Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Objective:To evaluate the efficacy and safety of the CLAE (cladribine + cytarabine + etoposide) regimen in refractory/relapsed T cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) .Methods:Patients with R/R T-ALL/LBL received the CLAE regimen in a prospective, multicenter, single-arm clinical study or compassionate use. From March 2019 to August 2024, data from 25 patients (18 in the study across five centers and 7 receiving compassionate treatment in Peking University Third Hospital) were collected. Outcomes included objective response rate, complete response (CR) rate, partial response (PR) rate after 1–2 cycles, bridging to allo-HSCT, progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects.Results:Median age was 29 years (range, 13–63) ; 17 were male. Among the 24 evaluable patients, CR rate was 33.3% overall and 41.2% among enrolled patients. Median OS and PFS time were 199 (46–1 310) and 49 (28–1 310) days, respectively. Cumulative OS rate at 6 months, 1 year, and 2 years was (52.1±10.2) %, (29.7±9.3) %, and (27.1±9.1) %, respectively; cumulative PFS rate was (32.6±9.6) %, (24.9±8.9) %, and (23.8±8.7) %, respectively. Among patients achieving CR or PR (8 cases), median OS and PFS were not reached. Cumulative OS rate at 6 months, 1 year, and 2 years was (86.8±12.0) %, (78.3±14.6) %, and (72.9±15.7) %, respectively, and the cumulative PFS rate was (86.4±12.1) %, (74.8±15.3) %, and (72.9±15.7) %, respectively. Adverse events were mainly hematologic; no treatment-related mortality occurred. Seven patients achieving CR were bridged to allo-HSCT, with 5 remaining in continuous remission.Conclusion:The CLAE regimen is safe and effective for R/R T-ALL/LBL, facilitating CR as a bridge to allo-HSCT and potentially improving patient prognosis.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Peer support can improve negative emotions, cognitive level, self-coping, and quality of life in adolescents and young adults with cancer. The rise of digital health technology has facilitated the rapid development of online medical interventions, providing an opportunity for the development of online peer support. This study reviewed the intervention modalities, application forms, application effects and should prospects of online peer support applied in adolescent and young adult cancer patients, to provide a reference for improving healthcare professionals to conduct high-quality online peer support interventions.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.