The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

OBJECTIVES: To study the clinical and imaging features of children with influenza-associated encephalopathy (IAE), and to investigate the influencing factors for prognosis. METHODS: A retrospective analysis was conducted on the medical data (clinical data, laboratory examinations, imaging data, and prognosis) of 23 children with IAE who were diagnosed and treated in Children's Hospital of Nanjing Medical University from May 2022 to April 2023. RESULTS: Among the 23 patients, 18 (78%) had influenza A and 5 (22%) had influenza B. All patients had fever and encephalopathy, and 20 patients (87%) had seizures, while 11 patients (48%) had persistent convulsions. There were 10 patients (43%) with an increase in alanine aminotransferase, 14 (61%) with an increase in aspartate aminotransferase, and 18 (78%) with an increase in lactate dehydrogenase. Abnormal imaging findings were observed in 20 patients (87%), among whom 10 (43%) had acute necrotizing encephalopathy. All 23 patients received peramivir or oseltamivir. Of all patients, 12 (52%) achieved complete recovery, 5 (22%) had varying degrees of neurological dysfunction, and 6 (26%) died. Compared with the good prognosis group, the poor prognosis group had significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (P<0.05). CONCLUSIONS Fever and convulsions are the most common symptoms of children with IAE, and acute necrotizing encephalopathy is the most common clinical imaging syndrome. Increases in alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase have a certain value in predicting poor prognosis.
Humans ; Influenza, Human/complications* ; Male ; Prognosis ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Child ; Brain Diseases/etiology*

OBJECTIVES: To evaluate the clinical efficacy of hospital-prepared Chinese medicine Feigan granules for influenza patients. This study has been registered at the International Traditional Medicine Clinical Trial Registry platform (ITMCTR2025000162). METHODS: A prospective observational study was conducted on influenza patients who visited the Fever Clinic of the First Affiliated Hospital, Zhejiang University School of Medicine between February and March 2024. Patients were divided into the observation group (Feigan granules combined with conventional Western medicine) and the control group (conventional Western medicine). Main symptoms (including fever, cough and sore throat) and secondary symptoms (including chest tightness, poor appetite, muscle soreness and dry mouth) were evaluated with traditional Chinese medicine (TCM) symptom scale on the first day of the patient's visit and the third day after treatment. The degrees of improvement in the TCM symptom scores before and after treatment were compared using paired rank-sum test, and the differences in the overall symptom efficacy index between two groups were compared using the Wilcoxon test. RESULTS: A total of 217 influenza patients were included. After treatment, the TCM symptom scores of both groups were significantly improved compared with those before treatment (all P<0.01). The median differences in the main symptom score before and after treatment in the observation and the control groups were 7 points (95%CI: 6.0-8.0) and 6 points (95%CI: 6.0-8.0), respectively. The median difference in the secondary symptom score was 3 points (95%CI: 2.0-4.0) in both groups. The median differences in the total score were 9 points (95%CI: 8.0-10.5) and 8 points (95%CI: 7.0-10.0) in the observation and control groups, respectively. In the subgroup with an initial cough score >2, the improvement rates of total score (97.06% vs. 92.59%) and secondary symptoms (92.31% vs. 85.11%) in observation group were significantly higher than those in the control group (P<0.05); while there was no significant difference in the improvement rate of the main symptoms (95.59% vs. 90.74%, P>0.05). CONCLUSIONS Feigan granules can improve the TCM syndromes of influenza patients, especially for patients with more severe cough.
Humans ; Prospective Studies ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Treatment Outcome

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Avian influenza H10N3 is a type of avian influenza virus that can occasionally infect humans and cause severe pneumonia and acute respiratory distress syndrome (ARDS). On December 25, 2024, a 23-year-old obese female patient with H10N3 avian influenza complicated with severe ARDS was admitted to the Fourth People's Hospital of Nanning. The patient was transferred to our department due to "fever, cough, and shortness of breath for 13 days". Physical examination revealed moist rales in bilateral lungs. Chest imaging showed large areas of ground-glass opacity and consolidation in both lungs. Based on the patient's medical history, clinical manifestations, and laboratory findings, she was diagnosed with human infection of H10N3 avian influenza, severe pneumonia, and severe ARDS. Supported by mechanical ventilation and extracorporeal membrane oxygenation (ECMO), daily monitoring of airway peak pressure, plateau pressure (Pplat), driving pressure (ΔP), and lung compliance was performed to guide the adjustment of tidal volume (VT) and positive end-expiratory pressure (PEEP) during invasive mechanical ventilation. Medications including anti-avian influenza virus agents, antibacterial drugs, and antifungals were administered. Eventually, the patient's condition improved gradually, and she was successfully weaned from ECMO. No ventilator-induced lung injury (VILI) or multiple organ dysfunction syndrome (MODS) related to ARDS occurred during ECMO support. However, during the final stage of ventilator weaning after the restoration of spontaneous breathing, a right pneumothorax occurred. Closed thoracic drainage was performed, after which the ventilator was successfully discontinued. The patient was successfully transferred out of the intensive care unit (ICU), recovered fully, and was discharged from the hospital. In the invasive mechanical ventilation management of patients infected with H10N3 avian influenza complicated by ARDS, monitoring airway peak pressure, Pplat, ΔP, and assessing pulmonary compliance may facilitate more standardized management of such ARDS patients and help reduce VILI.
Humans ; Female ; Influenza, Human/complications* ; Respiratory Distress Syndrome/complications* ; Respiration, Artificial/methods* ; Obesity/complications* ; Young Adult ; Extracorporeal Membrane Oxygenation ; Influenza A virus

The influenza virus is classified as a single-stranded negative-sense RNA virus in Orthomyxoviridae family, with epidemiological properties distinct from common cold. Previous studies have found that influenza infection can cause cardiac damage through various pathways, and patients with cardiovascular diseases are at relatively higher risk of adverse disease outcomes. Influenza vaccination has been proven to provide protective effect on patients with cardiovascular diseases. Currently, there is insufficient emphasis placed by cardiologists and cardiovascular disease patients on the prevention of influenza infection, leading to a low influenza vaccination rate in China. Therefore, based on the current clinical research progress and relevant guidelines, combined with the safety, feasibility and health economic benefits of influenza vaccinating in patients with cardiovascular diseases, as well as clinical experience from experts, this article proposes expert opinions on influenza vaccination in common cardiovascular diseases aiming to raise awareness of influenza prevention and benefiting patients.
Humans ; Cardiovascular Diseases/prevention & control* ; Influenza Vaccines/administration & dosage* ; Influenza, Human/prevention & control* ; Vaccination ; Expert Testimony

OBJECTIVE: Despite the global decrease in influenza infections during the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza remains a significant health issue. South Korea, known for its robust pandemic response and high influenza vaccination rates, offers a unique context for examining changes in vaccination trends during the pandemic. Using nationally representative data, we aimed to understand the impact of the pandemic on influenza vaccination behavior over a 12-year period and to identify vulnerable groups. METHODS: We analyzed influenza vaccination rates in South Korea between 2011-2022, focusing on pandemic-related impacts. The data of 2,426,139 adults (≥ 19 years) from the Korea Community Health Survey were used to assess demographic and sociological factors influencing vaccination behaviors. RESULTS: We observed an increase in influenza vaccination rates during the pre-COVID-19 period from 2011-2013 (weighted prevalence: 46.68% [95% confidence interval ( CI): 46.55-46.82]) to 2017-2019 (weighted prevalence: 52.50% [95% CI: 52.38-52.63]). However, a significant decline was observed in 2022, the late-COVID-19 pandemic period (weighted prevalence: 55.78% [95% CI: 55.56-56.01]), compared with the mid-pandemic period in 2021 (weighted prevalence: 59.12% [95% CI: 58.91-59.32]), particularly among populations traditionally prioritized for influenza vaccination, including older adults (≥ 65 years) and patients with chronic diseases and low educational and income levels. CONCLUSION The influenza vaccination rate in South Korea was significantly affected by the COVID-19 pandemic, showing a notable decrease among vulnerable demographic groups. This suggests the need for targeted public health strategies to address vaccine hesitancy and improve vaccination rates, particularly among high-risk populations.
Humans ; Republic of Korea/epidemiology* ; COVID-19/epidemiology* ; Adult ; Middle Aged ; Influenza Vaccines/administration & dosage* ; Male ; Female ; Influenza, Human/epidemiology* ; Aged ; Vaccination/statistics & numerical data* ; Young Adult ; Pandemics ; SARS-CoV-2

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells

Objective: To analyze the genetic characteristics of the first human infection with the G4 genotype of Eurasian avian H1N1 swine influenza virus (EA H1N1 SIV) in Shaanxi Province. Methods: The patient's throat swab samples were collected, and MDCK cells were inoculated for virus isolation to obtain the virus strain. The whole genome deep sequencing method was used to obtain the eight gene segments of the isolated strain. The nucleotide homology analysis was conducted through the Blast program in the GenBank database, and a phylogenetic tree was constructed to analyze the genetic characteristics of the virus. Results: The throat swab specimens of the case were confirmed as EA H1N1 SIV in the laboratory, and the isolated strain was named A/Shaanxi-Weicheng/1351/2022(H1N1v). Homology analysis found that the PB2, NP, HA, NA, and M genes of this isolate had the highest nucleotide homology with A/swing/Beijing/0301/2018 (H1N1), about 98.29%, 98.73%, 97.41%, 97.52%, and 99.08%, respectively. The phylogenetic tree showed that the isolate belonged to G4 genotype EA H1N1 SIV, with PB2, PB1, PA, NP and M genes from pdm/09 H1N1, HA and NA genes from EA H1N1, and NS gene from Triple-reassortant H1N1. The cleavage site of the HA protein was IPSIQSR↓G, which was the molecular characteristic of the low pathogenic influenza virus. No amino acid mutations associated with neuraminidase inhibitors were found in the NA protein. PB2 protein 701N mutation, PA protein P224S mutation, NP protein Q357K mutation, M protein P41A mutation, and NS protein 92D all indicated its enhanced adaptability to mammals. Conclusion: The patient is the first human infection with G4 genotype EA H1N1 SIV in Shaanxi province. The virus is low pathogenic, but its adaptability to mammals is enhanced. Therefore, it is necessary to strengthen the monitoring of such SIVs.
Swine ; Humans ; Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Phylogeny ; Genotype ; Influenza A virus ; China ; Birds ; Mammals