Flexible free-standing Fe-CoP-NAs/CC nanoarrays for high-performance full lithium-ion batteries.

In this study, a flexible, free-standing Fe-doped CoP nanoarrays electrode for superior lithium-ion storage has been successfully fabricated. The electrode combines the advantages of a Fe-doping and a flexible carbon cloth (CC) support, resulting in a high specific capacity (1356 mAh/g at 0.2 A/g) and excellent cycling stability (1138 mAh/g after 100 cycles). The cyclic voltammetry (CV) curves at different scan rates investigate the outstanding lithium storage behavior of Fe-CoP-NAs/CC which indicates a combined influence of diffusion behavior and capacitance behavior on the electrochemical process. The galvanostatic intermittent titration technique (GITT) analyzes the diffusion kinetics of Li+ which indicates the fast diffusion kinetics in the Fe-CoP/NAs/CC anode. The assembled Fe-CoP-NAs/CC//LiFePO4 battery exhibits a remarkable capacity of 325.2 mAh/g even at 5 A/g. And the battery also has good cycle stability, and still provides 498.1 mAh/g specific capacity after 200 cycles. Moreover, the Fe-CoP-NAs/CC//LiFePO4 soft-pack battery can continuously power the LEDs when it is bent at various angles which demonstrates its potential for use in wearable devices.

Design of a Multi-Position Alignment Scheme.

The current new type of inertial navigation system, including rotating inertial navigation systems and three-autonomy inertial navigation systems, has been increasingly widely applied. Benefited by the rotating mechanisms of these inertial navigation systems, alignment accuracy can be significantly enhanced by implementing IMU (Inertial Measurement Unit) rotation during the alignment process. The principle of suppressing initial alignment errors using rotational modulation technology was investigated, and the impact of various component error terms on alignment accuracy of IMU during rotation was analyzed. A corresponding error suppression scheme was designed to overcome the shortcoming of the significant scale factor error of fiber optic gyroscopes, and the research content of this paper is validated through corresponding simulations and experiments. The results indicate that the designed alignment scheme can effectively suppress the gyro scale factor error introduced by angular motion and improve alignment accuracy.

Effect of gold-conjugated resveratrol nanoparticles on glioma cells and its underlying mechanism.

BACKGROUND:  Glioblastoma is the most aggressive brain tumor with poor prognosis. Although Resveratrol (Rsv) is known to have therapeutic effects on glioma, the effects of gold-conjugated resveratrol nanoparticles (Rsv-AuNPs) on glioma cells are rarely reported. OBJECTIVE: We aimed to investigate the effects of Rsv-AuNPs on glioma cells and its underlying mechanism. METHOD: Human glioma cell line U87 was treated with different concentrations of Rsv-AuNPs. CCK-8, transwell, and wound healing assay were performed to measure the effects of Rsv-AuNPs on cell proliferation, invasion, and migration ability, respectively. Flow cytometry assay was used to detect the effects of Rsv-AuNPs on apoptosis. Changes of protein expressions related to proliferation, invasion, migration, and apoptosis were measured by Western blot assay. In addition, the inhibitory role of Rsv-AuNPs in the PI3K/AKT/mTOR signaling pathway was verified by using PI3K inhibitor LY294002. RESULTS: Rsv-AuNPs treatment significantly suppressed proliferation, migration, and invasion of U87 cells (all P < 0.05) and increased the apoptosis rate (P < 0.05). The changes of proteins related to proliferation, migration, invasion and apoptosis were consistent (all P < 0.05). Moreover, Rsv-AuNPs treatment significantly inhibited the phosphorylation of PI3K, AKT and mTOR proteins in U87 cells (P < 0.05). CONCLUSION: The present study found that Rsv-AuNPs inhibited the proliferation, migration, and invasion of U87 cells and induced apoptosis by inhibiting the activation of PI3K/AKT/mTOR signaling pathway. In the future, Rsv-AuNPs might be applied to the clinical treatment of glioma through more in-depth animal and clinical research.

Temperature-dependent decomposition of the CL-20/MTNP cocrystal after phase separation.

CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane)-based cocrystals are attractive energetic cocrystals with a potential for high energy and low sensitivity, which account for nearly one-third of energetic cocrystals. The applications of cocrystal explosives require in-depth understanding of their thermal kinetics behaviors. Although thermal kinetics of the decomposition of CL-20-based cocrystals having no melting point have been studied, relevant research of CL-20-based cocrystals having a melting point, which are also the most frequently observed type, is still rare. In this study, the CL-20/MTNP (1-methyl-3,4,5-trinitropyrazole) cocrystal was chosen as a typical CL-20-based cocrystal having a melting point to investigate its thermal kinetics behavior. The thermal decomposition of CL-20/MTNP was identified to be a typical heterogeneous reaction with phase separation before decomposition. Due to the presence of intermolecular hydrogen bonds between CL-20 and molten MTNP after phase separation, the thermal decomposition behavior of CL-20/MTNP was strongly temperature-dependent. The complex decomposition reaction was separated into its three constituent pathways to simplify the kinetic analysis. On the basis of in-depth understanding of the decomposition process, the best functions of mechanism and kinetic parameters for each process of CL-20/MTNP decomposition were obtained using the model-fitting method. Finally, important thermal safety indicators, such as TMRad and SADT were simulated by combining the established kinetic models. This study provides further insights into the entire reaction process of the CL-20/MTNP cocrystal and would help in its better applications.

Application of multi-channel in situ infrared spectroscopy: the case of PVB thermal aging.

Thermal kinetic parameters are important for establishing the relationship between the aging process, time, and temperature, which would help predict the thermal aging lifetime and stability in the application of polymer materials. We developed a multi-channel in situ detecting device, which provided an efficient method for IR spectrum measurement. The thermal aging process of polyvinyl butyral (PVB) at several constant temperatures (100 °C, 110 °C, 120 °C, 135 °C, and 150 °C) had been studied by the multi-channel in situ infrared reaction device. The kinetic parameters (Eα) were calculated from the absorbance intensity of -C-O-, -C[double bond, length as m-dash]O, -CH3, and -OH. The -OH proved to be the active site of PVB during thermal aging, and a possible thermal aging mechanism of PVB was proposed. We proved the method using a combination of a multi-channel in situ reaction device and FTIR was suitable to study the aging mechanism and kinetics of polymers.

The Mechanical Properties of Silicone Rubber Composites with Shear Thickening Fluid Microcapsules.

In this study, Sylgard 184 silicone rubber (SylSR) matrix composites with shear thickening fluid (STF) microcapsules (SylSR/STF) were fabricated. Their mechanical behaviors were characterized by dynamic thermo-mechanical analysis (DMA) and quasi-static compression. Their damping properties increased with the addition ofSTF into the SR in DMA tests and the SylSR/STF composites presented decreased stiffness and an obvious positive strain rate effect in the quasi-static compression test. Moreover, the impact resistance behavior of the SylSR/STF composites was tested by the drop hammer impact test. The addition of STF enhanced the impact protective performance of silicone rubber, and the impact resistance increased with the increase of STF content, which should be ascribed to the shear thickening and energy absorption of STF microcapsules in the composites. Meanwhile, in another matrix, hot vulcanized silicone rubber (HTVSR) with a mechanical strength higher than Sylgard 184, the impact resistance capacity of its composite with STF (HTVSR/STF) was also examined by the drop hammer impact test. It is interesting to note that the strength of the SR matrix obviously influenced the enhancement effect of STF on the impact resistance of SR. The stronger the strength of SR, the better the effect of STF on improving the impact protective performance of SR. This study not only provides a new method for packaging STF and improving the impact resistance behavior of SR, but is also beneficial for the design of STF-related protective functional materials and structures.

Effectiveness of an optional breastfeeding course for multidisciplinary undergraduate healthcare students: A quasi-experimental study.

AIMS: This study aimed to examine and quantify the effectiveness of an optional breastfeeding course for multidisciplinary undergraduate healthcare students and to provide advice for education improvement based on students' characteristics and learning feedback. BACKGROUND: Breastfeeding has received global awareness and educating undergraduate healthcare students is a prospective way to promote breastfeeding. This is the first report from mainland China to verify the education effects and formulate a proposal for improvement. DESIGN: A quasi-experimental study with a one-group pretest-posttest design. METHODS: An optional breastfeeding course covering eight topics based on the Health Belief Model was conducted for multidisciplinary students in a medical college. The Breastfeeding Knowledge Questionnaire, Iowa Infant Feeding Attitude Scale and Breastfeeding Promotion Intention Scale were completed for pre- and post-education comparison. The Wilcoxon signed-rank test, MannWhitney U test, KruskalWallis test and chi-square test were used for statistical analysis. The class average normalized gain and individual students' normalized gain were calculated to quantify the effectiveness from the perspective of learning gain. RESULTS: From March to November 2021, 102 students specialized mainly in nursing, clinical medicine, medical imaging technology and midwifery took the course. Knowledge, attitudes and intention scores improved significantly (Z = 8.70, 8.72, 7.64, respectively, p < .001) and the class average normalized gains were 81.0%, 52.3% and 70.6%, respectively. Insignificant differences were found for students of different genders and categories of specialties (p > .05). Students of first year had significantly higher individual normalized gains (p < .05). In learning feedback, the top-ranked advice for course improvement was to increase practice and experience (75.5%). CONCLUSIONS: This optional breastfeeding course produced medium to high learning gains for multidisciplinary healthcare undergraduates. Independent breastfeeding education based on behavioral theory for multidisciplinary students is recommended to be conducted in medical colleges. The addition of practice and experience may add value to such education.

Utilizing an Automated SERS-Digital Microfluidic System for High-Throughput Detection of Explosives.

The surface-enhanced Raman scattering (SERS) technique is a promising method for the detection of explosives such as 2,4,6-trinitrotoluene (TNT) and 3-nitro-1,2,4-triazol-5-one (NTO) because of its high sensitivity to trace substances. However, most SERS detection processes are often nonautomated as well as exhibit low efficiency and toxic exposure, which often poses potential danger to operators. Herein, we propose the integration of SERS with digital microfluidics (SERS-DMF) for automated, high-throughput, and high-sensitivity detection of explosives. First, we carefully designed a DMF chip comprising 40 drive electrodes and 8 storage electrodes to achieve a high-throughput process. And different concentrations of target molecules, silver nanoparticles (Ag NPs), and salts were loaded into the DMF chip. Then, the droplet aggregation, incubation, and detection processes were automatically controlled using the SERS-DMF platform. In addition, Ag NPs were efficiently aggregated by screening different types and concentrations of salts, resulting in "hotspots" and the SERS effect. With the help of the SERS-DMF platform, two explosive samples were automatically detected with high throughput and high sensitivity. The detection limits of TNT and NTO were 10-7 and 10-8 M, respectively. In addition, compared with nonautomatic operations, the SERS-DMF platform exhibited better reproducibility and higher efficiency for the detection of explosives. The proposed SERS-DMF thus has considerable potential as an analytical technique for detecting hazardous substances.

Fabrication of flexible AuNPs@ polyimide heating chips for in situ explosives SERS sensing in nature samples.

In this study, highly sensitive flexible AuNPs@ polyimide SERS heating chips (APHC) were fabricated for in situ collecting and detecting TNT. Large-scale AuNPs arrays were synthesized by liquid-liquid interface self-assembly and transferred to polyimide heating film as SERS substrates. 4-ATP and AgNPs functionalized on APHC were used as capture means and signal amplifiers, combining with TNT to form the AuNPs-TNT-AgNPs "sandwich" structure. This flexible APHC chip showed high sensitivity as enhancement factor was 5.5×105, and good repeatability and stability (RSD<10%). It was applied to detect TNT solutions with a low concentration of 10-9 M, and showed a good linear response in the range from 10-5 to 10-9 M (R2 = 0.986). In addition, the detection method also had good selectivity and no response to various TNT analogs. More important, combing with the thermal enrichment strategy, TNT dispersed in environmental samples such as soil, fruit and clothing would be enriched as vapor then collected and detected by APHC. This APHC device shows great potential for in situ sensing platforms, due to its sensitivity, high efficiency, and excellent portability.

Single-Position Complete Retroperitoneoscopic Radical Nephroureterectomy with Bladder Cuff Excision for Upper Urinary Tract Urothelial Carcinoma.

Purpose: We proposed a new technique, single-position complete retroperitoneoscopic radical nephroureterectomy (SCRNU), which proved to be efficient for the treatment of upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: In this study, we retrospectively evaluated 86 patients diagnosed with UTUC at our hospital from June 2013 to June 2021. The patients who underwent traditional retroperitoneoscopic nephroureterectomy (TRNU) (n = 28) and SCRNU (n = 58) were consecutively enrolled. Demographic characteristics, perioperative parameters, and follow-up data were collected and compared between the two groups. Results: Both procedures were performed effectively in 86 patients without converting to open surgery. The mean follow-up time was 45.4 months for the SCRNU group and 39 months for the TRNU group. All follow-up patients survived without incidence of bladder incision tumor. Further, the follow-up results showed that there was no significant difference in the recurrence rate of bladder tumor between the two methods. SCRNU group was superior to TRNU group because of shorter operating time, fewer perioperative complications, less postoperative pain, lower recurrence rate, and cheaper medical expenditure. Conclusions: The SCRNU technique is less invasive, have fewer complications, and has a better cosmetic outcome.

Characterization and acceleration of genome shuffling and ploidy reduction in synthetic allopolyploids by genome sequencing and editing.

Polyploidy and the subsequent ploidy reduction and genome shuffling are the major driving forces of genome evolution. Here, we revealed short-term allopolyploid genome evolution by sequencing a synthetic intergeneric hybrid (Raphanobrassica, RRCC). In this allotetraploid, the genome deletion was quick, while rearrangement was slow. The core and high-frequency genes tended to be retained while the specific and low-frequency genes tended to be deleted in the hybrid. The large-fragment deletions were enriched in the heterochromatin region and probably derived from chromosome breaks. The intergeneric translocations were primarily of short fragments dependent on homoeology, indicating a gene conversion origin. To accelerate genome shuffling, we developed an efficient genome editing platform for Raphanobrassica. By editing Fanconi Anemia Complementation Group M (FANCM) genes, homoeologous recombination, chromosome deletion and secondary meiosis with additional ploidy reduction were accelerated. FANCM was shown to be a checkpoint of meiosis and controller of ploidy stability. By simultaneously editing FLIP genes, gene conversion was precisely introduced, and mosaic genes were produced around the target site. This intergeneric hybrid and genome editing platform not only provides models that facilitate experimental evolution research by speeding up genome shuffling and conversion but also accelerates plant breeding by enhancing intergeneric genetic exchange and creating new genes.

Distribution of hepatitis B virus genotypes and subgenotypes: A meta-analysis.

ABSTRACT: Hepatitis B virus (HBV) genotypes and subgenotypes have distinct geographical distributions and influence a number of clinical disease features and responses to treatment. There are many reports on the distribution of HBV genotypes, but great differences are present between studies. What's more, a meta-analysis of HBV genotype- and subgenotype-distribution by country is lacking.A comprehensive literature search was performed in PubMed and a systematic search of full-length HBV sequences and S gene sequences was conducted in the GenBank database. HBV genotypes were checked and subgenotypes were determined by phylogenetic comparison of full-length HBV sequences or S gene sequences. STATA 12.0 was used for the analysis for countries with multiple datasets. BEAST 2.5.2 was used for Bayesian phylogenetic analysis to infer the evolutionary time scales of HBV.This study includes 309 datasets from 110 countries, including 188 relevant studies, 58 full-length gene datasets, and 63 S gene datasets. The meta-analysis was performed on 274 datasets from 75 countries. The distribution of genotypes is more detailed than those described by previous studies. While the overall genotype distribution is similar to that reported in previous studies, some notable aspects were different. The main genotypes present in south-eastern Africa, North Africa, and West Africa are genotypes A, D, and E, respectively. Genotypes G and H are mainly distributed in Mexico. Genotype F is mainly distributed in central and South America, but genotypes A and D are also common in Brazil, Cuba, and Haiti.This study provides a more accurate description of the distribution of HBV genotypes and subgenotypes in different countries and suggests that the differences in genotype distribution may be related to ethnicity and human migration.

Evaluation of dithiothreitol-oxidizing capacity (DOC) as a serum biomarker for chronic hepatitis B in patients exhibiting normal alanine aminotransferase levels: a pilot study towards better monitoring of disease.

BACKGROUND: Alanine aminotransferase (ALT) is the most commonly used serum biomarker for chronic liver diseases (CLDs) but may not accurately reflect hepatic disorders and easily underestimates hepatic fibrosis. The previously revised upper limit of normal (ULN) of ALT (19 U/L for women and 30 U/L for men) increases its sensitivity but yields higher numbers of false-positives. Moreover, CLDs patients with ALT lower than the revised ULN may nonetheless have progression of disease. Therefore there is a need of novel biomarkers to complement the use of ALT. Here we have evaluated measurements of serum dithiothreitol-oxidizing capacity (DOC) in cohorts of chronic hepatitis B patients with different stages of disease as an exploratory pilot study for this purpose. METHODS: Serum samples obtained from healthy persons and from chronic hepatitis B patients with normal ALT values were used for sensitivity evaluation. The hepatitis B patients encompassed end-stage liver diseases (ELD), chronic hepatitis B (CHB), CHB with persistently normal ALT (CHB-P) and inactive carriers (ICs). Sensitivity was also evaluated with samples from patients with other diseases. The study period was March 2018 to December 2020. FINDINGS: DOC was found to be a robust biomarker that may become complementary to ALT measurements, especially in patients displaying low ALT levels. ROC analyses indicated that the AUC values of DOC reached 0.983 and 0.956 in ELD and CHB patients exhibiting normal ALT levels, respectively. Importantly, the AUC values of DOC reached 0.852 and 0.844 in CHB-P patients and ICs, respectively. Such AUC values permit screening and continued monitoring, corresponding to over 30% and 50% sensitivity with 99% and 95% specificity for CHB-P and ICs, respectively. DOC was also significantly correlated with indicators for fibrosis, assessing both APRI (Pearson r = 0.4905, P < 0.0001) and FIB-4 (Pearson r = 0.4421, P < 0.0001). Surprisingly, the AUC values of DOC in the hepatitis B patients with ALT levels lower than the revised ULN were not compromised. In examined non-liver diseases, DOC was low and normal, including in patients with acute myocardial infection displaying increased ALT levels. INTERPRETATIONS: The results suggest that DOC can be promising as a complementary biomarker used in addition to ALT for monitoring of disease in chronic hepatitis B patients, especially when ALT levels are normal. DOC should be further evaluated for possible clinical use as biomarker also in other CLDs. FUNDING: This study was funded by the National Natural Science Foundation of China (Grant numbers: 31771971 and 32001013).

Assessing SARS-CoV-2 RNA levels and lymphocyte/T cell counts in COVID-19 patients revealed initial immune status as a major determinant of disease severity.

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokine profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied, but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission, significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.

Discrimination of False Negative Results in RT-PCR Detection of SARS-CoV-2 RNAs in Clinical Specimens by Using an Internal Reference.

Reverse transcription-polymerase chain reaction (RT-PCR) is an essential method for specific diagnosis of SARS-CoV-2 infection. Unfortunately, false negative test results are often reported. In this study, we attempted to determine the principal causes leading to false negative results of RT-PCR detection of SARS-CoV-2 RNAs in respiratory tract specimens. Multiple sputum and throat swab specimens from 161 confirmed COVID-19 patients were tested with a commercial fluorescent RT-PCR kit targeting the ORF1ab and N regions of SARS-CoV-2 genome. The RNA level of a cellular housekeeping gene ribonuclease P/MRP subunit p30 (RPP30) in these specimens was also assessed by RT-PCR. Data for a total of 1052 samples were retrospectively re-analyzed and a strong association between positive results in SARS-CoV-2 RNA tests and high level of RPP30 RNA in respiratory tract specimens was revealed. By using the ROC-AUC analysis, we identified Ct cutoff values for RPP30 RT-PCR which predicted false negative results for SARS-CoV-2 RT-PCR with high sensitivity (95.03%-95.26%) and specificity (83.72%-98.55%) for respective combination of specimen type and amplification reaction. Using these Ct cutoff values, false negative results could be reliably identified. Therefore, the presence of cellular materials, likely infected host cells, are essential for correct SARS-CoV-2 RNA detection by RT-PCR in patient specimens. RPP30 could serve as an indicator for cellular content, or a surrogate indicator for specimen quality. In addition, our results demonstrated that false negativity accounted for a vast majority of contradicting results in SARS-CoV-2 RNA test by RT-PCR.

Elevated Interleukin-6 Levels within 72 Hours Post Admission Are Associated with Disease Progression in Nonseptic Critically Ill Children.

It has been established that the innate and adaptive immune suppression was heterogeneous in septic and nonseptic critically ill patients, while the value of immune function in pediatric patients with nonseptic critical illness is limited. We conducted a single-center retrospective study to explore this issue. A total of 65 children with nonseptic illnesses were studied for lymphocyte subpopulations, immunoglobulin concentrations, complement concentrations, and cytokines in peripheral blood in the next 72 hours after admission to our Pediatric Intensive Care Unit (PICU). When compared to clinically recovered patients, patients with disease progression had a numerically lower but not significantly different median pediatric critical illness score and longer PICU median stays. The analysis of serum immunoglobulin (IgG, IgM, and IgA), serum complement (C3, C4) concentrations, and lymphocyte subpopulations showed no significantly difference between patients with and without relieved clinical symptoms by day 4. For the cytokine analysis, the level of IL-6 was significantly higher in patients with disease progression than that in patients who clinically recovered (p = 0.046). In the univariate Cox regression analysis, plasma IL-6 levels were associated with outcome. Multivariate analysis evidenced that the level of plasma IL-6 was one of the factors determining the length of hospital stays. In conclusions, our results demonstrate that increased IL-6 levels in the initial 72 hours post admission are associated with prolonged stays and disease progression in nonseptic critically ill children in the PICU.

The establishment of reference sequence for SARS-CoV-2 and variation analysis.

Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.

Combination therapy based on pegylated interferon alfa improves the therapeutic response of patients with chronic hepatitis B who exhibit high levels of hepatitis B e-antigen at 24 weeks: A retrospective observational study.

Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16-5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47-7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50-8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09-26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.

Host Genetic Determinants of Hepatitis B Virus Infection.

Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.