2025年 · 第05卷第03期

The hepatitis B virus (HBV) remains a formidable global health challenge. Chronic infection affects approximately 300 million people worldwide and serves as a leading cause of hepatocellular carcinoma.^[1]Despite decades of research, a true functional cure remains elusive, largely due to the persistence of the viral minichromosome-covalently closed circular DNA (cccDNA)^[2]-the resource of HBV replication. Upon binding to heparan sulfate proteoglycans and engaging the viral receptor sodium taurocholate co-transporting polypeptide (NTCP),^[3]HBV enters hepatocytes and transmits its genome into the nucleus. Once it is there, the viral relaxed circular DNA (rcDNA) genome undergoes repair and chromatinization, forming cccDNA.^[4]This cccDNA serves as a template for the transcription of five overlapping viral RNAs that are essential for viral protein synthesis.

The 2024 Clinical Practice Guidelines for Influenza of the World Health Organization (WHO) are an updated version of the 2022 Guidelines for the Clinical Management of Severe Illness from Influenza Virus Infections. The 2024 guidelines redefine risk factors for severe influenza, which is crucial for understanding treatment recommendations. The new guidelines not only focus on the clinical management of severe influenza and individuals at high risk of developing severe illness but also cover recommendations for managing non-severe influenza cases. Additionally, they provide guidance on using antiviral drugs to prevent influenza infection in individuals who have been exposed to the virus within the past 48 hours. The 2024 edition of the influenza guidelines involves the appropriate use of antiviral therapy, adjunctive therapies, and the rational application of antibiotics. For high-risk non-severe cases, baloxavir is conditionally recommended within 2 days of symptom onset, while oseltamivir is conditionally recommended for severe cases. Baloxavir is not recommended for non-severe cases without severe risk factors, and other antivirals like oseltamivir, laninamivir, peramivir, zanamivir, favipiravir, and arbidol are not recommended for non-severe patients. For severe cases, oseltamivir remains conditionally recommended, maintaining its importance from the 2022 guidelines. Antimicrobial drugs are not recommended unless there is evidence of bacterial infection. The WHO also advises against the use of corticosteroids, convalescent plasma, macrolides, mammalian target of rapamycin (mTOR) inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs) for severe cases. For seasonal influenza exposure, baloxavir, oseltamivir, laninamivir, or zanamivir is conditionally recommended for those at high risk of hospitalization postexposure, whereas these drugs are not recommended for others. Antiviral prophylaxis should not replace vaccination. For zoonotic influenza viruses, baloxavir, oseltamivir, laninamivir, or zanamivir is recommended for postexposure prophylaxis. The 2024 WHO guidelines recommend a nucleic acid amplification test (NAAT) for diagnosing suspected severe influenza and a digital immunoassay (DIA) or NAAT for non-severe influenza. Rapid testing is advised for high-risk nonsevere cases, followed by antiviral treatment if positive. For suspected severe influenza, high-sensitivity, high-specificity tests, such as NAATs or PCR, are recommended, with antiviral treatment initiated before test results if necessary. Both the guidelines of the WHO and those in China emphasize early antiviral treatment within 48 hours of symptom onset, particularly for severe or high-risk non-severe influenza. The guidelines in China, unlike those of the WHO, do not specify how to select a specific drug based on the condition of the patient but stress avoiding combination therapy with antiviral drugs with the same mechanism. In addition, China’s guidelines also recommend traditional Chinese medicine for influenza treatment. Both guidelines advise against corticosteroids in severe cases but differ in defining severity and risk factors. The WHO employs just two categories of influenza (severe or non-severe), whereas four categories (mild, moderate, severe, and critical) are used in China. The WHO includes those with novel influenza A virus infections among the high-risk group, and China includes children under 5 years and obese individuals in this group. The guidelines advocate for evidence-based, stratified management to reduce severe influenza complications and highlight the need for timely antiviral treatment based on patient risk assessment. Resource availability and co-infections can influence guideline implementation. Further research is needed to identify optimal strategies for specific populations.

Human immunodeficiency virus (HIV) infection is associated with significant metabolic disruptions, and understanding how these disruptions contribute to cardiovascular disease (CVD) is essential for improving patient management and therapeutic strategies. By integrating metabolomics and transcriptomics, we aimed to elucidate the cardiometabolic disease spectrum of people living with HIV (PLWH) and to identify biomarkers and pathways associated with disease progression in this population.

We conducted a cross-sectional observational study between October 2022 and June 2023 at the Third People’s Hospital of Shenzhen, China. Participants were categorized into one of four groups: HIV+ without metabolic abnormalities (healthy control [HC]), HIV + with untreated metabolic (UM) abnormalities (HIV + UM), HIV + with treated metabolic (TM) abnormalities (HIV + TM), and HIV + with CVD (HIV + CVD). Key metabolic and transcriptomic features were identified through a comparative analysis using untargeted metabolomics and RNA sequencing, followed by statistical and pathway enrichment analyses.

This study included 114 PLWH: HC group (n = 30), HIV + UM group (n = 19), HIV + TM group (n = 46), and HIV + CVD group (n = 19). Through comparative analyses of untargeted metabolomic and transcriptomic data across these four groups, we identified 580 dysmetabolic features (DMFs) based on significant changes between the HC group and the HIV + UM/TM groups, with no statistically significant differences in the HIV + UM/TM vs. HIV + CVD comparisons. Notably, 90.52% of these DMFs (525/580) exhibited reduced abundance in the HIV + CVD group. In contrast, 241 CVD-specific features were identified based on significant differences between the HIV + CVD group and the HIV + UM/TM groups. These features, primarily found in the HIV + CVD group, included metabolites and genes strongly associated with chronic inflammation and endothelial dysfunction—key processes in the pathogenesis of CVD among PLWH. Features that indicated a transition from metabolic abnormalities to CVD were termed escalation features (ESCFs). ESCFs included early biomarkers of lipid dysregulation, such as phosphatidylcholine (O-22:1/20:4), and upregulated genes, such as CAMP, both of which showed progressive changes from the HC group through the HIV + UM/TM groups to the HIV + CVD group. Features that indicated a reversal in expression trends—such as those increasing from the HC group to the HIV + UM/TM groups but decreasing in the HIV + CVD group, or vice versa—were termed de-escalation features (DSCFs). DSCFs included lipid species and genes involved in lipid metabolism and mitochondrial function. The integration of metabolomic and transcriptomic data revealed disruptions in pathways, such as glycerophospholipid and arachidonic acid metabolism, with concurrent upregulation of genes involved in cholesterol biosynthesis and the immune response. Receiver operating characteristic curve analysis based on the integration of metabolomic and transcriptomic data markedly improved CVD prediction among PLWH, with an area under the curve of 0.965, sensitivity of 84.2%, and specificity of 96.9%.

This study identified key metabolic and transcriptomic alterations associated with CVD among PLWH. These alterations, primarily driven by immune activation, inflammation, and metabolic dysregulation, reflect unique molecular characteristics of CVD in PLWH. Our findings underscore the importance of early detection and tailored interventions to manage CVD risk in this population, providing insights into potential biomarkers for disease progression.

Infection with hepatitis C virus (HCV) represents a continued worldwide health concern. There are an estimated 50 to 71 million people living with HCV worldwide. This number continues to fall with availability of curative treatment, and there is now a stated goal to reduce infections by 90% and deaths by 65% worldwide by 2030. Annual mortality estimates for HCV and its complications range from 230,000 to 400,000. Although these longer term complications are more prevalent in adults than children, HCV in pediatric patients remains a public health concern.

An 8- to 12-week course of direct-acting antiviral medications can produce a sustained viral response rate of 95% to 99% (an increase from the 50% rate with prior pegylated interferon and ribavirin). Pregnant women and children represent 2 classes of patients for whom antiviral therapy has not been widely applied. Although children over 3 years of age now can be treated with direct-acting antivirals, pregnant patients are screened but not routinely treated for HCV. Close linkage to care during the prenatal period or after delivery with follow-up for mother and child remains paramount. In this review we highlight a brief history of HCV, the difficulty of assessing the burden of disease in pregnancy and childhood, the risk of mother-to-child transmission, the revised 2024 Centers for Disease Control and Prevention testing guidance, care in pregnancy, burden of children co-infected with HCV and hepatitis B virus or human immunodeficiency virus, treatment regimens for children and adolescents, and prospects for vaccine development.

Recent research has shown that metabolic processes within immune cells are essential for both human immunodeficiency virus 1 (HIV-1) infection and the immune response. Throughout HIV-1 infection—from acute stages to chronic infection and viral latency—immune cells experience shifts in energy demands and metabolic pathways, paralleling T-cell exhaustion. Dysregulated immune metabolism compromises immune cell function, leading to immune dysfunction and persistent inflammation. Therefore, metabolic alterations in immune cells constitute a critical mechanism in HIV-1 progression and chronic inflammation. This review specifically explores the metabolic profiles and roles of T cells, monocytes-macrophages, dendritic cells, natural killer cells, and B cells at different stages of HIV-1 infection, emphasizing the effects of HIV-1 on the metabolic pathways of diverse immune cell types. These insights offer valuable therapeutic strategies aimed at inhibiting viral replication, restoring immune function, and controlling disease progression.

Acute kidney injury (AKI) associated with Coronavirus Disease 2019 (COVID-19) is a notable complication of COVID-19 that is difficult to diagnose and treat. This review summarizes the prevalence, pathophysiology, clinical presentation, and management of COVID-19-associated AKI (hereafter COVID-19 AKI). COVID-19 AKI is linked to a multisystem inflammatory syndrome and presents symptoms similar to those of AKI, which is associated with increased morbidity and death rates. The pathophysiological mechanisms of AKI include direct viral injury, cytokine storms, and systemic effects on the renin-angiotensin-aldosterone system. The diagnostic assessment of patients at risk for AKI involves screening for symptoms such as decreased urine output, fluid retention, and fatigue. In contrast, biomarkers like serum creatinine and blood urea nitrogen are used for early detection. The management strategies for COVID-19 AKI, such as avoiding nephrotoxic medications, are similar to those for AKI of other causes. Renal replacement therapy may be considered as a treatment option for severe COVID-19 AKI, particularly in cases of fluid overload, or electrolyte imbalances that cannot be managed with conservative treatments. Future research is essential to elucidate the pathophysiology, optimize diagnostic criteria, and develop targeted therapies for COVID-19 AKI. A multidisciplinary approach focusing on physical and mental health is crucial for comprehensive patient care. Addressing these gaps will necessitate substantial funding support to propel research efforts and improve patient outcomes.

Measles outbreaks are increasingly being reported worldwide, posing a global health problem of pandemic potential. Europe was particularly affected in 2024, with a surge in cases linked to a decrease in herd immunity caused by reduced vaccination rates. COVID-19 has worsened the already alarming situation due to the disruption of surveillance systems and access to vaccinations. Here, we discuss the issue of the global surge of measles, its clinical picture, and the role of vaccination, focusing in particular on the European region and describing the underlying causes and potential of a measles pandemic. The purpose of this review is to address current measles epidemiology, highlighting the risks of a potential measles pandemic and exploring possible strategies to address it.

Langya henipavirus (LayV) and Mojiang henipavirus (MojV) are emerging zoonotic pathogens that were first identified in China in 2018 and 2012 respectively, and are classified within the Henipavirus genus. This article presents an in-depth review of LayV and MojV, focusing on their structural properties, viral entrance, and consequences for human health. The pathogenic potential of these viruses is investigated in depth as well as the current diagnostic methods for identifying LayV and MojV. Furthermore, treatment methods for controlling LayV and MojV infections are assessed, with a particular emphasis on the critical need for tailored antiviral research. This review serves as a critical resource for researchers and healthcare professionals, offering an up-to-date synthesis of knowledge on LayV and MojV while underscoring their significance in public health.

Chronic infections caused by Strongyloides stercoralis and Schistosoma spp. can present with longstanding gastrointestinal symptoms that mimic irritable bowel syndrome (IBS). In this case report, we describe a patient who was misdiagnosed with IBS for several decades before receiving a definitive diagnosis of chronic helminthiasis. Treatment with first-line antihelminthics resulted in complete and sustained resolution of symptoms. We review the life cycle, epidemiology, clinical presentations, diagnosis, and management of chronic helminthiases in the context of IBS. We further discuss the impact of misdiagnosis on both the patient and the healthcare system. Given the significant individual and economic burdens of IBS and the diagnostic uncertainty associated with low sensitivity of standard diagnostic tests for helminth infections, healthcare professionals should maintain a low threshold for testing and empiric treatment in patients with relevant travel and medical history.