosis Child Pugh score class A (n=41), B (n=38), C (n=28), obstructive cholestasis (n=19), and age-matched healthy living kidney donors (n=24]. Patients with diabetes, insufficiently treated arterial hypertension or preexisting kidney disease were excluded. Freshly voided urine samples were analyzed by automatic flow cytometry (Sysmex UF 1000) and microscopic urinanalysis after Papanicolaou

staining of a smear preparation of the urine sedimentation. The specimens were

analyzed for presence and number of renal tubular epithelial cells (RTEC) and granular casts (GC). Results: Serum creatinine (SCr) concentrations (in mg/dL) and GFR determined by the CKD-EPI equation (in ml/h/1.73m2) were normal amongst all groups (0.76±0.16 medchemexpress and 102±15 in Childs A group, 0.78±0.17 and 101±12 in Childs B group, 0.84±0.23 and 95±19 in Childs C group, 0.85±0.2 and 93±21 in cholestasis group, 0.78±0.11 and 93.6±12.4 in living kidney donors). RTEC and GC as sensitive markers of tubular epithelial kidney injury were frequently found in liver cirrhosis (RTEC in 15%, GC in 8%) and cholestasis (RTEC in 33%, GC in 20%), whereas none of the healthy living kidney donors showed RTEC or GC upon urine cytology. Presence of RTEC significantly correlated with serum bile acid levels (correlation coefficient 0.207; p 0.015) Conclusions: Patients with cirrhosis or cholestasis and normal kidney function show RTEC and GC at increased numbers compared to controls. Microscopic urinanalysis may represent a useful, noninvasive and cheap diagnostic test to identify patients at high risk for AKI or subclinical kidney injury which needs to be evaluated in prospective clinical trials. Disclosures: none.

52 There appears to be a paracrine loop operative in which IL-6 potently down-regulates NTPD2 on PFs (without altering PF myofibroblastic differentiation); NTPD2 in turn regulates G protein–coupled P2Y receptors for extracellular adenosine triphosphate and other nucleotides, which mediate BDE proliferation.53

Additionally, non-HSC rat liver myofibroblasts express IL-6, providing a mechanism for autocrine regulation as well.54 The result is that loss of NTPD2, which is observed in biliary cirrhosis in rats and humans, leads to BDE hyperproliferation.55, 56 To complete the loop, IL-6 is released by BDE in response to extracellular adenosine triphosphate, providing a feed-forward mechanism for the continued production of IL-6 and the perpetuation of bile ductular proliferation.52 MCP-1 was first identified as a regulator of monocyte/macrophage chemotaxis,57 and may

selleck compound be important as a regulator of PF myofibroblastic differentiation and fibrogenesis. BDE express MCP-1 messenger RNA and are the liver cells expressing MCP-1 messenger RNA most strongly in chronic hepatitis.58 There is now direct evidence that BDE signal to PFs through MCP-1 release. MCP-1 up-regulates PF proliferation, myofibroblastic differentiation, and procollagen-1 messenger RNA expression and down-regulates NTPD2 expression. Furthermore, conditioned medium from BDE buy CP-868596 isolated from BDL-treated rats induced PF myofibroblastic differentiation, which was inhibited by an MCP-1 blocking antibody.59 The identity of the MCP-1

receptor expressed by PFs is not known. These cells fail to express the MCP-1 cognate receptor chemokine (C-C motif) receptor 2, although chemokine (C-C motif) receptor 2 null mice are protected from BDL-induced cirrhosis.59, 60 HSCs, initially studied almost exclusively as matrix-producing cells, are now known to have many complex functions.61 Although our understanding of PF-mediated fibrogenesis is still in its infancy, two additional points warrant mention. PFs appear to be the major elastin-expressing cells (aside from vascular smooth muscle cells) in the liver, and some investigators have shown that elastin deposition increases as PFs MCE proliferate and fibrosis progresses.35, 36 Although not all groups agree that elastin is specific for PFs (as opposed to HSCs),62 the data raise interesting points beyond the use of elastin as a marker for PFs. Elastic fibers, which are formed from fibrillin microfibrils, with or without a core of elastin, are important determinants of the mechanical properties of tissues, providing resilience, in contrast to the fibrillar collagens (typical of the liver scar) which provide rigidity. Fibrillin is expressed by both HSCs and PFs36, 63; thus, the elastic fibers around HSCs and PFs are structurally different.

52 There appears to be a paracrine loop operative in which IL-6 potently down-regulates NTPD2 on PFs (without altering PF myofibroblastic differentiation); NTPD2 in turn regulates G protein–coupled P2Y receptors for extracellular adenosine triphosphate and other nucleotides, which mediate BDE proliferation.53

Additionally, non-HSC rat liver myofibroblasts express IL-6, providing a mechanism for autocrine regulation as well.54 The result is that loss of NTPD2, which is observed in biliary cirrhosis in rats and humans, leads to BDE hyperproliferation.55, 56 To complete the loop, IL-6 is released by BDE in response to extracellular adenosine triphosphate, providing a feed-forward mechanism for the continued production of IL-6 and the perpetuation of bile ductular proliferation.52 MCP-1 was first identified as a regulator of monocyte/macrophage chemotaxis,57 and may

Ceritinib clinical trial be important as a regulator of PF myofibroblastic differentiation and fibrogenesis. BDE express MCP-1 messenger RNA and are the liver cells expressing MCP-1 messenger RNA most strongly in chronic hepatitis.58 There is now direct evidence that BDE signal to PFs through MCP-1 release. MCP-1 up-regulates PF proliferation, myofibroblastic differentiation, and procollagen-1 messenger RNA expression and down-regulates NTPD2 expression. Furthermore, conditioned medium from BDE STA-9090 datasheet isolated from BDL-treated rats induced PF myofibroblastic differentiation, which was inhibited by an MCP-1 blocking antibody.59 The identity of the MCP-1

receptor expressed by PFs is not known. These cells fail to express the MCP-1 cognate receptor chemokine (C-C motif) receptor 2, although chemokine (C-C motif) receptor 2 null mice are protected from BDL-induced cirrhosis.59, 60 HSCs, initially studied almost exclusively as matrix-producing cells, are now known to have many complex functions.61 Although our understanding of PF-mediated fibrogenesis is still in its infancy, two additional points warrant mention. PFs appear to be the major elastin-expressing cells (aside from vascular smooth muscle cells) in the liver, and some investigators have shown that elastin deposition increases as PFs 上海皓元 proliferate and fibrosis progresses.35, 36 Although not all groups agree that elastin is specific for PFs (as opposed to HSCs),62 the data raise interesting points beyond the use of elastin as a marker for PFs. Elastic fibers, which are formed from fibrillin microfibrils, with or without a core of elastin, are important determinants of the mechanical properties of tissues, providing resilience, in contrast to the fibrillar collagens (typical of the liver scar) which provide rigidity. Fibrillin is expressed by both HSCs and PFs36, 63; thus, the elastic fibers around HSCs and PFs are structurally different.

7B,C). These findings were further confirmed using Huh7 HCC cells (Fig. 7D,E). Collectively, these results demonstrate that HMGB1-mediated caspase-1 activation is required for hypoxia-induced invasion in HCC cells. To further assess the effect of HMGB1 on HCC cell invasion, constitutively active HMGB1 was stably transfected into the Hepa1-6 cell line. HMGB1 stably expressing cells (pEGFPN1-HMGB1) displayed a significant increase in cell-invasion ability, compared with vector controls (Fig. 8A). AZD6244 supplier In contrast to HMGB1 overexpression, stable knockdown of HMGB1 in Hepa1-6 cells, using short hairpin RNA (shRNA)

(Supporting Fig. 5), considerably decreased the invasiveness of Hepa1-6 cells, as evidenced by the Transwell assay (Fig. 8B). To determine whether HMGB1 participates in HCC metastasis in vivo, a murine lung metastasis model was utilized. Mice were injected via the tail vein with

luciferase-expressing tumors derived from HMGB1 shRNA and vector control clones and were monitored weekly Selleck AZD6738 for bioluminescent signals. Four weeks after injection, mice were sacrificed and their lungs were examined. Bioilluminescent signals in the lungs from the control group were much stronger than from the HMGB1 shRNA group (Fig. 8C,D). Furthermore, serum HMGB1 levels from the control group were 43.48 ±10.91 ng/mL, which were much higher than that from the HMGB1 shRNA-treated group (17.12 ± 4.56 ng/mL) (Fig. 8E). Tumor nodules were also more numerous in the control than in the shRNA group (Fig. 8F) and were confirmed with histology (data

not shown), demonstrating that HMGB1 can promote metastasis. HCC remains a leading cause of cancer-related death worldwide. This is despite the fact that a number of advances in both surgical (e.g., transplantation or resection) and ablative (e.g., transcatheter arterial chemoembolization or radiofrequency ablation) techniques have developed in the past several decades20 and is reflective of the advanced nature of disease with which many patients present as well as the lack of effective chemotherapeutic agents aimed at the treatment MCE公司 of widely metastatic disease. Though loss of tumor-suppressor gene function, oncogene activation, direct viral effects, and angiogenesis all appear to be involved in the development of HCC,21 the lack of effective chemotherapy speaks to a gap in knowledge as to the precise molecular events and pathways involved in tumor development and progression. Therefore, further elucidating such a mechanism is an important goal in developing novel strategies to both prevent and treat HCC. Hypoxia is a hallmark of diverse human solid tumors and is associated with tumor progression.8 The extent of hypoxia in a tumor may represent an independent indicator of poor prognosis22; however, the mechanism by which hypoxia affects cancer progression is still unclear.

7B,C). These findings were further confirmed using Huh7 HCC cells (Fig. 7D,E). Collectively, these results demonstrate that HMGB1-mediated caspase-1 activation is required for hypoxia-induced invasion in HCC cells. To further assess the effect of HMGB1 on HCC cell invasion, constitutively active HMGB1 was stably transfected into the Hepa1-6 cell line. HMGB1 stably expressing cells (pEGFPN1-HMGB1) displayed a significant increase in cell-invasion ability, compared with vector controls (Fig. 8A). BKM120 concentration In contrast to HMGB1 overexpression, stable knockdown of HMGB1 in Hepa1-6 cells, using short hairpin RNA (shRNA)

(Supporting Fig. 5), considerably decreased the invasiveness of Hepa1-6 cells, as evidenced by the Transwell assay (Fig. 8B). To determine whether HMGB1 participates in HCC metastasis in vivo, a murine lung metastasis model was utilized. Mice were injected via the tail vein with

luciferase-expressing tumors derived from HMGB1 shRNA and vector control clones and were monitored weekly Selleck Cisplatin for bioluminescent signals. Four weeks after injection, mice were sacrificed and their lungs were examined. Bioilluminescent signals in the lungs from the control group were much stronger than from the HMGB1 shRNA group (Fig. 8C,D). Furthermore, serum HMGB1 levels from the control group were 43.48 ±10.91 ng/mL, which were much higher than that from the HMGB1 shRNA-treated group (17.12 ± 4.56 ng/mL) (Fig. 8E). Tumor nodules were also more numerous in the control than in the shRNA group (Fig. 8F) and were confirmed with histology (data

not shown), demonstrating that HMGB1 can promote metastasis. HCC remains a leading cause of cancer-related death worldwide. This is despite the fact that a number of advances in both surgical (e.g., transplantation or resection) and ablative (e.g., transcatheter arterial chemoembolization or radiofrequency ablation) techniques have developed in the past several decades20 and is reflective of the advanced nature of disease with which many patients present as well as the lack of effective chemotherapeutic agents aimed at the treatment 上海皓元医药股份有限公司 of widely metastatic disease. Though loss of tumor-suppressor gene function, oncogene activation, direct viral effects, and angiogenesis all appear to be involved in the development of HCC,21 the lack of effective chemotherapy speaks to a gap in knowledge as to the precise molecular events and pathways involved in tumor development and progression. Therefore, further elucidating such a mechanism is an important goal in developing novel strategies to both prevent and treat HCC. Hypoxia is a hallmark of diverse human solid tumors and is associated with tumor progression.8 The extent of hypoxia in a tumor may represent an independent indicator of poor prognosis22; however, the mechanism by which hypoxia affects cancer progression is still unclear.

For some data sets, convergence was not achieved despite multiple trials with varying starting parameters. In these cases, we fitted multiple curves changing the value of a fixed asymptote (L∞) so that only a and b were estimated. This process continued, changing the value of L∞ by 1 cm, until the model with the lowest residual sum of squares was obtained. A total of 655 length and 632 girth measurements were recorded, approximately evenly represented by female (52%) and male (48%) seals. The sample distribution of measurements was uneven

across subpopulations, years, and ages (from age 1 to 20 yr), with a high proportion of young seals and most seals measured at French Frigate Shoals and Laysan Island (Table 1, Fig. 2). Nearly all seals had been born at the same subpopulation where they were measured. For example,

at all sites except Midway Atoll, only 0–4 seals Selleck Acalabrutinib selleck compound measured had been born elsewhere. At Midway Atoll, in contrast, only 27 of 43 (63%) measured seals had been born there. Notably, only 1 of 10 seals older than age 7 yr measured at Midway had been born there. Eight measurements were from seals that had moved to Midway Atoll from Pearl and Hermes Reef, three were from Kure Atoll, and four were from seals that had been born at French Frigate Shoals, rehabilitated in captivity, and released at either Midway or Kure Atoll. Previously rehabilitated seals from French Frigate Shoals also accounted for one and two measurements, respectively, at Pearl and Hermes Reef and

Kure Atoll. A total of 399 seals were measured at just one age, and 115 seals were measured twice (at two ages), seven were measured three times, and one was measured four times. The majority 上海皓元医药股份有限公司 of the repeat measurements involved young seals; 77% of the repeat measurements were at ages 2 and 3 yr. The rest were sprinkled among the older age classes. Laysan and French Frigate Shoals had the highest proportion of repeat length measurements (31% and 26%, respectively), whereas no repeat measurements occurred at Lisianski Island and Kure Atoll. To address potential influences of repeated measurements on results, we created a data set consisting of just one length measurement per individual seal (selected with a random number generator) and compared statistical results using these data to the full data set with repeated measures. We did not find evidence that length growth patterns differed among male and female monk seals. Beyond age 3 yr, sex-specific sample sizes at individual subpopulations were insufficient (in many cases zero, see Table 1), so that all sites were pooled to evaluate sex differences in growth curves. A model with separate parameters for the sexes was less well supported (AICc increased by 3.7) relative to a model with one set of parameters for both sexes.

Hadhsc and GDH were immunoprecipitated from isolated mitochondria according to Li et al.16 For GDH, the protein A beads were replaced with magnetic Dynabeads M-280 (Life Technologies) (80 μL). Lysine-acetylated proteins were immunoprecipitated according to Hirschey et al.17 in the presence of 10 mM nicotinamide. Islets and exocrine fractions were isolated from the pancreas according to the method described by Zmuda et al.18 Statistical analyses were performed using GraphPad Prism software. A nonparametric Mann-Whitney FK506 order U test was selected for comparing two groups. A nonparametric Kruskal-Wallis test with Dunn’s post-comparison was selected

for multiple group comparisons when the data did not approximate a normal distribution. Parametric analysis of variance (ANOVA) using a Bonferroni’s post-test was selected for multiple group comparisons when the sampled data approximated a normal distribution. Data are expressed as the mean ± SD. P values < 0.05 were considered statistically significant and are indicated in the figures as *comparison of −/− GW-572016 versus +/+ under the same experimental

conditions and §comparison of different conditions within −/− or +/+ groups. Additional methods are provided in the Supporting Information. All antibodies are listed in Supporting Tables 1 and 2. Hint2f/f mice displaying a lox site on each side of the Hint2 gene were bred with mice expressing the Cre recombinase under a ubiquitous promoter (Fig. 1A). Southern blotting revealed that Cre-mediated recombination had excised the Hint2 gene (Fig. 1B). Western blotting confirmed the absence of Hint2 in Hint2−/− livers and pancreas and its presence in Hint2+/+ livers, liver mitochondria, and pancreas (Fig. 1C,E). Immunostaining confirmed

the localization of Hint2 in hepatocytes (Fig. 1D) and its constant expression level throughout the 30-week study (Supporting Fig. 1). Hint2−/− mice appeared healthy at birth and were fertile. Hint2−/− mice weighed 26% more than Hint2+/+ mice at 20 weeks (Table MCE公司 1) and accumulated a greater abundance of retroperitoneal fat (data not shown). Liver weights were slightly higher in Hint2−/− mice at 10 and 20 weeks (Table 1). Plasma levels of alanine aminotransferase and aspartate aminotransferase were normal. Albumin concentrations were normal but increased slightly at 30 weeks in Hint2−/− mice. Livers of both groups showed an age-associated accumulation of intracytoplasmic lipid vacuoles (Fig. 2A), but this was more acute in Hint2−/− livers, particularly in the pericentral regions. Liver triglycerides at 20 weeks were higher in Hint2−/− mice than in Hint2+/+ mice (P < 0.05) (Fig. 2C). Cholesteryl esters were not different (Fig. 2D). To determine whether the absence of Hint2 induced structural changes, hepatocyte mitochondria from mice aged 25 and 50 weeks were examined via electron microscopy.

After 1 year of UDCA treatment, the serum albumin level was slightly but significantly elevated (P < 0.0001), the serum activities of ALP, GGT, AST, and ALT were decreased by about 50% (P < 0.0001), and the serum concentrations of total bilirubin and IgM were decreased by 30% (P < 0.0001) compared with baseline values. The patients were followed up under UDCA therapy for a mean period of 5.9 RG7204 solubility dmso ± 2.6 years

(median, 5.8 years; range, 1.3-14 years). An adverse outcome was recorded in 37 patients, including eight liver-related deaths, four liver transplantations, and 25 complications of cirrhosis (six ascites, nine variceal bleeding, five with both ascites and variceal bleeding, four with hepatic encephalopathy and ascites, and one hepatocellular carcinoma). The survival rates without

adverse outcome at 5 years and 10 years were 86% and 63%, respectively (Fig. 2). In univariate analysis, the baseline factors associated with an adverse outcome were a serum activity of ALP >3× ULN, GGT >5× ULN, AST >2× ULN, an abnormal serum concentration of total bilirubin, and a decreased serum level of albumin (Table 2). In multivariate analysis, a serum activity of ALP >3× ULN, elevated bilirubin level, and decreased albumin level were independent risk factors significantly associated with an adverse outcome (Supporting Table 1). The Barcelona, Paris, Rotterdam, Toronto, and Ehime definitions of biochemical responses to UDCA were evaluated for their ability to discriminate patients MCE公司 according check details to the long-term outcome (Table 3). For each definition, the rates of biochemical response after 3, 6, or 12 months of UDCA therapy were comparable. The highest rate of biochemical response was observed at the sixth month according to the Paris (71.0%), Barcelona (74.5%), and Toronto (69.0%) definitions, whereas the highest level occurred after 1 year of UDCA therapy according

to the Rotterdam (48.5%) and Ehime (58.0%) definitions. The Paris, Barcelona, Toronto, and Ehime definitions significantly discriminated the patients in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Responders differed significantly from nonresponders and had lower baseline bilirubin, ALT, AST, ALP, and GGT levels and higher albumin levels (Supporting Table 2). The responders were more likely to have early disease (by histological stage, P < 0.05; by the Dutch prognostic class,5 P < 0.001). The biochemical responses evaluated at 3, 6, and 12 months of UDCA treatment were highly comparable. We also examined the influence of the initial severity of disease on the prognostic performance of biochemical response at 3, 6, and 12 months. Both histological and nonhistological (the Dutch prognostic class5) criteria were used to grade the initial severity of the disease.

After 1 year of UDCA treatment, the serum albumin level was slightly but significantly elevated (P < 0.0001), the serum activities of ALP, GGT, AST, and ALT were decreased by about 50% (P < 0.0001), and the serum concentrations of total bilirubin and IgM were decreased by 30% (P < 0.0001) compared with baseline values. The patients were followed up under UDCA therapy for a mean period of 5.9 EPZ-6438 datasheet ± 2.6 years

(median, 5.8 years; range, 1.3-14 years). An adverse outcome was recorded in 37 patients, including eight liver-related deaths, four liver transplantations, and 25 complications of cirrhosis (six ascites, nine variceal bleeding, five with both ascites and variceal bleeding, four with hepatic encephalopathy and ascites, and one hepatocellular carcinoma). The survival rates without

adverse outcome at 5 years and 10 years were 86% and 63%, respectively (Fig. 2). In univariate analysis, the baseline factors associated with an adverse outcome were a serum activity of ALP >3× ULN, GGT >5× ULN, AST >2× ULN, an abnormal serum concentration of total bilirubin, and a decreased serum level of albumin (Table 2). In multivariate analysis, a serum activity of ALP >3× ULN, elevated bilirubin level, and decreased albumin level were independent risk factors significantly associated with an adverse outcome (Supporting Table 1). The Barcelona, Paris, Rotterdam, Toronto, and Ehime definitions of biochemical responses to UDCA were evaluated for their ability to discriminate patients MCE公司 according Selleck Lapatinib to the long-term outcome (Table 3). For each definition, the rates of biochemical response after 3, 6, or 12 months of UDCA therapy were comparable. The highest rate of biochemical response was observed at the sixth month according to the Paris (71.0%), Barcelona (74.5%), and Toronto (69.0%) definitions, whereas the highest level occurred after 1 year of UDCA therapy according

to the Rotterdam (48.5%) and Ehime (58.0%) definitions. The Paris, Barcelona, Toronto, and Ehime definitions significantly discriminated the patients in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Responders differed significantly from nonresponders and had lower baseline bilirubin, ALT, AST, ALP, and GGT levels and higher albumin levels (Supporting Table 2). The responders were more likely to have early disease (by histological stage, P < 0.05; by the Dutch prognostic class,5 P < 0.001). The biochemical responses evaluated at 3, 6, and 12 months of UDCA treatment were highly comparable. We also examined the influence of the initial severity of disease on the prognostic performance of biochemical response at 3, 6, and 12 months. Both histological and nonhistological (the Dutch prognostic class5) criteria were used to grade the initial severity of the disease.

Clinical physiological parameters such as age,

gender, BMI, body temperature, pulse rate, and blood pressure were evaluated, as well as routine laboratory data obtained on admission. Routine laboratory data included a complete blood cell count (CBC), hepatobiliary enzyme levels, renal function and blood sugar (BS) levels. The enrolled patients were subjected to subgroup analysis and categorized into three groups: (i) normal ALT defined as find more a serum ALT level of <42 IU/L, (ii) moderately elevated ALT defined as a serum ALT level between 42 IU/L and <840 IU/L (20 times above the institutional upper normal limit), and (iii) highly elevated ALT defined as a serum ALT level of >840 IU/L. The above three subgroups were evaluated statistically by analysis of variance (anova). If a significant difference was found, multiple comparisons (post hoc test) were performed with Tukey–Kramer and Steel–Dwass test. The risk related to elevated ALT was analyzed by univariate and multivariate logistic regression.

The results INK 128 purchase of logistic regression analysis were expressed as odds ratio with 95% confidence interval. Differences after these modifications were considered significant at P < 0.05. Analyses were performed by using Excel Statistics (2010, Social Survey Research Information, Tokyo, Japan). The backgrounds of the 37 enrolled patients are listed in Table 1. The ages of the patients ranged from 12 to 67 years (median age 24 years), and all MCE公司 were lean females with a mean BMI on admission of 13 kg/m2. The serum ALT level ranged widely from 11

to 2321 IU/L, with a median of 27 IU/L. Besides liver injury, physiological and laboratory abnormalities frequently associated with AN, such as bradycardia, hypothermia, hypotension, anemia, leukopenia, thrombocytopenia, hyponatremia, hypokalemia, and hypoglycemia were present in some of the enrolled patients. Elevated liver enzyme (serum ALT level ≥42 IU/L) was observed in 13 (35%) of the 37 cases. Highly elevated ALT was evident in four cases (11%), the median ALT level being 1986.5 IU/L. Patients in the moderately elevated ALT group accounted for 24% of the subjects overall (9/37), and the median ALT level was 71 IU/L. The median serum ALT level in the normal ALT group was 20.5 IU/L. The clinical parameters in these three groups are detailed in Table 2. Among the clinical parameters evaluated, body temperature, pulse rate, blood urea nitrogen (BUN), BUN/creatinine ratio, BS, and platelet count differed significantly among the groups (P < 0.05). These six parameters were further analyzed statistically, and this revealed that both BUN and the BUN/creatinine ratio were significantly higher in the high ALT group than in the normal ALT (P < 0.05) and moderate ALT (P < 0.05) groups, respectively (Fig. 1). Body temperature, BS and platelet count were significantly lower in the high ALT group than in the normal ALT (P < 0.05) and moderate ALT (P < 0.05) groups.