Guoqing Qian

Rapid and reliable detection of multidrug-resistant bacteria is essential for effective clinical management. In this study, we have developed a dual-mode aptasensing platform based on a core-shell MOF-on-MOF structure (UiO-66-NH₂@MOF-919) for the subtype-specific detection of carbapenem-resistant Klebsiella pneumoniae strains carrying NDM-1 and KPC-2. This bifunctional system integrates the peroxidase-like activity of the MOF-919 shell with the fluorescence quenching capability of the UiO-66-NH₂ core, enabling both colorimetric and fluorometric detection within a single platform. Benefiting from this design, the method achieves sensitive and selective detection over a wide linear range from 10 to 10⁸ CFU mL⁻¹, with low detection limits of 7 CFU mL⁻¹ for NDM-1 KP and 4 CFU mL⁻¹ for KPC-2 KP. The proposed platform exhibits good selectivity against non-target bacteria and strong anti-interference capability. Spiked recovery experiments in human serum, urine, and bronchoalveolar lavage fluid yielded recoveries ranging from 93.0% to 110.0% with RSDs below 5.0%, demonstrating good analytical accuracy and applicability in complex biological samples. Compared to conventional aptasensing systems, this approach enables dual-subtype detection within a single platform, improving analytical efficiency and practicality. This work provides a feasible strategy for MOF-on-MOF-based biosensing systems and shows promising potential for rapid clinical detection of drug-resistant bacteria.

An aptamer-gated metal-organic framework-based biosensing platform for highly sensitive detection of multidrug-resistant bacteria (MDRB) has been developed. This biosensing platform utilizes aptamers as specific "gated" switches, which are integrated with the UiO-66-NH₂ MOFs to construct a "gated" sensing system loaded with 3,3',5,5'-tetramethylbenzidine (TMB). The entry of target bacteria induces specific dissociation of sDNA/Apt, forming an aptamer-bacteria complex on the UiO-66-NH₂ surface while releasing TMB into the solution. Subsequently, the PCN-224-Mn nanozyme catalyzes the oxidation of TMB, generating a colorimetric signal. This biosensing platform demonstrates a broad linear range for detecting New Delhi metallo-β-lactamase-1 Klebsiella pneumoniae (NDM-1 KP) and multidrug-resistant Acinetobacter baumannii (MDR-AB), achieving ultra-high sensitivity with detection limits of 5 CFU/mL and 7 CFU/mL, respectively. The practical performance of this biosensing platform was evaluated through spiked recovery experiments. Its excellent recovery demonstrates that the method maintains high reliability and stability even when applied to complex real-world samples, providing an effective technical solution for addressing challenges in microbial detection in practical scenarios.

Purpose: Metabolic syndrome (MetS) in people living with HIV (PLWH) is more complicated and multifactorial than in the general population. HIV infection is increasingly recognized as a direct contributor to metabolic dysfunction. This study aims to assess the long-term risk of MetS in PLWH with low-level viremia (LLV) receiving antiretroviral therapy (ART). Patients and Methods: In this 6-year retrospective cohort study, we analysed 848 PLWH receiving ART. Participants were classified into three viremia categories: no LLV (all HIV viral loads < 50 copies/mL or undetectable), LLV 51– 200 (two consecutive viral loads between 51– 200 copies/mL), and LLV 201– 500 (two consecutive viral loads between 201– 500 copies/mL). MetS incidence was assessed using time-dependent Cox regression analysis, while immune and metabolic trajectories were analyzed via linear mixed models. To further validate the robustness of our primary findings, sensitivity analyses stratified by ART regimens were performed. Results: Over a median follow-up of 3.9 years, 31.3% of participants developed MetS. The incidence rates of MetS were 160.4, 136.6, and 83.0 cases per 1000 person-years in the LLV 201– 500, LLV 51– 200, and no LLV groups, respectively. Time-dependent Cox regression analysis demonstrated that LLV was an independent risk factor for MetS. Sensitivity analyses demonstrated that patients experiencing LLV, irrespective of ART regimen, had a persistently higher incidence of MetS. Additionally, LLV was associated with persistently elevated CD8 counts, reduced CD4 recovery, and worsening metabolic profiles. Conclusion: LLV independently predicts MetS risk in PLWH on ART. LLV should be regarded not only as a virological concern but also as a metabolic risk factor that warrants closer clinical attention in the post-ART era.

The COVID-19 pandemic has exacerbated the complexity of antimicrobial resistance (AMR) challenges. This study aimed to quantify risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) acquisition in COVID-19 patients, compare resistance profiles and laboratory biomarkers between carbapenem-susceptible K. pneumoniae (CS-KP) and CRKP strains, and identify clinical indicators predictive of CRKP co-infection. We conducted a retrospective analysis of COVID-19 patients with KP-positive cultures admitted to a tertiary hospital in China between January 2020 and May 2024. Antimicrobial susceptibility testing and multivariable logistic regression were employed to evaluate resistance patterns and risk factors. Among 342 COVID-19 patients with KP-positive, 262 (76.6%) were CSKP and 80 (23.4%) CRKP. Hypertension, prolonged hospitalization, and ICU admission were identified as independent risk factors for CRKP acquisition. CRKP group patients exhibited significantly worse laboratory tests, including elevated inflammatory markers, coagulopathy, and renal dysfunction, providing clinical markers for suspecting the presence of multi-drug resistant bacteria. Our findings reveal KP resistance profiles under COVID-19 pressures and underscore the necessity of early microbiological confirmation and precision antibiotic use.

Stress hyperglycemia ratio (SHR), an index reflecting relative hyperglycemia under stress conditions, has been linked to adverse outcomes in various clinical settings. However, its prognostic significance in individuals with nonalcoholic fatty liver disease (NAFLD) remains poorly understood. This study aimed to examine the association between SHR and mortality risk in adults with NAFLD. We analyzed 12,604 adults with NAFLD from the NHANES 1999–2018 database. Multivariable Cox proportional hazards models, restricted cubic spline (RCS) analysis, and Fine–Gray competing risk models were employed to evaluate associations between SHR and all-cause and cardiovascular mortality, During an overall mean follow-up time of 99.26 months, a U-shaped relationship was observed between SHR and all-cause mortality in adults aged 40–59 years and ≥ 60 years. Risk increased at both low and high SHR levels, with identified thresholds at 0.89 for middle-aged and 0.94 for older adults. No significant association was found with cardiovascular mortality. Findings were consistent across subgroups. SHR showed a U-shaped association with all-cause mortality in middle-aged and older adults with NAFLD. Monitoring SHR may help identify high-risk individuals and guide clinical management.

Background: Numerous studies have demonstrated that convalescent plasma therapy reduces mortality in coronavirus disease 2019 (COVID-19) patients. Current guidelines recommend nasal catheter oxygen therapy for most hypoxic patients during the early stages of the illness. However, limited data are available regarding the efficacy of convalescent plasma therapy in patients already receiving oxygen therapy. Given the widespread use of nasal catheter oxygen therapy in hypoxic COVID-19 patients and the increasing evidence supporting the efficacy of convalescent plasma, this study aimed to evaluate the efficacy and safety of convalescent plasma therapy in COVID-19 patients who were receiving early oxygen therapy. Methods: A retrospective study was conducted at the First Affiliated Hospital of Ningbo University, analyzing 112 COVID-19 patients treated with convalescent plasma from December 2022 to July 2023. Data on demographics, laboratory tests, and plasma doses were collected before and after convalescent plasma transfusion, alongside standard care. The primary outcome was 28-day mortality, with laboratory parameters as secondary outcomes. Results: On day 28, the mortality rate was 20% in the convalescent plasma group compared to 44% in the standard-care group (P=0.008). In severe COVID-19 cases, mortality was 34% in the convalescent plasma group versus 59% in the standard-care group (P=0.04). Among patients who received nasal catheter oxygen therapy for 48 hours or longer, mortality was 21% in the convalescent plasma group compared to 42% in the standard-care group (P=0.02). Conclusions: Convalescent plasma therapy administered to COVID-19 patients receiving nasal catheter oxygen therapy significantly reduced mortality at day 28.

The non-HDL cholesterol to HDL cholesterol ratio (NHHR) is a novel composite lipid index. However, its relationship with mortality, particularly in individuals with non-alcoholic fatty liver disease (NAFLD), remains unclear. The aim of this study was to explore the association between NHHR and both all-cause and cardiovascular mortality in adults with NAFLD in the United States. This study included 12,648 adult participants with NAFLD from the National Health and Nutrition Examination Survey (NHANES) database (1999–2018). Multivariate Cox proportional hazards models and restricted cubic spline (RCS) methods were employed to assess all-cause and cardiovascular mortality. Subgroup analyses were performed to verify the consistency of these associations. Over a median follow-up of 99.27 months, 1,659 participants died from all causes, including 460 from cardiovascular disease. RCS analysis revealed a U-shaped relationship between NHHR and all-cause mortality, no association was found between NHHR and cardiovascular mortality. The inflection points for all-cause mortality were 2.67. Subgroup analysis showed that a stronger association between NHHR and all-cause mortality in those with diabetes(P = 0.048). NHHR is associated with all-cause mortality in NAFLD patients, with distinct non-linear relationships, while it is not associated with cardiovascular mortality. NHHR monitoring may be valuable for assessing mortality risk, particularly in those with diabetes.

Since long COVID has hindered people from normal life, it is essential to understand its full spectrum of manifestation. However, it was heterogeneous in the existing studies and few large-scale studies have been conducted on Asian populations. Here, we conducted a multi-centre questionnaire-based study among Chinese people to explore the long COVID based on the definition of WHO. During March 20, 2023 and June 18, 2023, individuals with a history of confirmed or self-reported SARS-CoV-2 infection were recruited from three hospitals to fill out the questionnaire for long COVID. Each symptom was assigned with 0 to 3 points based on their severity. And the long COVID score was a sum of these points of each symptom. The reporting rate, time trend and risk factors of long COVID stratified by different systems were explored. 3,693 individuals were recruited for the study. The reporting rate of at least one persistent long COVID symptoms and symptoms impacting daily life was 30.2% (1,117) and 10.7% (394). Systemic symptoms (20.7%, 765) were most easily reported. The most common symptoms were fatigue (16.3%, 602), cough (6.3%, 234) and expectoration (5.5%, 203). The reporting rate of long COVID and long COVID score decreased over time during a 180-day follow-up period (P < 0.05). For long COVID, older age (OR: 1.63, 1.38–1.93), female (OR: 1.19, 1.03–1.38) and SARS-CoV-2 reinfection (OR: 3.56, 2.63–4.80) were risk factors; while number of COVID-19 vaccine doses (OR: 0.87, 0.81–0.94) was a protective factor. The use of traditional Chinese medicine (OR: 0.51, 0.37–0.71) was a protective factor for symptoms impacting daily life. Early interventions should be taken to minimize the impact of long COVID, especially for the elderly, females and those with SARS-CoV-2 reinfection. COVID-19 booster vaccination might play a potential role in minimizing the impact of long COVID.

Background: Lateral flow assay (LFA) has demonstrated high sensitivity and specificity for diagnosing cryptococcosis. However, its role in predicting therapeutic efficacy for pulmonary cryptococcosis (PC) remains underexplored.Methods: We conducted a retrospective analysis of HIV-negative patients with PC to describe the clinical profile and identify potential predictors of radiological prognosis.Results: All the 168 participants received antifungal therapy with a triazole agent. Of these, 84.5% experienced partial or complete absorption of pulmonary lesions. The results of the gamma test, chi-square trend test, and ordinal logistic regression all indicated that both baseline LFA and changes in LFA after treatment were significant predictors of imaging prognosis. The degree of radiological improvement was inversely associated with the baseline LFA positive grade(P for linear-by-linear association: 0.011, Spearman correlation coefficient = -0.17; γ= -0.368, P = 0.045). Patients with a decrease in LFA after therapy had significantly better radiological outcomes compared to those with equal or increased LFA(linear-by-linear association, P = 0.014, Spearman correlation coefficient = 0.188; γ = 0.371, P = 0.012). Additionally, favorable outcomes were more likely in patients with lesions confined to the right lung.Conclusions: LFA shows potential of monitoring radiological outcomes in pulmonary cryptococcosis.