Fasciola hepatica: Azetidine inhibition of bile duct hyperplasia in the infected rat

In controlled experiments the luminal bile duct perimeters were compared between rats infused with l-azetidine-2-carboxylic acid (AZC) (120 μmole/rat/day) and rats infused with saline after both groups had been implanted with adult Fasciola. The average bile duct lumen in the group receiving AZC did not enlarge relative to controls, and was about one-half the average perimeter of ducts from rats infused with saline that had worm implants. These results indicate that azetidine can inhibit bile duct hyperplasia induced by Fasciola which inhabit the duct. The results also support the hypothesis that the hyperplasia of fascioliasis is mediated through the release of free proline from the worms where it is present in high concentrations.     

Fasciola hepatica: collagen deposition and other histopathology in the rat host's bile duct caused by the parasite and by proline infusion

Bile ducts were examined histochemically to compare the effects of proline infusion with Fasciola hepatica implantation in rats. After 3 weeks of infusion or implantation, both proline and F. hepatica produced increases in the luminal perimeter and collagen content of the bile duct. However, the effect of the parasite was significantly greater than that of proline, and the parasite produced significant increases in the bile duct wall. These results corroborate earlier biochemical and histological studies indicating the important role of proline in the enlargement of the bile duct in fascioliasis.     

Sex hormones and aortic wall remodeling in an arteriovenous fistula

Background: An arteriovenous fistula (AVF) creates high blood flow through the artery and fistula. With this high flow, there is flow-induced remodeling and an increase in diameter, but no intimal hyperplasia. Estrogen has been shown to modify vascular remodeling, decreasing intimal hyperplasia after endothelial injury.Objective: These experiments tested the hypothesis that estrogen administration would decrease wall thickness in an AVE model. Because estrogen may decrease wall thickness, we also tested the hypothesis that testosterone would increase wall thickness.Methods: A fistula was created between the abdominal aorta and the inferior vena cava in Sprague-Dawley rats to generate high blood flow conditions in the aorta. Four groups of female animals were examined: sham, control with AVE ovariectomized (OVX) with AVE and OVX plus testosterone with AVE Four groups of male animals were also examined: sham, control with AVE castrated with AVE and castrated plus estrogen with AVE Five weeks after creation of the AVF, the aortas were collected and fixed; wall thickness was measured both proximal and distal to the AVEResults: Ovariectomy resulted in a significant decrease in estrogen levels (P < 0.01). Testosterone administration tended to increase testosterone levels in the OVX females, but values did not approach levels observed in the control males. No difference was noted in the proximal wall thickness between the control and the OVX animals. The OVX females receiving testosterone exhibited a significant increase in both proximal and distal wall thickness compared with control females (P < 0.001). In the male animals, there was no significant change in aortic wall thickness in the castrated rats compared with the controls. Estrogen administration in the castrated males resulted in a significant decrease in wall thickness in the proximal and distal aorta (P < 0.05).Conclusion: These studies suggest that, in a model of vascular remodeling, estrogen administration decreases wall thickness, and testosterone administration increases wall thickness.     

Fasciolicidal potential of proline analogues and proline biosynthesis inhibitors

Sheers Marion, Campbell Anne J., Beames D. J., Edwards S. R., Moore R. J. and Montague P. E. 1982. Fasciolicidal potential of proline analogues and proline biosynthesis inhibitors. International Journal for Parasitology12: 47–52. Hydroxylamine HCl and thiazolidine-4'-carboxylic acid, known inhibitors of important enzymes of proline biosynthesis, inhibited to a similar extent the arginine-dependent proline production by the liver fluke Fasciola hepofica; in vitro there appeared to be no correlation between inhibition of proline synthesis and deterioration of the fluke. Another known inhibitor, thiosemicarbazide, had no effect on arginine-dependent proline production in vitro. None of these compounds was effective in vivo either as a flukicidal agent per se or in the prevention of the establishment of fluke in the bile duct of rats. A variety of proline analogues was also tested for flukicidal activity in vitro and in vivo as well as for their ability to inhibit the establishment of fluke in the bile duct of rats. Only one was effective in vitro and none was effective in vivo. Also continuous administration of l-azetidine-2-carboxylic acid failed to prevent the establishment of an infection of liver fluke in the bile duct. It is concluded that there is little prospect of a successful approach to chemotherapy of fascioliasis in this area.     

Intestinal schistosomiasis among schoolchildren in Sana’a Governorate,Yemen: Prevalence,associated factors and its effect on nutritional status and anemia

Intestinal schistosomiasis is a neglected tropical disease, causing morbidity and mortality in tropical and subtropical countries. Despite the frequent implementation of mass drug administration with praziquantel, the reinfection with Schistosoma mansoni is still common in Yemen. In addition, there is a scarcity of information on the impact of S. mansoni on nutritional status and anemia among schoolchildren. The present study aimed to determine prevalence and risk factors of intestinal schistosomiasis and investigate its impact on nutritional status and anemia among schoolchildren in Sana’a Governorate, Yemen. It was conducted in 2018 on 445 schoolchildren aged 5–15 years. Biodata, socio-economic, demographic, behavioral and environmental data were collected using a standard questionnaire. S. mansoni was identified and quantified by microscopic examination of Kato-Katz fecal smear. Hemoglobin concentration and anthropometric measurements were estimated using standard methods. The prevalence of S. mansoni was higher in Al-Haimah Al-Dakheliah (33.9%) than Bani Mater (1.4%). Household without tap water (Adjusted Odds Ratio (AOR) = 2.9, 95% Confidence interval (CI): 1.12, 7.55, P = 0.028) was the independent risk factor of the infection. The prevalence of wasting and stunting was 25.0% (95%CI: 21.2%, 29.2%) and 45.8% (95%CI: 41.2%, 50.5%), respectively. The prevalence of underweight among schoolchildren aged 5–10 years was 27.3% (95%CI: 21.9%, 33.4%). The prevalence of anemia was 31.7% (95%CI: 27.5%, 36.2%) with 0.5%, 21.1% and 10.1% being severe, moderate and mild anemia, respectively. S. mansoni (AOR = 4.1, 95%CI: 2.16, 7.84, P < 0.001) and early adolescence (AOR = 6.8, 95%CI: 4.26, 10.82, P < 0.001) were independent predictors of stunting among schoolchildren. The early adolescent schoolchildren (AOR = 3.1, 95%CI: 1.86, 4.97, P < 0.001) and children from families with low (AOR = 2.1, 95%CI: 1.01, 4.15, P = 0.046) or moderate wealth (AOR = 2.3, 95%CI: 1.11, 4.77, P = 0.026) were significantly more wasted.Early adolescence (AOR = 1.8, 95%CI:1.14, 2.78, P = 0.011), female (AOR = 1.6, 95%CI: 1.03, 2.43, P = 0.038) and Al-Haimah Al-Dakheliah District (AOR = 3.4, 95%CI: 1.20, 9.55, P = 0.021) were independent risk factors for anemia. The study findings indicate highly focal prevalence of schistosomiasis in Sana’a Governorate with a public health significance that varies from low to high risk. Approximately half of schoolchildren were stunted, which was associated with S. mansoni infection and early adolescence. One quarter of schoolchildren were wasted with early adolescent schoolchildren and children from poor families being at high risk of wasting. Anemia was a moderate public health threat affecting the female and the early adolescent schoolchildren. The study suggests the implementation of control measures to combat schistosomiasis and integrated diseases control programmes to improve the health status of schoolchildren in Sana’a Governorate.     

Effects of oestrous synchronization with altrenogest in gilts on endometrial and embryonic characteristics

The use of altrenogest (ALT) supplementation for oestrous synchronization improves subsequent reproductive performance of gilts and sows. However, the causes of this improvement in reproductive performance after ALT treatment are not fully/clearly understood. The objective of this study was to evaluate the effects of ALT supplementation for oestrous synchronization in gilts on the endometrial glands and embryonic development characteristics at 28 days of pregnancy. Pregnant gilts were divided into two experimental treatments: Control (did not receive ALT; n = 9 gilts) and ALT (ALT feeding at 20 mg/day for 18 days; n = 9 gilts). At 28 days of pregnancy, six gilts from each treatment were slaughtered, and reproductive tracts were immediately evaluated. There was no statistical difference (P > 0.05) between treatments regarding ovulation rate, number of embryos, number of vital embryos and number of non-vital embryos. Embryo weight, length and embryonic vesicle weight were lower in ALT treatment compared with Control (P < 0.01), and it was lower in the cervical uterine region compared with apex uterine region, respectively (P < 0.05). Higher values of gland duct area, gland duct perimeter, percentage of the glandular area and total endometrial area were observed in ALT treatment compared with Control (P < 0.05). The use of ALT during 18 days for oestrous synchronization in gilts increased the gland duct area, perimeter and total endometrial area but did not increase the embryo number and embryo size at day 28 of pregnancy.     

Single Nucleotide Polymorphisms of Cytokine Genes are Associated with Fibrosis of the Intrahepatic Bile Duct Wall in Human Clonorchiasis

This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-γ (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), TNF-α (-308 G/A), and TGF-β1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-γ intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-α low-producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-γ and TNF-α genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-γ and low producing TNF-α), moderate, and low (low-producing IFN-γ and high producing TNF-α) risk groups. The incidence of IHDD was significantly different among these groups (P = 0.022): 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-γ and TNF-α genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.     

Hymenolepis microstoma: Correlation of histopathological host response and organ hypertrophy

The histological host response of female CF-1 mice to Hymenolepis microstoma involves dramatic changes in the host's bile duct and liver. These changes are similar to those described by previous investigators using different strains of mice. The histological changes which occur in bile duct and liver tissues of female CF-1 mice are accompanied by a significant hypertrophy of these organs; the wet weights of the bile duct and liver increase almost 2000 and 50%, respectively, in infected mice. No significant histopathological changes are found in the spleen or small intestine tissues of infected mice, yet the wet weight of both of these organs increases almost 100%. The magnitude of the histopathological changes which occur in the bile duct could possibly account for the increase in wet weight, i.e., there is significant fibrosis, but the histological changes in the liver, spleen, and small intestine do not appear to be of sufficient magnitude to account for the increases in wet weight.     

Differential impact of hepatic deficiency and total body inhibition of MTP on cholesterol metabolism and RCT in mice

Because apoB-containing lipoproteins are pro-atherogenic and their secretion by liver and intestine largely depends on microsomal triglyceride transfer protein (MTP) activity, MTP inhibition strategies are actively pursued. How decreasing the secretion of apoB-containing lipoproteins affects intracellular rerouting of cholesterol is unclear. Therefore, the aim of the present study was to determine the effects of reducing either systemic or liver-specific MTP activity on cholesterol metabolism and reverse cholesterol transport (RCT) using a pharmacological MTP inhibitor or a genetic model, respectively. Plasma total cholesterol and triglyceride levels were decreased in both MTP inhibitor-treated and liver-specific MTP knockout (L-Mttp^−/−) mice (each P < 0.001). With both inhibition approaches, hepatic cholesterol as well as triglyceride content was consistently increased (each P < 0.001), while biliary cholesterol and bile acid secretion remained unchanged. A small but significant decrease in fecal bile acid excretion was observed in inhibitor-treated mice (P < 0.05), whereas fecal neutral sterol excretion was substantially increased by 75% (P < 0.001), conceivably due to decreased intestinal absorption. In contrast, in L-Mttp^−/− mice both fecal neutral sterol and bile acid excretion remained unchanged. However, while total RCT increased in inhibitor-treated mice (P < 0.01), it surprisingly decreased in L-Mttp^−/− mice (P < 0.05). These data demonstrate that: i) pharmacological MTP inhibition increases RCT, an effect that might provide additional clinical benefit of MTP inhibitors; and ii) decreasing hepatic MTP decreases RCT, pointing toward a potential contribution of hepatocyte-derived VLDLs to RCT.     

Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages

BackgroundThe association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women.MethodsWe sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated.FindingsHousehold and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001).ConclusionCommunity-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes.     

Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice

High density lipoprotein cholesterol is thought to represent a preferred source of sterols secreted into bile following hepatic uptake by scavenger receptor class B type I (SR-BI). The present study aimed to determine the metabolic effects of an endothelial lipase (EL)–mediated stimulation of HDL cholesterol uptake on liver lipid metabolism and biliary cholesterol secretion in wild-type, SR-BI knockout, and SR-BI overexpressing mice. In each model, injection of an EL expressing adenovirus decreased plasma HDL cholesterol (P < 0.001) whereas hepatic cholesterol content increased (P < 0.05), translating into decreased expression of sterol-regulatory element binding protein 2 (SREBP2) and its target genes HMG-CoA reductase and LDL receptor (each P < 0.01). Biliary cholesterol secretion was dependent on hepatic SR-BI expression, being decreased in SR-BI knockouts (P < 0.001) and increased following hepatic SR-BI overexpression (P < 0.001). However, in each model, biliary secretion of cholesterol, bile acids, and phospholipids as well as fecal bile acid and neutral sterol content, remained unchanged in response to EL overexpression. Importantly, hepatic ABCG5/G8 expression did not correlate with biliary cholesterol secretion rates under these conditions. These results demonstrate that an acute decrease of plasma HDL cholesterol levels by overexpressing EL increases hepatic cholesterol content but leaves biliary sterol secretion unaltered. Instead, biliary cholesterol secretion rates are related to the hepatic expression level of SR-BI. These data stress the importance of SR-BI for biliary cholesterol secretion and might have relevance for concepts of reverse cholesterol transport.     

The common bile duct ligation in rat: a relevant in vivo model to study the role of mechanical stress on cell and matrix behaviour

Common bile duct ligation leads to bile accumulation and liver fibrosis. In this model, little attention has been dedicated to the modification of the common bile duct. We have studied by histochemistry and immunohistochemistry, 3 and 5 days after ligation, the connective tissue modifications of the common bile duct wall. After bile duct ligation, compared with normal bile duct, a strong increase of the bile duct diameter, due to bile stasis, and a thickness of the bile duct wall were observed; numerous myofibroblasts expressing α-smooth muscle actin appeared in parallel with the detection of many proliferating connective tissue cells. These myofibroblasts secreted very early high amount of elastic fibre components, elastin and fibrillin-1. Elastic fibre increase was also observed close to the epithelial cell layer. Procollagen type III deposition was also induced 3 days after ligation but decreased thereafter, underlining that myofibroblasts modify their synthesis of extracellular matrix components to comply with the request. We show here that common bile duct ligation represents an invaluable model to study myofibroblastic differentiation and extracellular matrix adaptation produced by an acute mechanical stress.     

Protective Effect of Gadolinium Chloride on Early Warm Ischemia/Reperfusion Injury in Rat Bile Duct during Liver Transplantation

Background

Activation of Kupffer cell (KC) is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl₃) on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury.

Methods

Sixty-five male Sprague-Dawley rats (200–250 g) were randomly divided into three experimental groups: a sham group (n = 15), a control group (n = 25), and a GdCl₃ group (n = 25). Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL) of serum were measured. Tumor necrosis factor-α (TNF-α), Capase-3 activity and soluble Fas (sFas) were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay.

Results

GdCl₃ significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05). TNF-α was lower in the GdCl₃ group than in the control group at 2, 6, 12 and 24 h (P<0.05). Preadministration of GdCl₃ significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl₃ group than in the control group (P<0.05).

Conclusions

GdCl₃ plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation.     

Protective and Anti-Pathology Effects of Sm Fructose-1,6-Bisphosphate Aldolase-Based DNA Vaccine against Schistosoma mansoni by Changing Route of Injection

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection.     

Schistosoma mansoni-Related Hepatosplenic Morbidity in Adult Population on Kome Island,Sengerema District,Tanzania

Schistosomiasis is one of the important neglected tropical diseases (NTDs) in Tanzania, particularly in Lake Victoria zone. This baseline survey was a part of the main study of integrated control of schistosomiasis and soil-transmitted helminths (STHs) aimed at describing morbidity patterns due to intestinal schistosomiasis among adults living on Kome Island, Sengerema District, Tanzania. Total 388 adults from Kome Islands (about 50 people from each village) aged between 12 and 85 years, were examined by abdominal ultrasound according to the Niamey protocol. Liver image patterns (LIPs) A and B were considered normal, and C-F as distinct periportal fibrosis (PPF). The overall prevalence of PPF was 42.2%; much higher in males than in females (47.0% in male vs 34.4% in females, P=0.007). Abnormal increase of segmental branch wall thickness (SBWT) and dilated portal vein diameter (PVD) were also more common in males than in females. Hepatosplenomegaly was frequently encountered; 68.1% had left liver lobe hepatomegaly and 55.2% had splenomegaly. Schistosoma mansoni-related morbidity is quite high among adults in this community justifying the implementation of integrated control strategies through mass drug administration, improved water supply (pumped wells), and health education that had already started in the study area.     

Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis

The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.     

New Diagnosis and Therapy Model for Ischemic-Type Biliary Lesions following Liver Transplantation—A Retrospective Cohort Study

Ischemic-type biliary lesions (ITBLs) are a major cause of graft loss and mortality after orthotopic liver transplantation (OLT). Impaired blood supply to the bile ducts may cause focal or extensive damage, resulting in intra- or extrahepatic bile duct strictures or dilatations that can be detected by ultrasonography, computed tomography, magnetic resonance cholangiopancreatography, and cholangiography. However, the radiographic changes occur at an advanced stage, after the optimal period for therapeutic intervention. Endoscopic retrograde cholangio-pancreatography (ERCP) and percutaneous transhepatic cholangiodrainage (PTCD) are the gold standard methods of detecting ITBLs, but these procedures cannot be used for continuous monitoring. Traditional methods of follow-up and diagnosis result in delayed diagnosis and treatment of ITBLs. Our center has used the early diagnosis and intervention model (EDIM) for the diagnosis and treatment of ITBLs since February 2008. This model mainly involves preventive medication to protect the epithelial cellular membrane of the bile ducts, regular testing of liver function, and weekly monitor of contrast-enhanced ultrasonography (CEUS) to detect ischemic changes to the bile ducts. If the liver enzyme levels become abnormal or CEUS shows low or no enhancement of the wall of the hilar bile duct during the arterial phase, early ERCP and PTCD are performed to confirm the diagnosis and to maintain biliary drainage. Compared with patients treated by the traditional model used prior to February 2008, patients in the EDIM group had a lower incidence of biliary tract infection (28.6% vs. 48.6%, P = 0.04), longer survival time of liver grafts (24±9.6 months vs. 17±12.3 months, P = 0.02), and better outcomes after treatment of ITBLs.     

Wnt/β‐catenin signalling controls bile duct regeneration by regulating differentiation of ductular reaction cells

Recently, the incidence of bile duct‐related diseases continues to increase, and there is no effective drug treatment except liver transplantation. However, due to the limited liver source and expensive donations, clinical application is often limited. Although current studies have shown that ductular reaction cells (DRCs) reside in the vicinity of peribiliary glands can differentiate into cholangiocytes and would be an effective alternative to liver transplantation, the role and mechanism of DRCs in cholangiole physiology and bile duct injury remain unclear. A 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐enriched diet was used to stimulate DRCs proliferation. Our research suggests DRCs are a type of intermediate stem cells with proliferative potential that exist in the bile duct injury. Meanwhile, DRCs have bidirectional differentiation potential, which can differentiate into hepatocytes and cholangiocytes. Furthermore, we found DRCs highly express Lgr5, and Lgr5 is a molecular marker for neonatal DRCs (P < .05). Finally, we confirmed Wnt/β‐catenin signalling achieves bile duct regeneration by regulating the expression of Lgr5 genes in DRCs (P < .05). We described the regenerative potential of DRCs and reveal opportunities and source for the treatment of cholestatic liver diseases.     

血清肿瘤标志物联合多层螺旋CT和核磁共振对胆管癌的诊断价值及其与组织侵袭分子的关系分析

目的:探讨血清癌抗原19-9(CA19-9)、糖类抗原125(CA125)、多层螺旋CT和核磁共振(MRI)联合检测对胆管癌的诊断价值,并分析肿瘤标志物与组织侵袭分子的相关性。方法:选择2017年1月至2018年8月赤峰学院附属医院收治的胆管癌患者62例作为胆管癌组,另选择同期我院收治的胆管良性病变患者55例作为胆管良性病变组。比较两组血清CA19-9、CA125水平以及组织侵袭分子含量,观察胆管癌患者和胆管良性病变患者的多层螺旋CT和MRI影像学征象,分析血清CA19-9、CA125、多层螺旋CT和MRI对胆管癌的诊断价值,并分析血清CA19-9、CA125水平与组织侵袭分子含量的相关性。结果:胆管癌组血清CA19-9、CA125水平高于胆总管良性病变组,胆管癌组织赖氨酰氧化酶样蛋白-2(LOXL2)、瞬时受体电位阳离子通道7(TRPM7)含量高于胆总管良性病变组,组织E钙黏素(E-cadherin)含量低于胆总管良性病变组(P0.05)。多层螺旋CT影像学征象:胆管癌可见胆总管、肝管内圆形或类圆形高密度影伴有管壁浸润,胆管内出现不规则结节,肿块与周围组织界限模糊,胆囊管及胆囊颈部浸润,肝叶萎缩,淋巴结肿大等;胆管良性病变则多为圆形或类圆形高密度影,管壁浸润、淋巴结肿大并不多见。MRI影像学征象:胆管癌肝内胆管与肝组织分界不清,肿块呈不规则或分叶状,胆囊增大,肝内外胆管不同程度扩张,胰管扩张,肝叶萎缩,淋巴结肿大;胆管良性病变胆管则多为"杯口状"低信号充盈缺损,胆管梗阻上方出现"鸟嘴样"改变等。血清CA19-9、CA125、多层螺旋CT和MRI联合检测对胆管癌诊断的灵敏度、特异度、准确度均高于CA19-9、CA 125、多层螺旋CT、MRI单独诊断。胆管癌患者血清CA19-9、CA125水平与组织LOXL2、TRPM7含量呈正相关,与组织E-cadherin含量呈负相关(P0.05)。结论:血清CA19-9、CA125、多层螺旋CT和MRI联合检测对胆管癌诊断具有较好的价值,患者血清CA19-9、CA125水平与组织侵袭分子存在相关性,可以为胆管癌恶性程度的评估提供依据。     

超声引导下肝内胆管置管治疗肝内胆管结石并发梗阻的临床效果观察

目的:探究超声引导下肝内胆管置管治疗肝内胆管结石并发梗阻的临床效果和安全性。方法:选择2014年1月至2018年1月于我院接受治疗的98例肝内胆管结石并发梗阻患者为研究对象,将患者按照入院顺序统一编号后,根据随机数字表法进行分为实验组与对照组,每组各49例患者。对照组患者于常规X线引导下行肝内胆管置管治疗,实验组患者在超声引导下实施肝内胆管置管治疗,对比两组患者穿刺次数、手术时间、术后并发症的发生情况,并对两组患者随访3个月,比较其结石残余率及治疗效果。结果:(1)实验组患者穿刺次数及操作时间均显著少于对照组(P0.05);(2)实验组患者术后各类并发症发生率为4.08%,明显低于对照组(20.41%,P0.05);(3)对照组患者后3个月的结石残余率为14.29%(7/49),实验组为2.04%(1/49),显著低于对照组(P0.05);(4)术后3个月,实验组患者治疗总有效率为97.96%,明显高于对照组(81.63%,P0.05)。结论:与常规X线引导下行肝内胆管置管治疗相比,超声引导下肝内胆管置管在治疗肝内胆管结石并发梗阻中具有较更好的治疗效果和安全性。