Shanghai Public Health Clinical Center

Amorphous carbon is widely employed as protective and dielectric layers in microelectronics, where its thermal transport properties play a critical role in heat dissipation. Although vibrational excitations in amorphous solids are generally classified into propagons, diffusons, and locons, the dominant heat carriers in amorphous carbon remain actively debated. In this work, we synthesize amorphous diamond-like carbon (DLC) nanowires (mass density: 1.71 g/cm3; sp3 fraction: 55.7%) and measure their thermal conductivity from 20 to 300 K using a suspended thermal bridge method. The measured thermal conductivity is slightly lower than previously reported for DLC films, due to relatively low mass density and sp3 ratio that govern thermal transport in amorphous carbons. Remarkably, the thermal conductivity exhibits a steep, nearly linear temperature dependence, in clear deviation from the predictions of the amorphous limit model. Further molecular dynamics simulations and quasi-harmonic Green–Kubo lattice dynamics calculations reproduce the experimental trend and reveal that heat conduction is overwhelmingly dominated by diffusons (98% at 300 K) in the frequency range of 4–60 THz. The nearly linear temperature dependence arises from the combined effects of the linear scaling of mode-specific heat with temperature and the weak temperature dependence of mode diffusivity. These results provide direct experimental evidence for diffuson-dominated thermal transport in amorphous DLC nanostructures and offer important physical insight for the design of disordered carbon materials with tailored thermal properties for nanoscale electronic applications.

ObjectivesOur previous study in hospitalised patients infected with avian A(H7N9) influenza virus identified CD84 amongst several genes associated with recovery. Yet, the correlation between CD84 and respiratory viral infection outcomes is far from established. We aimed to define CD84 dynamics in patient cohorts of respiratory disease and immune cell populations in influenza virus‐infected mice.MethodsExpression dynamics of CD84 and association with previously identified correlates of severe and fatal respiratory disease outcomes, OLAH and IL18R1, were analysed in A(H7N9) and COVID‐19 patient cohorts across disease severities. Using mouse models of influenza virus infection, CD84 expression on immune cell subsets was analysed over the course of infection.ResultsElevated CD84 levels in recovered A(H7N9) patients were accompanied by increased expression of genes for CD84‐associated adaptor proteins and other SLAM receptor family members. In these patients, high CD84 expression persisted until discharge, while remaining low throughout the disease in patients that succumbed. We found inverse correlations between CD84 with OLAH and IL18R1 levels in our A(H7N9) cohort, and in hospitalised COVID‐19 patients across respiratory disease severities. In influenza virus‐infected mice, CD84 was upregulated on a broad range of immune cell populations, particularly on activated and influenza virus‐specific T‐cell populations and correlated with less disease severity.ConclusionOur findings revealed the link between high CD84 expression in humans and recovery from respiratory viral infections. In mice, CD84 expression increased across a broad range of immune cell populations, with CD84 expression on activated T‐cell populations correlating with less severe disease.

It is challenging to develop multiresponsive polypeptide theranostics that can respond to the tumor microenvironment (TME) for highly efficient chemodynamic therapy (CDT) while simultaneously alleviating tumor hypoxia. Inspired by protein biomineralization and utilizing zwitterionic phosphorylcholine-bearing polycysteine as a multivalent template, herein, a kind of MnOx/CaCO3-embedded polypeptide nanomodulator (PCMC) was easily constructed by a one-pot method. Upon the redox reaction of MnOx with intracellular glutathione (GSH), released Mn2+ mediated a Fenton-like reaction to transform endogenous H2O2 into cytotoxic ·OH, enabling GSH depletion-enhanced CDT, while MnOx also consumed H2O2 into O2 to relieve hypoxia. Meanwhile, the Ca2+ release from CaCO3 in the PCMC induced calcium overload to generate reactive oxygen species (ROS), synergizing with MnOx to boost CDT for killing 4T1 cells. The hypoxia staining assay and intracellular GSH and Ca2+ measurements corroborated that the PCMC effectively alleviated hypoxia and depleted intracellular GSH while inducing calcium overload in 4T1 cells. Remarkably, PCMC could accumulate in tumors, implement a T1-weighted magnetic resonance imaging (MRI) in 4T1 tumor-bearing mice, and achieve a synergistic CDT antitumor efficacy while heavily alleviating tumor hypoxia, as evidenced by means of H&E, TUNEL, ROS, and HIF-1α assays. Importantly, this work offers a versatile strategy for designing the TME-responsive polypeptide/metal ion hybrid nanoparticles to amplify CDT and alleviate hypoxia in tumors, opening an avenue for the MRI-guided drug/dye-free cancer theranostics.

The recurrent emergence of ACE2‑using sarbecovirus underscores the need for a broadly protective vaccine. Here, we mapped the antigenic landscape of sarbecovirus receptor-binding domains (RBDs) and identified three distinct clusters. We then engineered a single "three‑in‑one" immunogen, 3Rs-NC, incorporating representative RBDs from each cluster into a single scaffold. Intranasal administration of 3Rs-NC with a flagellin-derived mucosal adjuvant (KFD), which possess excellent safety profile potential for clinical usage, elicited high titers of RBD-specific serum IgG and mucosal IgA, as well as potent neutralizing antibody responses in mice. Furthermore, KFD-adjuvanted 3Rs-NC conferred sustained protection in both the upper and lower respiratory tracts against SARS-CoV-2 Omicron BA.1 and SARS-like coronavirus WIV1. Additionally, 3Rs-NC immunization protected mice from lethal challenge of SARS-like coronavirus rRsSHC014S, with more efficient protection observed in female mice than male mice. This needle-free formulation offers a potent, broad-spectrum vaccine candidate against current and emerging ACE2-using sarbecoviruses, functioning as a modular "three-in-one" vaccine platform ready for rapid deployment in future coronavirus outbreaks.

Catheter-associated urinary tract infections (CAUTIs) impose significant clinical and economic burdens on healthcare systems globally. Patients in obstetrics and gynecology face unique vulnerabilities; however, population-specific risk factors and prevention strategies remain inadequately studied from a public health perspective. This study aimed to identify clinical profiles and modifiable risk factors for CAUTIs in hospitalized obstetrics and gynecology patients, thereby informing evidence-based CAUTI prevention strategies. A retrospective case-control study was conducted among inpatients at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, from November 2021 to February 2024. The case group comprised all consecutive eligible patients (n = 131) with symptomatic CAUTIs. Controls (n = 131) were matched to cases at a 1:1 ratio based on hospitalization period, primary diagnosis, treatment type, and age (± 5 years). Multivariate logistic regression analyses were performed to identify independent risk factors. Multivariate analysis of 262 obstetrics and gynecology inpatients identified four modifiable risk factors for CAUTIs, including being nutritionally at-risk upon admission (OR = 4.189, 95% CI: 1.402 ~ 12.513, P = 0.010), discharge with an indwelling urinary catheter (OR = 5.526, 95% CI: 2.352 ~ 12.985, P < 0.001), multiple catheterizations (≥ 2) (OR = 16.642, 95% CI: 2.057 ~ 134.617, P = 0.008), and a hospital stay exceeding 7 days (OR = 2.547, 95% CI: 1.423 ~ 4.560, P = 0.002). Fever was the predominant clinical symptom (85.5%), and Escherichia coli was identified as the primary pathogen (59.4%). Targeted public health interventions should prioritize nutritional screening, catheter minimization protocols, standardized discharge planning for catheterized patients, and the reduction of prolonged hospitalizations. Healthcare policy must integrate these evidence-based strategies to mitigate the burden of CAUTIs in women’s health settings.

Chronic hepatitis B (CHB) is the leading cause of acute-on-chronic liver failure (ACLF) in China and other Asian countries. A defining immunopathological feature of hepatitis B virus-related ACLF (HBV-ACLF) is immune paralysis, which significantly increases susceptibility to secondary bacterial infections and contributes to poor clinical outcomes. A critical determinant of this immunosuppressed state is impaired antigen presentation due to reduced human leukocyte antigen DR (HLA-DR) expression on monocytes; however, the epigenetic mechanism underlying HLA-DR downregulation in HBV-ACLF remains unclear. Methyl-CpG-binding domain protein 2 (MBD2), an epigenetic reader of DNA methylation, has been implicated in the regulation of monocyte-macrophage function in inflammatory diseases, but its role in HBV-ACLF pathophysiology remains to be fully elucidated. In this study, bulk RNA sequencing (RNA-seq) of circulating monocytes from patients with HBV-ACLF showed a transcriptional profile consistent with immune paralysis, characterized by suppressed antigen presentation and inflammatory pathways, alongside pronounced activation of epigenetic regulatory programs. MBD2 expression was subsequently assessed using immunohistochemistry (IHC), reverse transcription quantitative PCR (RT-qPCR), and flow cytometry. Monocyte MBD2 expression was significantly upregulated in HBV-ACLF and was positively correlated with disease severity (r = 0.2797, P =0.0182), systemic inflammation indices, and clinical prognosis. To delineate the mechanistic role of MBD2, an MBD2-knockout THP-1 cell model was established and subjected to integrated RNA-seq and assay for transposase-accessible chromatin sequencing (ATAC-seq) following differentiation and lipopolysaccharide (LPS) stimulation. The results showed that MBD2 deficiency significantly increased chromatin accessibility and transcriptional activation of genes involved in antigen presentation and pro-inflammatory responses, including pathways related to major histocompatibility complex (MHC) class II synthesis. Concurrently, enhanced promoter accessibility and activation of transcription factors associated with HLA-II class expression were observed, and increased surface HLA-DR expression was confirmed by flow cytometry. Collectively, these findings suggest that MBD2 epigenetically represses HLA-DR expression in monocytes, leading to impaired antigen presentation and immune paralysis, thereby predisposing patients with HBV-ACLF to secondary bacterial infections. Therefore, MBD2 may serve as a novel biomarker for disease progression and a potential therapeutic target for restoring immunological competence in patients with ACLF.

BackgroundPorto-sinusoidal vascular disorder (PSVD) is often misdiagnosed as liver cirrhosis due to overlapping clinical presentations and imaging features. This study conducted a blinded, independent imaging review to identify and compare the distinct imaging features between the two diseases, and to develop and validate a predictive model for differentiating PSVD from cirrhosis.MethodsPatients with histologically and clinically confirmed PSVD or cirrhosis and available contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans were retrospectively enrolled in the study. Imaging features were independently and systematically analyzed by two abdominal radiologists, who were blinded to the case grouping. Inter-reader discrepancies were resolved by consensus. The key features for analysis included liver surface nodularity (LSN), regenerative nodules (RNs), signs of portal hypertension (PH), and reticular delayed enhancement of the hepatic parenchyma. CT, MRI, and combined predictive models were developed to identify the top performing model, which was then selected and validated on an independent test cohort. Model performance was evaluated based on the area under the curve (AUC), sensitivity, and specificity.ResultsIn total, 106 patients with PSVD and 104 patients with cirrhosis were included for imaging evaluation and model development. The data of an additional 36 patients with PSVD and 51 patients with cirrhosis were collected for independent model testing. PSVD exhibited the same pronounced PH imaging features as cirrhosis, including grade 1–3 splenomegaly (77/106, 72.6% vs. 67/104, 64.4%; P>0.05), collateral vessels (103/106, 97.2% vs. 94/104, 90.4%; P>0.05), and ascites (35/106, 33.0% vs. 32/104, 30.8%; P>0.05). In addition, PSVD showed more increased small branches of intrahepatic blood vessels than cirrhosis (79/106, 74.5% vs. 41/104, 39.4%; P<0.001). Conversely, PSVD exhibited fewer cirrhosis-specific imaging features, such as reticular delayed enhancement of the hepatic parenchyma (10/48, 20.8% vs. 50/53, 94.3%; P<0.001), RNs (3/48, 6.3% vs. 29/53, 54.7%; P<0.001), and LSN (27/106, 25.5% vs. 75/104, 72.1%; P<0.001). In the validation set, the MRI model [AUC: 0.970, 95% confidence interval (CI): 0.912–1.0], which incorporated four imaging features (reticular delayed enhancement, RNs, LSN and increased small intrahepatic vascular branches), showed superior discriminatory performance compared to the CT model (AUC: 0.825, 95% CI: 0.646–1.0), with a sensitivity of 0.818 and a specificity of 0.889. While the combined model (AUC: 0.97, 95% CI: 0.912–1.0) did not improve upon the performance of the MRI model alone, with sensitivity of 0.821 and specificity of 0.889. Thus, we recommend the MRI model as the preferred modality for diagnosing PSVD. The MRI model also achieved optimal performance in the independent test set, with an AUC of 0.988 (95% CI: 0.967–1), sensitivity of 0.972, and specificity of 0.826.ConclusionsPatients presenting with severe PH imaging features but lacking typical cirrhosis imaging features should be thoroughly evaluated for PSVD. MRI is the preferred imaging modality. Our MRI-based predictive model reliably differentiates PSVD from cirrhosis, offering a non-invasive method for enhancing the suspicion of PSVD.

The acidic tumor microenvironment (TME) in solid tumors, driven by abnormal metabolism and lactic acid accumulation, suppresses chimeric antigen receptor-T (CAR-T) cell efficacy while posing safety risks from on-target, off-tumor toxicity (OTOT). This study aims to develop a novel CAR-T technology that leverages lactic acid as a tumor-specific trigger to achieve precise control of CAR activity. The objective is to enable adaptation to the acidic TME while maintaining robust anti-tumor efficacy and mitigating OTOT. We engineered a lactic acid-responsive promoter (LARP) using RNA sequencing-identified lactic acid-sensitive genes. This promoter was integrated into HER2-targeting CAR to construct LAR CAR-T cells. CAR expression dynamics under acidic vs neutral conditions were quantified via flow cytometry. Phenotypic profiling (memory markers), in vitro cytotoxicity, and cytokine secretion were assessed. In vivo OTOT was evaluated in our previously constructed humanized HER2 mice, while anti-tumor efficacy and OTOT were further tested in this mouse model bearing tumors. Our findings demonstrate that the LARP responds to lactic acid, leading to increased CAR expression in acidic conditions. The ex vivo-expanded LAR CAR-T cells exhibited an enhanced memory phenotype and superior tumor-killing capacity in vitro under acidity. In vivo, LAR CAR-T cells achieved tumor eradication comparable to conventional CAR-T cells and exhibited significantly enhanced safety profiles, characterized by the absence of acute hepatotoxicity and minimal off-target organ toxicity. Our LARP strategy exploits tumor acidity as a precise low/high switch for CAR-T cells. By restricting potent CAR expression to the acidic TME while minimizing activity in normal tissues, LAR CAR-T overcomes key barriers of efficacy and OTOT in solid tumors. This lactic acid-sensing paradigm offers a clinically translatable platform for precise immunotherapy.

Childhood tuberculous meningitis (TBM) often leads to death or severe neurological sequelae. We aimed to evaluate clinical characteristics of childhood TBM and identify risk factors for severe neurological sequelae. A retrospective analysis was conducted on the consecutive clinical data of inpatient with TBM under 15 years admitted to Shanghai Public Health Clinical Center from 2013 to 2024. Patients were divided into two age groups: <5 yearsand 5–14 years. Demographic characteristics, clinical symptoms, laboratory tests, imaging findings, treatment regimens, and outcomes at 12 months post-treatment were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for severe neurological sequelae. This study enrolled 107 children, 61 under 5 years (57.0%), and 46 were 5–14 years (43.0%). The < 5 years group had a higher proportion of TBM stage III cases (29.5% vs. 2.2%, p <0.001) than the 5–14 years group. The < 5 years group had higher proportions of concurrent pulmonary tuberculosis, altered consciousness, signs of increased intracranial pressure, hydrocephalus, and ventricular enlargement compared to the 5–14 years group. At the same time, the Glasgow Coma Scale score was significantly lower. At 12 months post-treatment, the < 5 years group showed significantly higher rates of unfavourable prognosis and drug-induced liver injury. The incidence of severe neurological sequelae was 20.6% (22/107). Univariate regression revealed that TBM stage III, altered consciousness, coma, signs of upper motor neuron damage, hydrocephalus, and external ventricular drainage were associated with severe neurological sequelae. Multivariate regression identified coma as an independent risk factor for severe neurological sequelae in pediatric TBM (aOR = 6.17, 95% CI: 1.94–19.56, P = 0.002). This study demonstrates that younger children (< 5 years) with TBM present with more severe conditions, higher complication rates, and poorer prognoses. Coma is an independent risk factor for severe neurological sequelae. In clinical practice, early recognition of TBM in younger children and aggressive comprehensive treatment for comatose patients should be emphasized to facilitate the development of early individualized intervention strategies and optimize treatment outcomes for this population.