Liuluan Zhu

Pneumocystis jirovecii pneumonia (PCP) prophylaxis is established in people with human immunodeficiency virus (HIV), but guidance for non-HIV, non-malignant immunocompromised adults remains fragmented. We searched eight databases and registries through 18 May 2026 (PROSPERO CRD420261396046). Because the evidence did not support a clinically exchangeable network, we evaluated four linked routes: comparative effectiveness, active-regimen safety, trimethoprim-sulfamethoxazole (TMP-SMX) discontinuation burden, and descriptive second-line evidence. Fifty-four full-length peer-reviewed reports were included. The primary effectiveness synthesis comprised 27 studies, 34,473 participants, and 243 PCP events. Compared with no prophylaxis, standard-dose TMP-SMX (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.18–0.48; low certainty) and low-dose TMP-SMX (OR 0.08, 95% CI 0.03–0.18; low certainty) were associated with lower PCP incidence. Lower-intensity TMP-SMX strategies were associated with fewer treatment-limiting discontinuations than standard/conventional-dose TMP-SMX (OR 0.234, 95% CI 0.145–0.377). Across 33 TMP-SMX studies/cohorts, the pooled discontinuation proportion was 12.3% (95% CI 9.4–15.9%). Breakthrough PCP occurred in 0.5% of 1056 second-line recipients. TMP-SMX had the clearest protective association; however, low-dose evidence did not establish superiority or non-inferiority, and second-line data did not permit comparative estimates or regimen ranking.

To explore the protective effect of knock-down the expression of B lymphocyte induced maturation protein 1 (Blimp1) gene on early liver injury in carbon tetrachloride (CCl₄)-induced mouse model of liver fibrosis. C57BL/6 mice were intraderitoneal injected with 5% CCl₄ olive oil solution to create mouse model of hepatic fibrosis. The expression of Blimp1 gene in the mice was reduced by intraderitoneal injection of short hairpin RNA (shRNA) adeno-associated virus (AAV). The mice were randomly divided into 3 groups: blank test group (n=10), CCl₄+AAV-shRNA-NC group (n=10) and CCl₄+AAV-shRNA-Blimp1 group (n=10). After 27 days of preparation of the CCl₄ mouse model, animal materials were carried out. Western blot and real-time PCR were used to detect the levels of Blimp1, α-smooth muscle actin (α-SMA), collagen type Ⅰ alpha 1 (COL1A1), collagen type Ⅲ alpha 1 (COL3A1), and their mRNA expression levels of liver tissue in each group. The serum of each group was separated to measure aspartate transaminase (AST) and alanine transaminase (ALT) by automatic biochemical analyzer. The pathological changes of liver tissue and the degree of liver fibrosis in the mice were detected by pathological staining including hematoxylin-eosin staining, Masson, and Sirius red. The expression levels of Blimp1 protein in the liver of CCl₄+AAV-shRNA-NC group (2.036±0.244, t=3.690, P=0.002) were significantly increased than that of the blank test group. In the CCl₄+AAV-shRNA-Blimp1 group, the expression of Blimp1 protein decreased to the basal level (0.783±0.249, t=6.223, P=0.003). Compared with the serum levels of ALT [(1 957.8±633.6) U/L] and AST [(1 808.8±260.1) U/L] in the CCl₄+AAV-shRNA-NC group, the serum levels of ALT [(894.0±360.1) U/L, t=3.998, P=0.003] and AST [(820.0±100.6) U/L, t=6.141, P=0.004] in the CCl₄+AAV-shRNA-Blimp1 group were significantly decreased. The pathological results of the CCl₄+AAV-shRNA-Blimp1 group showed that compared with the CCl₄+AAV-shRNA-NC group, the infiltration of inflammatory cells in the liver tissue was reduced and the degree of fibrosis was alleviated. The level of α-SMA (0.676±0.064, t=7.930, P=0.001), COL1A1 (1.426±0.143, t=6.364, P=0.003) and COL3A1 (1.124±0.198, t=3.440, P=0.026) of liver in the CCl₄+AAV-shRNA-Blimp1 group were significantly decreased than that of CCl₄+AAV-shRNA-NC group, and the mRNA expression levels were altered as well as their protein levels. Blimp1 plays an important role in CCl₄-induced liver fibrosis in mice, and knock-down the expression of Blimp1 gene is beneficial to protect early liver injury in mice.

Mortality from Pneumocystis pneumonia (PCP) continues to increase among non-human immunodeficiency virus (HIV) patients. Previous studies have reported that a considerable proportion of patients experience deterioration of their disease when glucocorticoids or other immunosuppressants are withdrawn. However, the underlying mechanisms responsible for this phenomenon remain poorly understood. Our findings, based on a comparative analysis of immune function in glucocorticoid-induced PCP mice at the time of glucocorticoid continuation and glucocorticoid withdrawal, suggested that the damage to lung tissues in PCP mice was significantly exacerbated and lung function deteriorated following glucocorticoid withdrawal. Mechanistically, our investigations revealed that PCP mice underwent immune reconstitution and developed immune reconstitution inflammatory syndrome (IRIS) after glucocorticoid withdrawal, which resulted in enhanced immune responses to pre-existing Pneumocystis. Prophylactic G-CSF neutralization in vivo prior to glucocorticoid withdrawal attenuated withdrawal-induced IRIS but also impaired Pneumocystis clearance. This study elucidated that the exacerbation of infection in PCP mice after glucocorticoid withdrawal is analogous to the clinical phenomenon and demonstrated that it is caused by the immune reconstitution that occurs after glucocorticoid withdrawal and resulting IRIS while also showing that G-CSF plays an important role in this process. This provides clinical comprehension of the progression of disease in non-HIV PCP patients.

Neutrophils, the most abundant white blood cells in human circulation, play a crucial role in innate immunity. One of their key defense mechanisms is the formation of neutrophil extracellular traps (NETs), web-like structures composed of chromatin and antimicrobial proteins that help capture and neutralize pathogens. While previous studies have identified a limited set of NET-associated proteins, the comprehensive proteomic landscape of NETs induced by different stimuli remains largely unexplored. In this study, we used data-independent acquisition mass spectrometry to analyze the proteomic composition of NETs induced by five distinct stimuli: β-glucan, lipopolysaccharide, polyinosinic-polycytidylic acid sodium, resiquimod, and severe fever with thrombocytopenia syndrome bunyavirus. Across all conditions, we identified 5,868 NET-associated proteins, revealing significant stimulus-dependent differences in protein composition. Notably, differentially expressed proteins were detected in each condition, highlighting unique proteomic signatures that may reflect distinct immune responses. This dataset offers key insights into the proteomic diversity of NETs and their role in immune regulation, providing a foundation for future research on NET-mediated immunity in infectious and inflammatory diseases.

Sepsis, a life-threatening condition marked by systemic inflammation and multi-organ dysfunction, poses a persistent clinical challenge. Post-translational modifications (PTMs) dynamically regulated inflammatory signaling, immune responses, and cell death, positioning them as a pivotal focus in sepsis research. This review systematically explores the regulatory networks of five key PTMs – phosphorylation, ubiquitination, SUMOylation, acetylation, and lactylation – in sepsis. In this review, we highlight recent discoveries of genes and molecules that modulate these PTMs, influencing inflammation and organ dysfunction, and evaluate their potential as therapeutic targets or prognostic biomarkers. Furthermore, we discuss how PTMs offer novel therapeutic opportunities, providing novel insights to address the shortcomings of traditional anti-infective approaches.

Sepsis is a life-threatening condition characterized by a dysregulated immune response to infection, leading to systemic inflammation and organ dysfunction. Macrophage polarization plays a critical role in pathogenesis of sepsis, and the influence of B lymphocyte-induced maturation protein-1 (Blimp-1) on this polarization is an underexplored yet pivotal aspect. This study aimed to elucidate the role of Blimp-1 in macrophage polarization and metabolism during sepsis. Using a murine cecal ligation and puncture model, we observed elevated Blimp-1 expression in M2 macrophages. Knockdown of Blimp-1 by macrophage-targeted adeno-associated virus in this model resulted in decreased survival rates, exacerbated tissue damage, and impaired M2 polarization, underscoring its protective role in sepsis. In vitro studies with bone marrow-derived macrophage (BMDM), RAW264.7, and THP-1 cells further demonstrated Blimp-1 promotes M2 polarization and modulates key metabolic pathways. Metabolomics and dual-luciferase assays revealed Blimp-1 significantly influences purine biosynthesis and the downstream Ornithine cycle, which are essential for M2 macrophage polarization. In vitro studies with BMDM further suggested that the purine biosynthesis and Ornithine cycle metabolic regulation is involved in Blimp-1’s effects on M2 macrophage polarization, and mediates Blimp-1’s impact on septic mice. Our findings unveil a novel mechanism by which Blimp-1 modulates macrophage polarization through metabolic regulation, presenting potential therapeutic targets for sepsis. This study highlights the significance of Blimp-1 in orchestrating macrophage responses and metabolic adaptations in sepsis, offering valuable insights into its role as a critical regulator of immune and metabolic homeostasis.

Portal vein thrombosis (PVT) is a challenging complication in liver cirrhosis, with no currently available sensitive diagnostic markers. This study aimed to investigate the potential of neutrophil extracellular traps (NETs) and Deoxyribonuclease (DNase) as diagnostic indicators for PVT in chronic hepatitis B (CHB)-related decompensated cirrhosis.

Sepsis is a life-threatening condition characterized by a dysregulated immune response to infection, leading to systemic inflammation and organ dysfunction. Macrophage polarization plays a critical role in pathogenesis of sepsis, and the influence of B lymphocyte-induced maturation protein-1 (Blimp-1) on this polarization is an underexplored yet pivotal aspect. This study aimed to elucidate the role of Blimp-1 in macrophage polarization and metabolism during sepsis. Using a murine cecal ligation and puncture model, we observed elevated Blimp-1 expression in M2 macrophages. Knockdown of Blimp-1 in this model resulted in decreased survival rates, exacerbated tissue damage, and impaired M2 polarization, underscoring its protective role in sepsis. In vitro studies with bone marrow-derived macrophages, RAW264.7, and THP-1 cells further demonstrated Blimp-1 promotes M2 polarization and modulates key metabolic pathways. Metabolomics and dual-luciferase assays revealed Blimp-1 significantly influences purine biosynthesis and the downstream Ornithine cycle, which are essential for M2 macrophage polarization. Our findings unveil a novel mechanism by which Blimp-1 modulates macrophage polarization through metabolic regulation, presenting potential therapeutic targets for sepsis. This study highlights the significance of Blimp-1 in orchestrating macrophage responses and metabolic adaptations in sepsis, offering valuable insights into its role as a critical regulator of immune and metabolic homeostasis.