[36, 37] The yield from brush cytology is variable,

[36, 37] The yield from brush cytology is variable, selleck chemicals and positive diagnosis ranges from 44–80%.[36, 38] To date, there has been no prospective control study on the yield of tissue acquisition in HCCA. Pooled data from over 800 CCA patients reported sensitivity of 42%, specificity of 98%, and positive predictive value (PPV) of 98% among patients with confirmed cancer.[36] It has been reported that at least five brush passes, removal of the brush and catheter together, and inclusion of washings from the brush catheter may increase yield.[39] Intraductal fine-needle

aspiration (FNA) had a sensitivity of just 34%, with specificity of 100% and PPV of 100%.[36] Although intraductal biopsies have shown the highest AZD3965 supplier yield for detection of malignancy, with a pooled sensitivity of 56%, specificity

of 97%, and PPV of 97%,[36, 39] intraductal biopsy in HCCA stricture is a cumbersome technique and may result in a lower diagnostic yield than the result reported in all CCAs. A “smash prep” protocol showed the overall sensitivity of 76% for all cancers with 100% specificity. The highest diagnostic yields for tissue sampling at Endoscopic retrograde cholangiopancreatography (ERCP) were obtained by using a combination of two or three standard techniques at the same setting. Ponchon et al. found that combining brush cytology (35% sensitivity) and forceps biopsy (43% sensitivity) yielded a sensitivity of 86%.[40] The Indiana group reported a sensitivity of 73% in CCA Liothyronine Sodium subset using triple samplings with brush cytology, FNA, and forceps biopsy. The addition of a 2nd or 3rd sampling modality consistently increased diagnostic yield.[41] Therefore, we recommend at least a combination of two techniques such as brushing and forceps biopsy for all suspicious strictures. 5. Carbohydrate

antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are moderately specific for CCA. The presence of cholestasis and cholangitis lower the specificity of serum CA 19-9 Level of agreement: a—63%, b—37%, c—0%, d—0%, e—0% Quality of evidence: II-2 Classification of recommendation: B CA 19-9 and CEA are the two markers best studied with respect to CCA, but their utility is limited by poor sensitivity in early stage malignancy, and marginally elevated levels (> 100U/mL) may be associated with benign conditions.[42-47] Many studies have looked at their diagnostic utility in the setting of both PSC-related CCA and non-PSC-related CCA.[42-47] By using the serum cutoff value of more than 180 U/mL in some large series,[42-49] the sensitivity was moderate at 53%–79% and the specificity was fair to excellent at 83%–98%. However, the specificity of CA 19-9 in diagnosing biliary malignancy is reduced by the presence of either cholangitis or cholestasis.

These interactions presumably stabilize the β1-α1 loop region, wi

These interactions presumably stabilize the β1-α1 loop region, with a further stabilization arising from a water-mediated hydrogen bond between TUDC’s sulfonic acid moiety and the amide nitrogen of Tyr153. Apparently, the stabilization leads to helix α1 straightening and becoming continuous, which results in an inward movement of the

central region of α1 and the T-junction formation. In contrast, the sulfonic acid moiety of TC interacts STI571 datasheet simultaneously with MIDAS and LIMBS, reminiscent of the coordination of carboxylate groups of an RGD peptide40 or eptifibatide41 bound to αvβ3 or a mutant of αIIbβ3, respectively. No further interaction is observed between the sulfonic acid moiety and the surrounding

protein and, hence, no stabilization of the β1-α1 loop region can be expected. Accordingly, the break in helix α1 persists, and no inward movement of the helix is observed. The difference in β1 integrin activation between TUDC and TC must be rooted in the differences in the substitution pattern of the cholan scaffolds (Supporting Scheme 1): although the simulations started from very similar binding modes of the bile acids (Supporting Fig. 6), different, yet stable, orientations of the cholan scaffold develop in the course of the simulation (Fig. 6D). The cholan scaffold of TC is oriented almost perpendicular to the one of TUDC, which is favored by hydrogen bond formation of the 7α-OH group of Pembrolizumab cost TC with Ser265 and Asp268 Sinomenine (Supporting Table 1). In TUDC, the configuration at C7 is inverted, which drastically reduces hydrogen bond interactions of the 7β-OH group with the α5 subunit (Supporting Table 1). In contrast, the presence of the 12α-OH group in TC does not seem to be responsible for the nonactivating behavior of TC because the group does not make any interactions with the α5 subunit in the binding mode found. Support for the hypothesis

that it is the configuration of C7 that determines whether β1-integrin becomes activated or not is provided by the fact that TCDC does not activate β1-integrin either: whereas TCDC lacks a 12α-OH group, in contrast to TC, it does have a 7α-OH group, as does TC (Supporting Scheme 1). Overall, the differences in the orientation of the cholan scaffold lead to differences in the orientation of the sulfonic acid moieties, with the above-described consequences for β1-integrin activation. In summary, TUDC has the unique property to directly interact with α5β1 integrins inside the hepatocyte. The resulting conformational change triggers β1 integrin activation and initiates integrin-dependent signaling, which explains not only the choleretic and cytoprotective effects of this therapeutically used bile acid but also its hepatocyte-specificity. The authors thank the “Zentrum für Informations und Medientechnologie” (ZIM) at the Heinrich Heine University for computational support.

Fl/fl (WT) and GFAP-cre NOX4 knockout mice (NOX4HSCKO) were pair-

Fl/fl (WT) and GFAP-cre NOX4 knockout mice (NOX4HSCKO) were pair-fed for 5 weeks and liver histology, steatosis; triglyceride content and reactive oxidative species (ROS) were studied by lucigenin assay. TNF, IL-1, IL-6, MCP-1, Ly6C, and CCR2 expression Neratinib in vitro were assessed by real time qPCR. In vitro, primary HSC were treated with acetaldehyde (Ac) and the expression of NOX4 was assessed. HSC isolated from WT or NOX4HSCKO mice were

treated with actinomy-cin D (ActD) with or without Ac and total RNA was extracted at 0, 6, 12 and 24 hours, and CCR2 mRNA stability was assessed. Results: NOX4 mRNA increased and NOX4 was highly expressed in patients with alcoholic liver disease. In the WT mice fed the ethanol diet, liver TG content (p <0.05), lucigenin intensity and MDA values were increased compared to the pair fed mice, but not in the NOX4HSCKO mice on the ethanol diet. In the WT mice on the ethanol diet, TNF (p <0.05), IL-6 (p <0.05), MCP-1 (p <0.05), Ly6C (p <0.01) and CCR2 (p <0.01) expression were significantly increased whereas the expression of these transcripts

was attenuated in the NOX4HSCKO mice on the ethanol diet (p <0.05, CCR2; p <0.01). NOX4 was induced in primary HSC by Ac exposure (p <0.01). Ac treatment increased H 89 price CCR2 mRNA expression in WT primary HSC (p <0.01), but not in the NOX4KO primary HSC (p = 0.03). In WT primary HSC treated with Ac, CCR2 mRNA stability was increased compared to NOX4KO primary HSC (p <0.01). In conclusion, NOX4 is induced in early alcoholic liver injury in HSC and regulates CCR2 mRNA stability, affecting inflammatory macrophage recruitment. NOX4 could be an important treatment target in Methocarbamol alcoholic liver injury. Disclosures: Natalie Torok – Consulting: Genentech/Roche The following people have nothing to disclose: Yu Sasaki, Joy Jiang, Tzu-I Chao, Jijing Tian Background & aim. Chili (Capsicum spp.) is one of the many

domesticated plants of Mesoamerica that dates back to 3000 B.C. Despite its pungency, it is a preferred staple food of the Mexican diet to date and its high consumption may be due to the TAS2R38. This receptor has also been associated to the perception of bitter taste compounds such as astringent alcoholic beverages. TAS2R38 expresses two haplotypes: PAV and AVI. Recently, it has been reported that homozygous carriers for the AVI haplotype have a higher alcohol intake. The aim of this study was to determine the prevalence of the TAS2R38 gene haplotypes and its association with alcohol intake among the population of West Mexico. Methods. In a cross-sectional study, a total of 702 unrelated individuals were analyzed, including two Amerindian groups (84 Nahuas and 99 Huicholes or Wixarikas), two Caucasian groups (32 from Villa Purificacion (VP) and 33 from Los Altos) and 454 Mestizos from Guadalajara, Jalisco in West Mexico.

Feld – Advisory Committees or Review Panels: Idenix, Merck, Janss

Feld – Advisory Committees or Review Panels: Idenix, Merck, Janssen, Gilead, STAT inhibitor AbbVie, Merck, Theravance, Bristol Meiers Squibb; Grant/Research Support: AbbVie, Boehringer Ingelheim, Janssen, Gilead, Merck The following people have nothing to disclose: Angela C. Cheung, Javier M. Meza-Cardona, Matthew Kowgier Background & Aims: It has been postulated that primary sclerosing cholangitis (PSC) develops through immune mediated mechanisms triggered by complex gene-environment interactions in susceptible individuals. However, the relationships between PSC and the environment are largely unknown. While

tobacco use has been reported to have a negative association with PSC, other exposures particularly dietary habits and methods of food preparation have not been well explored. Our aims were to validate or refute associations reported in previous studies

and to identify novel environmental exposures among PSC patients. Methods: We performed a case-control analysis utilizing self-administered questionnaires. Cases were recruited from 8 academic medical centers across North America and controls were recruited from the Mayo Clinic during annual visits for preventive health care. Responses between cases (n=1000) and controls (n=663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n=741; without IBD n=259). Results: A history of smoking was

inversely associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4-0.7) Selumetinib mouse but not among PSC patients without IBD (OR, 0.9; 95% CI 0.7-1.2). Moreover, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT) (OR, 0.5; 95% CI 0.4-0.7) and were more likely to have recurrent urinary tract infections (UTI’s) (OR, 1.6; 95% CI 1.2-2.3) when compared to controls. Furthermore, PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3-0.6), vegetables (OR, 0.9; 95% CI 0.8-0.9) and grilled/barbecued meat PRKACG (OR, 0.8; 95% CI 0.7-0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well-done (OR, 1.3; 95% CI 1.2-1.5). Conclusions: To date, this is the largest study (which represents approximately 3% of the estimated PSC patient population in the United States) that examines environmental exposures and PSC. IBD (rather than PSC) was associated with smoking. Women with PSC were more likely to have recurrent UTI’s and less likely to receive HRT. Furthermore, dietary intake and methods of food preparation differs in PSC patients when compared to controls. Estrogen, recurrent UTI’s and dietary habits may be relevant to the pathogenesis of PSC and warrant further study.

Feld – Advisory Committees or Review Panels: Idenix, Merck, Janss

Feld – Advisory Committees or Review Panels: Idenix, Merck, Janssen, Gilead, KU57788 AbbVie, Merck, Theravance, Bristol Meiers Squibb; Grant/Research Support: AbbVie, Boehringer Ingelheim, Janssen, Gilead, Merck The following people have nothing to disclose: Angela C. Cheung, Javier M. Meza-Cardona, Matthew Kowgier Background & Aims: It has been postulated that primary sclerosing cholangitis (PSC) develops through immune mediated mechanisms triggered by complex gene-environment interactions in susceptible individuals. However, the relationships between PSC and the environment are largely unknown. While

tobacco use has been reported to have a negative association with PSC, other exposures particularly dietary habits and methods of food preparation have not been well explored. Our aims were to validate or refute associations reported in previous studies

and to identify novel environmental exposures among PSC patients. Methods: We performed a case-control analysis utilizing self-administered questionnaires. Cases were recruited from 8 academic medical centers across North America and controls were recruited from the Mayo Clinic during annual visits for preventive health care. Responses between cases (n=1000) and controls (n=663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n=741; without IBD n=259). Results: A history of smoking was

inversely associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4-0.7) MLN0128 concentration but not among PSC patients without IBD (OR, 0.9; 95% CI 0.7-1.2). Moreover, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT) (OR, 0.5; 95% CI 0.4-0.7) and were more likely to have recurrent urinary tract infections (UTI’s) (OR, 1.6; 95% CI 1.2-2.3) when compared to controls. Furthermore, PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3-0.6), vegetables (OR, 0.9; 95% CI 0.8-0.9) and grilled/barbecued meat Methane monooxygenase (OR, 0.8; 95% CI 0.7-0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well-done (OR, 1.3; 95% CI 1.2-1.5). Conclusions: To date, this is the largest study (which represents approximately 3% of the estimated PSC patient population in the United States) that examines environmental exposures and PSC. IBD (rather than PSC) was associated with smoking. Women with PSC were more likely to have recurrent UTI’s and less likely to receive HRT. Furthermore, dietary intake and methods of food preparation differs in PSC patients when compared to controls. Estrogen, recurrent UTI’s and dietary habits may be relevant to the pathogenesis of PSC and warrant further study.

96, 97 In selected patients with INCPH (eg, abdominal discomfor

96, 97 In selected patients with INCPH (e.g., abdominal discomfort or hypersplenism patients), these interventions can be regarded as effective therapeutic modalities. Based on the high prevalence of thrombophilia and incidence of portal vein thrombosis in INCPH patients, several investigators

have incriminated thrombosis of small intrahepatic portal veins as an important etiological factor in the development of this disorder.6, 30 Additionally, a trend toward poor prognosis has been reported in patients with INCPH who develop portal vein thrombosis.6 As a result, anticoagulation therapy has been proposed by Sotrastaurin cost several investigators to prevent disease progression and to maintain portal vein patency.6, 32, 98 However, considering the fact that gastrointestinal Dasatinib mouse bleeding is the main complication of INCPH and the uncertain role of thrombophilia in the pathogenesis, this treatment is still a matter of debate and cannot be generally implicated until more solid data are present. Nonetheless, we believe that anticoagulation therapy must be considered in patients

with underlying prothrombotic conditions and in patients who develop portal vein thrombosis. Generally, patients with isolated INCPH have a normal liver function and the complications of portal hypertension can be managed successfully with endoscopic therapy and shunting. However, several reports describing liver transplantation in patients with INCPH have been published. The reported indications requiring liver transplantation in these patients were medical unmanageable portal hypertension, hepatopulmonary syndrome, hepatic encephalopathy, and progressive those hepatic failure.49, 63, 78 Recently, Karsinskas et al. described a small cohort of INCPH patients treated with liver transplantation.63 The main indication for liver transplantation was medically unmanageable severe portal hypertension; a minority was listed because of hepatic encephalopathy. Notwithstanding the fact that resistant bleeding in INCPH patients should be treated with portosystemic shunting before considering the option of

liver transplantation, only two patients underwent pretransplantation portosystemic shunting procedures (e.g., TIPS and mesocaval shunt). Presumably, the high frequency of cirrhosis misdiagnoses in these patients led to early referral for liver transplantation. To prevent unnecessary liver transplantation in these patients, early discrimination between cirrhosis and INCPH is extremely important. Based on small-sized cohorts (with limited follow-up), post-transplantation outcome in these patients is good and INCPH tends not to recur.63, 99, 100 Data on the etiology and management of INCPH are scarce, and currently applied diagnostic and therapeutic algorithms are based on personal experience or data from limited numbers of patients.

28%

28%. find protocol In patients over 60 years old mortality is significantly higher than those below 60 years old. Among 56 cases of patients with hemorrhagic shock, 24 cases of hepatic cirrhosis, esophageal variceal bleeding in 22 cases, accounting for 91.67%, duodenal ulcer in 2 cases, accounting for 9.33%. 56 cases of hemorrhagic shock patients, the incidence rate of the esophageal and gastric variceal hemorrhage is most, followed by duodenal ulcers, two a total of 35 cases, accounting for 62.5% of all patients. The third was gastric ulcer, 5 cases, accounting for 8.92%. The mortality

of esophageal carcinoma with bleeding is highest, is 100%, Secondly, esophageal variceal bleeding, 50.55%. Acute gastric mucosal lesion in a case of death, because the original renal failure patients. Conclusion: Hepatic cirrhosis esophageal varices and duodenal ulcer are the two main causes of hemorrhagic shock and death, The highesist mortality was esophageal carcinoma complicated with hemorrhagic shock. With the increase of age, increased mortality.

Key Word(s): 1. hemorrhagic shock; 2. gastrointestinal; 3. esophageal cancer; 4. duodenal ulcer; Presenting Author: YUSUKE HIGUCHI Additional Authors: KOUJI NAKAMICHI Corresponding Author: YUSUKE HIGUCHI Affiliations: FukuokaTokushukai Medical Center Objective: The clipping method and EBL (Endoscopic bang ligation) are useful as a cure for bleeding from a diverticulum of colon. The clipping Fostamatinib research buy method has a high re-bleeding rate and it was reported that the EBL is more useful. However, the progress Orotidine 5′-phosphate decarboxylase and the complication after the EBL are unclear, and it cannot be said that it has still spread. We experienced two cases of bleeding from a diverticulum of colon treated with the EBL,

and we observed postoperative progress. Methods: The patients were a 69-years old man and an 83-years old man with the chief complaint of bloody stool. Previously one of them was treated the bleeding from a diverticulum of sigmoid colon by the clipping method. They had anemia, and underwent an endoscopic examination on the next day after the consult. Results: The fresh flowing or pulsating bleeding was found from a diverticulum of sigmoid colon. The patients had been treated with the EBL. After the treatment, the perforation of intestinal tract and re-bleeding were not occurred. One month after, we found ulcer, scar and the disappearance of the diverticulum itself. Conclusion: We could recognize the disappearance of the diverticulum without adverse effects after the bleeding from a diverticulum of colon treated with the EBL. It is precious the report of the progress after the treatment with the EBL. We also present a review of the literature. Key Word(s): 1. EBL; 2.

As a practical consideration, such species are likely to be sympa

As a practical consideration, such species are likely to be sympatric with many other species, creating abundant opportunities buy GSK2118436 for mis-identification. Simultaneously, they are likely to show diversity in song characteristics due to multiple selective pressures on song form (Seddon, 2005; Podos & Warren, 2007). Evolutionarily, a large geographic range

allows for greater diversification due to drift (cultural or genetic) and local adaptation (Edwards et al., 2005; Price, 2007; Benedict & Bowie, 2009). Widely distributed birds will necessarily occur at a range of geographic locations with varying climates, elevations and habitats, all of which have been shown to influence bird song properties (Ryan & Brenowitz, 1985; Bertelli & Tubaro, 2002; Kirschel et al., 2009). Ecologically, varied habitat features may cause diversifying selection on acoustic traits due to differing sound transmission properties of the habitat (Morton, 1975; Wiley & Richards, 1982; Slabbekoorn & Smith, 2002a). Variation in the strength and outcomes of local sexual selection can also generate diversity (Andersson, 1994). Among song-learning birds, like cisticola warblers, song form can be shaped by both genetic and cultural evolution (Slater, 1989). Rattling cisticolas Cisticola chiniana belong Palbociclib mouse to a genus including 40 plus species of drab brown birds, which have long confounded recreational birders and ornithologists alike (Lynes, 1930; Ryan, 2006; Nguembock et al.,

2007). Individuals in the field and museum study skins are regularly mis-identified (R. C. K. Bowie, unpubl. data). Within this genus, song features are markedly more divergent

than morphology and may therefore be better indicators of species affiliation (Lynes, 1930; Erard et al., 1997). The rattling cisticola is widely distributed across sub-Saharan Africa with a range that begins at a longitude 10° north ID-8 of the equator and extends to 30° south (Fig. 1) (Sinclair & Ryan, 2003; Ryan, 2006). Rattling cisticolas are found in woodland, savannah and scrub habitats where they are often the most abundant or obvious cisticola species (Sinclair & Ryan, 2003; Ryan, 2006). These traits eliminate location and habitat preference as important clues to species identity when birds are encountered in the field. Existing descriptions indicate that rattling cisticola songs are extremely variable but have a stereotyped structure consisting of two parts: several introductory notes, followed by a more rapidly paced end phrase that may form a trill. Building on this simple description of song structure, there is a need for better description of song form, including quantification of the diversity of syllable structures and geographic variation (Erard et al., 1997). Bird songs may vary across many parameters, including the shape and frequency of syllables, the timing of syllable or song delivery and the sequence of different syllable or song types (Williams, 2006; Catchpole & Slater, 2008).

Voxels with an absolute value of t greater than 31 (P < 001, un

Voxels with an absolute value of t greater than 3.1 (P < .001, uncorrected for multiple comparisons) and within a spatially contiguous cluster size greater than 100 voxels were considered significant differences between blindness and sightedness. The regions with significant group differences are listed in Table 2. Compared with SC, the contracted regions are primarily located in the left early ICG-001 occipital lobe (Fig 1) in EB. By contrast, expanded regions are located in the left higher level visual association areas, posterior cingulated cortex, and cerebellum

(Fig 2) in EB. The statistical results were superimposed on the selected template image. Given that it was a single SC image, the Brodmann areas were checked by mapping the selleck Brodmann areas image template (provided in MRIcro software, http://www.cabiatl.com/mricro/) to our template. The result on a significant volume contraction occurring in the left lower visual areas (BA 17/18) of EB is consistent with previous findings.[7], [8], [12], [18], [19] The early visual cortex of EB is suggested to be structurally atrophic. However, the volume change in the right early visual cortex was not detected within a significant threshold (P < .001, uncorrected for multiple comparisons) in the statistic map. This result can possibly be attributed to the serious value of the

threshold. When the significance threshold value was adjusted to a higher value (P < .005, uncorrected for multiple comparisons), there was volume reduction at the local region in the right visual cortex (BA 17/18), thereby validating our supposition. This finding indicates that the volume reduction in the left-brain hemisphere is much more significant than that in the right. To some degree, this may be related to the right-handedness of all the participants. Compared with the results of Leporé and colleagues,[12] no significant differences were detected in the frontal and parietal lobes. On the contrary, regions in BA 19 showed significant

increases in volume in EB. Notably, the volumes of local regions in the posterior cingulated cortex (BA 23, BA 31) increased in EB. Consistent with previous studies, volume increase was also detected in the cerebellum in both sides. To evaluate whether the results were influenced by total brain size, the data were Parvulin reanalyzed by removing the global scaling factor derived from the initial affine transformation. No significant differences were detected in the unscaled data. Functional plasticity in the visual cortex of EB has been demonstrated in several previous studies.[20-24] However, aside from those that use VBM, there have been few reports to date on the structural plasticity in the visual cortex of EB. The main objective of the VBM method is to detect and analyze the differences in the entire brain, including the GM and WM between groups of people.[25], [26] In previous structural MRI studies, the VBM method was commonly used.

5%, P = 022)

5%, P = 0.22). selleck inhibitor Using a fixed-effects model, the prevalence of homozygous MTHFR C677T mutation was significantly higher in BCS patients than in healthy controls (OR = 2.01, 95% CI = 1.12–3.61, P = 0.02) (Fig. 3a). The subgroup analysis of Asian studies demonstrated a significantly higher prevalence of homozygous MTHFR C677T mutation in BCS patients than in healthy controls (Table 2). However, one European study did not show any significant difference between them. Four studies compared the prevalence of heterozygous MTHFR C677T mutation between BCS patients and healthy controls. The heterogeneity among studies was not

significant (I2 = 0%, P = 0.83). Using a fixed-effects model, the prevalence of heterozygous MTHFR C677T mutation was similar between BCS patients and healthy controls (OR = 0.97, 95% CI = 0.64–1.49, P = 0.90) (Fig. 4a). Regardless

of Asian or European studies, the subgroup analyses did not show any significant difference between them (Table 2). Two studies compared the prevalence of hyperhomocysteinemia between BCS RG 7204 patients and healthy controls. The heterogeneity among studies was not significant (I2 = 0%, P = 0.74). Using a fixed-effects model, the prevalence of hyperhomocysteinemia was significantly higher in BCS patients than in healthy controls (OR = 2.57, 95% CI = 1.19–5.51, P = 0.02) (Fig. 5a). One Asian study showed a significantly higher prevalence of hyperhomocysteinemia in BCS patients than in healthy controls; contrarily, another European study did not show any significant difference between them (Table 2). Four studies compared the plasma homocysteine level between BCS patients and

healthy controls. The heterogeneity among studies was significant (I2 = 75.6%, P = 0.006). Using a random-effects model, the plasma homocysteine level was significantly higher in BCS patients than in healthy controls (WMD = 3.30, 95% CI = 0.94–5.66, P = 0.006) (Fig. 6a). The subgroup analysis of Asian studies showed a significantly higher plasma homocysteine level in BCS patients than PJ34 HCl in healthy controls; contrarily, the subgroup analysis of European studies did not show any significant difference between them (Table 2). Six studies compared the prevalence of total MTHFR C677T mutation between non-cirrhotic PVT patients and healthy controls. The heterogeneity among studies was not significant (I2 = 17.9%, P = 0.30). Using a fixed-effects model, the prevalence of total MTHFR C677T mutation was similar between the two groups (OR = 1.35, 95% CI = 0.80–2.29, P = 0.26) (Fig. 2b). Funnel plot demonstrated that all included studies laid within the 95% CI, implying no proof of publication bias (Fig. S2). Similarly, Egger test did not demonstrate any significant publication bias (bias = 1.853826, 95% CI = −1.182272 to 4.889924, P = 0.1653).