Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.

Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of ß-barrel pore-forming toxins with a ß-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E. faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.

Targeting Recycling Endosomes to Potentiate mRNA Lipid Nanoparticles.

mRNA lipid nanoparticles (LNPs) have emerged as powerful modalities for gene therapies to control cancer and infectious and immune diseases. Despite the escalating interest in mRNA-LNPs over the past few decades, endosomal entrapment of delivered mRNAs vastly impedes therapeutic developments. In addition, the molecular mechanism of LNP-mediated mRNA delivery is poorly understood to guide further improvement through rational design. To tackle these challenges, we characterized LNP-mediated mRNA delivery using a library of small molecules targeting endosomal trafficking. We found that the expression of delivered mRNAs is greatly enhanced via inhibition of endocytic recycling in cells and in live mice. One of the most potent small molecules, endosidine 5 (ES5), interferes with recycling endosomes through Annexin A6, thereby promoting the release and expression of mRNA into the cytoplasm. Together, these findings suggest that targeting endosomal trafficking with small molecules is a viable strategy to potentiate the efficacy of mRNA-LNPs.

Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.

Fusion of transmitter-containing vesicles with plasma membranes at the synaptic and neuromuscular junctions mediates neurotransmission and muscle contractions, respectively, thereby underlying all thoughts and actions. The fusion process is driven by the coupled folding and assembly of three synaptic SNARE proteins--syntaxin-1 and SNAP-25 on the target plasma membrane (t-SNAREs) and VAMP2 on the vesicular membrane (v-SNARE) into a four-helix bundle. Their assembly is chaperoned by Munc18-1 and many other proteins to achieve the speed and accuracy required for neurotransmission. However, the physiological pathway of SNARE assembly and its coupling to membrane fusion remains unclear. Here, we review recent progress in understanding SNARE assembly and membrane fusion, with a focus on results obtained by single-molecule manipulation approaches and electric recordings of single fusion pores. We describe two pathways of synaptic SNARE assembly, their associated intermediates, energetics, and kinetics. Assembly of the three SNAREs in vitro begins with the formation of a t-SNARE binary complex, on which VAMP2 folds in a stepwise zipper-like fashion. Munc18-1 significantly alters the SNARE assembly pathway: syntaxin-1 and VAMP2 first bind on the surface of Munc18-1 to form a template complex, with which SNAP-25 associates to conclude SNARE assembly and displace Munc18-1. During membrane fusion, multiple trans-SNARE complexes cooperate to open a dynamic fusion pore in a manner dependent upon their copy number and zippering states. Together, these results demonstrate that stepwise and cooperative SNARE assembly drive stagewise membrane fusion.

Dynamics and number of trans-SNARE complexes determine nascent fusion pore properties.

The fusion pore is the first crucial intermediate formed during exocytosis, yet little is known about the mechanisms that determine the size and kinetic properties of these transient structures. Here, we reduced the number of available SNAREs (proteins that mediate vesicle fusion) in neurons and observed changes in transmitter release that are suggestive of alterations in fusion pores. To investigate these changes, we employed reconstituted fusion assays using nanodiscs to trap pores in their initial open state. Optical measurements revealed that increasing the number of SNARE complexes enhanced the rate of release from single pores and enabled the escape of larger cargoes. To determine whether this effect was due to changes in nascent pore size or to changes in stability, we developed an approach that uses nanodiscs and planar lipid bilayer electrophysiology to afford microsecond resolution at the single event level. Both pore size and stability were affected by SNARE copy number. Increasing the number of vesicle (v)-SNAREs per nanodisc from three to five caused a twofold increase in pore size and decreased the rate of pore closure by more than three orders of magnitude. Moreover, pairing of v-SNAREs and target (t)-SNAREs to form trans-SNARE complexes was highly dynamic: flickering nascent pores closed upon addition of a v-SNARE fragment, revealing that the fully assembled, stable SNARE complex does not form at this stage of exocytosis. Finally, a deletion at the base of the SNARE complex, which mimics the action of botulinum neurotoxin A, markedly reduced fusion pore stability. In summary, trans-SNARE complexes are dynamic, and the number of SNAREs recruited to drive fusion determines fundamental properties of individual pores.

The decreased risk of hepatocellular carcinoma in hepatitis B virus-related cirrhotic portal hypertension patients after laparoscopic splenectomy and azygoportal disconnection.

BACKGROUND: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH). METHODS: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences. RESULTS: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002). CONCLUSION: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.

Plantar Pressure Distribution and Posture Balance During Walking in Individuals with Unilateral Chronic Ankle Instability: An Observational Study.

BACKGROUND Patients with chronic ankle instability (CAI) can present with abnormal gait. The purpose of this study was to evaluate plantar pressure distributions and posture balance during walking in unilateral CAI patients. MATERIAL AND METHODS We recruited 24 unilateral CAI patients and 24 healthy individuals; plantar pressure analysis was conducted using the Footscan® 3D pressure system. The following parameters were assessed and recorded: peak force/weight (PF/W), time to peak force (TPF), time to boundary (TTB), and COP velocity. The differences between the affected and unaffected side of the CAI group and control group were determined. Pearson correlation analysis and univariate analysis was used to investigate the correlation between plantar pressure parameters and related factors. RESULTS The comparison of PF/W showed that the plantar pressure of both sides in the CAI group were laterally distributed. The comparison of TPF, TTB, and COP velocity in different groups showed that the posture balance on the affected side of CAI patient was more impaired than the unaffected side and the control group. Male patients with CAI tend to have better posture balance than females, and a low CAIT score is correlated with poor posture balance. CONCLUSIONS The plantar pressure on both sides in unilateral CAI patients was laterally distributed and their balance function was impaired. It is necessary for CAI patients to receive functional training of both sides during rehabilitation, and plantar pressure analysis is promising for diagnosis and evaluation of CAI.

Radiofrequency ablation is an inferior option to liver resection for solitary hepatocellular carcinoma ≤ 5 cm without cirrhosis: A population-based study with stratification by tumor size.

BACKGROUND: About 10%-20% of all individuals who develop hepatocellular carcinoma (HCC) do not have cirrhosis. Comparisons are rarely reported regarding the effectiveness of radiofrequency ablation (RFA) and liver resection (LR) in survival of HCC without cirrhosis and stratification by tumor size ≤ 5 cm. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database and identified 1505 patients with a solitary HCC tumor ≤ 5 cm who underwent RFA or LR during 2004-2015. Patients were classified into non-cirrhosis and cirrhosis groups and each group was categorized into three subgroups, according to tumor size (≤ 30 mm, 31-40 mm, 41-50 mm). RESULTS: In patients without cirrhosis, LR showed better 5-year HCC cancer-specific survival than RFA in all tumor size subgroups (≤ 30 mm: 82.51% vs. 56.42%; 31-40 mm: 71.31% vs. 46.83%; 41-50 mm: 74.7% vs. 37.5%; all P < 0.05). Compared with RFA, LR was an independent protective factor for HCC cancer-specific survival in multivariate Cox analysis [≤ 30 mm: hazard ratio (HR) = 0.533, 95% confidence interval (CI): 0.313-0.908; 31-40 mm: HR = 0.439, 95% CI: 0.201-0.957; 41-50 mm: HR = 0.382; 95% CI: 0.159-0.916; all P < 0.05]. In patients with cirrhosis, for both tumor size ≤ 30 mm and 31-40 mm groups, there were no significant survival differences between RFA and LR in multivariate analysis (all P > 0.05). However, in those with tumor size 41-50 mm, LR showed significantly better 5-year HCC cancer-specific survival than RFA in both univariate (54.72% vs. 23.06%; P < 0.001) and multivariate analyses (HR = 0.297; 95% CI: 0.136-0.648; P = 0.002). CONCLUSIONS: RFA is an inferior treatment option to LR for patients without cirrhosis who have a solitary HCC tumor ≤ 5 cm.

Publisher Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

In the version of this paper originally published, important figure labels in Fig. 3d were not visible. An image layer present in the authors' original figure that included two small dashed outlines and text labels indicating ROI 1 and ROI 2, as well as a scale bar and the name of the cell label, was erroneously altered during image processing. The figure has been corrected in the HTML and PDF versions of the paper.

Author Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

The version of this paper originally published cited a preprint version of ref. 12 instead of the published version (Proc. Natl. Acad. Sci. USA 115, 5594-5599; 2018), which was available before this Nature Methods paper went to press. The reference information has been updated in the PDF and HTML versions of the article.

Predictors of portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection in hepatitis B cirrhosis: a prospective study.

BACKGROUND: The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus. METHODS: From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP. RESULTS: Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222-25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466-9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively. CONCLUSION: Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/ . The name of research registered is "Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection." The trial registration identifier at clinicaltrials.gov is NCT02247414.

Clinical effects of cluster technology optimization and innovations on laparoscopic splenectomy and azygoportal disconnection: a single-center retrospective study with 500 consecutive cases.

BACKGROUND: In Asia, laparoscopic splenectomy and azygoportal disconnection (LSD) has been widely regarded as a preferential treatment modality for cirrhotic portal hypertension (PH). However, LSD involves high surgical risk, technical challenges, and many potential postoperative complications. Technology optimization and innovation in LSD aiming to solve to these difficulties has scarcely been reported. In this retrospective study, we aimed to evaluate the clinical therapeutic effect of our cluster technology optimization and innovation on LSD for PH. METHODS: From February 2012 to January 2020, 500 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism underwent LSD in our department. According to different operation periods, patients were divided into the early-, intermediate-, and late-period groups. We collected information regarding clinical characteristics of all patients as well as their preoperative and postoperative follow-up data. RESULTS: Compared with the early-period group, operation time and postoperative hospital stay were all significantly different and gradually declined from the intermediate- and late-period groups, respectively (all P < 0.05). Intraoperative blood loss of these three groups was gradually decreased, with significant differences (P < 0.05). The incidences of delayed gastric emptying and diarrhea in the late-period group were all significantly lower than those in the early- and intermediate-period groups, respectively (all P < 0.05). Compared with the early-period group, the incidence of variceal re-bleeding was significantly lower in the intermediate- and late-period groups (all P < 0.05). CONCLUSION: Our cluster technology optimization and innovation of LSD not only contributed to faster recovery and fewer complications but also enhanced surgical safety for patients. It is worth promoting this approach among patients with EVB and hypersplenism secondary to cirrhotic PH.

Functional cooperation of α-synuclein and VAMP2 in synaptic vesicle recycling.

The function of α-synuclein (α-syn) has been long debated, and two seemingly divergent views have emerged. In one, α-syn binds to VAMP2, acting as a SNARE chaperone-but with no effect on neurotransmission-while another posits that α-syn attenuates neurotransmitter release by restricting synaptic vesicle mobilization and recycling. Here, we show that α-syn-VAMP2 interactions are necessary for α-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function.

Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) that are functionally brighter; detect submicromolar to millimolar amounts of glutamate; and have blue, cyan, green, or yellow emission profiles. These variants could be imaged in vivo in cases where original iGluSnFR was too dim, resolved glutamate transients in dendritic spines and axonal boutons, and allowed imaging at kilohertz rates.

Association of HMOX-1 with sporadic Alzheimer's disease in southern Han Chinese.

BACKGROUND AND PURPOSE: The aim of this study was to discover the associations between HMOX-1 and Alzheimer's disease (AD). METHODS: A total of 500 AD patients and 500 healthy controls were recruited in this study. Polymer chain reaction was used. RESULTS: There was a statistically significant difference between AD patients and controls in both the dominant and recessive models of HMOX-1 rs2071746 after adjustment for age, gender and education (dominant model: p = 0.047, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.00-1.78, adjusted; recessive model: p = 0.049, OR 1.34, 95% CI 1.00-1.80, adjusted). There was also a trend for an association between the dominant model and late-onset AD after adjustment for age, gender and education (dominant model: p = 0.084, OR 1.37, 95% CI 0.96-1.95, adjusted). CONCLUSIONS: We found an association between the dominant and recessive models of HMOX1 rs2071746 and AD.

Modified (Bai-Jiang style) vagus nerve-preserving versus conventional laparoscopic splenectomy and azygoportal disconnection: a randomized clinical trial.

BACKGROUND: Digestive system complications are among the most important causes of postoperative poor quality of life after open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD). We firstly developed a modified vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (MVLSD). In this study, we aimed to evaluate whether MVLSD is feasible and safe and to determine whether MVLSD can effectively eliminate postoperative digestive system complications, in comparison with CLSD. METHOD: In this randomized controlled single-center study, 60 patients with cirrhosis were randomly assigned to undergo either CLSD (n = 30) or MVLSD (n = 30) between April and December 2018. The primary outcome was delayed gastric emptying (DGE). Endoscopic physicians were blinded to group assignments. RESULTS: One patient who received MVLSD withdrew from the study. There were no significant differences in intraoperative blood loss, incidence of blood transfusion, time to off-bed activity, time to first flatus, and postoperative hospital stay between the two groups. Compared with CLSD, operation time and incidences of DGE, diarrhea, epigastric fullness, and overall postoperative complications were all significantly reduced in the MVLSD group (all P < 0.05). Compared with CLSD, MVLSD was associated with significantly increased weight and albumin levels at 1, 6, and 12 months postoperatively versus preoperative values (all P < 0.05). The curative effect of resolving gastroesophageal variceal bleeding was similar between the groups. CONCLUSION: MVLSD is not only a technically feasible and safe procedure, it is also succinct and convenient. Furthermore, MVLSD effectively reduces postoperative digestive system complications, contributing to improved quality of life.

Novel noninvasive liver fibrotic markers to predict postoperative re-bleeding after laparoscopic splenectomy and azygoportal disconnection: a 1-year prospective study.

BACKGROUND: Esophagogastric variceal re-bleeding (EGVR) is a common and potentially lethal complication after open or laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension. Currently, noninvasive biomarkers for predicting EGVR are lacking. This prospective study focused on developing a noninvasive and convenient clinical model for predicting postoperative EGVR. METHODS: Between September 2014 and March 2017, we enrolled 164 patients with cirrhosis who successfully underwent LSD. Based on the absence or presence of EGVR, patients were divided into EGVR and non-EGVR groups. We used correlation analysis to determine significant candidate variables among the liver fibrotic markers procollagen type III (PC-III), hyaluronidase (HA), laminin (LN), and type IV collagen (C-IV). RESULTS: Postoperative EGVR occurred in 22 (13.41%) patients. Correlation analyses showed that LN (r = 0.375; p < 0.001) and C-IV (r = 0.349; p < 0.001) were significantly positively associated with EGVR. The area under the receiver operating characteristic curve (AUC) of LN was 0.817 (95% confidence interval [CI] 0.722-0.913); that of C-IV was 0.795 (95% CI 0.710-0.881). In logistic multivariate regression, cutoff values LN ≥ 64 µg/L and of C-IV ≥ 65 µg/L were independent risk factors for EGVR. LN ≥ 64 µg/L combined with C-IV ≥ 65 µg/L was the best performing model, with AUC 0.867 (95% CI 0.768-0.967). CONCLUSION: LN and C-IV are potential markers to predict EGVR. Combining the two markers showed satisfactory ability to predict EGVR in patients with cirrhosis and portal hypertension after LSD.

Phosphatidylinositol 4,5-bisphosphate drives Ca2+-independent membrane penetration by the tandem C2 domain proteins synaptotagmin-1 and Doc2ß.

Exocytosis mediates the release of neurotransmitters and hormones from neurons and neuroendocrine cells. Tandem C2 domain proteins in the synaptotagmin (syt) and double C2 domain (Doc2) families regulate exocytotic membrane fusion via direct interactions with Ca2+ and phospholipid bilayers. Syt1 is a fast-acting, low-affinity Ca2+ sensor that penetrates membranes upon binding Ca2+ to trigger synchronous vesicle fusion. The closely related Doc2ß is a slow-acting, high-affinity Ca2+ sensor that triggers spontaneous and asynchronous vesicle fusion, but whether it also penetrates membranes is unknown. Both syt1 and Doc2ß bind the dynamically regulated plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), but it is unclear whether PIP2 serves only as a membrane contact or enables specialized membrane-binding modes by these Ca2+ sensors. Furthermore, it has been shown that PIP2 uncaging can trigger rapid, syt1-dependent exocytosis in the absence of Ca2+ influx, suggesting that current models for the action of these Ca2+ sensors are incomplete. Here, using a series of steady-state and time-resolved fluorescence measurements, we show that Doc2ß, like syt1, penetrates membranes in a Ca2+-dependent manner. Unexpectedly, we observed that PIP2 can drive membrane penetration by both syt1 and Doc2ß in the absence of Ca2+, providing a plausible mechanism for Ca2+-independent, PIP2-dependent exocytosis. Quantitative measurements of penetration depth revealed that, in the presence of Ca2+, PIP2 drives Doc2ß, but not syt1, substantially deeper into the membrane, defining a biophysical regulatory mechanism specific to this high-affinity Ca2+ sensor. Our results provide evidence of a novel role for PIP2 in regulating, and under some circumstances triggering, exocytosis.

Correction to: A Mathematical Model for the Kinetics of the MalFGK2 Maltose Transporter.

The original version of this article unfortunately contained a mistake. The co-author Dr. Franck Duong Van Hoa first name and last name were misinterpreted in the original publication.

A Mathematical Model for the Kinetics of the MalFGK[Formula: see text] Maltose Transporter.

The MalFGK[Formula: see text] transporter regulates the movement of maltose across the inner membrane of E. coli and serves as a model system for bacterial ATP binding cassette (ABC) importers. Despite the wealth of biochemical and structural data available, a general model describing the various translocation pathways is still lacking. In this study, we formulate a mathematical model with the goal of determining the transporter reaction pathway, specifically looking at the order of binding events and conformation changes by which transport proceeds. Fitting our mathematical model to equilibrium binding data, we estimate the unknown equilibrium parameters of the system, several of which are key determinants of the transport process. Using these estimates along with steady-state ATPase rate data, we determine which of several possible reaction pathways is dominant, as a function of five underdetermined kinetic parameter values. Because neither experimental measurements nor estimates of certain kinetic rate constants are available, the problem of deciding which of the reaction pathways is responsible for transport remains unsolved. However, using the mathematical framework developed here, a firmer conclusion regarding the dominant reaction pathway as a function of MalE and maltose concentration could be drawn once these unknown kinetic parameters are determined.

Effects of laparoscopic splenectomy and azygoportal disconnection on liver synthesis function and cirrhosis: a 2-year prospective study.

BACKGROUND: Laparoscopic splenectomy and azygoportal disconnection (LSD) is widely used for the treatment of esophagogastric variceal haemorrhage and hypersplenism owing to cirrhotic portal hypertension. However, whether LSD improves liver synthesis function and cirrhosis remains unclear. The aim of this study is to investigate the effect of LSD on liver synthesis function and cirrhosis based on a prospective 2-year follow-up study. METHODS: A total of 118 patients with cirrhotic portal hypertension who underwent LSD were included in this study. We analysed clinical data including routine blood parameters, liver function, liver-synthesised proteins (antithrombin III, protein S, and protein C), liver fibrotic markers (type IV collagen (IV-C), procollagen type III (PC-III), laminin, and hyaluronidase), portal vein diameter, and portal blood flow velocity. RESULTS: Postoperative portal vein diameter and portal blood flow velocity all showed gradual declines during the 2-year follow-up; compared with preoperative values, these were all significantly decreased from postoperative week (POW) 1 (all P < 0.001). Postoperative Child-Pugh scores and total bilirubin, albumin, international normalised ratio, antithrombin III, protein S, protein C, IV-C, PC-III, laminin, and hyaluronidase levels also all showed gradual improvements during the 2-year follow-up; compared with preoperative levels, these were all significantly improved from postoperative month (POM) 6, POW 1, POM 3, POM 3, POM 3, POM 6, POM 18, POW 1, POM 3, POM 24, and POM 18, respectively (all P < 0.05). CONCLUSION: LSD not only decreases portal hypertension and improves liver function, it also enhances liver synthesis function and reduces liver fibrosis.