A Radical Strategy for the Alkylation of Amides with Alkyl Halides by Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis.

Amide alkylation is a fundamental process in organic chemistry. However, the low nucleophilicity of amides means that divergent coupling with alkyl electrophiles is often not achievable. To circumvent this reactivity challenge, individual amine synthesis followed by amidation with standard coupling agents is generally required. Herein, we demonstrate a radical solution to this challenge by using an amine-borane complex and copper catalysis under oxidative conditions. While borohydride reagents are generally used as reducing agents in ionic chemistry, their conversion into amine-ligated boryl radicals diverts their reactivity toward halogen-atom transfer. This enables the conversion of alkyl halides into the corresponding alkyl radicals for amide functionalization via copper catalysis. The process is applicable to the N-alkylation of primary amides employing unactivated alkyl iodides and bromides, and it was also showcased in the late-state functionalization of both complex amide- and halide-containing drugs.

Exploring Uncharted Territory: Spectroscopic Evidence on a Novel Tetrel Bond with -C≡C- Triple Bond.

This study presents an investigation of the 2-butynyl alcohol···CO2 adduct, combining pulsed jet Fourier transform microwave spectroscopy with quantum chemical calculations. Two distinct isomers have been observed in the pulsed jet with a relative population ratio of 3/2. It marks the first instance of microwave spectroscopic evidence, to the best of our knowledge, suggesting the existence of a CCO2···π-C≡C- tetrel bond (π-C≡C-···π*CO2 interaction) in both observed isomers. This study highlights the importance of noncovalent interactions involving CO2 in reactant complexes, paving the way for more efficient applications of CO2 by understanding the physical basis of these noncovalent bonds.

Does innovative city pilot policy improve carbon reduction? Quasi-experimental evidence from China.

A new direction for China in exploring sustainable development is the Innovative City Pilot Policy (ICPP), which provides policy guidance for accelerating carbon peaking and carbon neutrality by reducing carbon emissions. With data from 282 cities spanning 2006-2018, this paper examines ICPP's effect on carbon intensity (CI) through a multi-period difference-in-differences (DID) model, as well as exploring the mediating effect, moderating effect, heterogeneity, and spatial spillover effects. The results show that ICPP reduces CI significantly by enhancing technology innovation (TI), and when industrial structure (IS) is added, the effect of ICPP is expanded. The ICPP gains additional advantages in reducing CI by optimizing the efficiency of resource allocation (ERA). Compared with the concentration of human capital (HCL), the amount of scientific research institutes (SRI) has a slightly greater moderating effect. ICPP impacts considering location, size, and hierarchy heterogeneity. ICPP has a greater impact on mitigating CI in the western, larger size, and provincial capital cities. There are positive spillover effects of the ICPP on neighboring CI. To support the idea that ICPP can effectively contribute to CI reduction, this paper provides empirical evidence and theoretical guidelines.

Functional profiling of CHAP domain-containing peptidoglycan hydrolases of Staphylococcus aureus USA300 uncovers potential targets for anti-staphylococcal therapies.

The bacterial pathogen Staphylococcus aureus employs a thick cell wall for protection against physical and chemical insults. This wall requires continuous maintenance to ensure strength and barrier integrity, but also to permit bacterial growth and division. The main cell wall component is peptidoglycan. Accordingly, the bacteria produce so-called peptidoglycan hydrolases (PGHs) that cleave glycan strands to facilitate growth, cell wall remodelling, separation of divided cells and release of exported proteins into the extracellular milieu. A special class of PGHs contains so-called 'cysteine, histidine-dependent amidohydrolase/peptidase' (CHAP) domains. In the present study, we profiled the roles of 11 CHAP PGHs encoded by the core genome of S. aureus USA300 LAC. Mutant strains lacking individual CHAP PGHs were analysed for growth, cell morphology, autolysis, and invasion and replication inside human lung epithelial cells. The results show that several investigated CHAP PGHs contribute to different extents to extracellular and intracellular growth and replication of S. aureus, septation of dividing cells, daughter cell separation once the division process is completed, autolysis and biofilm formation. In particular, the CHAP PGHs Sle1 and SAUSA300_2253 control intracellular staphylococcal replication and the resistance to ß-lactam antibiotics like oxacillin. This makes the S. aureus PGHs in general, and the Sle1 and SAUSA300_2253 proteins in particular, attractive targets for future prophylactic or therapeutic anti-staphylococcal interventions. Alternatively, these cell surface-exposed enzymes, or particular domains of these enzymes, could be applied in innovative anti-staphylococcal therapies.

Dissection and Fine-Mapping of Two QTL Controlling Grain Size Linked in a 515.6-kb Region on Chromosome 10 of Rice.

Grain size is a primary determinant of grain weight, which is one of the three essential components of rice grain yield. Mining the genes that control grain size plays an important role in analyzing the regulation mechanism of grain size and improving grain appearance quality. In this study, two closely linked quantitative trait loci (QTL) controlling grain size, were dissected and fine-mapped in a 515.6-kb region on the long arm of chromosome 10 by using six near isogenic line populations. One of them, qGS10.2, which controlled 1000 grain weight (TGW) and grain width (GW), was delimited into a 68.1-kb region containing 14 annotated genes. The Teqing allele increased TGW and GW by 0.17 g and 0.011 mm with the R2 of 12.7% and 11.8%, respectively. The other one, qGL10.2, which controlled grain length (GL), was delimited into a 137.3-kb region containing 22 annotated genes. The IRBB52 allele increased GL by 0.018 mm with the R2 of 6.8%. Identification of these two QTL provides candidate regions for cloning of grain size genes.

Conformational equilibria in acrolein-CO2: the crucial contribution of n → π* interactions unveiled by rotational spectroscopy.

Using gas phase Fourier-transform microwave spectroscopy complemented by theoretical analysis, this study delivers a comprehensive depiction of the physical origin of the 'n → π* interaction' between CO2 and acrolein, one of the most reactive aldehydes. Three distinct isomers of the acrolein-CO2 complex, linked through a C⋯O tetrel bond (or n → π* interaction) and a C-H⋯O hydrogen bond, have been unambiguously identified in the pulsed jet. Relative intensity measurements allowed estimation on the population ratio of the three isomers to be T1/T2/C1 ≈ 25/5/1. Advanced theoretical analyses were employed to elucidate the intricacies of the noncovalent interactions within the examined complex. This study not only sheds light on the molecular underpinnings of n → π* interactions but also paves the way for future exploration in carbon dioxide capture and utilization, leveraging the fundamental principles uncovered in the study of acrolein-carbon dioxide interactions.

Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study.

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Model of predicting fear of cancer recurrence in patients with digestive tract cancer: A cross-sectional study.

AIMS: To investigate the incidence of fear of cancer recurrence in patients with digestive tract cancers analyse its influencing factors, and further establish a visual risk prediction model. DESIGN: A cross-sectional study. METHODS: A cross-sectional survey was conducted among 570 patients with digestive tract tumours admitted to a local hospital, from May 2023 to December 2023 by convenient sampling method. Univariate analysis and logistic analysis were performed on the influencing factors, and the risk prediction nomogram model of fear of cancer recurrence in patients with digestive tract cancer was constructed by using R 4.1.3 software. ROC curve was used to evaluate the differentiation of the nomogram model. The calibration curve and Hosmer-Lemeshow goodness of fit test were used to evaluate the consistency of the model. This study was reported using the TRIPOD checklist. RESULTS: In this study, 272 (47.7%) patients developed fear of recurrence. The risk prediction model of recurrence fear column chart for digestive tract cancer patients incorporated six variables of gender, therapy, alimentary tract haemorrhage, pain, depression and social support. The C-statistic was (.976), and the calibration curve showed that the predicted probability was more in line with the actual probability of occurrence, and the decision curve showed that the predictive model had better practicality. CONCLUSION: The column-line diagram prediction model constructed in this study is effective and facilitates timely intervention and management by healthcare professionals based on their risk factors. IMPACT: Nomogram is helpful to calculate the risk probability of FCR in patients with digestive tract cancer, identify FCR patients in time, and formulate comprehensive and personalized countermeasures, to provide a good quality of life and prolong the survival cycle of patients with digestive tract cancer. PATIENT OR PUBLIC CONTRIBUTION: Participants were hospitalized patients or patients with digestive tract cancer undergoing follow-up. First of all, before the investigation and research, a team is formed to discuss the concept, research purpose, method, significance, etc., and determine the research tools. Second, by reasonably explaining the study to patients to seek informed consent from the patient and sign it, patients filled in the questionnaire independently. For patients with low education levels who could not fill in the questionnaire, the team members made objective explanations to help them choose reasonable options.

Visible-Light-Mediated Ring-Opening Geminal Dibromination of Alkenes via Alkoxy Radicals Enabled by Electron Donor-Acceptor Complex.

An electron donor-acceptor complex was utilized to generate alkoxy radicals from alcohols under mild conditions using visible light. This approach was combined with a hydroxybromination process to achieve the deconstructive functionalization of alkenes, leading to the production of geminal dibromides. Mechanistic investigations indicated the intermediacy of hypervalent iodine (III) compounds.

Interface Structures on Mechanically Polished Surface of Spinel Ferrite and Its Effect on the Magnetic Domains.

Soft magnetic spinel ferrites are indispensable parts in devices such as transformers and inductors. Mechanical surface processing is a necessary step to realize certain shapes and surface roughness in producing the ferrite but also has a negative effect on the magnetic properties of the ferrite. In the past few years, a new surface layer was always believed to form during the mechanical surface processing, but the change of atomic structure on the surface and its effect on the magnetic structure remain unclear. Herein, an interface structure consisting of a rock-salt sublayer, distorted NiFe2O4 sublayer, and pristine NiFe2O4 was found to form on mechanically polished single-crystal NiFe2O4 ferrite. Such an interface structure is produced by phase transformation and lattice distortion induced by the mechanical processing. The magnetic domain observation and electrical property measurement also indicate that the magnetic and electrical anisotropy are both enhanced by the interface structure. This work provides deep insight into the surface structure evolution of spinel ferrite by mechanical processing.

Straight intramedullary MultiLoc nails for displaced proximal humeral fractures: health status, radiographic results, clinical outcome, and complications.

BACKGROUND: The treatment of the displaced proximal humerus fractures (PHF) still facing a lot of unsolved problems. The aim of this study was to evaluate the clinical effect of MultiLoc nails for the treatment of PHF and present outcomes of patients with different Neer's classification and reduction quality. METHODS: Adult patients with PHFs were recruited and treated with MultiLoc nail. Intraoperative data, radiographic and functional outcomes, as well as occurrence of postoperative complications were assessed. RESULTS: 48 patients met inclusion and exclusion criteria and were included in this study. The DASH Score were 32.2 ± 3.1 points at 12 months, and 37.3 ± 2.5 points at the final follow-up. The mean ASES score at 12 months and final follow-up were 74.4 ± 6.2 and 78.8 ± 5.1, respectively. The mean CM Score in all 48 patients reached 68 ± 6.4 points at the final follow-up, relative side related CM Score 75.2 ± 7.7% of contralateral extremity. The incidence rate of complications was 20.8%. Patients with fracture mal-union, adhesive capsulitis were observed but no secondary surgeries were performed. There was no significantly difference of DASH Score 12 months after surgery and at the last follow-up among patients with different Neer's classification or reduction quality. However, functional outcomes such as ASES score and CM score were significantly influenced by severity of fracture and the quality of fracture reduction. CONCLUSIONS: Our study demonstrated that MultiLoc nails is well suited for proximal humeral fractures, with satisfactory health status recovery, good radiographic results, positive clinical outcomes and low rates of complications. The treatment for four part PHF still faces great challenges. Accurate fracture reduction was an important factor for good functional result.

Retinal light damage: From mechanisms to protective strategies.

Visible light serves as a crucial medium for vision formation.;however, prolonged or excessive exposure to light is recognized as a significant etiological factor contributing to retinal degenerative diseases. The retina, with its unique structure and adaptability, relies on the homeostasis of cellular functions to maintain visual health. Under normal conditions, the retina can mount adaptive responses to various insults, including light-induced damage. Unfortunately, exposure to intense and excessive light triggers a cascade of pathological alterations in retinal photoreceptor cells, pigment epithelial cells, ganglion cells, and glial cells. These alterations encompass disruption of intracellular REDOX and Ca²âº homeostasis, pyroptosis, endoplasmic reticulum stress, autophagy, and the release of inflammatory cytokines, culminating in irreversible retinal damage. We first delineate the mechanisms of retinal light damage through 4 main avenues: mitochondria function, endoplasmic reticulum stress, cell autophagy, and inflammation. Subsequently, we discuss protective strategies against retinal light damage, aiming to guide research toward the prevention and treatment of light-induced retinal conditions.

Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer.

Small-cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer, characterized by limited treatment options, early and frequent metastasis. However, the determinants of metastasis in SCLC are poorly defined. Here, we show that estrogen-related receptor gamma (ERRγ) is overexpressed in metastatic SCLC tumors, and is positively associated with SCLC progression. ERRγ functions as an essential activator of extracellular matrix (ECM) remodeling and cell adhesion, two critical steps in metastasis, by directly regulating the expression of major genes involved in these processes. Genetic and pharmacological inhibition of ERRγ markedly reduces collagen production, cell-matrix adhesion, microfilament production, and eventually blocks SCLC cell invasion and tumor metastasis. Notably, ERRγ antagonists significantly suppressed tumor growth and metastasis and restored SCLC vulnerability to chemotherapy in multiple cell-derived and patient-derived xenograft models. Taken together, these findings establish ERRγ as an attractive target for metastatic SCLC and provide a potential pharmacological strategy for treating this lethal disease.

Single-cell atlas profiling revealed cellular characteristics and dynamic changes after PD-1 blockade therapy of brain metastases from laryngeal squamous cell carcinoma.

Brain metastasis (BM) in laryngeal squamous cell carcinoma (LSCC) is uncommon but prognosis is poor. Anti-PD-1 immunotherapy benefits some advanced LSCC cases, yet its efficiency is limited by tumor complexity. We analyzed paired metastatic tumor samples from before and after immunotherapy using single-cell RNA sequencing (scRNA-seq), along with a primary LSCC dataset and bulk RNA sequencing. This identified changes post-immunotherapy and revealed differences in single-cell transcriptomes among LSCC, primBM, and neoBM. Our findings show that anti-PD-1 treatment suppresses metastasis-promoting pathways like VEGF and EMT in cancer cells, and alters immune cell functions. Notably, it upregulates T cell activation, leading to CD8 T cell exhaustion from excess heat shock proteins, notably HSPA8. However, CD8 T cell cytotoxic functions improve post-treatment. In myeloid cells, anti-PD-1 therapy enhances antigen presentation and promotes a proinflammatory shift post-metastasis. Additionally, NUPR1 is linked to BM in LSCC, and NEAT1 is a potential metastatic cancer cell cycle participant. Our study provides insights into cancer heterogeneity and the impact of PD-1 immunotherapy on metastasis, aiding precise diagnosis and prognosis.

How can the digital economy reduce carbon emissions? Empirical evidence from China.

China is transitioning into the digital economy era. The advancement of the digital economy could offer a fresh mechanism to attain carbon peak and carbon neutrality objectives. Applications of the digital economy, such as smart energy management, intelligent transport systems, and digital agricultural technologies, have significantly reduced carbon emissions by optimizing resource use, reducing energy waste, and improving production efficiency. This research does so by devising a theoretical model that looks into the multi-faceted power of the digital economy under a two-sector paradigm. Utilising a panel model, a mediation effect model and a spatial Durbin model to assess the digital economy's power on carbon emissions. This research has determined that the digital economy can significantly diminish carbon emissions, with green tech innovations and industrial transformation being key contributors. The spatial spillover effect was used for the digital economy to aid in lowering carbon emissions in adjacent districts and upgrading better environmental stewardship. The influence of the digital economy has better performance in lowering carbon emissions in mid-western China than in the eastern area. This paper deepens understanding of the drivers of low-carbon growth and the significance, mechanism and regional disparities of the digital economy's effect on reducing carbon emissions. It offers valuable policy insights and guidance for globally achieving digital economy growth, reducing carbon emissions and reaching carbon peak and neutrality goals.

Skin metastasis from ovarian cancer with somatic BRCA1 mutation: A case report and literature review.

Skin metastasis from ovarian cancer is rare, and its prognosis is poor. Effective therapeutic strategies are currently lacking, but the combination of various treatment methods shrink the tumor and relieve symptoms. The present study reports a rare case of advanced ovarian cancer with skin metastases and intestinal wall thickening, along with a BRCA1 DNA repair associated (BRCA1) mutation. After standard first-line treatment and non-standard second-line treatment, the patient developed skin metastases. The patient's skin itching, pain and lesions were completely relieved after administering bevacizumab in combination with paclitaxel and carboplatin. After 4 months, skin metastases recurred along with anal distension during maintenance treatment with oral poly(ADP ribose) polymerase (PARP) inhibitors. The patient was treated again with bevacizumab combined with docetaxel, and the anal distension was significantly relieved. Angiogenesis therapy combined with chemotherapy is effective, but that the disease-free survival time is short, and PARP inhibitor maintenance effect is limited even in cases with a BRCA1 gene mutation.

KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.

BACKGROUND: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. METHODS: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. RESULTS: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. CONCLUSIONS: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. HIGHLIGHTS: Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma.

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

Divergent impacts of fertilization regimes on below-ground prokaryotic and eukaryotic communities in the Tibetan Plateau.

Chemical nutrient amendment by human activities can lead to environmental impacts contributing to global biodiversity loss. However, the comprehensive understanding of how below- and above-ground biodiversity shifts under fertilization regimes in natural ecosystems remains elusive. Here, we conducted a seven-year field experiment (2011-2017) and examined the effects of different fertilization on plant biodiversity and soil belowground (prokaryotic and eukaryotic) communities in the alpine meadow of the Tibetan Plateau, based on data collected in 2017. Our results indicate that nitrogen addition promoted total plant biomass but reduced the plant species richness. Conversely, phosphorus enrichment did not promote plant biomass and exhibited an unimodal pattern with plant richness. In the belowground realm, distinct responses of soil prokaryotic and eukaryotic communities were observed under fertilizer application. Specifically, soil prokaryotic diversity decreased with nitrogen enrichment, correlating with shifts in soil pH. Similarly, soil eukaryotic diversity decreased with increased phosphorous inputs, aligning with the equilibrium between soil available and total phosphorus. We also established connections between these soil organism communities with above-ground plant richness and biomass. Overall, our study contributes to a better understanding of the sustainable impacts of human-induced nutrient enrichment on the natural environment. Future research should delve deeper into the long-term effects of fertilization on soil health and ecosystem functioning, aiming to achieve a balance between agricultural productivity and environmental conservation.

Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis.

BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.