[Correlation of miR-155 Expression with Drug Sensitivity of FLT3-ITD+ Acute Myeloid Leukemia Cell Line and Its Mechanism].

OBJECTIVE: To investigate the correlation of miR-155 expression with drug sensitivity of FLT3-ITD+ acute myeloid leukemia (AML) cell line and its potential regulatory mechanism. METHODS: By knocking out miR-155 gene in FLT3-ITD+ AML cell line MV411 through CRISPR/Cas9 gene-editing technology, monoclonal cells were screened. The genotype of these monoclonal cells was validated by PCR and Sanger sequencing. The expression of mature miRNA was measured by RT-qPCR. The treatment response of doxorubicin, quizartinib and midostaurin were measured by MTT assay and IC50 of these drugs were calculated to identify the sensitivity. Transcriptome sequencing was used to analyze change of mRNA level in MV411 cells after miR-155 knockout, gene set enrichment analysis to analyze change of signaling pathway, and Western blot to verify expressions of key molecules in signaling pathway. RESULTS: Four heterozygotes with gene knockout and one heterozygote with gene insertion were obtained through PCR screening and Sanger sequencing. RT-qPCR results showed that the expression of mature miR-155 in the monoclonal cells was significantly lower than wild-type clones. MTT results showed that the sensitivity of MV411 cells to various anti FLT3-ITD+ AML drugs increased significantly after miR-155 knockout compared with wild-type clones. RNA sequencing showed that the mTOR signaling pathway and Wnt signaling pathway were inhibited after miR-155 knockout. Western blot showed that the expressions of key molecules p-mTOR, Wnt5α and ß-catenin in signaling pathway were down-regulated. CONCLUSION: Drug sensitivity of MV411 cells to doxorubicin, quizartinib and midostaurin can be enhanced significantly after miR-155 knockout, which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.

Constructing a P2W18O626--Containing Hybrid Photocatalyst via Noncovalent Interactions for Enhanced H2 Production.

Polyoxometalates (POMs) have gained significant research attention because of their excellent properties in photocatalytic (PC) hydrogen production. Exploring POM-based compounds for heterogeneous photocatalysis is an ongoing task. Here, we obtain a water-insoluble inorganic-organic hybrid compound, (P2W18O62)3(C12N3H10)6(C12N3H11)6·9.5H2O (P-PW), formed by Dawson-type POM P2W18O626- (P2W18) anions and protonated 2-(pyridin-4-yl)-1H-benzo[d]imidazole (PHB) cations via noncovalent interactions. In the presence of the sacrificial agent triethanolamine, P-PW exhibits a PC H2 generation rate of 0.418 mmol/g/h, surpassing that of P2W18 and PHB by 15 and 17 times, respectively. This enhancement in PC performance of P-PW can be attributed to its band structure change from the precursor compounds, leading to increased light absorption and therefore more efficient PC hydrogen production.

Short- and long-term outcomes of Roux-en-Y and Billroth II with Braun reconstruction in total laparoscopic distal gastrectomy: a retrospective analysis.

BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.

Comparison of proximal gastrectomy with double-flap technique and double-tract reconstruction for proximal early gastric cancer: a meta-analysis.

Surgical resection is the main treatment for proximal gastric cancer, but there is no consensus on its reconstruction. We carried out a meta-analysis to evaluate the effects of double-tract reconstruction (DTR) and double-flap technique (DFT) on postoperative quality of life in patients with proximal gastric cancer. Systematic searches of PubMed, Web of Science, EBSCO, and the Cochrane Library were performed. Literature for the last 5 years was searched without language restrictions. The cutoff date for the search was 12 April 2023. Literature and research searches were conducted independently by two researchers and data were extracted. Statistical analyses were performed using Review Manager (Revman) 5.4 software. Fixed models were used when heterogeneity was small and random-effects models were used for meta-analysis when heterogeneity was large. The study was registered with PROSPERO, CRD 42023418520. Surgical time was significantly shorter in the DTR group than in the DFT group (P = 0.03). There were no significant differences between DFT and DTR in terms of age, gender, pathological stage, preoperative body mass index, surgical bleeding, and perioperative complications. There was no statistically significant difference between the two groups in terms of reflux esophagitis and PPI intake, but DFT was superior to DTR in weight improvement at 1 year after surgery (P < 0.0001). Compared with DTR, DFT reconstruction is more demanding and time-consuming, but its postoperative nutritional status is better, so it should be the first choice for GI reconstruction in most patients with early proximal gastric cancer. However, DTR should be the best choice for patients who have difficulty operating.

Cerium Synchronous Doping in Anatase for Enhanced Photocatalytic Hydrogen Production from Ethanol-Water Mixtures.

Cerium element with a unique electric structure can be used to modify semiconductor photocatalysts to enhance their photocatalytic performances. In this work, Ce-doped TiO2 (Ce/TiO2) was successfully achieved using the sol-gel method. The structural characterization methods confirm that Ce was doped in the lattice of anatase TiO2, which led to a smaller grain size. The performance test results show that the Ce doped in anatase TiO2 significantly enhances the charge transport efficiency and broadens the light absorption range, resulting in higher photocatalytic performance. The Ce/TiO2 exhibited a photocurrent density of 10.9 µA/cm2 at 1.0 V vs. Ag/AgCl, 2.5 times higher than that of pure TiO2 (4.3 µA/cm2) under AM 1.5 G light. The hydrogen (H2) production rate of the Ce/TiO2 was approximately 0.33 µmol/h/g, which is more than twice as much as that of the pure anatase TiO2 (0.12 µmol/h/g). This work demonstrates the effect of Ce doping in the lattice of TiO2 for enhanced photocatalytic hydrogen production.

Effects of Dexmedetomidine on Systemic Inflammation and Postoperative Complications in Laparoscopic Pancreaticoduodenectomy: A Double-blind Randomized Controlled Trial.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) may induce intense inflammatory response which might be related to the patient's outcomes. Clinical dexmedetomidine (DEX) has been widely used for opioid-sparing anesthesia and satisfactory sedation. The objective of this study was to investigate the influence of DEX on inflammatory response and postoperative complications in LPD. METHODS: Ninety-nine patients undergoing LPD were randomly assigned to two groups: normal saline (NS) and DEX. The primary outcome was the neutrophil-to-lymphocyte ratio (NLR) differences postoperatively within 48 h. Secondary outcomes were postoperative complications, the length of postoperative hospital stay and the incidence of ICU admission. Other outcomes included anesthetics consumption and intraoperative vital signs. RESULTS: NLR at postoperative day 2 to baseline ratio decreased significantly in the DEX group (P = 0.032). Less major complications were observed in the DEX group such as pancreatic fistula, delayed gastric emptying and intra-abdominal infection (NS vs. DEX, 21.7% vs. 13.6%, P = 0.315; 10.9% vs. 2.3%, P = 0.226; 17.4% vs. 11.4%, P = 0.416, respectively) though there were no statistical differences. Three patients were transferred to the ICU after surgery in the NS group, while there was none in the DEX group (P = 0.242). The median postoperative hospital stay between groups were similar (P = 0.313). Both intraoperative propofol and opioids were less in the DEX group (P < 0.05). CONCLUSIONS: Intraoperative DEX reduced the early postoperative inflammatory response in LPD. It also reduced the use of narcotics that may related to reduced major complications, which need additional research further.

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

Background: Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear. Objectives: This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata. Methods: genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks. Result: Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, p = 3.03×10-3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3. Conclusion: This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.

Cerium-Doped Iron Oxide Nanorod Arrays for Photoelectrochemical Water Splitting.

In this work, a simple one-step hydrothermal method was employed to prepare the Ce-doped Fe2O3 ordered nanorod arrays (CFT). The Ce doping successfully narrowed the band gap of Fe2O3, which improved the visible light absorption performance. In addition, with the help of Ce doping, the recombination of electron/hole pairs was significantly inhibited. The external voltage will make the performance of the Ce-doped sample better. Therefore, the Ce-doped Fe2O3 has reached superior photoelectrochemical (PEC) performance with a high photocurrent density of 1.47 mA/cm2 at 1.6 V vs. RHE (Reversible Hydrogen Electrode), which is 7.3 times higher than that of pristine Fe2O3 nanorod arrays (FT). The Hydrogen (H2) production from PEC water splitting of Fe2O3 was highly improved by Ce doping to achieve an evolution rate of 21 µmol/cm2/h.

Pollen Carbon-Based Rare-Earth Composite Material for Highly Efficient Photocatalytic Hydrogen Production from Ethanol-Water Mixtures.

The unique electronic structure of rare-earth elements makes their modified semiconductor photocatalysts show great advantages in solar energy conversion. Herein, the pollen-like N, P self-doped biochar-based rare-earth composite catalyst (Er/LP-C) has been successfully synthesized, which combines the advantages of biochar and Er and is used for the first time in the field of photocatalytic hydrogen production from ethanol-water mixtures. Experimental results confirmed that the performance of photocatalytic hydrogen production under the full spectrum is up to 33.70 µmol/g in 6 h; this is due to the introduction of Er, which improves the carrier concentration, separation and transfer efficiency, and the driving force for the reduction reaction.

N, P Self-Doped Porous Carbon Material Derived from Lotus Pollen for Highly Efficient Ethanol-Water Mixtures Photocatalytic Hydrogen Production.

Porous biochar materials prepared with biomass as a precursor have received widespread attention. In this work, lotus pollen (LP) was used as the carbon source, a variety of the pollen carbon photocatalyst were prepared by a two-step roasting method. A series of characterizations were carried out on the prepared samples, and it was found that the average particle size was about 40 µm. They also exhibit a typical amorphous carbon structure and a porous structure with a network-like interconnected surface. The photocatalytic hydrogen production performances of lotus pollen carbon (LP-C) and commercial carbon black (CB) were measured under the full spectrum illumination. LP-C-600 showed the best hydrogen production performance (3.5 µmol·g-1·h-1). In addition, the photoelectrochemical (PEC) measurement results confirmed that the LP-C materials show better incident photon-current efficiency (IPCE) performance than the CB materials in the neutral electrolyte. This is because the unique surface wrinkling, hierarchical porous structure, and the N, P self-doping behavior of the LP-C samples are able to improve the light utilization efficiency and the carrier separation/transfer efficiency, thereby further improving the overall hydrogen production efficiency.

Auditory Sensory Gating in Children With Cochlear Implants: A P50-N100-P200 Study.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear. Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance. Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children. Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

Design and Solvothermal Synthesis of Polyoxometalate-Based Cu(II)-Pyrazolate Photocatalytic Compounds for Solar-Light-Driven Hydrogen Evolution.

Polyoxometalates (POMs) are known for their photocatalytic hydrogen production activity, but their solubility and limited stability often restrict their practical applications. Herein, we designed and solvothermally synthesized two new Cu-H2bpz (3,3',5,5'-tetramethyl-4,4'-bipyrazole, abbreviated as H2bpz) compounds, namely, Cu0.5(H2bpz)(NO3) (1) and Cu(Hbpz)(Cl)·DMF (2), and three new polyoxometalate-based Cu(II)-pyrazolate compounds, namely, Cu(PW12O40)0.5(H2bpz)2(H2O)·(OH)0.5(H2O)5.5 (3), Cu(HPMo12O40)(H2bpz)2(H2O)2·(H2O)4 (4), and Cu2(SiW12O40)(H2bpz)3(H2O)3·(H2O)6 (5). Compound 3 (Cu(PW12O40)0.5(H2bpz)2(H2O)·(OH)0.5(H2O)5.5) exhibits the best photocatalytic activity of 44.4 µ L h-1 g-1, which may be related to the stability of compounds. Herein, the solvothermal method has been proven to be an effective method in synthesizing stable organic-inorganic hybrid compounds with soluble POMs, metal ions, and organic ligands. Thus, heterogeneous catalysts with outstanding solar-light-driven photocatalytic properties were obtained.

[Effect of Inhibiting NCL Expression on Drug-Resistance of Chronic Myeloid Leukemia Cell Line K562 and Its Resistant Cells].

OBJECTIVE: To construct a K562 and adriamycin-resistant K562 (KAR) cell line with stably down-regulation of NCL (nucleolin) expression, and to investigate the effect of NCL down-regulation on the drug resistance in K562 and KAR cells. METHODS: K562 and KAR cells were infected with lentivirus, and stably transfected cell clones were obtained by puromycin screening. The cell proliferation was detected by MTS assay, the cell apoptosis was detected by flow cytometry, and the expression level of drug resistance related genes was detected by real-time PCR. RESULTS: The K562 and KAR cells with stable down-regulation of NCL were successfully constructed. Compared with the control group, the proliferation of K562 and KAR cells with down-regulating NCL expression decreased significantly (P ＜0.05), the apoptosis of cells increased significantly (P ＜0.05), and cell resistance to adriamycin was down-regulated. CONCLUSION: Inhibition of NCL expression may increase the sensitivity of cells to adriamycin, which may be related with the promotion of apoptosis of K562 and KAR cells.

Metalization of Li2S particle surfaces in Li-S batteries.

The Li-S battery is the most promising candidate for future electric vehicles. The study of stabilities and conductivities of Li2S nanoparticles, which are used as pre-lithiated cathode materials, is crucial for the development of Li-S batteries. Here, we investigate the atomic and electronic structures as well as stabilities of Li2S surfaces and nanoparticles using density functional theory (DFT) and classical electrostatic models. We show that Li2S nanoparticles have octahedral shape and consist of only (111) facets. At low concentrations of Li, the surfaces of nanoparticles are metalized non-polar Li2S(111) surfaces. The metalization is found to be due to the depletion of valence bands of surface states. However, for higher concentrations of Li, the nanoparticle faces are insulator non-polar Li2S(111) surfaces. This study suggests that Li2S nanoparticles with (111) surfaces are very promising cathode materials for Li-S batteries.

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis.

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. METHODS: From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. RESULTS: With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ² = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ² = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ² = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ² = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ² = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients.

Electrooxidation of ethylene glycol and glycerol on Pd-(Ni-Zn)/C anodes in direct alcohol fuel cells.

The electrooxidation of ethylene glycol (EG) and glycerol (G) has been studied: in alkaline media, in passive as well as active direct ethylene glycol fuel cells (DEGFCs), and in direct glycerol fuel cells (DGFCs) containing Pd-(Ni-Zn)/C as an anode electrocatalyst, that is, Pd nanoparticles supported on a Ni-Zn phase. For comparison, an anode electrocatalyst containing Pd nanoparticles (Pd/C) has been also investigated. The oxidation of EG and G has primarily been investigated in half cells. The results obtained have highlighted the excellent electrocatalytic activity of Pd-(Ni-Zn)/C in terms of peak current density, which is as high as 3300 A g(Pd)(-1) for EG and 2150 A g(Pd)(-1) for G. Membrane-electrode assemblies (MEA) have been fabricated using Pd-(Ni-Zn)/C anodes, proprietary Fe-Co/C cathodes, and Tokuyama A-201 anion-exchange membranes. The MEA performance has been evaluated in either passive or active cells fed with aqueous solutions of 5 wt % EG and 5 wt % G. In view of the peak-power densities obtained in the temperature range from 20 to 80 °C, at Pd loadings as low as 1 mg cm(-2) at the anode, these results show that Pd-(Ni-Zn)/C can be classified amongst the best performing electrocatalysts ever reported for EG and G oxidation.

Electrochemical milling and faceting: size reduction and catalytic activation of palladium nanoparticles.

Improved performance through milling: A method for enhancing the catalytic activity of supported metal nanoparticles is reported. This method enhances the activity for the ethanol electro-oxidation of a supported palladium catalyst. The much higher catalytic performance is ascribed to the increased electrochemically active surface area as well as the generation of high-index facets at the milled nanoparticle surface.

Sinistral portal hypertension: clinical features and surgical treatment of chronic splenic vein occlusion.

OBJECTIVE: Sinistral, or left-sided, portal hypertension (SPH) is a rare cause of upper gastrointestinal hemorrhage. This retrospective analysis summarizes the clinical features of SPH and the results of surgical treatment. SUBJECTS AND METHODS: Between 2000 and 2009, patients from our hospital diagnosed with SPH were identified. Diagnosis of SPH was based on evidence of isolated splenic vein thrombosis, splenomegaly, gastroesophageal varices and exclusion of other causes of portal hypertension. RESULTS: Eight males and 5 females were included in the study, with a mean age of 43.5 ± 6.4 years (range: 31-68 years). Liver function was normal in all patients. Causes of SPH were chronic pancreatitis (n = 7), pancreatic cancer (n = 3), pancreatic cysts (n = 2) and neuroendocrine tumor (n = 1). The main clinical manifestations were gastrointestinal hemorrhage in 7 cases (53.8%), upper abdominal pain in 10 (76.9%) and hypersplenism in 12 (92.3%). All patients had splenomegaly and gastroesophageal varices. Twelve patients underwent splenectomy and 1 received surgical removal of a pancreatic cyst. No major gastrointestinal tract rebleed occurred after a mean follow-up of 46 months (±7 months). Two patients died of pancreatic cancer and 1 of acute myocardial infarction during follow-up. CONCLUSIONS: SPH should be suspected in patients with upper gastrointestinal varices as well as unexplained splenomegaly with normal liver function. Surgical intervention such as splenectomy offers a good long-term outcome in symptomatic patients.