Shuaiwen Huang

Background: This study aims to identify the key factors influencing the loss of hepatitis B surface antigen (HBsAg) and durability of functional cure. Understanding these factors is crucial for identifying patient groups that may benefit from a pegylated interferon alpha (Peg-IFN-α) induced “functional cure” for hepatitis B, as well as for optimizing strategies to achieve and sustain HBsAg loss. Methods: The study utilized real-world data, including 378 patients with chronic hepatitis B virus (HBV) infection who received treatment with Peg-IFN-αfor 24 weeks or longer. Patients were grouped based on their response at 24 and 48 weeks of treatment, and predictive factors for the response were calculated through regression analysis. Additionally, 195 subjects who achieved HBsAg loss were included to assess factors influencing the durability of HBsAg loss. The primary endpoint was reverse seroconversion of HBsAg (HBsAg-RS). Results: The findings suggest that the degree of HBsAg at baseline and HBsAg decline at 12/24 weeks of treatment is critical for predicting treatment response. Factors affecting durability include age, nucleoside treatment, baseline hepatitis B core antibody (anti-HBc) levels, the consolidation of Peg-IFN-α therapy, and hepatitis B surface antibody (anti-HBs) levels at the time of treatment discontinuation. Higher anti-HBs levels at discontinuation and higher baseline anti-HBc levels were associated with a reduced risk of HBsAg-RS. Moreover, a significant linear dose-response relationship was observed between anti-HBs levels and the risk of HBsAg-RS after HBsAg loss. Conclusions: These results provide valuable insights for predicting responses to Peg-IFN-αtherapy and identifying high-risk groups for HBsAg-RS following HBsAg loss. This information may help refine strategies for achieving and maintaining HBsAg loss and guide post-HBsAg loss monitoring and management procedures.

One of the key features of chronic hepatitis B virus (HBV) infection is the inability to mount sufficient and coordinated adaptive immune responses against HBV. Recent studies on HBV-specific B cells and antibody to hepatitis B surface antigen (anti-HBs) have shed light on their role in the pathogenesis of chronic hepatitis B (CHB). Anti-HBs is recognized as a protective immune marker, both for HBV infection clearance and following vaccination, and it is also considered an important indicator of functional cure for CHB. Notably, functional impairment of HBV-specific B cells may be reversible. The restoration of HBV-specific B cell function, along with the induction of an anti-HBs antibody response, is regarded as pivotal for terminating chronic HBV infection and achieving functional cure. This article reviews the significance of anti-HBs in both the infection and clearance of HBV, and discusses the potential of neutralizing antibodies and therapeutic vaccines as promising future strategies.

Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up.

Objectives: Dietary supplements have gained attention among people with diabetes as an alternative and complementary treatment, yet there is a limited understanding of supplement use and the motivations behind it. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from the 2009–2020 period were analyzed, including data on 5784 people with diabetes aged 20 years or older. Dietary supplement use was self-reported. Trends in supplement use were examined across three periods: 2009–2012, 2013–2016, and 2017–2020. Statistical analyses were conducted while considering NHANES’s complex survey design to provide nationally representative estimates for the general noninstitutionalized population of the United States. Results: A total of 61.72% of individuals reported using dietary supplements with a notable increase over time. Supplement users were generally older, more likely to be female, better educated, and had superior blood glucose control with lower smoking rates compared to non-users. Common supplements included multivitamins, multimineral supplements, vitamin D, calcium, zinc, vitamin C, and fish oil. Only 44.58% of individuals used dietary supplements based on medical advice, with the rest opting for self-directed usage. The primary specific health reasons for supplement use were to improve bone health and heart health and enhance the immune system. Conclusions: Dietary supplement use is prevalent among people with diabetes, and most diabetic supplement use is self-directed, which reflects a growing trend toward complementary therapies. Healthcare providers are encouraged to inquire about patients’ use of supplements and offer appropriate guidance as an integral component of comprehensive diabetes management.

This study aimed to investigate the relationship between the utilization of household water treatment devices (UHWTD) and both overall and cause-specific mortality, addressing the lack of comprehensive prospective research in this area. The study was a population-based prospective cohort study using data from the US National Health and Nutrition Examination Survey (NHANES 1999–2010). Among the 30,322 participants included in the study, the group without UHWTD (No UHWTD) was younger but reported worse baseline health compared to the UHWTD group. During an average follow-up period of 14.3 years, 6811 participants died. After adjusting for age, sex, and other covariates, No UHWTD was significantly associated with a higher risk of overall (adjusted hazard ratio [aHR]: 1.221, 95% Confidence Interval [CI]: 1.147–1.300), heart (aHR: 1.405, 95% CI: 1.241–1.589), cancer (aHR: 1.176, 95% CI: 1.003–1.379), Alzheimer’s disease (aHR: 1.404, 95% CI: 1.027–1.919), and nephrosis (aHR: 1.613, 95% CI: 1.026–2.537) mortality compared to UHWTD. Moreover, those main association almost remained after further adjustment for water source. Additionally, we observed a lower detection rate of bromoform, chloroform, bromodichloromethane, and dibromochloromethane in tap water when household water treatment devices was used compared to No UHWTD. The utilization of household water treatment devices in this prospective cohort was associated with modest reductions in the risk of overall, heart, cancer, Alzheimer’s disease, and nephrosis mortality. These findings suggest that the use of household water treatment devices may have the potential to influence health outcomes and extend life expectancy.

Cancer-associated muscle wasting is a widespread syndrome in people with cancer and is characterized by weight loss and muscle atrophy, leading to increased morbidity and mortality. However, the tumor-derived factors that affect the development of muscle wasting and the mechanism by which they act remain unknown. To address this knowledge gap, we aimed to delineate differences in tumor molecular characteristics (especially secretion characteristics) between patients with and without sarcopenia across 10 tumor types from The Cancer Genome Atlas (TCGA). We integrated radiological characteristics from CT scans of TCGA cancer patients, which allowed us to calculate skeletal muscle area (SMA) to confirm sarcopenia. We combined TCGA and GTEx (The Genotype-Tissue Expression) data to analyze upregulated secretory genes in 10 tumor types compared with normal tissues. Upregulated secretory genes in the tumor microenvironment and their relation to SMA were analyzed to identify potential muscle wasting biomarkers (560 samples). Meanwhile, their predictive values for patient survival was validated in 3530 samples in 10 tumor types. A total of 560 participants with transcriptomic data and SMA were included. Among those, 136 participants (24.28%) were defined as having sarcopenia based on SMA. Enrichment analysis for upregulated secretory genes in cancers revealed that pathways associated with muscle wasting were strongly enriched in tumor types with a higher prevalence of sarcopenia. A series of SMA-associated secretory protein-coding genes were identified in cancers, which showed distinct gene expression profiles according to tumor type, and could be used to predict prognosis in cancers (p value ≤ 0.002). Unfortunately, those genes were different and rarely overlapped across tumor types. Tumor secretome characteristics were closely related to sarcopenia. Highly expressed secretory mediators in the tumor microenvironment were associated with SMA and could affect the overall survival of cancer patients, which may provide a valuable starting point for the further understanding of the molecular basis of muscle wasting in cancers. More importantly, tumor-derived pro-sarcopenic factors differ across tumor types and genders, which implies that mechanisms of cancer-associated muscle wasting are complex and diverse across tumors, and may require individualized treatment approaches.

The Neural Calcium Sensor1 (NCS1) is a crucial protein that binds to Ca2⁺ and is believed to play a role in regulating tumor invasion and cell proliferation. However, the role of NCS1 in immune infiltration and cancer prognosis is still unknown. Our study aimed to explore the expression profile, immune infiltration pattern, prognostic value, biological function, and potential compounds targeting NCS1 using public databases. High expression of NCS1 was detected by immune histochemical staining in LIHC (Liver hepatocellular carcinoma), BRCA (Breast invasive carcinoma), KIRC (Kidney renal clear cell carcinoma), and SKCM (Skin Cutaneous Melanoma). The expression of NCS1 in cancer was determined by TCGA (The Cancer Genome Atlas Program), GTEx (The Genotype-Tissue Expression), the Kaplan–Meier plotter, GEO (Gene Expression Omnibus), GEPIA2.0 (Gene Expression Profiling Interactive Analysis 2.0), HPA (The Human Protein Atlas), UALCAN, TIMER2.0, TISIDB, Metascape, Drugbank, chEMBL, and ICSDB databases. NCS1 has genomic mutations as well as aberrant DNA methylation in multiple cancers compared to normal tissues. Also, NCS1 was significantly different in the immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltrate-associated cells in different cancers, which could be used for the typing of immune and molecular subtypes of cancer and the presence of immune checkpoint resistance in several cancers. Univariate regression analysis, multivariate regression analysis, and gene enrichment analysis to construct prognostic models revealed that NCS1 is involved in immune regulation and can be used as a prognostic biomarker for SKCM, LIHC, BRCA, COAD, and KIRC. These results provide clues from a bioinformatic perspective and highlight the importance of NCS1 in a variety of cancers.

Arteriosclerosis is the common pathological basis of hypertension-related target organ damage, and pulse wave velocity (PWV) is commonly used to assess the degree of arterial stiffness. Previous studies have reported the correlation between peripheral blood inflammatory indicators and PWV in hypertensives, but few studies examined the role of immune cells in arteriosclerosis in the context of human hypertension. In order to enrich the understanding of this topic, we conducted a cross-sectional study on hospitalized hypertensives in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2015 to February 2017 to investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and peripheral blood lymphocyte subsets. Sixty-four eligible patients were enrolled in our study. The patients’ blood pressure, height, body weight, and baPWV were collected, along with the lab results of their peripheral complete blood count, blood chemistry, and lymphocyte subsets. We studied the Spearman correlation between baPWV and lymphocyte subsets and other variables. We further used multivariable stepwise linear regression analysis and the results showed that baPWV was significantly correlated with age, height, systolic blood pressure, and the level of T lymphocytes (CD3⁺CD45⁺) in hypertensive patients (β = 8.77, P = 0.006; β = −17.50, P = 0.001; β = 6.70, P = 0.002, and β = −7.093, P = 0.024, respectively). According to our findings, baPWV was independently and negatively correlated with the level of peripheral blood T lymphocytes in hypertensives, and infiltration of T lymphocytes into the vessels wall may be a key part of the immune mechanism of arteriosclerosis in hypertension.