A Density-Based Multilevel Terrain-Adaptive Noise Removal Method for ICESat-2 Photon-Counting Data.

The photon point clouds collected by the high-sensitivity single-photon detector on the Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) are utilized in various applications. However, the discretely distributed noise among the signal photons greatly increases the difficulty of signal extraction, especially the edge noise adjacent to signals. To detect signal photons from vegetation coverage areas at different slopes, this paper proposes a density-based multilevel terrain-adaptive noise removal method (MTANR) that identifies noise in a coarse-to-fine strategy based on the distribution of noise photons and is evaluated with high-precision airborne LiDAR data. First, the histogram-based successive denoising method was used as a coarse denoising process to remove distant noise and part of the sparse noise, thereby increasing the fault tolerance of the subsequent steps. Second, a rotatable ellipse that adaptively corrects the direction and shape based on the slope was utilized to search for the optimal filtering direction (OFD). Based on the direction, sparse noise removal was accomplished robustly using the Otsu's method in conjunction with the ordering points to identify the clustering structure (OPTICS) and provide a nearly noise-free environment for edge searching. Finally, the edge noise was removed by near-ground edge searching, and the signal photons were better preserved by the surface lines. The proposed MTANR was validated in four typical experimental areas: two in Baishan, China, and two in Taranaki, New Zealand. A comparison was made with three other representative methods, namely differential, regressive, and Gaussian adaptive nearest neighbor (DRAGANN), used in ATL08 products, local distance statistics (LDS), and horizontal ellipse-based OPTICS. The results demonstrated that the values of the F1 score for the signal photon identification achieved by the proposed MTANR were 0.9762, 0.9857, 0.9839, and 0.9534, respectively, which were higher than those of the other methods mentioned above. In addition, the qualitative and quantitative results demonstrated that MTANR outperformed in scenes with steep slopes, abrupt terrain changes, and uneven vegetation coverage.

Resampling-Detection-Network-Based Robust Image Watermarking against Scaling and Cutting.

Watermarking is an excellent solution to protect multimedia privacy but will be damaged by attacks such as noise adding, image filtering, compression, and especially scaling and cutting. In this paper, we propose a watermarking scheme to embed the watermark in the DWT-DCT composite transform coefficients, which is robust against normal image processing operations and geometric attacks. To make our scheme robust to scaling operations, a resampling detection network is trained to detect the scaling factor and then rescale the scaling-attacked image before watermark detection. To make our scheme robust to cutting operations, a template watermark is embedded in the Y channel to locate the cutting position. Experiments for various low- and high-resolution images reveal that our scheme has excellent performance in terms of imperceptibility and robustness.

Discovery of a novel series of guanidinebenzoates as gut-restricted enteropeptidase and trypsin dual inhibitors for the treatment of metabolic syndrome.

A novel series of guanidinebenzoate enteropeptidase and trypsin dual inhibitors has been discovered and SAR studies were conducted. Optimization was focused on improving properties for gut restriction, including increased aqueous solubility, lower cellular permeability, and reduced oral bioavailability. Lead compounds were identified with efficacy in a mouse fecal protein excretion study.

Optimization of physicochemical properties of pyridone-based EP3 receptor antagonists.

A novel series of pyridone-based EP3 receptor antagonists was optimized for good physical properties and oral bioavailability in rodents. The lead compounds 3h, 3l and 4d displayed good in vitro profiles, moderate to good metabolic stability and good rodent PK profiles with low clearance, high oral exposure and acceptable half-life.

Targeting Enteropeptidase with Reversible Covalent Inhibitors To Achieve Metabolic Benefits.

Inhibition of the serine protease enteropeptidase (EP) opens a new avenue to the discovery of chemotherapeutics for the treatment of metabolic diseases. Camostat has been used clinically for treating chronic pancreatitis in Japan; however, the mechanistic basis of the observed clinical efficacy has not been fully elucidated. We demonstrate that camostat is a potent reversible covalent inhibitor of EP, with an inhibition potency (k inact/KI) of 1.5 × 104 M-1s-1 High-resolution liquid chromatography-mass spectrometry (LC-MS) showed addition of 161.6 Da to EP after the reaction with camostat, consistent with insertion of the carboxyphenylguanidine moiety of camostat. Covalent inhibition of EP by camostat is reversible, with an enzyme reactivation half-life of 14.3 hours. Formation of a covalent adduct was further supported by a crystal structure resolved to 2.19 Å, showing modification of the catalytic serine of EP by a close analog of camostat, leading to formation of the carboxyphenylguanidine acyl enzyme identical to that expected for the reaction with camostat. Of particular note, minor structural modifications of camostat led to changes in the mechanism of inhibition. We observed from other studies that sustained inhibition of EP is required to effect a reduction in cumulative food intake and body weight, with concomitant improved blood glucose levels in obese and diabetic leptin-deficient mice. Thus, the structure-activity relationship needs to be driven by not only the inhibition potency but also the mechanistic and kinetic characterization. Our findings support EP as a target for the treatment of metabolic diseases and demonstrate that reversible covalent EP inhibitors show clinically relevant efficacy. SIGNIFICANCE STATEMENT: Interest in targeted covalent drugs has expanded in recent years, particularly so for kinase targets, but also more broadly. This study demonstrates that reversible covalent inhibition of the serine protease enteropeptidase is a therapeutically viable approach to the treatment of metabolic diseases and that mechanistic details of inhibition are relevant to clinical efficacy. Our mechanistic and kinetic studies outline a framework for detailed inhibitor characterization that is proving essential in guiding discovery efforts in this area.

Hierarchical MoS2 /Carbon Composite Microspheres as Advanced Anodes for Lithium/Sodium-Ion Batteries.

It is crucial to design advanced electrodes with large Li/Na-ion storage capacities for the development of next-generation battery systems. Herein, hierarchical MoS2 /C composite microspheres were constructed by facile template-free self-assembly sulfurization plus post-carbonization. Cross-linked MoS2 nanosheets and outer carbon layer are organically combined together to form composite microspheres with diameters of 400-500 nm. Due to enhanced electrical conductivity and good structural stability, the MoS2 /C composite microspheres exhibit substantially improved Li/Na-ion storage performance. Compared to unmodified MoS2 , MoS2 /C composite microspheres deliver higher Li/Na-ion storage capacity (Li+ : 1017 mA h g-1 at 100 mA g-1 and Na+ : 531 mA h g-1 at 100 mA g-1 ), as well as better rate capability (Li+ : 434 mA h g-1 at 1 Ag-1 and Na+ : 102 mA h g-1 at 1 Ag-1 ) and capacity retention (Li+ : 902 mA h g-1 after 200 cycles and Na+ : 342 mA h g-1 over 100 cycles). The superior Li/Na-ion storage performance is mainly attributed to the unique porous microsphere architecture with increased electrode/electrolyte interfaces and more diffusion paths for Li/Na ion insertion. Additionally, the carbon coating can not only improve the electronic conductivity, but also suppress the shuttle effect of polysulfides.

Pretreatment microRNA levels can predict HBsAg clearance in CHB patients treated with pegylated interferon α-2a.

BACKGROUND: To investigate the predictive capability of microRNAs (miRNAs) prior treatment for HBsAg clearance in chronic hepatitis B (CHB) treated with pegylated interferon α-2a (PEG-IFNα-2a). METHODS: The treatment effect was determined by HBsAg clearance and subjects were classified into HBsAg clearance group and non HBsAg clearance group. Differential miRNAs expression in peripheral blood mononuclear cells (PBMC) was screened using microarrays in an identification cohort (n = 20) and validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in a confirmation cohort (n = 47). Receiver operating characteristic curve (ROC), logistic regression and gene ontology (GO)/Pathway analyses were used to evaluate the predictive capability of selected miRNAs for HBsAg clearance and determine their mechanistic roles. RESULTS: Twenty-seven subjects (40.3%) acquired HBsAg clearance, ten in the identification cohort and seventeen in the confirmation cohort. Four miRNAs out of twelve (miR-3960, miR-126-3p, miR-335-5p, miR-23a-3p) were verified to be differential expressed by qRT-PCR in the confirmation cohort. Their expression patterns were consistent with the microarray results. Their levels were lower in the response group compared with the nonresponse group (p < 0.05). The areas under curve (AUC) were 0.8333 (p = 0.001), 0.751 (p = 0.01), 0.7294 (p = 0.013), 0.6275 (p = 0.094) and positive predict values (PPV) were 84.62, 60.00, 70.00, 28.57% for miR-3960, miR-126-3p, miR-335-5p, and miR-23a-3p respectively. The AUC and PPV of the combination of miR-3960 and miR-126-3p were 0.8529 and 92.31%, which were better than using miR-3960 alone, but the differences were not statistically significance (p > 0.05). CONCLUSIONS: We identified differential expressed miRNAs between response and nonresponse groups of PEG-IFNα-2a treatment and demonstrated that miR-3960 was the optimal predictor for HBsAg clearance compared with other miRNAs, but it requires to be further comfired in larger cohort studies. TRIAL REGISTRATION: ChiCTR ChiCTR-ROC-16008735, registered retrospectively on 28 June, 2016.

On-treatment changes of liver stiffness at week 26 could predict 2-year clinical outcomes in HBV-related compensated cirrhosis.

BACKGROUND & AIMS: It is unclear whether liver stiffness measurement (LSM) dynamic changes after anti-HBV treatment could predict the risk of liver-related events (LREs), particularly in patients with HBV-related compensated cirrhosis. METHODS: Treatment-naïve patients with HBV-related compensated cirrhosis were enrolled. All patients were under entecavir-based antiviral therapy, and followed up every 26 weeks for 2 years. The association between LSM and LREs was analysed by Cox proportional hazard model and Harrell C-index analysis. RESULTS: A total of 438 patients were included in the study. At the follow-up of 104 weeks, LREs developed in 33/438 (7.8%) patients, including 16 episodes of decompensation, 18 HCC and 3 deaths. The median LSM remained high from 20.9, 18.6, 20.4 to 20.3 Kpa at week 0, 26, 52 and 78 among patients with LREs, whereas the LSM decreased from 17.8, 12.3, 10.6 to 10.2 Kpa in patients without LREs respectively. Percentage changes of LSM at 26 weeks from baseline were significantly associated with LREs (excluding 11 cases occurred within the first 26 weeks), with a crude hazard ratio of 2.94 (95% CI: 1.73-5.00) and an albumin-adjusted hazard ratio of 2.47 (95% CI: 1.49-4.11). The Harrell C-index of these 2 models for predicting 2-year LREs were 0.68 (95% CI: 0.56-0.80) and 0.75 (95% CI: 0.65-0.85) respectively. Nomograms were developed to identify individuals at high risk for point-of-care application. CONCLUSIONS: Dynamic changes of LSM alone, or combined with baseline albumin, could predict LREs in patients with HBV-related compensated cirrhosis during antiviral therapy.

Construction of Nitrogen-Doped Carbon-Coated MoSe2 Microspheres with Enhanced Performance for Lithium Storage.

Exploring advanced anode materials with highly reversible capacity have gained great interests for large-scale lithium storage. A facile two-step method is developed to synthesize nitrogen-doped carbon coated MoSe2 microspheres via hydrothermal plus thermal polymerization. The MoSe2 microspheres composed of interconnected nanoflakes are homogeneously coated by a thin nitrogen-doped carbon (N-C) layer. As an anode for lithium ion batteries, the MoSe2 /N-C composite shows better reversibility, smaller polarization, and higher electrochemical reactivity as compared to the unmodified MoSe2 microspheres. The MoSe2 /N-C electrode delivers a high specific capacity of 698 mAh g-1 after 100 cycles at a current density of 100 mA g-1 and good high rate performance (471 mAh g-1 at a high current density of 2000 mA g-1 ). The improved electrochemical performance is attributed to the conductive N-C coating and hierarchical microsphere structure with fast ion/electron transfer characteristics.

Performance Enhancement of a Sulfur/Carbon Cathode by Polydopamine as an Efficient Shell for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are considered to be among the most promising next-generation high-energy batteries. It is a consensus that improving the conductivity of sulfur cathodes and impeding the dissolution of lithium polysulfides are two key accesses to high-performance LSBs. Herein we report a sulfur/carbon black (S/C) cathode modified by self-polymerized polydopamine (pDA) with the assistance of polymerization treatment. The pDA acts as a novel and effective shell on the S/C cathode to stop the shuttle effect of polysulfides. By the synergistic effect of enhanced conductivity and multiple blocking effect for polysulfides, the S/C@pDA electrode exhibits improved electrochemical performances including large specific capacity (1135 mAh g-1 at 0.2 C), high rate capability (533 mAh g-1 at 5 C) and long cyclic life (965 mAh g-1 after 200 cycles). Our smart design strategy may promote the development of high-performance LSBs.

Evaluation of anti-diabetic effect and gall bladder function with 2-thio-5-thiomethyl substituted imidazoles as TGR5 receptor agonists.

A novel series of 2-thio-5-thiomethyl substituted imidazoles was discovered to be potent TGR5 agonists that possessed glucose-lowering effects while inhibiting gall bladder emptying in mice.

Design, synthesis and SAR of a novel series of heterocyclic phenylpropanoic acids as GPR120 agonists.

A novel series of 5-membered heterocycle-containing phenylpropanoic acid derivatives was discovered as potent GPR120 agonists with low clearance, high oral bioavailability and in vivo antidiabetic activity in rodents.

An Excess of the Proinflammatory Cytokines IFN-γ and IL-12 Impairs the Development of the Memory CD8+ T Cell Response to Chlamydia trachomatis.

The obligate intracellular bacterium Chlamydia trachomatis is the most common cause of bacterial sexually transmitted disease in the United States and the leading cause of preventable blindness worldwide. Transfer of cultured Chlamydia-specific CD8(+) T cells or vaccination with recombinant virus expressing an MHC I-restricted Chlamydia Ag confers protection, yet surprisingly a protective CD8(+) T cell response is not stimulated following natural infection. In this study, we demonstrate that the presence of excess IL-12 and IFN-γ contributes to poor memory CD8(+) T cell development during C. trachomatis infection of mice. IL-12 is required for CD8(+) T cell expansion but drives effector CD8(+) T cells into a short-lived fate, whereas IFN-γ signaling impairs the development of effector memory cells. We show that transient blockade of IL-12 and IFN-γ during priming promotes the development of memory precursor effector CD8(+) T cells and increases the number of memory T cells that participate in the recall protection against subsequent infection. Overall, this study identifies key factors shaping memory development of Chlamydia-specific CD8(+) T cells that will inform future vaccine development against this and other pathogens.

Protective immunity against Chlamydia trachomatis can engage both CD4+ and CD8+ T cells and bridge the respiratory and genital mucosae.

Understanding the cellular populations and mechanisms responsible for overcoming immune compartmentalization is valuable for designing vaccination strategies targeting distal mucosae. In this study, we show that the human pathogen Chlamydia trachomatis infects the murine respiratory and genital mucosae and that T cells, but not Abs, elicited through intranasal immunization can protect against a subsequent transcervical challenge. Unlike the genital infection where CD8(+) T cells are primed, yet fail to confer protection, we found that intranasal priming engages both CD4(+) and CD8(+) T cells, allowing for protection against genital infection with C. trachomatis. The protection is largely dependent on IFN-γ secretion by T cells. Moreover, different chemokine receptors are critical for C. trachomatis-specific CD4(+) T cells to home to the lung, rather than the CXCR3- and CCR5-dependent migration observed during genital infection. Overall, this study demonstrates that the cross-mucosa protective immunity against genital C. trachomatis infection following intranasal immunization is not dependent on Ab response but is mediated by not only CD4(+) T cells but also by CD8(+) T cells. This study provides insights for the development of vaccines against mucosal pathogens that threaten reproductive health worldwide.

Changing etiologies and outcome of liver failure in Southwest China.

BACKGROUND: The prognosis of liver failure depends greatly on the underlying cause, and there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts. METHODS: We screened out 3171 liver failure cases from 25467 patients hospitalized in our department between 2000 and 2012 according to Chinese criteria, and determined their etiologies and prognosis. RESULTS: 97.3 % cases were associated with at least one of 25 identified factors. The 3 leading etiologies were HBV (91.6 %), alcohol (18.1 %) and antiviral therapy (AVT) related hepatitis B flares (6.7 %). Acute-on-chronic liver failure (ACLF) accounted for 92.1 % of all cases. 96.5 % ACLF cases were associated with HBV, in which the percentage of AVT related flares increased from 0 % in 2000 up to 11.5 % in 2012, and hepatitis virus superinfection declined from peak 19.3 % in 2002 down to 2.5 % in 2012. Three-month spontaneous survival (SS) rate of 3171 cases was 31.4 %, but improved from 17.4 % in 2000 up to 40.4 % in 2012. SS was significantly different among various etiological groups (P = 0.000). In HBV related liver failure aged 25 to 54 years, males accounted for 87.6 %, and had a progressively decreased SS with increasing age. From 25 to 54 years, SS was lower in male than in female HBV related liver failure, and having significant difference in cases of ages 40 to 44 years (27.6 % versus 50.9 %, P = 0.001). CONCLUSION: Etiologies of liver failure were numerous and varied in southwest China. HBV was the most leading cause of liver failure, especially in ACLF. AVT related flares had become the third leading cause of ACLF. The prognosis of liver failure remained poor, but had markedly improved in recently 3 years. Middle-aged male HBsAg carriers had an extremely higher risk for liver failure and worse prognosis compared to female. 1. Etiologies of liver failure were numerous and varied in southwest China. HBV infection is the main cause of liver failure in southwest China, especially the major cause of ACLF. Antiviral related liver failure, especially the NUCs withdrawal induced ACLF were extremely increased, which has replaced the superinfection as the third important cause of HBV-ACLF. 2. The prognosis of liver failure is still poor, but the spontaneous survival rate showed a trend of steady rise in recent years. The prognosis of patients with liver failure caused by different causes also exists certain difference, the more damage factors bulls the worse prognosis. 3. The prognosis of the HBV and HCV reactivation induced by the steroids was poor.Interferon treatment of CHB in ACLF although rare, but should be taken into consideration seriously. 4. Patients with liver failure caused by different etiologies showed larger differences of gender and age distribution. Gender and age are the important factors with the occurrence and prognosis of HBV-ACLF.

IFNγ inhibits the cytosolic replication of Shigella flexneri via the cytoplasmic RNA sensor RIG-I.

The activation of host cells by interferon gamma (IFNγ) is essential for inhibiting the intracellular replication of most microbial pathogens. Although significant advances have been made in identifying IFNγ-dependent host factors that suppress intracellular bacteria, little is known about how IFNγ enables cells to recognize, or restrict, the growth of pathogens that replicate in the host cytoplasm. The replication of the cytosolic bacterial pathogen Shigella flexneri is significantly inhibited in IFNγ-stimulated cells, however the specific mechanisms that mediate this inhibition have remained elusive. We found that S. flexneri efficiently invades IFNγ-activated mouse embryonic fibroblasts (MEFs) and escapes from the vacuole, suggesting that IFNγ acts by blocking S. flexneri replication in the cytosol. This restriction on cytosolic growth was dependent on interferon regulatory factor 1 (IRF1), an IFNγ-inducible transcription factor capable of inducing IFNγ-mediated cell-autonomous immunity. To identify host factors that restrict S. flexneri growth, we used whole genome microarrays to identify mammalian genes whose expression in S. flexneri-infected cells is controlled by IFNγ and IRF1. Among the genes we identified was the pattern recognition receptor (PRR) retanoic acid-inducible gene I (RIG-I), a cytoplasmic sensor of foreign RNA that had not been previously known to play a role in S. flexneri infection. We found that RIG-I and its downstream signaling adaptor mitochondrial antiviral signaling protein (MAVS)--but not cytosolic Nod-like receptors (NLRs)--are critically important for IFNγ-mediated S. flexneri growth restriction. The recently described RNA polymerase III pathway, which transcribes foreign cytosolic DNA into the RIG-I ligand 5'-triphosphate RNA, appeared to be involved in this restriction. The finding that RIG-I responds to S. flexneri infection during the IFNγ response extends the range of PRRs that are capable of recognizing this bacterium. Additionally, these findings expand our understanding of how IFNγ recognizes, and ultimately restricts, bacterial pathogens within host cells.

[Effect of L-ornithine L-aspartate granules in treating chronic liver disease in patients with high-level serum gamma-glutamyltransferase].

OBJECTIVE: To explore the clinical effect of L-ornithine L-aspartate (LOLA) granules in treating chronic liver disease in patients with high-level serum gamma-glutamyltransferase (G-GT) using a 24-week treatment course. METHODS: Two-hundred patients with chronic liver disease and above normal G-GT were given a 12-week course of LOLA granules (9 g/d) and then classified into the following three groups according to the change in serum Gamma-GT:group I:patients with Gamma-GT level returned to normal;group II:patients with serum Gamma-GT level that was reduced during the treatment; group III:patients with serum Gamma-GT level that did not decrease or that increased to a higher level than at start of treatment.After the 12-week treatment course, the patients in group I were divided into three subgroups for receipt of a control drug (compound glycyrrhizin, 50mg/d) or an additional 12-week course of Gamma-GT at a reduced dose (LOLA granules 3 g/d) or at the original dose; groups II and III were maintained on the initial dose for an additional 12 weeks.The groups were reassessed at the end of the second 12-week course (at the end of week 24 of the study's observation period).Count data were compared using the x2 test and measurement data were compared using the t-test. RESULTS: In group I, the serum Gamma-GT level was 90.9% at the end of the first 12-week course and dropped to a mean level of 52.2% for both of the subgroups that received the reduced and original dose after the additional 12 weeks of LOLA granules treatment; the difference from week 12 to week 24 was significant (x2=8.213, P less than 0.05).The 24-week change in serum Gamma-GT levels for the group I reduced and original dose subgroups vs.the control subgroup were also significantly different from those seen in groups II and III (P less than 0.05).The percentage of patients in group I who achieved normal level serum Gamma-GT after 24 weeks of treatment (78.6%) was significantly higher than that for the control group (vs.55.0%, x2=11.452, P less than 0.05).When the patients in group 1 who had received the 12 additional weeks of LOLA granules treatment were measured again at two weeks after the treatments had been discontinued (end of week 26), the percentage of patients with normal serum Gamma-GT level was 92.7%, with only three cases showing obviously abnormal levels; in contrast, the group I patients in the control group of the second 12-week study period had on 66.7% of patients with normal-level serum Gamma-GT.The difference in change between the treated groups (both reduced and original dose) and the control group was significant (x2=14.964, P less than 0.05). CONCLUSION: Patients whose serumGamma-GT levels returned to normal after receipt of LOLA granules for 12 weeks benefitted from an additional 12 weeks of consolidation treatment, and those given the treatment at the original dose benefitted most.Compared with the compound glycyrrhizin, LOLA granules provided a better maintenance of resolved Gamma-GT level.Therefore, the effect of LOLA appears to be reliable and stable as well as safe for clinical use.

Correlation investigation between core microbe inoculation and the evolution of flavor characteristics during the storage of sturgeon caviar (Acipenser gueldenstaedtii).

The volatile and non-volatile compounds were monitored to investigate the microbial evolution associated with the characteristic flavors for sturgeon caviar during refrigeration. The results revealed that the composition of volatile compounds changed significantly with prolonged refrigeration time, especially hexanal, nonanal, phenylacetaldehyde, 3-methyl butyraldehyde, and 1-octen-3-ol. The nonvolatile metabolites were mainly represented by the increase of bitter amino acids (Thr. Ser, Gly, Ala, and Pro) and a decrease in polyunsaturated fatty acids, especially an 18.63 % decrease in 5 months of storage. A total of 332 differential metabolites were mainly involved in the biosynthetic metabolic pathways of α-linolenic acid, linoleic acid, and arachidonic acid. The precursors associated with flavor evolution were mainly phospholipids, including oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. The most abundant at the genus level was Serratia, followed by Arsenophnus, Rhodococcus, and Pseudomonas, as obtained by high-throughput sequencing. Furthermore, seven core microorganisms were isolated and characterized from refrigerated caviar. Among them, inoculation with Mammalian coccus and Bacillus chrysosporium restored the flavor profile of caviar and enhanced the content of nonvolatile precursors, contributing to the characteristic aroma attributes of sturgeon caviar. The study presents a theoretical basis for the exploitation of technologies for quality stabilization and control of sturgeon caviar during storage.

Efficacy of pegylated interferon α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy.

BACKGROUND: Improving the HBe seroconversion rate of patients without HBeAg loss after long-term lamivudine therapy has become an urgent clinical problem that we have to face. Unfortunately, there is no consensus on the mananement of these patients. The aim of this study was to evaluate the efficacy of pegylated interferon (PEG-IFN) α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy. METHODS: Fifty patients with chronic hepatitis B without the loss of HBeAg after ≥96 weeks of lamivudine treatment were enrolled to withdraw from treatment to induce a biochemical breakthrough. Patients who achieved a biochemical breakthrough within 24 weeks received 48-weeks of PEG-IFN α2a therapy, and were then assessed during a subsequent 24-week follow-up period. RESULTS: Forty-three (86.0%) patients achieved a biochemical breakthrough within 24 weeks of lamivudine withdrawal. The rates of combined response (both undetectable HBV DNA and HBeAg loss) and HBsAg loss were alone 51.2% and 20.9%, respectively after 48 weeks of PEG-IFN α2a therapy, and 44.2% and 18.6%, respectively, at 24 weeks after treatment cessation. The end-of-treatment combined response rate was 65.4% among patients with a baseline HBsAg <20,000 IU/mL, which was significantly higher than 29.4% of patients with HBsAg ≥20,000 IU/mL (P=0.031). For patients with HBsAg levels <1,500 IU/mL at 12 and 24 weeks therapy, the end-of-treatment combined response rate was 68.2% and 69.0%, which were both significantly higher than patients with HBsAg ≥1,500 IU/mL (33.3% and 14.3%; P=0.048 and 0.001). The end-of-treatment combined response rate was significantly higher among patients with HBV DNA<105 copies/mL (76.2%) compared to patients with HBV DNA ≥105 copies/mL (27.3%) after 24 weeks of therapy (P=0.004). CONCLUSION: Retreatment with PEG-IFN α2a was effective and safe for patients without HBeAg loss after the withdrawal of long-term lamivudine therapy. HBsAg levels at the baseline, 12 and 24 weeks of therapy, and HBV DNA levels at 24 weeks of therapy, can predict the effect of PEG-IFN α2a after 48 weeks of therapy.