Post-infectious symptoms of COVID-19-such as persistent dyspnea, psychological disturbances, and reduced quality of life-continue to pose significant health challenges for convalescent patients. Traditional Chinese Medicine (TCM) has been widely used as a complementary therapeutic approach to alleviate post-COVID sequelae. This retrospective study evaluated the clinical effects of 2 TCM prescriptions, Fuzheng Yifei Formula (FZYF) and Fuzheng Anshen Formula (FZAS), on the psychological state, dyspnea, and quality of life among patients recovering from COVID-19. Medical records of 114 COVID-19 convalescent patients treated at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine were retrospectively reviewed. Based on the treatment regimen, patients were categorized into 2 groups: FZYF (n = 77) and FZAS (n = 37). Clinical data were collected at baseline, 7 days, 14 days, and during follow-up. Changes in psychological status, dyspnea severity, and quality-of-life scores were analyzed using validated assessment tools, including the General Health Questionnaire (GHQ-12), the Modified Borg Scale, and the 36-Item Short Form Survey (SF-36) Health Survey. Both FZYF and FZAS were associated with significant improvements in psychological well-being, with mean GHQ-12 scores decreasing from 14.5 at baseline to 9 at follow-up (P < .05). Dyspnea symptoms improved across both groups, with an average reduction of 3.5 points on the Modified Borg Scale. The SF-36 results indicated notable enhancements in both physical and mental health domains, showing mean improvements of 22% and 23%, respectively. No statistically significant difference was found between the 2 formulas, although FZYF showed slightly superior benefits in respiratory symptom relief. The retrospective analysis suggests that the FZYF may help alleviate long-term respiratory and psychological symptoms among COVID-19 convalescents, thereby potentially improving their overall quality of life. The FZAS, while showing comparable trends of benefit, appeared to exert relatively greater influence on mental and emotional well-being. However, these findings should be interpreted with caution given the non-randomized design and limited sample size, and further validation through large-scale controlled studies is warranted.

Infectious diseases caused by viruses or bacteria pose a serious threat to human life and health system, such as influenza, COVID‐19, and sepsis. They are characterized by obstacles of pathogen clearance, immune dysfunction, or microbial dysbiosis. Conventional therapies are facing tremendous challenges such as antibiotic resistance and viral rapid mutations. Chinese herbal medicine‐derived extracellular vesicles‐like particles (CHM‐EVLPs), a novel strategy, have exhibited great potential for infectious disease therapy. These natural CHM‐EVLPs possess unique advantages in clearing pathogens, orchestrating host immune homeostasis, repairing tissue barrier, and mitigating microbial dysbiosis. Besides, they can deliver some therapeutic drugs for targeted therapy as nano carriers. Good biocompatibility and organotropism also endowed them satisfactory security. These advantages might assist CHM‐EVLPs overcome the limitations of traditional therapeutics. Thus, this review first summarizes the basic information of CHM‐EVLPs regarding preparation methods and bioactive components. Then, the pathological mechanisms of infectious diseases and the protective effects of CHM‐EVLPs through interaction with these mechanisms will be comprehensively discussed. Finally, future perspectives of CHM‐EVLPs for infectious diseases treatment are proposed. Overall, as a bridge connecting traditional herbal medicine and nanotechnology, CHM‐EVLPs offer a high‐efficiency, sustainable, and multitarget approach to treat infectious diseases.

Objective:Wenyang Jiedu Granule (WYJD) is an effective traditional Chinese medicine (TCM) preparation that has been generally applied for treating respiratory infectious diseases. Clinical observations involving thousands of cases have demonstrated that WYJD could alleviate disease progression and improve symptoms in treating respiratory viral infections, including SARS-CoV-2 and influenza virus. However, the chemical basis and underlying mechanisms of WYJD against influenza A virus (IAV)-induced pneumonia remain to be elucidated. This study aimed to reveal the underlying mechanisms of WYJD in treating IAV-induced pneumonia by a combined strategy of network pharmacology, transcriptomics and experimental validation. Methods:The pneumonia model was established in BALB/c mice via infection with H1N1 IAV to evaluate the therapeutic effects of WYJD on IAV-induced pneumonia. Firstly, ultra-high performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometer/tandem mass spectrometer (UPLC-Q Exactive Orbitrap-MS/MS) was employed to analyze the main chemical components in WYJD-containing serum. Subsequently, the effects of WYJD on IAV-induced pneumonia were assessed through pathological observation, plaque forming assay, biochemical analysis, Evans blue staining assay, and immunofluorescence assay. Mechanistically, an integrated approach of network pharmacology and transcriptomics was applied to explore the potential active components, targets and related pathways of WYJD against IAV-induced pneumonia. Fluorescence TUNEL assay, quantitative real-time PCR (qRT-PCR) and Western blotting were utilized for experimental validation and mechanistic studies. Results:Using UPLC-Q Exactive Orbitrap-MS/MS, a total of 25 prototypes and 15 metabolites were identified in the serum of mice after WYJD administration. WYJD treatment showed protective effects on IAV-induced pneumonia by inhibiting inflammation and lung barrier damage in the IAV-induced pneumonia mice model. Network pharmacology combined with transcriptomics analysis indicated that WYJD exerted therapeutic effects against IAV-induced pneumonia mainly through the synergistic effects of 11 active components, which regulated ten critical signaling pathways via 86 targets. Further experimental validation demonstrated that WYJD could alleviate IAV-induced pneumonia via the IL-17 signaling pathway, Toll-like receptor 7‌ (TLR7)/Myeloid differentiation primary response dene 88 (MyD88)/mitogen-activated protein kinases (MAPKs)/activator protein 1 (AP-1) signaling pathway and apoptosis. Conclusion:This study revealed the main active components and mechanisms of WYJD against IAV-induced pneumonia through the IL-17 signaling pathway, TLR7/MyD88/MAPKs/AP-1 signaling pathway and apoptosis, which provides novel insights into the clinical application of WYJD in treating influenza and its complications.

BACKGROUND:Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols. METHODS:This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software. RESULTS:A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I2 = 98.2%, p < 0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited. CONCLUSION:Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.

Sepsis research has long been constrained by limited labeled data and models designed for specific tasks that primarily rely on tabular inputs, overlooking the valuable insights contained in clinical text. To address these limitations, we propose the Sepsis Data Representation Model (SepsisDRM), an embedding model that jointly processes tabular and textual data to capture comprehensive patient representations. Trained on a dataset comprising 19,526 sepsis patients, SepsisDRM demonstrates strong generalization across diverse sepsis-related tasks without task-specific tuning. It effectively stratifies patients into four clinically interpretable phenotypes and achieves robust performance in predicting 28-day outcomes, with AUC scores of 0.92, 0.94, and 0.78 on retrospective, prospective, and external datasets, respectively. As the first embedding model developed specifically for sepsis, SepsisDRM establishes a novel paradigm for sepsis research and offers a promising approach for studies in other fields that involve the integration of both tabular and textual data.

ABSTRACT The global spread of plasmid-mediated colistin resistance gene mcr-1 poses a significant threat to public health. Although international travel is a known driver of antimicrobial resistance, the role of domestic travel in high-prevalence settings remains unclear. We conducted a prospective cohort study of 81 healthy volunteers traveling in China (June–September 2022). Fecal samples collected before and after travel were screened for mcr-1 -positive Escherichia coli (MCRPEC). Antimicrobial resistance genes (ARGs), virulence factors (VFs), plasmid replicons, and gut microbial dynamics were investigated using whole-genome sequencing and 16S rRNA sequencing. Risk factors were analyzed using logistic regression analysis. Of the 81 participants who were negative for mcr-1 at baseline, 12 (14.8%) acquired mcr-1 after travel. Acquisition was associated with residence near poultry farms (odds ratio [OR] = 5.9, P = 0.04) and diarrhea during travel (OR = 11.22, P = 0.027). MCRPEC exhibited marked genetic diversity comprising 10 sequence types and the carriage of additional 23 ARGs and nine adherence-associated VFs. mcr-1 was located on IncI2, IncX4, IncHI2, or IncP plasmids, with 91.7% ( n = 11) transferable in conjugation assays. Gut microbiome analysis showed increased α -diversity, but a stable community structure, indicating colonization without major disruption. Our study demonstrated that domestic travel in China substantially contributes to the dissemination of mcr-1 . Poultry exposure and gastrointestinal disturbances are key risk factors. Genetic diversity, plasmid transferability, and co-carriage of resistance and virulence determinants highlight the risk of onward spread. Antimicrobial resistance surveillance should extend beyond international travel and incorporate domestic mobility within a “One Health” framework.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, leading to organ dysfunctions. Acute respiratory distress syndrome (ARDS) is the most common complication of sepsis with high mortality and pathological characteristics of uncontrolled neutrophil extracellular trap (NET) release and excessive inflammation. However, current therapeutic strategies for sepsis-induced ARDS face limitations, including potential toxicity, suboptimal efficacy, and poor bioavailability. In this timely study, we encapsulated 10-shogaol (SA), a natural anti-inflammatory compound derived from Zingiber officinale, into liposomes to yield SA-Lipo for the treatment of endotoxemia-induced ARDS. SA-Lipo initially demonstrated stable physicochemical properties, reliable biocompatibility, and increased bioavailability. A series of in vitro experiments subsequently validated that SA-Lipo significantly inhibited inflammation, oxidative stress, and excessive NET release. The in vivo evaluation in an endotoxemia-induced ARDS mouse model further revealed that SA-Lipo attenuated pulmonary dysfunction, alleviated lung edema, reduced inflammatory mediators, and promoted repair of pulmonary pathological injury. Mechanistically, RNA sequencing of lung tissues suggested that SA-Lipo may exert its therapeutic effects by inhibiting multiple immune- and inflammation-related signaling pathways. Molecular docking, western blotting, and immunofluorescent staining supported the potential of SA-Lipo to inhibit the activation of the proinflammatory MyD88/NF-κB pathway and PAD4/Cit-H3-mediated NET release in endotoxemia-induced ARDS, although the causal relationship between these two cascades remains unclear. Taken together, our findings consolidated the availability of a new lipid-nanomedicine SA-lipo for the treatment of endotoxemia-induced ARDS via controlling NET release and excessive inflammation, hence providing a promising therapeutic strategy for acute inflammatory lung diseases.

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome, is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization. However, current therapeutic strategies for ALI are controversial due to their side effects, restricted administration routes, or poor targeted delivery. The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy. One such compound is the bergapten, a coumarin, which has been isolated from Ficus simplicissima Lour. However, it's been used as an anti-cancer drug and it's effects on ALI remain unexplored. The poor solubility and biodistribution of bergapten heavily limit its application. In this timely report, we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome, named as Ber-lipo. A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial–endothelial integrity. In a lipopolysaccharide (LPS)-induced ALI mouse model, Ber-lipo can target inflamed lungs and significantly improve lung edema, tissue injury, and pulmonary function, relieve body weight loss, pulmonary permeability, and proinflammatory status, and especially maintain a balance of M1/M2 macrophage polarization. Furthermore, RNA sequencing analysis showed Ber-lipo's potential in effectively treating inflammatory lung diseases such as pneumonia, inhibiting proinflammatory signals, and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues. Molecular docking and Western blot analyses validated that Ber-lipo suppressed the activation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression. In conclusion, this study demonstrates for the first time that new inhalable nanomedicine (Ber-lipo) can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway, hence providing a promising strategy for enhanced ALI therapy in the clinic.

OBJECTIVE:To develop a core outcome set (COS) for clinical trials on post COVID-19 condition (PCC), that is, what, when, and how to measure PCC. METHOD:A comprehensive collection of outcomes (including their measurement methods and phases) was launched via literature review and clinician and patient surveys. Two rounds of Delphi surveys were conducted under the predefined criteria for rating, followed by a consensus meeting to finalize the COS for PCC (COS-PCC). RESULTS:Fifty-two outcomes within 7 categories and 206 measurement methods were identified. Sixty participants from five stakeholder groups completed the first round of the Delphi survey and 41 the second. Consensus was reached among 36 representatives on four domains of respiratory, physical, neuropsychological, and health conditions, including nine core outcomes and their respective measurement methods of priority: dyspnea (modified Medical Research Council scale), cough (Leicester Cough Questionnaire), exercise capacity (6-min walk test), fatigue (Fatigue Severity Scale), pain (Numerical Rating Scale), sleeping disturbance (Pittsburgh Sleep Quality Index), anxiety (Generalized Anxiety Disorder Scale-7), depression (Patient Health Questionnaire-9), and health status (36-item Short Form Health Survey); 16 optional measurement methods achieved consensus for supplement. Measuring phases of each core outcome were prioritized by importance through short and long terms of PCC. CONCLUSIONS:The COS-PCC highlights the key PCC concerns and provides an essential outcome set for PCC assessment in clinical trials and evidence synthesis. With improving the understanding of PCC and accumulating research evidence, the COS-PCC needs to be continuously updated and improved in practice.

Non-cystic fibrosis bronchiectasis is associated with frequent and diverse microbial infections, yet an overall understanding of microbial presence across different disease stages is lacking. A meta-analysis assessed lung microbes in adults with non-CF bronchiectasis, collecting data using both culture-based and sequencing approaches through three international databases and three Chinese databases. Subgroups were categorized by disease stage: the stable group (S), the exacerbation group (E), and unclassified data consolidated into the undetermined group (U). Culture data were analysed in random-effects meta-analyses while sequencing data were processed using QIIME 2. A total of 98 studies were included with data from 54,384 participants worldwide. Pseudomonas aeruginosa was the most frequently isolated bacterium (S: 26[19–34]

ObjectiveThis study aims to identify early warning indicators of COVID-19 severity by integrating modern medical biomarkers with traditional Chinese medicine (TCM) tongue features.MethodsA retrospective observational study was conducted on 409 hospitalized COVID-19 patients from two centers in China. Patients were stratified into severe (n = 50) and non-severe (n = 359) groups based on the 10th edition of China’s diagnostic guidelines. Data included demographics, clinical symptoms, tongue characteristics, and laboratory parameters. Univariate analyses (chi-square/Fisher’s exact tests) and stepwise logistic regression were performed to identify key predictors.ResultsAge (p < 0.001), fever (p < 0.001), elevated procalcitonin (PCT, p < 0.001), thick tongue fur (p = 0.003), and fat tongue shape (p = 0.002) were significant predictors of severity. The combined model integrating these factors demonstrated superior predictive performance (Nagelkerke R2 = 0.741).ConclusionIntegrating TCM tongue features (thick fur and fat shape) with clinical biomarkers (age, fever, and PCT) enhances early identification of severe COVID-19, particularly in resource-limited settings.

Traditional Chinese medicine has unique advantages in preventing and treating COVID-19, and Fuzheng Jiedu decoction (FZJDD) was reported to be effective against COVID-19 in clinical trials. To investigate the potential mechanisms and material basis of FZJDD against SARS-CoV-2, we performed SARS-CoV-2 target protein inhibition analyses and a metabolite full spectrum analysis of FZJDD. Interestingly, FZJDD was found to block the binding of SARS-CoV-2 Spike protein with the receptor ACE2 and inhibit the activity of SARS-CoV-2 3CLpro. Moreover, FZJDD can regulate the TNF and the MAPK signaling pathway to inhibit the inflammatory response and alleviate the “cytokine storm”. A total of 298 compounds were identified in FZJDD, among them, caffeic acid and octyl gallate were found to be the potential therapeutic agents of FZJDD. Importantly, FZJDD can broadly inhibit coronavirus infection, including SADS-CoV and porcine epidemic diarrhea virus (PEDV) live viruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 mutant pseudotyped viruses, which might be ascribed to the broad-spectrum anti-coronavirus activity of caffeic acid and octyl gallate. In conclusion, this study reveals the mechanisms and material basis of FZJDD against SARS-CoV-2 and identifies the broad-spectrum anti-coronavirus activity of FZJDD for the first time. Our data provide empirical evidence for the development and application of FZJDD.

Introduction:Long-term SARS-CoV-2-IgG antibody durability after natural infection remains a critical determinant of long-term protection. However, the factors that affect long-term IgG antibody durability are not fully understood. Methods:This study delves into the clinical and host genetic factors influencing the level of long-term anti-SARS-CoV-2-receptor-binding domain IgG (RBD-IgG) antibodies after natural infection during the first wave of the COVID-19 pandemic (17 January to 24 June 2020). The cohort, comprising 572 COVID-19 patients from Wuhan, China, had no exposure to COVID-19 vaccines, variants, or antiviral treatments, enabling a focused analysis of the virus's direct impact. Results:We found that the rate of RBD-IgG seropositivity 6 months after infection remained high (94.58%). Through a generalized linear model and mediation analysis, older age, independent of disease severity, was found to be a key independent factor associated with higher post-infection RBD-IgG titers. Hypothesis-generating analyses through a genome-wide association study revealed that rs117929853 (p = 3.6 × 10-8), a variant located upstream of the xanthine dehydrogenase gene (XDH), was significantly associated with RBD-IgG persistence, suggesting a potential mechanistic link between XDH polymorphisms and sustained humoral immunity. Conclusion:The study underscores the significant role of age and genetic factors in the pathogenesis of sustained humoral immunity, which requires further validation.

Ethnopharmacological relevance: Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI). Aim of the study: This research sought to explore the impact and underlying mechanisms of FZJDD on ALI caused by the H1N1 virus in mice. Materials and methods: FZJDD was characterized using UHPLC-MS/MS. A mouse model infected with H1N1 virus was used to examine the therapeutic and protective benefits of FZJDD in a living organism, by monitoring body weight fluctuations, lung index, histopathological changes, lung injury scores, and survival rates. Lung tissues underwent haematoxylin-eosin staining, western blotting, qRT-PCR and plaque reduction assay. Blood serum was gathered to assess levels of IL-1 beta, IL-6, TNF-alpha through ELISA testing. The impact of FZJDD on the NLRP3 inflammasome was further evaluated in macrophages. Results: FZJDD treatment significantly mitigated weight loss, reduced lung index, alleviated histopathological injury, and improved the survival rates in mice with H1N1 virus-induced ALI, demonstrating a protective effect against influenza virus infection. qRT-PCR and Western blot assays revealed that FZJDD treatment ameliorated the hyperinflammatory response caused by the H1N1 virus in lung tissue by suppressing NLRP3 inflammasome activation, without impacting viral replication. In vitro experiments additionally verified that FZJDD treatment can suppress the activation of the NLRP3 inflammasome triggered by the H1N1 virus. Conclusion: Our findings demonstrate that FZJDD treatment can mitigate ALI caused by H1N1 virus and enhance the survival rate in mice, while it doesn't lower viral titers in the lungs. FZJDD achieves these outcomes by curbing excessive inflammation and blocking the activation of NLRP3 inflammasome.

BACKGROUND:Fuzheng Jiedu granules (FZJD) is widely used for COVID-19 in China, with early studies indicating reduced mortality in severe cases. However, with emerging variants and shifted treatment focus on preventing severity and relieving symptoms, high-level clinical evidence, especially for high-risk patients, remains lacking. METHODS:A randomized controlled trial (ChiCTR2200058181 ) was performed to assess FZJD's efficacy and safety in high-risk adults with non-severe COVID-19. The primary outcome was the proportion of progression to severe COVID-19 after enrollment, with secondary outcomes focusing on the time to resolution of main symptoms. RESULTS:From November 2021 to July 2022, 231 eligible patients were randomized to receive either 15 g of FZJD (n = 119) or placebo (n = 112) thrice daily for 14 days. Patients receiving FZJD (1/101, 1.0 % [95 % CI, 0.0 %, 5.4 %]) had a numerically lower progression proportion to severe COVID-19 than those receiving placebo (2/95, 2.1 % [95 % CI, 0.3 %, 7.4 %]), although with a non-significant difference of -1.1 % (95 % CI, -7.4 %, 6.2 %; p = 0.545) after adjusted by center. FZJD use was associated with significantly shorter time to sustained disappearance of cough (median days, 10.0 vs. 12.0, HR, 1.46 [1.03, 2.07], p = 0.022), fever (median days, 6.0 vs. 7.0, HR, 1.69 [1.03, 2.76], p = 0.031), and chest distress (median days, 7.0 vs. 11.0, HR, 3.28 [1.23, 8.73], p = 0.031). Patients experience comparable adverse events in the two groups (2.7 % in FZJD vs. 1.9 % in placebo). CONCLUSION:Among high-risk COVID-19 patients, FZJD showed obvious symptom improvements and numerically lower disease progression than placebo, without additional adverse events.

BACKGROUND:The emerging ST80 vancomycin-resistant Enterococcus faecium (VREfm) lineage, linked to the increases of clinical infections in China and Japan, raises concerns about environmental transmission. Hospital wastewater systems are recognized reservoirs for antimicrobial-resistant bacteria, but their role in disseminating ST80 VREfm remains unclear. This study investigates VREfm prevalence in hospital wastewater and genomic links between patients and hospital wastewater. METHODS:From December 2023 to May 2024, a total of 262 wastewater samples were collected from three hospitals in Guangzhou, China. VREfm was identified using vancomycin-supplemented media. Antimicrobial susceptibility was assessed using the broth dilution method. Ninety-five patient-derived VREfm genomes in the same hospitals were included. Whole-genome sequencing and bioinformatic analysis were performed to reveal genomic characterizations and genetic transmission links. RESULTS:VREfm was detected in 54.6 % (143/262) of samples. All isolates carried vanA, with 25.9 % (37/143) co-harboring vanA and vanM. The dominant ST80 lineage (43.4 %, n = 62) was linked to recent regional prevalence. A novel sequence type ST2460, belonging to CC17, emerged as the second most prevalent (27.2 %, n = 39). ST80 isolates exhibited enriched antimicrobial resistance genes, correlating with multidrug resistance phenotypes and high resistance rates. Genomic analysis revealed that 95.7 % (132/138) of ST80 isolates from wastewater and patients exhibited close genetic relatedness (median of SNP = 19, IQR: 14-23) and were linked within cross-source transmission networks, supported by the high similarity of a shared p23VRE019-like plasmid. CONCLUSIONS:Hospital wastewater is a critical reservoir for high-risk VREfm clones, particularly the outbreak-associated ST80 lineage. The persistence of VREfm in effluents and evidence of cross-source transmission underscores the urgent need for enhanced environmental surveillance. Integrated strategies addressing environmental reservoirs are essential to combat the growing threat of VREfm.

Acute respiratory distress syndrome (ARDS) is a life-threatening disease. In the clinical management of ARDS, current treatments such as glucocorticoids and protease inhibitors encounter significant challenges due to their high toxicity, limited administration routes, or poor targeting. These limitations highlight the urgent need for innovative therapeutic strategies. Songorine (Son), a compound derived from the herb Aconitum carmichaelii Debeaux, possesses good antioxidant and anti-inflammatory properties, exhibiting great potential for treating ARDS. However, its clinical application is partially constrained by low aqueous solubility and uncertain efficacy for ARDS. In this study, we developed a lung-targeted lipid nanomedicine by encapsulating Son in dipalmitoyl phosphatidylcholine (DPPC) liposomes (Son@liposome, Son-lipo). In a lipopolysaccharide-induced ARDS mouse model, we demonstrated that Son-lipo effectively targeted inflamed lung tissues with commendable biocompatibility. Further, Son-lipo significantly alleviated multiple ARDS phenotypes such as endothelial barrier damage, lung edema, pulmonary dysfunction, and alveolar lesion, which involved uncontrolled inflammation, oxidative stress, and cell apoptosis. RNA sequencing and Western blotting analyses revealed that Son-lipo inhibited the activation of the TLR4/NF-κB/NLRP3 pathway responsible for ARDS. In conclusion, our study successfully developed an inhalable lipid-nanomedicine (Son-lipo) as a novel therapeutic strategy for ARDS. It elucidates the formulation's ability to mitigate ARDS by repairing the endothelial barrier and reversing the inflammatory microenvironment, thereby providing a promising candidate drug for improving clinical management of ARDS.

BACKGROUND:Euchrenone A10 (A10), an isoprenylated flavanone isolated from Glycyrrhiza (licorice), exhibits significant bioactivities, including anti-inflammatory and antioxidant effects. However, the effects and mechanisms underlying A10's protective role in sepsis-associated acute lung injury (SALI) remain incompletely understood. OBJECTIVE:This study aims to elucidate the pharmacological effects of A10 and the underlying mechanisms by which it protects against SALI, using both in vitro and in vivo experiments. METHODS:To evaluate the effects of A10 against SALI, mice were pretreated with A10 (12.5, 25, or 50 mg/kg) or dexamethasone (Dex, 50 μg/kg) prior to sepsis induction via intraperitoneal administration of lipopolysaccharide (LPS, 10 mg/kg) or cecal ligation and puncture (CLP). Survival rates, pulmwasy function, bronchoalveolar lavage fluid inflammatory cell infiltration, protein exudation, and lung histopathology were systematically assessed. Molecular docking and biolayer interferometry (BLI) were employed to characterize the interactions between S100A8/A9 and A10 or paquinimod (paq). Complementary in vitro studies using LPS (150 ng/ml)-stimulated Raw264.7 macrophages were conducted to examine A10's effects on inflammatory gene expression. RESULTS:To evaluate the therapeutic effects of A10, we employed LPS-induced SALI and CLP-induced ALI models. A10 dose-dependently alleviated pulmonary injury and improved survival rates in septic mice. Notably, A10 inhibited the expression of S100A8/A9 and suppressed the TLR4/MyD88/NF-κB signaling pathway in both in vivo and in vitro models. Mechanistic studies using molecular docking and BLI indicated that A10 directly binds to S100A8/A9, thereby blocking its interaction with the TLR4 receptor. Furthermore, in vivo and in vitro experiments confirmed that A10 shares the same binding site on S100A8/A9 as the S100A9-specific inhibitor paq, competitively displacing paq and inhibiting downstream TLR4/MyD88/NF-κB signaling. CONCLUSION:A10 exerts its anti-inflammatory effects by binding to the S100A8/A9 protein, thereby inhibiting the TLR4-NF-κB inflammatory cascade. These properties highlight its therapeutic potential as monotherapy for SALI.

Background:Fuzheng Jiedu (FZJD) granules are widely used to treat coronavirus disease (COVID-19) since their market approval, but their clinical effectiveness remains uncertain. In this study, we aimed to evaluate the effectiveness of FZJD in reducing disease progression in high-risk adults with COVID-19. Methods:A multicenter, retrospective cohort study involving high-risk adults with non-severe COVID-19 was conducted in China from May 2021 to December 2022. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2200058097; https://www.chictr.org.cn/bin/project/edit?pid=160010). Patients were categorized into two groups based on the administration of FZJD granules. The outcomes included disease progression, mechanical ventilation, intensive care unit (ICU) admission, and mortality. Propensity-score analyses and multivariable regression were performed to assess the effectiveness of FZJD granules. The effectiveness was further analyzed in different subgroups. Results:A total of 1,644 patients (54.7% female patients; mean age, 62.3 years) were included, with 27.4% (451/1,644) receiving FZJD granules. After propensity score matching (PSM), 320 FZJD granule receivers and 320 non-receivers were matched. Those receiving FZJD granules were associated with lower risks of disease progression [adjusted odds ratio (OR), 0.21; 95% confidence interval (CI), 0.06-0.73], mechanical ventilation (OR, 0.15; 95% CI, 0.03-0.66), and ICU admission (OR, 0.08; 95% CI, 0.01-0.64) than those not receiving FZJD granules. The lower risk of disease progression in the FZJD group was confirmed by multivariable regression analysis and various propensity-score analyses. Furthermore, subgroup analyses demonstrated significant treatment benefits in patients with moderate COVID-19 at admission (no progression to severe disease) or in those who were not fully vaccinated (OR, 0.06; 95% CI, 0.01-0.50). Conclusion:FZJD administration was significantly associated with a reduced risk of disease progression in high-risk adults with mild-to-moderate COVID-19.