Aerobic glycolysis of bronchial epithelial cells rewires Mycoplasma pneumoniae pneumonia and promotes bacterial elimination.

The immune response to Mycoplasma pneumoniae infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by M. pneumoniae infection in an in vitro model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during M. pneumoniae infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from M. pneumoniae-infected epithelial cells enhances the secretion of both interleukin (IL)-1ß and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R). In vivo experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.

Pressure-Driven Polymorphic Transition, Emergent Insulator-To-Metal Transition, and Photoconductivity Switching in Violet Phosphorus.

Polymorphic phase transition is an essential phenomenon in condensed matter that the physical properties of materials may undergo significant changes due to the structural transformation. Phase transition has thus become an important means and dimension for regulating material properties. Herein, this study demonstrates the pressure-induced multi-transition of both structure and physical properties in violet phosphorus, a novel phosphorus allotrope. Under compression, violet phosphorus undergoes sequential polymorphic phase transitions. Concomitant with the first phase transition, violet phosphorus exhibits emergent insulator-metal transition, superconductivity, and dramatic switching from positive to negative photoconductivity. Remarkably, the resistance of violet phosphorus shows a sudden drop of around 107 along with the phase transition. In addition, piezochromism from translucent red to opaque black and suppression of photoluminescence are observed upon compression. Of particular interest is that the sample irreversibly transforms into black phosphorus with a pronounced discrepancy in physical properties from the pristine violet phosphorus after decompression. The abundant polymorphic transitions and property changes in violet phosphorus have significant implications for designing novel pressure-responsive electronic/optoelectronic devices and exploring concealed polymorphic transition materials.

An Ultrathin Composite Polymer Electrolyte Dual-Reinforced by a Polymer of Intrinsic Microporosity (PIM-1) and Poly(tetrafluoroethylene) (PTFE) Porous Membrane.

The performances of solid-state polymer electrolytes are urgently required to be further improved for high energy density lithium metal batteries. Herein, a highly reinforced ultrathin composite polymer electrolyte (PLPP) is successfully fabricated in a large scale by densely filling the well-dispersed mixture of polyethylene oxide (PEO), Li-salt (LiTFSI) and a polymer of intrinsic microporosity (PIM-1) into porous poly(tetrafluoroethylene) (PTFE) matrix. Based on the macro-plus-micro synergistic enhancement of the PTFE with excellent mechanical properties and the soluble PIM-1 with suitable functional groups, the PLPP electrolyte exhibits excellent properties including mechanical stress, thermal stability, lithium-ion transference number, voltage window and ionic conductivity, which are all superior to the typical PEO/LiTFSI electrolytes. As a result, the Li/PLPP/Li symmetric cell can stably cycle for > 2000 h, and the LiFePO4/PLPP/Li full cell exhibits excellent rate performance (>10 C) and high cycling stability with an initial capacity of 158.8 mAh g-1 and a capacity retention of 78.8% after 300 cycles. In addition, the excellent mechanical properties as well as the wide voltage window reasonably result in the stable operation of full cells with either high-loading cathode up to 28.1 mg cm-2 or high voltage cathode with high energy density.

HMGB1 regulates autophagy of placental trophoblast through ERK signaling pathway.

OBJECTIVE: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth. METHODS: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role. RESULTS: Our findings indicate that HMGB1flox/floxElf5cre/+ mouse display fetal growth restriction (FGR), characterized by decreased placental and fetal weight and impaired bone development. And the absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes. CONCLUSIONS: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development.

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. MATERIALS AND METHODS: In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. RESULTS: Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. CONCLUSIONS: We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.

Investigation of the immune escape mechanism of Treponema pallidum.

BACKGROUND: Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subspecies pallidum (T. pallidum), which is a public health problem that seriously affects human health worldwide. T. pallidum is characterized by early transmission and immune escape and is therefore termed an "invisible pathogen". METHODS: This review systematically summarizes the host's innate and adaptive immune responses to T. pallidum infection as well as the escape mechanisms of T. pallidum. PURPOSE: To lay the foundation for assessing the pathogenic mechanism and the systematic prevention and treatment of syphilis. CONCLUSION: The immune escape mechanism of T. pallidum plays an important role in its survival. Exploring the occurrence and development of these mechanisms has laid the foundation for the development of syphilis vaccine.

Improved bone and renal safety in younger tenofovir disoproxil fumarate experienced chronic hepatitis B patients after switching to tenofovir alafenamide or entecavir.

INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.

The effect of age on task switching: updated and extended meta-analyses.

Cognitive flexibility is one of the crucial abilities for human survival. As people get older, whether their flexibility ability will be affected is one of the core research topics in aging research. Researchers have developed a task-switch paradigm in laboratories to mimic daily-life shifting task-set scenarios. However, the empirical evidence is equivocal. Considering every single study may have a biased sample; therefore, we hoped to combine smaller studies, making them into one extensive investigation, which may help show an actual effect. In the current study, we used two meta-analysis techniques, the Brinley plot (along with the State-trace plot) and conventional meta-analysis, to re-evaluate whether healthy aging influences cognitive flexibility. The results of the Brinley plot analysis showed no evidence of switch-specific age-related impairment as indexed by the local switch cost. Yet, older adults performed more slowly than younger adults across task conditions. The conventional meta-analysis further showed that the currently available findings were heterogenous and exhibited publication bias. Therefore, this study suggests that researchers should interpret their results cautiously while using a task-switching paradigm to address older adults' shifting abilities. More parametric variables must be considered and developed in a task-switching paradigm to enhance its sensitivity and reveal older adults' actual shifting ability.

Benefit of [18F]-FDG PET/CT for treatment-naïve nasopharyngeal carcinoma.

BACKGROUND: To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. METHODS: The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. RESULTS: PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p < 0.001; 88.0% vs. 81.1%, p < 0.001; 0.863 vs. 0.796, p < 0.05) in diagnosing lymph nodes. Accordingly, MRI-staged T3N0-3M0 patients showed nondifferent survival rates, as they were the same T3N1M0 if staged by PET/CT. In addition, patients staged by PET/CT and MRI showed higher survival rates than those staged by MRI alone (p < 0.05), regardless of the Epstein-Barr virus DNA load. Interestingly, SUVmax-N, nodal necrosis, and extranodal extension were highly predictive of survival. The radiologic score model based on these factors performed well in risk stratification with a C-index of 0.72. Finally, induction chemotherapy showed an added benefit (p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). CONCLUSION: PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.

Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1.

Endothelial microparticles (EMPs) can be released in chronic kidney disease (CKD). Plasma concentration of high inorganic phosphate (HP) is considered as a decisive determinant of vascular calcification in CKD. We therefore explored the role of HP-induced EMPs (HP-EMPs) in the vascular calcification and its potential mechanism. We observed the shape of HP-EMPs captured by vascular smooth muscle cells (VSMCs) dynamically changed from rare dots, rosettes, to semicircle or circle. Our results demonstrated that HP-EMPs could directly promote VSMC calcification, or accelerate HP-induced calcification through signal transducers and activators of transcription 3 (STAT3)/bone morphogenetic protein-2 (BMP2) signaling pathway. AEG-1 activity was increased through HP-EMPs-induced VSMC calcification, in arteries from uremic rats, or from uremic rats treated with HP-EMPs. AEG-1 deficiency blocked, whereas AEG-1 overexpression exacerbated, the calcium deposition of VSMCs. AEG-1, a target of miR-153-3p, could be suppressed by agomiR-153-3p. Notably, VSMC-specific enhance of miR-153-3p by tail vein injection of aptamer-agomiR-153-3p decreased calcium deposition in both uremia rats treated with HP-EMPs or not. HP-EMPs could directly induce VSMCs calcification and accelerate Pi-induced calcification, and AEG-1 may act as crucial regulator of HP-EMPs-induced vascular calcification. This study sheds light on the therapeutic agents that influence HP-EMPs production or AEG-1 activity, which may be of benefit to treat vascular calcification.

Development and validation of radiologic scores for guiding individualized induction chemotherapy in T3N1M0 nasopharyngeal carcinoma.

OBJECTIVES: We aimed to develop and validate radiologic scores from [18F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC). METHODS: A total of 542 T3N1M0 patients who underwent pretreatment [18F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation. RESULTS: The sensitivity of [18F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p < 0.001) for diagnosing histologically proven metastatic cervical lymph nodes. Radiologic lymph node characteristics were independent risk factors for FFS (all p < 0.05). High-risk patients (n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort. CONCLUSIONS: T3N1M0 patients were accurately staged by both [18F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC. KEY POINTS: • [18F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes. • Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients. • High-risk patients identified by the radiologic score based on [18F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy.

Association between triglyceride-glucose index and nonalcoholic fatty liver disease in type 2 diabetes mellitus.

BACKGROUND: Lipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population. METHODS: A total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD. RESULTS: Logistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03-5.27; P < 0.001) for NAFLD in the highest TyG quartile after adjustment for known confounders. In stratified analysis, an elevated TyG index were more remarkably associated with NAFLD in younger patients (< 65 years; OR, 2.35; 95% CI, 1.83-3.02; P < 0.001), females (OR, 2.69; 95% CI, 1.67-4.32; P < 0.001), patients with BMI < 25 kg/m2 (OR, 2.80; 95% CI, 2.01-3.91; P < 0.0001), and with lower high-density lipoprotein cholesterol (< 1 mmol/L; OR, 2.76; 95% CI, 1.98-3.83; P < 0.001). CONCLUSION: The TyG index is significantly associated with NAFLD and shows superior ability for identify NAFLD risk compared with other lipid and glycemic parameters in T2DM.

Towards Exploring Large Molecular Space: An Efficient Chemical Genetic Algorithm.

Generating molecules with desired properties is an important task in chemistry and pharmacy. An efficient method may have a positive impact on finding drugs to treat diseases like COVID-19. Data mining and artificial intelligence may be good ways to find an efficient method. Recently, both the generative models based on deep learning and the work based on genetic algorithms have made some progress in generating molecules and optimizing the molecule's properties. However, existing methods need to be improved in efficiency and performance. To solve these problems, we propose a method named the Chemical Genetic Algorithm for Large Molecular Space (CALM). Specifically, CALM employs a scalable and efficient molecular representation called molecular matrix. Then, we design corresponding crossover, mutation, and mask operators inspired by domain knowledge and previous studies. We apply our genetic algorithm to several tasks related to molecular property optimization and constraint molecular optimization. The results of these tasks show that our approach outperforms the other state-of-the-art deep learning and genetic algorithm methods, where the z tests performed on the results of several experiments show that our method is more than 99% likely to be significant. At the same time, based on the experimental results, we point out the insufficiency in the experimental evaluation standard which affects the fair evaluation of previous work. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-0970-3.

Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells.

Foxo transcription factors regulate cell cycle progression, cell survival and DNA-repair pathways. Here we demonstrate that deficiency in Foxo3 resulted in greater expansion of T cell populations after viral infection. This exaggerated expansion was not T cell intrinsic. Instead, it was caused by the enhanced capacity of Foxo3-deficient dendritic cells to sustain T cell viability by producing more interleukin 6. Stimulation of dendritic cells mediated by the coinhibitory molecule CTLA-4 induced nuclear localization of Foxo3, which in turn inhibited the production of interleukin 6 and tumor necrosis factor. Thus, Foxo3 acts to constrain the production of key inflammatory cytokines by dendritic cells and to control T cell survival.

Distribution and factors associated with serum HBV pregenomic RNA levels in Chinese chronic hepatitis B patients.

Correlations between serum hepatitus B virus (HBV) pregenomic RNA (pgRNA), hepatitus B surface antigen (HBsAg), and hepatitus B core-related antigen (HBcrAg) levels, and influencing factors of serum HBV pgRNA levels in Chinese chronic hepatitis B (CHB) patients are rarely reported. This was a retrospective cohort study consisting of 204 outpatients with CHB. Serum levels of HBV pgRNA, HBsAg, and HBcrAg were quantitative measured in frozen blood samples. The linear regression and multivariate logistic regression analysis were performed to determine associated factors of serum HBV pgRNA levels. In this cohort, the median serum HBV pgRNA level was 4.12 log10 copies/ml and 33.33% (68/204) of them had serum HBV pgRNA under low limit of detection (LLD) (<500 copies/ml); and the percentage of patients with serum HBV pgRNA under LLD in hepatitis B e antigen (HBeAg)-positive patients was significantly lower than that in HBeAg-negative patients (15.75% [23/46] vs. 77.59% [45/58], p < .001). Overall, serum HBV pgRNA strongly correlated with HBcrAg (r = 0.760, p < .001), and moderately correlated with HBV DNA (r = 0.663, p < .001) and HBsAg (r = 0.670, p < .001). As compared with HBsAg and HBV DNA, only HBcrAg showed stable correlation with serum HBV pgRNA both in HBeAg-positive and HBeAg-negative patients. Serum HBV pgRNA level differed between HBeAg-positive and HBeAg-negative patients; and it had better and more stable correlation with serum HBcrAg than serum HBV DNA and HBsAg, irrespective of HBeAg status.

Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: A comprehensive review.

Staphylococcus aureus is one of the leading hospital-associated and community-associated pathogens, which has caused a global public health concern. The emergence of methicillin-resistant S. aureus (MRSA) along with the widespread use of different classes of antibiotics has become a significant therapeutic challenge. Antibiotic resistance is a disturbing problem that poses a threat to humans. Treatment options for S. aureus resistant to ß-lactam antibiotics include glycopeptide antibiotic, cyclic lipopeptide antibiotic, cephalosporins and oxazolidinone antibiotic. The most representative types of these antibiotics are vancomycin, daptomycin, ceftaroline and linezolid. The frequent use of the first-line drug vancomycin for MRSA treatment has increased the number of resistant strains, namely vancomycin intermediate resistant S. aureus (VISA) and vancomycin resistant S. aureus (VRSA). A systematic literature review of relevant published studies in PubMed before 2020 was conducted. In recent years, there have been some reports on the relevant resistant mechanisms of vancomycin, daptomycin, ceftaroline and linezolid. In this review, we have summarized the antibiotic molecular modes of action and different gene mutants at the whole-genome level, which will aid in further development on new drugs for effective MRSA treatment based on describing different resistance mechanisms of classic antibiotics.

Optimal drug administration manner would rescue partial virological response in chronic hepatitis B patients with entecavir or tenofovir treatment.

Not all treatment-naïve patients receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy can achieve complete virological response, and many factors may be related with the outcome of partial virological response. This study aimed to determine whether the manner of drug administration affects the antiviral efficacy of ETV/TDF monotherapy. All eligible patients were divided into complete or partial response cohorts based on their virological response following 24-week therapy. Factors related with partial response were evaluated. Patients with partial response were further grouped depending on whether they later adjusted the manner of drug administration, and the antiviral efficacy was compared between the two groups during prolonged treatment. A total of 518 patients were enrolled. Suboptimal drug administration (OR 77.511, P = .000), positive-HBeAg (OR 3.191, P = .000) and ETV treatment (OR 2.537, P = .001) were identified as independent risk factors for partial response. Among patients with partial response, 213 were in the adjusted group and 76 were in the unadjusted group. The percentages of patients with undetectable serum HBV DNA (78.9% vs 31.6%, P < .001) and with normal alanine aminotransferase (ALT) (88.7% vs 68.4%, P < .001) were both higher in the adjusted group than that in unadjusted group following a further 6-month therapy. In conclusion, the manner of drug administration is an important factor influencing the efficacy of ETV/TDF therapy, and optimal drug administration manner can help to increase antiviral efficacy and rescue patients with partial response.

Tenofovir monotherapy versus tenofovir plus entecavir combination therapy in HBeAg-positive chronic hepatitis patients with partial virological response to entecavir.

AIMS: The aim of this retrospective study was to compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy and TDF + entecavir (ETV) combination therapy for chronic hepatitis B (CHB) patients with the partial virological response (PVR) to ETV. METHODS: CHB patients with PVR to ETV were switched to TDF monotherapy or TDF + ETV combination therapy. The primary efficacy outcome was a virological response (VR), and the secondary efficacy outcomes were hepatitis B e antigen (HBeAg) seroconversion and alanine aminotransferase (ALT) normalization. The primary safety outcomes were changes in serum creatinine and serum phosphorus levels. RESULTS: A total of 143 patients were investigated, including 63 patients in the TDF monotherapy group and 80 patients in the TDF + ETV combination therapy group. Baseline demographics and clinical characteristics were comparable between groups. The median age of patients was 44.5 years, and 76.2% of them were male. The VR rate in TDF + ETV group was higher than that of the TDF group at 48 weeks (88.8% vs 71.4%; P = .009). At 48 weeks, the HBeAg seroconversion rate of TDF + ETV group was higher than that of the TDF group (30% vs 15.9%; P = .049). There was no significant difference in the proportion of patients with elevated ALT in the TDF group and TDF + ETV group at 48 weeks (9.5% vs 7.5%; P = .665). After adjusting the treatment regimen, serum creatinine levels increased slightly and serum phosphorus level decreased slightly in both groups. CONCLUSIONS: TDF + ETV combination therapy for 48 weeks had a higher VR rate than TDF monotherapy in CHB patients with PVR to ETV.

Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.