Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report.

BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION: We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS: The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

Interactions between polycyclic musks and human lactoferrin: Multi-spectroscopic methods and docking simulation.

Galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-γ-2-benzopyrane; HHCB) and Tonalide (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene; AHTN) are "pseudo-persistent" pollutants that can cause DNA damage, endocrine disruption, organ toxicity, and reproductive toxicity in humans. HHCB and AHTN are readily enriched in breast milk, so exposure of infants to HHCB and AHTN is of concern. Here, the molecular mechanisms through which HHCB and AHTN interact with human lactoferrin (HLF) are investigated using computational simulations and spectroscopic methods to identify indirectly how HHCB and AHTN may harm infants. Molecular docking and kinetic simulation studies indicated that HHCB and AHTN can interact with and alter the secondary HLF structure. The fluorescence quenching of HLF by HHCB, AHTN was static with the forming of HLF-HHCB, HLF-AHTN complex, and accompanied by non-radiative energy transfer and that 1:1 complexes form through interaction forces. Time-resolved fluorescence spectroscopy indicated that binding to small molecules does not markedly change the HLF fluorescence lifetime. Three-dimensional fluorescence spectroscopy indicated that HHCB and AHTN alter the peptide chain backbone structure of HLF. Ultraviolet-visible absorption spectroscopy, simultaneous fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and circular dichroism spectroscopy indicated that HHCB and AHTN change the secondary HLF conformation. Antimicrobial activity experiments indicated that polycyclic musks decrease lactoferrin activity and interact with HLF. These results improve our understanding of the mechanisms involved in the toxicities of polycyclic musks bound to HLF at the molecular level and provide theoretical support for mother-and-child health risk assessments.

Collateral circulation caused by end-stage hepatic alveolar echinococcosis.

BACKGROUND: Hepatic alveolar echinococcosis (HAE), as a benign parasitic disease with malignant infiltrative activity, grows slowly in the liver, allowing sufficient time for collateral vessels to emerge in the process of vascular occlusion. METHODS: The portal vein (PV), hepatic vein and hepatic artery were observed by enhanced CT and the inferior vena cava (IVC) by angiography, respectively. Analysis of the anatomical characteristics of the collateral vessels helped to look into the pattern and characteristics of vascular collateralization caused by this specific etiology. RESULTS: 33, 5, 12 and 1 patients were included in the formation of collateral vessels in PV, hepatic vein, IVC and hepatic artery, respectively. PV collateral vessels were divided into two categories according to different pathways: type I: portal -portal venous pathway (13 cases) and type II: type I incorporates a portal-systemic circulation pathway (20 cases). Hepatic vein (HV) collateral vessels fell into short hepatic veins. The patients with IVC collateral presented with both vertebral and lumbar venous varices. Hepatic artery collateral vessels emanating from the celiac trunk maintains blood supply to the healthy side of the liver. CONCLUSIONS: Due to its special biological nature, HAE exhibited unique collateral vessels that were rarely seen in other diseases. An in-depth study would be of great help to improve our understanding related to the process of collateral vessel formation due to intrahepatic lesions and its comorbidity, in addition to providing new ideas for the surgical treatment of end-stage HAE.

ERCP management of acute cholangitis caused by rupture of Echinococcus hepaticus into the biliary tract.

Background: Hepatic cystic echinococcosis (HCE) rupture into the biliary tract, one of the most common and refractory complications, is treated by laparotomy to remove hydatid lesions. The aim of this article was to investigate the role of endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of this particular disease. Patients and Methods: This was is a retrospective analysis of 40 patients with HCE ruptured into the biliary tract in our hospital from September 2014 to October 2019. They were divided into two groups, ERCP group (group A, n = 14) and conventional surgery group (group B, n = 26). Group A was treated with ERCP first to control infection and improve the general condition before undergoing laparotomy at an optional stage while group B was treated with laparotomy directly. First, the infection parameters and liver, kidney and coagulation functions of group A patients before and after ERCP were compared to evaluate treatment effectiveness. Second, the intraoperative and post-operative parameters during the laparotomy of group A were compared with group B to evaluate the impact of ERCP treatment on laparotomy. Results and Conclusions: White blood cell, NE%, platelet, procalcitonin, C-reactive protein, interleukin-6, Total bilirubin (TBIL), alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, alanine transaminase (ALT), ALT and Cr in group A significantly improved by ERCP (P < 0.05); during laparotomy, the bleeding amount and hospital stay in group A were better (P < 0.05); moreover, concerning the post-operative complications, the incidence of acute renal failure and coagulation dysfunction in group A was significantly less (P < 0.05). ERCP, which not only quickly and effectively controls infection and improves the patient's systemic condition but also provides good support for subsequent radical surgery, enjoys good prospects for clinical application.

Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection.

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45+ lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8+ T-cell populations, only CD8+ mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4+ T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8+ T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.

Massive sympathetic nerve infiltration in advanced hepatic alveolar echinococcosis: a case report and review of the literature.

BACKGROUND: Alveolar echinococcosis is a zoonotic disease that mostly affects the liver, with vascular invasion and a protean clinical symptom. However, no reports of sympathetic nerve infiltration in hepatic alveolar echinococcosis have been reported. Here, we report a case of hepatic alveolar echinococcosis in a 33-year-old man. In this end-stage case, the lesion was heavily involved in the large vessels and biliary tract, and immunohistochemistry also incidentally revealed extensive nerve infiltration in the specimens after surgical treatment. Subsequently, neural classification was identified. CASE PRESENTATION: We herein report a case of advanced hepatic alveolar echinococcosis with macrovascular invasion and sympathetic nerve infiltration. In this case, inferior vena cava (IVC), the portal vein and bile duct were infiltrated. Ultimately, according to our experience, ex vivo liver resection and autotransplantation (ELRA) was the optimal treatment way to perform for this unresectable patient. Samples were collected from normal liver tissue, junction tissue and the lesion. Hematoxylin-eosin (HE) staining was used to confirm the diagnosis. Neural infiltration was observed by immunohistochemical staining with protein gene product 9.5 (PGP9.5). Fluorescence colocalization was determined with PGP9.5 and tyrosine hydroxylase (TH). These results suggest that a large amount of sympathetic nerve infiltration occurred at the junction. CONCLUSION: This study suggests that advanced hepatic alveolar echinococcosis shows infiltrating growth, often invades the large vessels and biliary ducts, and may be accompanied by sympathetic nerve infiltration.

MFGM components promote gut Bifidobacterium growth in infant and in vitro.

PURPOSE: Infant gut microbiota which plays an important role in long-term health is mainly shaped by early life nutrition. However, the effect of nutrients on infants gut microbiota is less researched. Here, we present a study aiming to investigate in vitro a modified formula that is supplemented with milk fat globule membrane (MFGM) that were missing in common formulas when compared with human milk and to assess the impact of feeding scheme on microbiota and metabolism. METHODS: A total of 44 infants including 16 from breast milk feeding, 13 from common formula feeding and 15 from modified formula feeding were analyzed, and A cross-sectional sampling of fecal and urine was done at 1 month-of-age. Stool microbiota composition was characterized using high-throughput DNA sequencing, and urinary metabolome was profiled by nuclear magnetic resonance (NMR). In vitro growth experiment of Bifidobacterium with key components from MFGM was performed and analyzed by both DNA and RNA. RESULTS: Stool samples from the infants who were breastfed had a higher relative abundance of Bifidobacterium and a lower relative abundance of Escherichia than the formula-fed infants. The stool microbiome shifts were associated with urine metabolites changes. Three substances including lactadherin, sialic acid and phospholipid, key components of MFGM were significantly positively correlated to Bifidobacterium of stool samples from infants, and stimulated the growth rate of Bifidobacterium significantly by provided energy in vitro growth experiment with RNA analysis. CONCLUSIONS: These findings suggest that the key components from MFGM could improve infants' health by modulating the gut microbiome, and possibly supporting the growth of Bifidobacterium. REGISTRATION: Clinicaltrials.gov NCT02658500 (registered on January 20, 2016).

Application of hepatic lobe hyperplasia techniques in the treatment of advanced hepatic alveolar echinococcosis: a single-centre experience.

BACKGROUND: This study was designed to investigate clinical efficiency and application indications of hepatic lobe hyperplasia techniques for advanced hepatic alveolar echinococcosis (AE) patients. METHODS: A retrospective case series covering 19 advanced hepatic AE patients admitted to the First Affiliated Hospital of Xinjiang Medical University from September 2014 to December 2021 and undergoing hepatic lobe hyperplasia techniques due to insufficient remnant liver volume were analyzed. Changes of liver function, lesions volume, remnant liver volume, total liver volume before and after operation have been observed. RESULTS: Among the patients, 15 underwent portal vein embolization (PVE). There was no statistical difference in total liver volume and lesions volume before and after PVE (P > 0.05). However, the remnant liver volume was significantly increased after PVE (P < 0.05). The median monthly increase rate in future liver remnant volume (FLRV) after PVE stood at 4.49% (IQR 3.55-7.06). Among the four patients undergoing two-stage hepatectomy (TSH), FLRV was larger than that before the first stage surgery, and the median monthly increase rate in FLRV after it stood at 3.34% (IQR 2.17-4.61). Despite no statistical difference in total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) in all patients with PVE, four patients who underwent TSH showed a decrease in ALT, AST and GGT. During the waiting process before the second stage operation, no serious complications occurred in all patients. CONCLUSIONS: For patients suffering from advanced hepatic AE with insufficient FLRV, PVE and TSH are safe and feasible in promoting hepatic lobe hyperplasia.

Long-term postoperative outcomes of Roux-en-Y cholangiojejunostomy in patients with benign biliary stricture.

BACKGROUND: Although there are common postoperative complications, Roux-en-Y cholangiojejunostomy is still broadly used as a standard surgical procedure for patients with biliary stricture. This study aimed to explore long-term risk factors of cholangiojejunostomy in patients with biliary stricture who underwent revisional cholangiojejunostomy. METHODS: Clinical data of 61 patients with biliary stricture undergoing revisional cholangiojejunostomy were retrospectively analyzed. These patients were classified into two groups (patients with traumatic biliary stricture and non-traumatic biliary stricture). Postoperative complications and survival time were successfully followed up. RESULTS: Among the patients, 34 underwent revisional cholangiojejunostomy due to traumatic biliary stricture, and 27 underwent revisional cholangiojejunostomy due to non-traumatic biliary surgery. Although there was no statistical difference in most clinical data between two groups, biliary dilation or not during the first surgery, cholelithiasis or not during the first surgery, long-term complications after first surgery, cholelithiasis or not during the second surgery, identifying abnormalities during the second surgery and long-term complications after second surgery were significantly different. All patients were successfully followed up and average follow-up time for patients with traumatic and non-traumatic biliary stricture was (88.44 ± 35.67) months and (69.48 ± 36.61) months respectively. Survival analysis indicated that there was no statistical difference in overall survival between two groups. Additionally, cox proportional hazard analysis demonstrated that first preoperative bilirubin level, short-term complication after first surgery and identifying abnormalities during the second surgery were independent risk factors that may have significant effects on patients' overall survival and long-term prognosis after cholangiojejunostomy. Among the intraoperative abnormal findings, residual lesions after the first operation had significant effects on the patients overall survival in the earlier stage. Relatively, anastomotic stoma stricture and biliary output loop problems had obvious effects on patients' overall survival at later stages. CONCLUSION: First preoperative bilirubin level, short-term complication after first surgery and abnormal findings during the second surgery were independent risk factors of revisional cholangiojejunostomy, which may affect patients' long-term survival. Therefore, surgeons should minimize incidence of postoperative complications through fully evaluating optimal operative time and standardizing surgical procedures.

Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment.

Human cystic echinococcosis, caused by the larval stage of Echinococcus granulosus sensu lato, has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce a lesion microenvironment; however, cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironments are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, perilesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between perilesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of type 2 innate lymphoid cells (ILC2s) and plasmacytoid dendritic cells (pDCs) were higher in perilesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was upregulated in these cells. Seven subsets of CD4+ T cell populations were found, and there were more regulatory-CD4+ T cells (Treg-CD4+) and Th2-CD4+ T cells in perilesion tissue than in adjacent normal tissue. There was close contact between CD4+ T cells and ILC2s and pDCs, which caused upregulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in perilesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the cystic echinococcosis (CE) lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironments at a single-cell level and provides potential target signatures for diagnosis and immunotherapies.

Th1/Th2/Th17 cytokine profile in hepatic cystic Echinococcosis patients with different cyst stages.

AIMS: The study aimed to investigate possible correlation between expression level of Th1/Th2/Th17-type profile and cyst viability in the systemic and local immunity of hepatic cystic Echinococcosis (CE) patients. METHODS AND RESULTS: Expression of Th1-type interleukin (IL)-2, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, Th2-type IL-4, IL-6, IL-10 and Th17-type IL-17A was examined in the serum and liver samples of hepatic CE patients with different cyst stages. Compared with healthy controls, Th1/Th2/Th17-type cytokines were significantly increased in the serum of hepatic CE patients. Moreover, expression of these cytokines was also at higher level in the inflammatory cell band of peri-lesion liver (PL) tissues than that in the adjacent normal (AN) liver tissues. Interestingly, elevation of Th1-type and Th17-type cytokines was more evident in PL tissues of patients with inactive cysts. Relatively, Th2-type cytokines were predominant in PL tissues of patients with active cysts. CONCLUSION: Our findings provide new insights that Th1/Th2/Th2-type cytokine profile was associated with cyst stages. In hepatic CE patients with inactive cysts, Th1 and Th17-type cytokines were predominant. Comparatively, Th2-type cytokines were more evident in hepatic CE patients with active cysts, which may provide basis for the immune response diversity in hepatic CE patients with different cyst stages.

Quantitative evaluation of range and metabolic activity of hepatic alveolar echinococcosis lesion microenvironment using PET/CT and multi-site sampling method.

BACKGROUND: Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its' metabolic activity regarding different lesion characteristics. METHODS: A prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of 18F-FDG standard uptake value (SUV, n = 75) was calculated, and range of 18F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges. RESULTS: Altogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values. CONCLUSIONS: PET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.

Double versus single T-tube drainage for frank cysto-biliary communication in patients with hepatic cystic echinococcosis: a retrospective cohort study with median 11 years follow-up.

BACKGROUND: Partial peri-cystectomy (PPC) is one of the major surgical approaches for hepatic cystic echinococcosis (CE) and has been practiced in most centers worldwide. Cysto-biliary communication (fistula, leakage, rupture) is a problematic issue in CE patients. T-tube is a useful technique in situations where an exploration and decompression are needed for common bile duct (CBD). However, postoperative biliary complications for cystic cavity still remains to be studied in depth. METHODS: A retrospective cohort analysis of CE cases in our single center database from 2007 March to 2012 December was performed. Patients (n = 51) were divided into two cohorts: double T-tube drainage (one at CBD for decompression and one at the fistula for sustaining in cystic cavity, n = 23) group and single T-tube drainage cohort (only one at CBD for decompression, n = 28). Short-/long-term postoperative complications focusing on biliary system was recorded in detail and they were followed-up for median 11 years. RESULTS: Overall biliary complication rates for double and single T-tube drainages were 17.4% vs. 39.3% (P > 0.05). Short-term complications ranged from minor to major leakages, cavity infection and abscess formation, and prevalence was 17.4% vs. 21.4% (P > 0.05) respectively for double and single T-tube groups; most importantly, double T-tube drainage group had obvious advantages regarding long-term complications (P < 0.05), which was biliary stricture needing surgery and it was observed only in single T-tube drainage group. CONCLUSIONS: Double T-tube drainage had better outcomes without procedure-specific postoperative biliary complications than single T-tube drainage. Meanwhile, we recommend long-term follow-up when comparing residual cavity related biliary complications in CE patients as it could happen lately.

Ex vivo liver resection and autotransplantation as alternative to allotransplantation for end-stage hepatic alveolar echinococcosis.

BACKGROUND & AIMS: Radical resection is the best treatment for patients with advanced hepatic alveolar echinococcosis (AE). Liver transplantation is considered for selected advanced cases; however, a shortage of organ donors and the risk of postoperative recurrence are major challenges. The aim of this study was to assess the clinical outcomes of ex vivo liver resection and autotransplantation for end-stage AE. METHODS: In this prospective study, 69 consecutive patients with end-stage hepatic AE were treated with ex vivo resection and liver autotransplantation between January 2010 and February 2017. The feasibility, safety and long-term clinical outcome of this technique were assessed. RESULTS: Ex vivo extended hepatectomy with autotransplantation was successful in all patients without intraoperative mortality. The median weight of the graft and AE lesion were 850 (370-1,600) g and 1,650 (375-5,000) g, respectively. The median duration of the operation and anhepatic phase were 15.9 (8-24) h and 360 (104-879) min, respectively. Six patients did not need any blood transfusion. Complications higher than IIIa according to Clavien classification were observed in 10 patients. The 30-day-mortality and overall mortality (>90 days) were 7.24% (5/69) and 11.5% (8/69), respectively. The mean hospital stay was 34.5 (12-128) days. Patients were followed-up systematically for a median of 22.5 months (14-89) without recurrence. CONCLUSION: This is the largest series assessing ex vivo liver resection and autotransplantation in end-stage hepatic AE. This technique could be an effective alternative to liver transplantation in patients with end-stage hepatic AE, with the advantage that it does not require an organ nor immunosuppressive agents. LAY SUMMARY: Ex vivo liver resection and autotransplantation were performed in a large series of patients with end-stage hepatic alveolar echinococcosis. The results showed that this surgical option was feasible, with acceptable postoperative mortality, but 100% disease-free survival in survivors. Careful patient selection, as well as precise assessment for size and quality of the remnant liver are key to successful surgery.

VEGF-C-mediated cardiac lymphangiogenesis in high salt intake accelerated progression of left ventricular remodeling in spontaneously hypertensive rats.

High salt (HS) diet can accelerate the progress of hypertensive left ventricular (LV) remodeling. But the detailed mechanism remains poorly understood. We hypothesized HS intake could impact cardiac lymphangiogenesis through tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway which might play an important role in HS intake accelerated LV remodeling. Eight-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were randomized to 0.5% NaCl (Low salt, LS) and 8% NaCl (high salt, HS) diets for 12 weeks. LV remodeling was determined by echocardiography. LV invasive hemodynamic analysis and morphologic staining (cardiomyocyte hypertrophy, collagen deposition, TonEBP expression, macrophage infiltration and lymphatic density) were performed at the time of sacrifice. The blood pressure of SHR-HS group was significantly increased compared to SHR-LS and WKY groups. Meanwhile, The LV chamber size was markedly enlargement, LV function apparently compromised accompanied with a severe macrophage infiltration, and fibrosis in the perivascular and interstitium of LV compared with SHR-LS group. Furthermore, the expression levels of VEGF-C, TonEBP, and lymphatic markers in SHR-HS group were significantly increased parallel with apparent lymphangiogenesis compared with SHR-LS group. Our work indicates that TonEBP/VEGF-C signaling pathway was up-regulated in HS intake accelerated hypertensive LV remodeling process that may be valuable for further investigation.

Nanosecond pulsed electric field (nsPEF) disrupts the structure and metabolism of human Echinococcus granulosus protoscolex in vitro with a dose effect.

The number of interventional treatments for hepatic cystic echinococcosis is increasing, but the chemicals or high temperatures used in these methodologies cause biliary complications, thus limiting their clinical applications. This experimental study aimed to apply a novel, non-thermal, non-chemical ablation method termed nanosecond pulsed electric field (nsPEF) for the treatment of human hepatic cystic echinococcosis. The nsPEF treatment parameters against protoscolices from human hepatic cystic echinococcosis were optimized in vitro. The efficacy and mechanism of nsPEF treatment were also investigated. Fresh protoscolices were isolated from human hepatic cystic echinococcosis and were exposed to 300 ns of nsPEF with different field strengths (0, 7, 14, 21, and 29 kV/cm) and pulse numbers (50 and 100 pulses). Then, the viability of the nsPEF-treated protoscolices was evaluated in vitro. Morphological and ultra-structural changes were visualized with H&E staining and scanning electron microscopy. The membrane enzyme activity of alkaline phosphatase (AP) and gamma-glutamyl-transpeptidase (GGT) was measured. nsPEF caused dose-dependent protoscolex death. One-hundred pulses of nsPEF at 21 kV/cm or higher caused a significant increase in the death rate of protoscolices. nsPEF induced significant lethal damage with 50 pulses at 21 or 29 kV/cm and with 100 pulses at 14, 21, or 29 kV/cm, accompanied by morphological destruction and increased levels of AP and GGT membrane enzymes. Thus, nsPEF induced dose-dependent protoscolex mortality and caused destruction of protoscolices and increased membrane enzymes. The mechanism may involve direct damage to the membrane structures of the protoscolices, promoting enzyme exhaustion and disruption of metabolism.

Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice.

CONTEXT: Astragaloside IV (ASI) is a major and active saponin derivative of Astragalus membranaceus (Fisch) Bge. The anti-inflammatory properties of ASI are important for its cardioprotective effects. However, the molecular mechanisms of the protective effect of ASI on lipopolysaccharide (LPS)-induced cardiac dysfunction is yet to be elucidated. OBJECTIVE: This study was designed to investigate the therapeutic effects and possible mechanisms of ASI against LPS-induced septic cardiac dysfunction and inflammation in mice. MATERIALS AND METHODS: Mice were intraperitoneally injected with ASI (20 mg/kg) for 1 week before LPS challenge (10 mg/kg, i.p.). Left ventricular performance and morphology were analyzed using echocardiography 6 h after LPS induction. Activities of lactate dehydrogenase (LDH) in serum were measured and serum levels of cardiac troponin I (cTnI) were quantified by ELISA. Serum levels of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-1ß were also quantified by ELISA. The protein expressions of NF-кB p65 and p-AKT in heart tissues were detected using Western blot analysis. RESULTS: LPS administration deteriorated cardiac function and was attenuated by ASI pretreatment. ASI attenuated LPS-induced the increase of LDH and cTnI activities in mice. ASI also prevented NF-кB activation and subsequent myocardial inflammatory responses in endotoxemic mice. The effects of ASI were closely associated with the phosphatidylinositol-3-kinase (PI3K/AKT) signaling pathway, as characterized by ASI-induced activation in phospho-Akt. ASI also extended the lifespan of toxemic mice. CONCLUSION: ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-кB and activating PI3K/AKT signaling pathway.

Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial.

IMPORTANCE: The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain. OBJECTIVE: To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013. INTERVENTIONS: Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes). MAIN OUTCOMES AND MEASURES: The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year. RESULTS: Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, -11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar. CONCLUSIONS AND RELEVANCE: Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01696110.