06). At 5 years, the recurrence rate in both groups was similar (12% versus 14%; P = 0.94). Table 2 shows the results of univariate analysis for prognostic factors of recurrence in each group separately (LDLT and DDLT). The predictive factors of recurrence were similar in both groups, and were related to a more aggressive tumor (i.e., number of nodules, diameter of largest nodule, preoperative AFP levels, presence of satellite nodules and vascular invasion by the tumor) and to selecting patients beyond established and validated selection criteria (Milan and UCSF). The numbers of recurrences were small in both groups (LDLT, n = 4; DDLT, n = 27), hence a separate multivariate

analysis could not be performed. However, because the pattern of recurrence Ixazomib cell line in both groups was similar, multivariate analysis was performed combining the 2 groups (all 31 patients who had recurrence after LT). On multivariate analysis, among the preoperative variables, transplantation patients with tumors beyond UCSF criteria (P = 0.007) emerged as an independent predictive factor for recurrence (Table 3). Edmonson grade III-IV (P = 0.04) and presence of microscopic vascular invasion (P = 0.009) on the specimen were the other independent poor predictive factors for recurrence. We tested only UCSF criteria in multivariate analysis and not Milan criteria, number, or diameter of nodules

(all of which were significant on univariate analysis) to obviate colinearity. UCSF criteria essentially include the Milan criteria. Similarly, patients with macroscopic vascular FDA-approved Drug Library purchase invasion are already included in the larger group of patients with microscopic vascular invasion. The OS in the two groups (LDLT versus DDLT) after listing (intention-to-treat) and after transplantation (only for those patients with HCC confirmed on the explanted liver) were similar (P = 0.68 and P = 0.36, respectively) (Figs. 2A,B). On multivariate analysis, blood transfusion and microscopic vascular invasion emerged as independent poor prognostic factors for OS

on an intention-to-treat basis (data not shown). There was a trend toward MCE公司 worse survival outcomes in those patients beyond Milan or UCSF criteria who underwent LDLT compared with those who underwent DDLT (P = 0.06 in both cases) (Figs. 3 and 4). There was no difference in the site of recurrence between the two groups (P = 0.77). In the LDLT group, of the four recurrences, two patients had extrahepatic recurrences (one in the lungs and one in the bony skeleton), one patient had an intrahepatic recurrence, and one patient had a recurrence in the liver, lungs, and suprarenal glands. In the DDLT group, of the 14 recurrences, six patients had an extrahepatic recurrence (four pulmonary, one in the bony skeleton, and one in the adrenal glands), six patients had intrahepatic recurrence, and two patients had both intrahepatic and extrahepatic recurrence.

Attentional control, however, encompasses multiple cognitive processes, which may be differentially affected by TLE. One aspect of attentional control that, to our knowledge, has not been examined in these patients is the capacity to perform two distinct tasks concurrently. Although decrements in dual-task performance have been found in neuropsychological groups who are characteristically impaired on other tests of attentional control (Baddeley, Della Sala, Papagno, & Spinnler, 1997; Oram, Geffen, Geffen, Kavanagh, & McGrath, 2005), Olaparib mouse other studies suggest that dual-task performance is dissociable from other forms of attentional control. For example,

Dalrymple-Alford, Kalders, Jones, and Watson (1994) found that patients with Parkinson’s disease performed normally on traditional measures of attentional control, but displayed significant dual-task impairments. In contrast, Baddeley et al. (1997) reported the reverse dissociation

in a sample of frontal patients without behavioural problems. To date, evaluating the status of attentional control in TLE has predominantly relied on drawing conclusions across different studies that have deployed different measures and tested different epilepsy cohorts. To provide a comprehensive evaluation of attentional control in TLE, we administered both a dual-task coordination test and a range of other attentional control measures, including set shifting, sustained attention, selective attention, and divided attention tasks. Participants: Quizartinib price Eighteen TLE surgery candidates (Mage = 35.6, SD = 8.9) who were referred by Hull and East Yorkshire Hospital NHS Trust for neuropsychological assessment participated in the study. The demographic and clinical features of the sample are presented in Table 1. All patients were on optimum antiepileptic medication, but had epileptogenic abnormality. MRI scans confirmed unilateral hippocampal

sclerosis to the left side in seven patients and to the right side in 11 patients. EEG evidence ascribed the focus of epileptogenic activity to the left side in the seven patients with left hippocampal sclerosis, to the right side in nine of the medchemexpress 11 patients with right hippocampal sclerosis and bilaterally in two right hippocampal patients. One right TLE patient had undergone an anterior temporal lobectomy and was being assessed as a part of his post-surgical evaluation. A control group comprising 22 healthy adults (Mage = 36.1, SD = 13.7) was recruited through opportunity sampling. All participants had normal or corrected to normal vision. The dual-task procedure involved participants conducting a tracking task and a digit recall task simultaneously in accordance with the method described by Baddeley et al. (1997).

5A). NAC cotreatment GDC-0449 order did not significantly affect CPZ-inhibited TA uptake up to 24 hours, but partially reduced this inhibition after 48 hours. Noticeably, CPZ did not affect NTCP activity during the first 6 hours of treatment. Because CYP3A4 transcripts were augmented after 24-hour CPZ treatment, we also assessed the effects of CPZ on CYP3A4 activity (Fig. 5B). A dose-dependent increase in the formation of 6β-hydroxytestosterone was found after a 48-hour CPZ treatment. NAC had no effect on the induction of CYP3A4 activity after 48 hours of cotreatment, suggesting that CPZ-induced CYP3A4 was ROS-independent (data not shown). To compare

CPZ-induced cholestasis to cholestasis-like condition caused by BA overload, HepaRG cells were incubated with the two primary BA, cholic and chenodeoxycholic acids, at 25- 500 μM, and cell viability was assessed by the MTT test after 24-hour exposure (Fig. 6A). Whereas no cytotoxicity was observed with up to 200 μM BA, cell viability dropped to 40% with 500 μM cholic and chenodeoxycholic acids. Moreover, ROS generation was assessed by DHE staining and the H2-DCFDA assay at different timepoints, ranging from 30 minutes to 24 hours. Superoxide anions were detected in hepatocyte-like cells after 6 hours of exposure to 500 μM of either BA (Fig. 6B). In parallel, formation

of hydrogen peroxides was detected from 6-hour exposure to 500 μM chenodeoxycholic acid and only after 24-hour treatment with 500 μM cholic acid (Fig. 6C). No ROS generation was evidenced with low Estrogen antagonist concentrations up to 200 μM BA whatever the time of treatment (data not shown). Noteworthy, no alteration of the mitochondrial membrane potential was evidenced before 6-hour exposure to 500 μM

of either BA (Fig. 6D). In addition, expression of genes modulated by CPZ was analyzed and found to vary depending on BA concentrations after a 24-hour exposure (Table 2A). Thus, genes involved in the canalicular efflux transport system were either strongly (BSEP) or slightly (MDR3) up-regulated, whereas expression of other genes remained unchanged with low concentrations of either BA. By contrast, BSEP and MDR3 were down-regulated with 500 μM BA. Noticeably, genes related to oxidative stress (HO-1 and Nrf2) were 上海皓元医药股份有限公司 overexpressed, whereas NTCP and CYP8B1 were inhibited with 500 μM BA. In addition, MRP4 transcripts were enhanced with 500 μM cholic acid but decreased with 500 μM chenodeoxycholic acid. A decrease in CYP3A4 mRNAs was obtained in cells overloaded with subtoxic or toxic concentrations of BA. In addition, after a 6-hour exposure of HepaRG cells to the two BA, BSEP and MDR3 were overexpressed by 200 μM or lower concentrations, whereas only CYP8B1 was down-regulated by 500 μM chenodeoxycholic acid. Moreover, HO-1 and Nrf2 expression was induced by 200 and 500 μM chenodeoxycholic acid and only by 500 μM cholic acid (Table 2B).

Long-term follow up studies of both infliximab and adalimumab have demonstrated good safety and durable efficacy.21,22 Comparable results with adalimumab were obtained in CLASSIC I, II and CHARM.8 Overall, 58% of patients responded to induction therapy, with 52% achieving ongoing response, and 40% achieving remission at one year. Improved

responses have been seen with higher buy ITF2357 induction doses,23 and these may confer higher rates of remission. Certolizumab pegol was evaluated in PRECISE 1 and 2, with response rates of 35 and 64%, respectively.9,24 Of responders in PRECISE 2, 63% maintained their response and 48% were in remission at week 26. Differing response rates between these trials have not yet been explained. (Table 1) Fistulizing Crohn’s disease.  The efficacy of biological agents

for fistulae in CD is most firmly established for infliximab. Response rates of 69% and remission rates of 49% were observed following a three dose induction with infliximab.27 Of these patients, 46% maintained this response on scheduled maintenance therapy, so that 20% remained in remission at one year.28 Patients with fistulae treated with infliximab are less likely to require surgery.29 These therapeutic benefits are thought to extend to the sub-group with recto-vaginal fistulae.30 Data from Japan also demonstrate the long-term efficacy of infliximab in maintenance therapy for perianal CD.31 While CHARM and PRECISE were not primarily designed to investigate treatment of fistulae, short-term efficacy was demonstrated in both studies. One

third of patients selleck inhibitor treated with adalimumab had closure of fistulae at one year.8 When treated with certolizumab pegol, 54% of those with fistulae who responded to induction had closure of fistulae at the conclusion of the trial.24 Postoperative recurrence of Crohn’s disease.  Anti-TNF therapy may reduce postoperative recurrence of CD. The use of infliximab 5 mg/kg within 4 weeks of surgery followed by maintenance for 1 year, reduced postoperative endoscopic recurrence from 85% to 9%.32 There is a need to identify individuals at the highest risk of clinical recurrence as many patients are unlikely to medchemexpress require maintenance biologic therapies. In a Japanese prospective randomized open-labeled trial of infliximab in the prevention of postoperative CD recurrence, the 3-year remission rate on infliximab was 93.3% compared with 56.3% for the control arm (P < 0.03). C-reactive protein normalization and mucosal healing were also significantly higher in the group receiving infliximab.33 A multicenter Australian trial examining the utility of adalimumab in patients at higher risk of CD postoperative recurrence has recently completed recruitment.34 Refractory ulcerative colitis.  Anti-TNF therapy is effective in patients with refractory moderate-severe UC. Infliximab has a 66% response rate, double that of the placebo response.

HA-tagged Cas FL and Cas ΔSH3 (Fig. 4A)28 were retrovirally introduced into NP31 cells, and the expression levels of their protein products were examined by western blotting with an anti-HA antibody that detects exogenous Cas and selleckchem also with an anti-Cas antibody that detects endogenous and exogenous Cas. As shown in Fig. 4B, Cas FL and Cas ΔSH3 were expressed at almost comparable levels (left panel) that were approximately 5 to 6 times greater than those of endogenous Cas (right panel). To examine the effect of SH3 deletion on Cas-mediated signaling, cells were plated onto fibronectin (FN)-coated dishes, and the cell lysates were subjected to immunoprecipitation

followed by western blotting. As shown in Fig. 4C, anti-HA and anti-Cas2 immunoprecipitates blotted by an anti-phosphotyrosine antibody (4G10) buy Midostaurin showed that Cas ΔSH3 was much less tyrosine-phosphorylated than Cas FL (left panel), and tyrosine phosphorylation of endogenous Cas was barely detectable in Cas ΔSH3–expressing cells (right

panel). In addition, as shown in Fig. 4D, anti-CrkII immunoprecipitates blotted by anti-HA or anti-Cas2 antibodies revealed that Cas ΔSH3 was far less efficiently coprecipitated with CrkII than Cas FL (left panel), and CrkII did not detectably coprecipitate endogenous Cas in lysates from Cas ΔSH3–expressing cells (right panel). These findings indicate that Cas ΔSH3 functions as a reduction-of-function molecule in NP31 cells as CasΔex2/Δex2 does in mouse embryonic fibroblasts (MEFs).32 To examine the suppressive function of Cas ΔSH3 on actin stress fiber formation, parental,

Cas FL–expressing, and Cas ΔSH3–expressing NP31 cells were subjected to cytoskeletal staining. As shown in Fig. 5A, prominent actin stress fiber formation was detected in parental cells and to a comparable extent in Cas FL–expressing cells (indicated by arrows in the lower left and middle panels). In contrast, no obvious actin stress fibers were formed and only dotlike actin filaments were observed in Cas ΔSH3–expressing NP31 cells (indicated by arrowheads in the lower right panel). We then investigated the formation 上海皓元医药股份有限公司 of fenestrae in NP31 cells by electron microscopy because the architectural control of fenestrae is regulated by the actin cytoskeleton.1, 3, 7 Parental and Cas FL–expressing NP31 cells exhibited a number of fenestrae of various diameters (left and middle panels in Fig. 5B). Counting of the fenestrae per square micrometer showed that although the number of fenestrae in Cas FL–expressing cells was slightly higher than that in parental cells (5.80 ± 0.37 for parental cells and 6.13 ± 0.39 for Cas FL–expressing NP31 cells), the difference was not statistically significant (left and middle bars in Fig. 5C).

17-19 miR-33 has also been shown to regulate fatty acid oxidation in hepatic cell lines.20 Nevertheless, despite these important advances, the full extent of posttranscriptional control of lipid metabolism by miRNAs remains incompletely understood and has not been systematically investigated.21 Using an unbiased in silico approach, which should be generally applicable toward the identification of key regulatory miRNAs in any biological process, we predicted miR-27b as a regulatory hub in lipid metabolism. Furthermore, we demonstrated that hepatic miR-27b is responsive to lipid levels and regulates the expression

(messenger RNA [mRNA] and protein) of key metabolic genes, including angiopoietin-like 3 (ANGPTL3) and glycerol-3-phosphate acyltransferase 1 (GPAM), which have been implicated previously in the pathobiology BMN 673 in vitro of lipid-related disorders. ELISA, enzyme-linked immunosorbent assay; FDR, false-discovery rate; HFD, high-fat diet; miRNAs, GDC-0068 clinical trial microRNAs; ORF, open reading frame; PCR, polymerase chain reaction; UTRs, untranslated regions. Eight-week-old wildtype C57BL/6J mice were placed on either normal chow diet (4% fat, NIH-31 open chow, Zeigler Brothers, Gardners, PA) or a high-fat Western

diet (21% fat, 42% calories from fat, ad libitum, TD88137, Harlan-Teklad, Frederick, MD) for 3 weeks (19-21 days). Adult (8-10 weeks) female apolipoprotein E null mice (Apoe−/−, C57BL/6J background; Jackson Laboratory, Bar Harbor, ME) were placed on either normal chow or cocoa butter diet with sodium cholate (16% fat, 37% calories from fat, 1.25% cholesterol, 0.125% choline chloride, 0.5% sodium cholate, TD90221, Harlan-Teklad) for 4 weeks (28 days). Mouse livers were excised and homogenized (100 mg) in Qiazol Total RNA extraction buffer. All mice were housed and the relevant studies

were completed under active protocols approved by the National Institutes of Health, National Heart, Lung, medchemexpress and Blood Institute Animal Care and Use Committee. All protocols complied with, and all animals received humane care according to, the criteria outlined in the NIH “Guide for the Care and Use of Laboratory Animals. miRNA isolation and Illumina sequencing were completed as reported.22 Details are provided in the Supporting Methods. Target sites (seed, centered) were predicted for miR-27b in both the 3′ untranslated regions (UTRs) and the open reading frames of the 151 lipid metabolism genes. Details of target site prediction and the identification of candidate miRNA regulatory hubs by Monte Carlo simulations are provided in the Supporting Methods. Human hepatocytes (Huh7) were cultured in F12 Dulbecco’s modified Eagle’s medium (DMEM), supplemented with 10% fetal bovine serum, penicillin (100 U/mL), and streptomycin (100 μg/mL), and maintained at 37°C with 5% CO2.

17-19 miR-33 has also been shown to regulate fatty acid oxidation in hepatic cell lines.20 Nevertheless, despite these important advances, the full extent of posttranscriptional control of lipid metabolism by miRNAs remains incompletely understood and has not been systematically investigated.21 Using an unbiased in silico approach, which should be generally applicable toward the identification of key regulatory miRNAs in any biological process, we predicted miR-27b as a regulatory hub in lipid metabolism. Furthermore, we demonstrated that hepatic miR-27b is responsive to lipid levels and regulates the expression

(messenger RNA [mRNA] and protein) of key metabolic genes, including angiopoietin-like 3 (ANGPTL3) and glycerol-3-phosphate acyltransferase 1 (GPAM), which have been implicated previously in the pathobiology LEE011 price of lipid-related disorders. ELISA, enzyme-linked immunosorbent assay; FDR, false-discovery rate; HFD, high-fat diet; miRNAs, Doxorubicin microRNAs; ORF, open reading frame; PCR, polymerase chain reaction; UTRs, untranslated regions. Eight-week-old wildtype C57BL/6J mice were placed on either normal chow diet (4% fat, NIH-31 open chow, Zeigler Brothers, Gardners, PA) or a high-fat Western

diet (21% fat, 42% calories from fat, ad libitum, TD88137, Harlan-Teklad, Frederick, MD) for 3 weeks (19-21 days). Adult (8-10 weeks) female apolipoprotein E null mice (Apoe−/−, C57BL/6J background; Jackson Laboratory, Bar Harbor, ME) were placed on either normal chow or cocoa butter diet with sodium cholate (16% fat, 37% calories from fat, 1.25% cholesterol, 0.125% choline chloride, 0.5% sodium cholate, TD90221, Harlan-Teklad) for 4 weeks (28 days). Mouse livers were excised and homogenized (100 mg) in Qiazol Total RNA extraction buffer. All mice were housed and the relevant studies

were completed under active protocols approved by the National Institutes of Health, National Heart, Lung, 上海皓元医药股份有限公司 and Blood Institute Animal Care and Use Committee. All protocols complied with, and all animals received humane care according to, the criteria outlined in the NIH “Guide for the Care and Use of Laboratory Animals. miRNA isolation and Illumina sequencing were completed as reported.22 Details are provided in the Supporting Methods. Target sites (seed, centered) were predicted for miR-27b in both the 3′ untranslated regions (UTRs) and the open reading frames of the 151 lipid metabolism genes. Details of target site prediction and the identification of candidate miRNA regulatory hubs by Monte Carlo simulations are provided in the Supporting Methods. Human hepatocytes (Huh7) were cultured in F12 Dulbecco’s modified Eagle’s medium (DMEM), supplemented with 10% fetal bovine serum, penicillin (100 U/mL), and streptomycin (100 μg/mL), and maintained at 37°C with 5% CO2.

19 HSC cotransplantation markedly enhanced expression of CD62L on infiltrated CD11b+ cells, but not others (Supporting Fig. 1B). The antigen stimulatory activity of these purified CD11b+ cells was examined in a one-way mixed leukocyte reaction (MLR) culture

where carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled B6 spleen T cells were stimulated by CD11b+ cells pulsed with BALB/c spleen cell lysate (without pulsing served as controls). CD11b+ cells from islet/HSC grafts elicited weaker proliferative response in both CD4 and CD8 T cells with less IFN-γ production, but generated more CD4+Foxp3+ cells compared to the islet-alone group (Fig. 2B). To determine their immune regulatory activity, the isolated CD11b+ cells were added to the culture of CFSE-labeled T cells at a ratio of 1:10. T-cell proliferation was elicited by anti-CD3 mAb. Addition of CD11b+ cells from islet/HSC, but not from buy Carfilzomib islet alone grafts, markedly suppressed the proliferative response and IFN-γ production in both CD4+ and CD8+ T cells. This was associated with markedly Depsipeptide reduced T-cells numbers (Fig. 2C, right panels, P < 0.05, islet versus islet/HSC) due to enhanced T-cell apoptosis as determined by annexin V staining (Fig. 2C). Taken together, these data on CD11b+ cells in islet/HSC grafts demonstrated many characteristics of MDSC: CD11clow,

MCE公司 immature phenotype, expressing high iNOS and arginase1, immune inhibitory activity,16, 20 suggesting that cotransplanted HSC are potent inducers of MDSC. MDSC have

been shown to mediate development of Treg cells.18 To study the correlation of MDSC and Treg cells induced by HSC cotransplantation, CD11b+CD11c− cells and CD4+Foxp3+ cells were kinetically analyzed by immunohistochemistry and flow cytometry in the grafts, draining LN, and spleen following transplant. CD11b+CD11c− cells were remarkably increased in islet/HSC grafts, peaking on POD 7, compared to islet alone, gradually declined thereafter, and hardly found in long-term survival grafts (Fig. 3A). An increase in CD11b+CD11c− cells was also seen in dLN and spleen, and remained high there in the recipients with long-term survival grafts (Fig. 3B,C). The changes of CD11b+CD11c− cells (MDSC) were well correlated with that of CD4+Foxp3+ Treg cells, suggesting a close relationship of the two cell populations. Induction of MDSC has been shown to require inflammatory stimulation.21, 22 We hypothesized that HSC might lose their ability to induce MDSC when IFN-γ stimulation was blocked. This was tested by using HSC from IFN-γR1−/− mice for islet cotransplantation. Following transplantation, the graft CD11b+ and CD4+ cells were evaluated by both immunohistochemistry and flow cytometry for expression of CD11c and Foxp3, respectively. As shown in Fig.

Median operative time was 600 min, range MAPK inhibitor 340–989 min, and the length of stay was 19 days, range 15–38 days. Infection (median 11%, range 5–21%), biliary (median 5%, range 0–31%), bleeding (median

7%, range 0–33%), and vascular (median 7%, range 0–12%) complications were most commonly recorded. Two studies reported 23–24% reoperation rates, but no other reoperations occurred in any other study.[23, 30] Acute rejection occurred in 4%, range 0–12%, of patients. Four patients required retransplantations. Median mortality rate was 5%, range 0–24% (Table 6). The median follow-up was 29 months, range 11–77 months. Median disease-free survival was not yet reached in 10 of the studies. The median 1-year disease-free survival was 86%, range 47–100%; median 3-year disease-free survival was 68%, range 29–100%; and median 5-year disease-free survival was 67%, range 29–100%. Two studies reported a median overall survival of 45.6 and 61 months;[20, 31] however, the remaining 14 studies had not yet reached median overall survival at publication of results. The median 1-year overall survival was 89%, range 59–100%; median 3-year overall survival was 80%, range 52–100%; and median 5-year overall survival was 62%, range 41–89%

(Table 7). Primary liver transplantation is recognized as the most effective treatment of primary HCC within the Milan criteria, but is limited by organ shortage.[36] Efficacy of this treatment is affected by disease progression during PD-0332991 cell line prolonged waiting times.[8] Primary hepatic resection is a widely adopted modality of treatment for primary HCC with reasonable long-term survival outcomes but is associated with high rates of disease recurrence. Poon et al. suggest a treatment strategy of primary hepatic resection as the treatment of patients with HCC within the Milan criteria, with SLT reserved MCE公司 for those with disease recurrence.[8] This strategy may potentially reduce

disease progression for patients waiting for liver transplantation and reduce the number of transplantations required. The pathological specimen obtained from a primary resection can also assist surgeons in identifying those patients at high risk of recurrence, who would most likely benefit from an SLT.[16, 37] The theoretical rate of patients eligible for SLT at recurrence has been reported to be as high as 60–80%.[8, 38] Although early clinical studies demonstrated the relative safety of this treatment strategy,[14, 20] there have been concerns about prior primary resection increasing the difficulty of SLT, negating potential outcome benefits. Inclusion criteria for primary hepatic resection were generally consistent among studies. Initial resection was indicated in patients with good residual hepatic function, few tumor nodules (ideally solitary nodule), absence of intraoperative evidence of macrovascular invasion, absence of extrahepatic malignancy, and anatomically resectable disease.

Identification of patients who clearly fulfill the diagnostic criteria for HRS is difficult, as is the recruitment of critically ill patients in clinical trials. Accordingly, the largest trials were multicentered and multinational. This increases the clinical

heterogeneity as well as the external validity, making it possible to extrapolate the results to larger patient populations in similar specialized centers. Another important limitation of the present review is related to the methodological quality of the included trials. Our primary meta-analysis was not stable to sensitivity analyses of bias control. Unfortunately, we were unable to perform valid regression analyses to determine the risk of publication bias and other NVP-BGJ398 clinical trial biases. The risk that such meta-regression analyses would be false-negative was considerable due to the limited number of trials

in individual meta-analyses. PS-341 price Likewise, our results are unlikely to be stable to trial sequential analyses with adjustments for the multiple testing invariably associated with meta-analyses.31 On the other hand, because we included mortality, the results were less susceptible to bias than subjective outcome measures.22 Three of the included trials compared different active treatment regimens.28–30 Although the availability of noradrenalin and lower costs makes this treatment option interesting, the pharmacological effects of this drug are not identical to those of terlipressin. An assessment of whether noradrenalin and

terlipressin have similar effects requires evidence from noninferiority or equivalence trials.32, 33 To demonstrate that the 上海皓元 experimental treatment is not worse than the comparator, a pre-specified amount known as the noninferiority or equivalence margin should be defined. The margin should be included in the sample size calculations, and both intention-to-treat and per-protocol analyses should be performed. In accordance with previous epidemiological studies of clinical trials,32, 33 these basic requirements were not met in the trials from the present review. Accordingly, no conclusions regarding noninferiority or equivalence can be made. For several of the included trials, sample size calculations were not reported. Accordingly, we were unable to determine whether sample size calculations were performed and the preset sample size achieved, the trials were terminated prematurely, or the trial was terminated at an arbitrary point. One of the included trials on terlipressin plus albumin versus albumin was terminated after an interim analysis suggested that 2,000 patients would be required to achieve adequate statistical power.17 The specific criteria for the interim analysis were not clearly reported. The control group mortality rates for trials on terlipressin plus albumin were 63% to 100% compared with 83% for the trial terminated prematurely.