2026年 · 第06卷第02期

With the advancement of combination antiretroviral therapy (cART), the global number of new human immunodeficiency virus (HIV) infections and HIV-related mortality has significantly declined. However, the high proportion of "late presentation" (defined as presenting to care with a low CD4 cell count or AIDS-defining events) among HIV-infected individuals remains a significant challenge in HIV prevention and treatment. HIV late presentation is associated with increased clinical risk, complex management, and higher risk of transmission, and represents a significant barrier to achieving the "95-95-95" targets and ending the HIV epidemic. Currently, both nationally and internationally, there is a lack of specific clinical guidelines for this population. Therefore, the China Association for Promotion of Health Science and Technology convened experts in the field to discuss the definition, clinical characteristics, risks, and cART of late presenters based on the latest research evidence and clinical practices both domestically and internationally. Specific recommendations were formulated to guide healthcare professionals in their clinical practice.

Background: The neonate and infant periods are critical time windows for diagnosing and treating congenital syphilis (CS) so as to prevent its adverse outcomes. In order to assist pediatricians in achieving early diagnoses and to standardize evaluations and treatments of early CS, this retrospective study described the clinical characteristics, management, and outcomes of infants with early symptomatic CS in Beijing, China, and compared the characteristics of neonatal syphilis with those of post-neonatal syphilis, aiming to enhance the prognosis for affected children. Methods: Clinical data, including demographics, clinical manifestations, laboratory test results, imaging reports, treatments, and follow-up outcomes, were collected from the electronic medical record system of Beijing Ditan Hospital, Capital Medical University (a tertiary-level general teaching hospital specializing in infectious diseases). The data pertained to patients admitted to the hospital from January 1, 2008, to December 31, 2024, who were diagnosed with early CS and met the inclusion criteria of this study. Nonparametric tests were used to compare the neonatal and post-neonatal groups for non-normally distributed continuous data, and χ2 tests were used for categorical data. Results: A total of 121 infants with early symptomatic CS were included in this study. Typical skin lesions (n = 97, 80.2%), hepatomegaly (n = 65, 53.7%), and fever (n = 50, 41.3%) were the most common symptoms. Liver damage was the most prevalent abnormality (n = 87, 71.9%), followed by hematological abnormalities, including anemia (n = 68, 56.2%) and thrombocytopenia (n = 30, 24.8%). In addition, 45 of the infants exhibited bone involvement, 29 had abnormal cerebrospinal fluid (CSF) analysis, and 28 had renal injury. Jaundice and elevated direct bilirubin levels occurred significantly more frequently in neonates (36 cases in total, with 50.0% [18 cases] and 63.9% [23 cases] respectively), whereas infants with post-neonatal CS (85 cases in total) were more prone to having hepatomegaly (63.5%, 54 cases), fever (50.6%, 43 cases), nasal congestion (32.9%, 28 cases), and cough (31.8%, 27 cases), as well as a higher incidence of elevated white blood cell count (72.9%, 62 cases) and a toluidine red unheated serum test (TRUST) titer ≥1:128 (83.5%, 71 cases). A total of 120 infants completed the anti-syphilis treatment. Of these, 96.7% (116 cases) were fully cured of syphilis-related damage. Moreover, 101 of the 120 infants who completed the treatment had serological follow-up, with 94.1% (95 cases) showing negative or ≥4-fold reduced TRUST titers. Conclusion: Infants diagnosed with CS after the neonatal period exhibited more frequent and complex symptoms, a higher incidence of leukocytosis, and a greater likelihood of complications, underscoring the importance of early diagnosis.

Background: Despite widespread vaccination efforts, pertussis remains a significant global public health concern, particularly among children. This study aimed to assess the burden and temporal trends of pertussis globally, regionally, and nationally by age, sex, and socio-demographic index (SDI) among children aged 0-14 years from 1990 to 2021, which is critical for informing targeted prevention strategies. Methods: We analyzed data from the Global Burden of Disease Study (GBD) 2021 on pertussis incidence, disability-adjusted life years (DALYs), mortality, and years lived with disability. The estimated annual percentage changes (EAPCs) were calculated to quantify temporal trends. Joinpoint regression analysis was used to identify the points at which significant changes in the trend occurred. To update the temporal trend analyses beyond 2021, we also incorporated the most recent pertussis estimates for relevant countries and territories from the GBD 2023 dataset. Results: Globally, approximately 19.9 million new cases of pertussis were recorded among children aged 0-14 years (age-standardized incidence rate 1,022.1 per 100,000 population) and 11.9 million DALYs (age-standardized DALY rate 608.7 per 100,000 population) in 2019. The age-standardized incidence of pertussis decreased by an EAPC of 1.7 from 1990 to 2009 and by 1.3 from 2010 to 2019, and declined further by 2021, probably due to Coronavirus Disease 2019 control measures. However, this overall downward trend masked considerable regional variation. Between 2010 and 2019, 11 out of 21 GBD regions experienced rising incidence, particularly in Tropical Latin America, Central Europe, and Central Latin America. Among high-SDI countries, pertussis incidence increased substantially in Cyprus (EAPC 17.62) and Finland (EAPC 19.66) from 2011 to 2019. In 2019, infants under 1 year old exhibited the highest pertussis incidence, and girls consistently had higher rates than boys across all age groups. In 2023, the highest age-standardized incidence was observed in the United States Virgin Islands among high SDI countries (1,597.5 per 100,000 population) and in Bosnia and Herzegovina among high-middle SDI countries (1,074.3 per 100,000 population). Conclusions: Although the age-standardized incidence and DALYs of pertussis have declined among children aged 0-14 since 1990, the disease has resurged in about half of the regions worldwide. Pertussis-related incidence and DALYs were higher in infants under 1 year old and girls. Maternal vaccination, continuous surveillance, and tailored public health interventions should be targeted toward vulnerable populations to prevent pertussis resurgence.

Background: Immunometabolism plays a vital role in the immunopathogenesis of people living with human immunodeficiency virus type 1 (HIV-1) (PLWH). However, the precise relationship between metabolic profiles and T-cell dysfunction in this population remains unclear. This study aimed to investigate the metabolic reprogramming and underlying mechanisms contributing to T-cell dysfunction in PLWH, highlighting potential pathogenic mechanisms during chronic HIV-1 infection. Methods: This study re-analyzed single-cell RNA sequencing data from the Genome Sequence Archive of the Beijing Institute of Genomics Data Center, Chinese Academy of Sciences. The dataset comprised samples from healthy donors (HD), HIV-1-infected treatment-naive patients (TN), and patients undergoing antiviral therapy. Various analytical approaches—including functional analysis, transcription factor analysis, network analysis, and enrichment analysis—were performed to assess T-cell functional and metabolic characteristics, as well as to identify potential targets within metabolic-epigenetic or non-epigenetic regulatory axes involved in T-cell dysfunction. Results: By analyzing the transcriptional profiles, a total of 58,752 CD4+ T cells and 68,907 CD8+ T cells were identified and annotated. Among these, the naive subset CD8-CCR7 was significantly reduced in TN patients compared to HD (P < 0.05), whereas CD4-CCR7 showed a decreasing trend. Conversely, the effector subset CD8+ activated effector/memory T cells (CD8-EMRA) were significantly increased in TN patients (P < 0.05), while cytolytic CD4+ T cells (CD4-CTL) displayed an increasing trend. ART did not effectively reverse these alterations. Additionally, naive subsets and CD8-EMRA cells were associated with disease progression. Further analysis revealed that naive subsets exhibited hyper-activation and increased differentiation, whereas effector subsets showed excessive activation and a strong interferon (IFN) response in PLWH compared to HD (P < 0.05). Intriguingly, we observed substantial metabolic alterations linked to immune dysfunction within the four T-cell subsets. Specifically, elevated levels of the methyltransferases absent, small, or homeotic-like 1 (ASH1L) and SET domain containing 1B (SETD1B) may have promoted the differentiation and exhaustion of the CD4-CCR7 subset via the ASH1L/SETD1B-H3K4me3-FOXP1 axis. These enzymes were also associated with the exhaustion of CD8-CCR7 cells in TN patients through ASH1L/SETD1B-H3K4me3 axis. Additionally, isocitrate dehydrogenase 2 (IDH2)-mediated production of α-ketoglutarate (α-KG) may have contributed to the dysfunction of CD8-CCR7 cells by activating Janus kinase (JAK)-signal transducer and activator of transcription (STAT)3-dependent interferon signaling during HIV-1 infection. Conversely, increased activity of SET domain containing 2 methyltransferase was closely linked to hyperactivation, a strong type I interferon response, and cellular senescence in CD4-CTL cells from TN patients. Furthermore, heightened expression of solute carrier family 7 member 5 correlated with exhaustion of effector subsets in TN individuals. The IDH2-STAT1 axis may have also played a crucial role in driving the over-activation and exhaustion of CD8-EMRA cells through interferon signaling pathways. Conclusion: These findings indicate that amino acid- and IDH2-related metabolism may contribute to the dysfunction of both naive and effector subsets by metabolic-epigenetic or non-epigenetic regulatory axes in PLWH.

Background: Increasing evidence has suggested that the early initiation of antiviral treatment promotes better treatment responses in young children with chronic hepatitis B (CHB), including functional cure. But there are limited studies regarding the clinical responses of antiviral treatment for these children. This study aims to explore the relationship between age at the initiation of antiviral therapy and hepatitis B surface antigen (HBsAg) loss among pediatric patients. Methods: We systematically searched five electronic databases and reviewed relevant research, and then conducted two-arm and single-arm meta-analyses of treatment responses among children with CHB to explore the effect of baseline age on treatment responses. Finally, based on the different clinical phases of CHB, treatment regimens, and observation end points, subgroup analysis was also conducted to find possible influence factors during the treatment. The primary outcome was HBsAg loss. Results: Eighteen studies involving 2,459 children with CHB were analyzed in this systematic review and meta-analysis. Children aged 1-7 years with CHB exhibited better treatment responses than those aged 8-18 years (odds ratios: HBsAg loss, 5.584 [4.069-7.664] ; HBV DNA suppression, 1.946 [1.356-2.793]; hepatitis B e antigen [HBeAg] loss, 2.369 [1.612-3.482]; HBeAg seroconversion, 3.094 [2.196-4.360]; and HBsAg seroconversion, 4.970 [1.503-16.439]), especially among children with CHB in the immune-clearance phase. The pooled rates of HBV DNA suppression, HBeAg loss, HBeAg seroconversion, HBsAg loss, and HBsAg seroconversion of children aged 1-7 versus 8-18 years were 85.7% versus 71.2% (P > 0.05), 74.4% versus 52.0% (P < 0.01), 70.6% versus 38.9% (P < 0.01), 54.5% versus 18.8% (P < 0.001), and 62.0% versus 17.5% (P < 0.05), respectively. Conclusions: Baseline age at the initiation of antiviral treatment is associated with HBsAg loss in children with CHB. Since all the available data came from observational studies, our findings should be validated by further multicohort randomized controlled trials.

Functional (clinical) cure is considered a desirable therapeutic endpoint of antiviral therapy for chronic hepatitis B (CHB). Recent studies have detected transcriptionally active covalently closed circular DNA (cccDNA) and integrated hepatitis B virus (HBV) DNA (iDNA) in the liver tissue of patients who achieved functional cure. More than that, a small subset of these patients even showed positive staining for hepatitis B surface antigen (HBsAg) in hepatocytes. Notably, compared to uncured patients, functionally cured patients demonstrate significantly restored HBV-specific immune responses. Based on these findings, it is clear that although cccDNA or iDNA are not completely cleared in certain functionally cured patients, the circulating viral markers are largely undetectable, even with the sensitive measuring methods that are routinely used. This is because, virologically, the residual viral genomic DNA in functionally cured patients is often genetically or epigenetically modified or undergoes post-transcriptional splicing and editing that prevents viral protein expression and productive replication. More importantly, the restored host immune responses further suppress viral protein production and HBV DNA replication to undetectable levels in peripheral blood. Thus, this form of functional cure for CHB might be described more accurately as an "undetectable" state of circulating virologic markers under the control of a restored host immune response against HBV infection. This resembles occult HBV infection to some extent, as replicative forms of HBV DNA—such as relaxed circular DNA and/or cccDNA—persist in the liver, accompanied by a risk of reactivation. As a result, consolidation therapy following serum HBsAg loss and continued follow-up monitoring after discontinuation of treatment become crucial. This review provides a comprehensive overview of the status of CHB patients who achieved functional cure, explains its underlying reasons, and assesses its relevance to clinical treatment and practice.

Invasive fungal disease (IFD) has become a critical complication in patients with end-stage liver disease (ESLD), marked by a rising prevalence and the emergence of drug-resistant strains in recent decades. The heightened susceptibility to IFD in ESLD stems from liver-related immune dysfunction, structural changes, and iatrogenic factors, such as invasive procedures, broad-spectrum antibiotics, and immunosuppressive therapies. Timely diagnosis is essential for effective management, yet it remains challenging. This review examines both conventional culture-based and advanced culture-independent diagnostic techniques, including polymerase chain reaction-based assays and the T2Candida Panel. Treatment strategies are stratified according to diagnostic certainty (proven, probable, or possible IFD), although therapeutic efficacy is often limited by antifungal hepatotoxicity and drug resistance. We summarize current treatment recommendations for common IFD pathogens, with an emphasis on pharmacokinetic considerations and dose adjustments in ESLD patients. Given the growing clinical burden of IFD in ESLD, further research is urgently needed to optimize IFD management and prophylaxis in this high-risk population. This review also outlines key priorities for addressing future challenges in diagnosis and therapy.

Melioidosis, caused by Burkholderia pseudomallei, is a serious infection with a wide range of clinical presentations; however, thyroid gland involvement is exceptionally rare.We present the case of a 56-year-old woman with poorly controlled diabetes who developed painful anterior neck swelling. Imaging suggested a thyroid lesion, and aspiration revealed pus. Culture and polymerase chain reaction confirmed B. pseudomallei. She was treated with intravenous ceftazidime followed by long-term oral cotrimoxazole and was completely cured on four-month follow-up. This case illustrates the need to consider melioidosis in the differential diagnosis of thyroid abscesses, especially in diabetic patients from tuberculosis endemic areas, and emphasises the importance of early targeted therapy.

Tsukamurella species are rare, aerobic, gram-positive actinomycetes that are increasingly recognized as opportunistic pathogens affecting immunocompromised patients, such as those suffering from epidermolysis bullosa. Epidermolysis bullosa is a rare genetic disorder characterized by skin fragility that predisposes patients to chronic wounds and recurrent skin infections. The case of interest in this work was a 22-year-old male with a complex medical history, including the aforementioned disorder. He was admitted to the hospital’s emergency department, presenting with fluctuating low-grade fever and recurrent bleeding of the skin lesion on his flank. Infectious workup was sent, after which appropriate intravenous fluids were administered for resuscitation, along with broad-spectrum antibiotics. During the patient’s hospitalization, he was found to have Tsukamurella pulmonis and methicillin-resistant Staphylococcus aureus bacteremia, which was treated with vancomycin administered intravenously. Treatment resulted in significant improvement. This case adds to the limited body of studies describing T. pulmonis as a human pathogen. It highlights the importance of considering such rare opportunistic infectious agents in immunocompromised patients with chronic wounds and indwelling catheters. The study serves as a reference for clinicians, emphasizes the therapeutic challenges encountered in managing this infection in high-risk populations, and sheds the light on the need for established policies and clinical guidelines.