Science Progress最新文献

ObjectiveTraditional indicators of obesity, such as body mass index (BMI), fail to precisely capture the independent impact of fat distribution on gallstone disease (GSD). This study aimed to investigate the nonlinear association between body fat ratio (BFR) and the risk of GSD and to identify a critical threshold value.MethodWe conducted a cross-sectional observational analysis of 1952 adults from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). BFR was measured by dual-energy X-ray absorptiometry, and GSD was defined by standardized questionnaire data. Weighted logistic regression, restricted cubic spline (RCS), and threshold effect models were employed to examine the association between BFR and GSD risk, as well as to determine the inflection point.ResultsA significant J-shaped nonlinear association was observed between BFR and GSD risk (P for non-linearity < 0.001). Threshold analysis identified 29.1% (95% CI: 27.5-30.7%) as the critical inflection point, beyond which each 1% increase in BFR was associated with a 14% higher odds of GSD (OR = 1.14, 95% CI: 1.09-1.19). After multivariate adjustment, each additional 1% increase in BFR remained independently associated with a 7% increased risk (OR = 1.07, 95% CI: 1.02-1.13). Compared with participants in the lowest quartile, those in the highest quartile (BFR≥39.2%) exhibited a 2.66-fold higher risk of GSD. Subgroup analyses demonstrated stronger associations in males (OR ≈ 1.12 per 1% BFR increase) and Hispanics (OR ≈ 1.20 per 1% BFR increase).ConclusionsBFR of ≥29.1% represents a critical threshold beyond which GSD risk significantly increases. These findings suggest an association that warrants further investigation into whether routine monitoring of BFR could serve as a valuable screening tool in high-risk populations, and precise intervention strategies should consider gender and ethnic differences to effectively mitigate metabolic-related gallstone disease.

ObjectivesAlthough bone marrow mesenchymal stromal cells (BMSCs) are extensively used in biomedicine, they have yet to be used in the commercial development of a tissue engineered medicine. It has been argued that the major roadblock in their commercial deployment is the lengthy in vitro culture periods required for the development of implantable tissue surrogates. Macromolecular crowding (MMC) has been shown to enhance and increase extracellular matrix deposition in eukaryotic cell culture, allowing for the accelerated development of tissue facsimiles.MethodsWith these in mind, human BMSCs were cultured under MMC conditions and the developed tissue-engineered medicine was assessed in vitro and in vivo in a humanised athymic nude mouse excisional wound splinting model.ResultsStarting with basic cell function analysis, MMC did not significantly affect cell metabolic activity, viability and proliferation. Electrophoresis and immunofluorescence analyses revealed that MMC significantly increased collagen type I and collagen type IV deposition, without significantly affecting collagen type III deposition. Flow cytometry analysis demonstrated similar CD44, CD73, CD90, CD146, HLA-ABC, CD31, CD45, CD80 and CD86 expression between the without and the with MMC groups. Interestingly though the MMC group had higher CD105 and lower HLA-DR expression than the without MMC group. Preclinical analysis revealed similar wound closure, scar index and epidermal thickness between the without and the with MMC groups, largely attributed to issues encountered with the model.ConclusionsOverall, this preliminary study demonstrates the potential of MMC in the accelerated development of functional and extracellular matrix-rich human BMSC-based tissue-engineered medicines.

Odontogenic cysts are well-known maxillofacial pathologies with variable biological behaviour. Decompression has been widely used as a conservative, structure-preserving management strategy. This report presents a radiographic comparison of reduction patterns following decompression in two individual cases, one dentigerous cyst and one odontogenic keratocyst. Two patients presenting with cystic jaw lesions - one detected during radiographic investigation and the other presenting with progressive swelling - were managed using decompression as the initial treatment. Standardised radiographic measurements were performed, and the Standard Lesion Area Index and Percentage of Reduction were calculated at serial follow-up intervals. The dentigerous cyst demonstrated gradual reduction, achieving 94.4% shrinkage at 12 months and complete radiographic resolution by 44 months, with no radiographic evidence of recurrence. In contrast, the odontogenic keratocyst showed a more rapid initial reduction, with 58% shrinkage at 5 months, followed by a plateau at approximately 90% shrinkage by 24 months and radiographic evidence of recurrence at 44 months. Direct long-term radiographic comparison of dentigerous cyst and odontogenic keratocyst reduction following the same decompression protocol remains limited in the published literature. The literature synthesis indicated that decompression typically requires 8 to 24 months, with dentigerous cysts generally demonstrating more favourable radiographic responses than odontogenic keratocysts. Decompression and marsupialisation are non-definitive approaches, as definitive management requires subsequent enucleation of the lesions. These case-based observations suggest that decompression may be sufficient for selected dentigerous cysts, whereas odontogenic keratocysts require prolonged monitoring and are more likely to necessitate secondary surgical intervention. The findings should be interpreted cautiously in view of the very small number of cases.

ObjectiveSepsis is a heterogeneous syndrome, and identifying its subphenotypes may enhance clinical management. Hypothermia may be an indicator of poor outcomes in septic patients.MethodsThis retrospective observational study included septic patients with hypothermia identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Group-based trajectory modeling was used to identify temperature trajectory subphenotypes. Cox proportional hazards model, inverse probability of treatment weighting, and doubly robust estimation were used to explore the association between the subphenotypes and clinical outcomes.ResultsA total of 1816 patients were included in the analysis, and their 48-hour temperature trajectories were categorized into three classes. The Cox proportional hazard model revealed that compared with class 2, class 1 was associated with increased 7-day mortality (HR 1.90; 95% CI 1.18-3.07; P = 0.009), whereas class 3 was associated with reduced 28-day mortality (HR 0.81; 95% CI 0.66-1.00; P = 0.045). The doubly robust estimation methods yield similar results.ConclusionsWe identified three temperature trajectories from septic patients with hypothermia, with significant variability in clinical characteristics and outcomes. A better understanding of temperature trajectories may help with the early identification of deteriorating patients with "cold sepsis."

Medial meniscus extrusion (MME) is the displacement of the meniscus beyond the edge of the medial tibial plateau. Proposed etiologies for MME include biologic degeneration of meniscal tissue, the result of a medial meniscus posterior root tear (MMPRT), and the failure of the meniscotibial ligament. Standard MMPRT repairs do not address this MME, as it often persists or worsens postoperatively, even with successful root healing. New techniques, such as centralization sutures, have been developed to supplement the standard MMPRT repair technique. Systematic reviews and randomized controlled trials confirm that the addition of a centralization suture significantly reduces MME, improves joint contact pressures, and enhances patient-reported outcomes. Even though postoperative extrusion still exists after centralization suture use, likely due to the degenerative nature of the meniscus, this represents a shift towards improved knee joint preservation. Continuing progress in this field requires standardization of measurement and diagnosis, establishing the minimal clinically important difference of postoperative extrusion for a successful MMPRT repair, and long-term clinical evidence. This narrative review will explore current understanding of MME, current treatment options, and topics to guide future research.

Malakoplakia is a rare inflammatory condition characterized by the accumulation of granulomatous masses due to the incomplete destruction of infectious pathogens by monocytes and macrophages. While it commonly affects the genitourinary tract, pulmonary malakoplakia is infrequent and often associated with immunocompromised states. We present the case of a woman in her early 40s with rheumatoid arthritis who developed localized pulmonary malakoplakia in the airway. Initially presenting with constitutional symptoms and respiratory distress, she underwent a diagnostic evaluation revealing an endobronchial mass with neoplastic characteristics. Histopathological examination confirmed the presence of Michaelis-Gutmann bodies, pathognomonic for malakoplakia. Despite initial improvement postresection, the patient experienced disease recurrence 1 year later. Pulmonary malakoplakia, although rare, poses diagnostic challenges due to its resemblance to malignant lesions. Treatment typically involves antibiotic therapy, low-dose steroids, and localized resections. Differential diagnoses include primary or secondary malignancies, necessitating histopathological evaluation for accurate diagnosis. Malakoplakia should be considered in immunocompromised individuals presenting with pulmonary nodules or masses, especially without malignancy risk factors.

ObjectiveThe infection of the endograft after thoracic endovascular aortic repair (TEVAR) is a rare but potentially life-threatening complication. Unfortunately, clinical reports, large case-series or randomized studies are scarce or not available yet, and the optimal management of this complication is under debate. The aim of this review is collecting and analysing data on current practice and outcomes for the treatment of infected endografts after TEVAR.MethodsA search on PubMed/MEDLINE and EMBASE for studies reporting endograft infections after TEVAR was conducted up to January 2023. Data on study design, patients demographic, infection (time from TEVAR to infection, vascular imaging, bacterial samples), clinical strategies, outcome and follow-up were extracted and analysed. The outcome after surgical and conservative treatment was compared.ResultsThirty-six articles (5 case-series; 31 case reports) were deemed eligible for this review. A total of 57 patients (mean age: 62.5 ± 13.9 years) with endograft infections after TEVAR were included. Fever and pain were the two major clinical presentations. Mean time from TEVAR to diagnosis was 19.7 ± 36.4 months. The top four isolated microorganism were Staphylococcus aureus (25%), Candida albicans (15.6%), Streptococcus (12.5%) and Pseudomonas (7.8%). Patients were treated conservatively (36.8%) or surgically (63.2%). Surgical treatments were extra-anatomic aortic bypass (50%), in-situ aortic replacement (38.9%) and graft preservation (11.1%). Overall hospital mortality was 33.3% (30-day mortality: 26.4%). The mortality was 52.4% after conservative treatment and 22.2% after surgery (p = 0.0397). Among patients who underwent surgery, the mortality was 28.6% after in-situ aortic replacement and 22.2% after extra-anatomic aortic bypass (p = 0.5387). Major in-hospital causes of death after surgery were multiple organ failure and respiratory failure (6/8 patients).ConclusionEndograft infection after TEVAR is rare but it carries a high risk of mortality. In selected patients, the surgical treatment seems to be safer, with a lower mortality rate when compared to alternative conservative options.

ObjectiveTo validate a serial multimodal ultrasound (MMUS) protocol for assessing dynamic tibialis anterior changes in detecting intensive care unit-acquired weakness (ICUAW) and to develop a diagnostic algorithm.MethodsIn a prospective cohort of 97 high-risk adults (mean age 60.7±13.7 years; 73.2% male; SOFA score ≥8 for ≥3 days), MMUS quantified structural (thickness, echogenicity), hemodynamic (perfusion grade, peak systolic velocity [PSV]), and mechanical (elastic modulus) parameters of the tibialis anterior at ICU admission (Day 1) and Day 7. ICUAW was diagnosed per American Thoracic Society guidelines. Serum biomarkers (IL-6, PCT, CRP) were correlated with sonographic changes. Diagnostic models were constructed using binary logistic regression and evaluated by ROC analysis.Results31 patients (32.0%) developed ICUAW. By Day 7, the ICUAW group showed greater structural deterioration (echogenicity progression: 54.8% vs. 16.7%, P < 0.001), hemodynamic changes (PSV: 7.60 ± 1.72 vs. 6.35 ± 1.78 cm/s, P < 0.001), and faster stiffness increase (elastic modulus rate: 14.1±12.3% vs. 5.4±6.0%, P < 0.001). Day 7 PSV correlated with IL-6 (r = 0.59), PCT (r = 0.50), and CRP (r = 0.68) (all P < 0.05). A 7-parameter model achieved an AUC of 0.917 (95%CI: 0.857-0.978) with an NPV of 92.4%.ConclusionDynamic MMUS captures ICUAW pathophysiology. The proposed algorithm shows potential as a non-invasive bedside tool for early risk stratification, pending multicenter validation.

To reveal the mechanical response and energy conversion mechanism of deep gas-bearing layered coal under impact loads, coal samples from a gas outburst mine in Gansu Province were taken as the research object. Based on a three-dimensional combined dynamic-static load testing system, impact tests were conducted on coal samples with different bedding angles β (0°, 30°, 45°, 60°, and 90°) under a gas pressure of 0.8 MPa. A preset axial static load of 2 MPa and confining pressure of 4 MPa were applied, followed by loading with an impact pressure of 0.6 MPa. The stress-strain curves, mechanical parameters, failure modes, and energy evolution laws were analyzed. The results show that the peak strength presents a U-shaped distribution with the change of bedding angle: it reaches the highest values at 0° (160.41 MPa) and 90° (164.66 MPa), and the lowest at 45° (124.96 MPa). This is because the shear stress concentration effect on the bedding plane is the strongest at 45°, making it easy for cracks to propagate along the bedding. The peak strain also shows a U-shaped trend, reaching 0.03 at 90°and stabilizing at 0.026 at 30°and 45°, which reflects the differences in the deformation mechanisms of coal samples under different angles. In terms of energy evolution, the total energy density (U) and dissipated energy density (U_d) are higher and grow faster at 0°and 90°, while the elastic energy density (U_e) shows obvious post-peak release only at 0°. In the range of 30°∼60°, the values of U and U_d are low, and the release of U_e is weak, which is consistent with the low energy consumption characteristics of shear failure along the bedding. The failure mode changes regularly with the bedding angle: multi-directional fragmentation at 0°, shear fragmentation along the bedding mainly at 30°∼45° (the most severe fragmentation at 45°), and cross-bedding splitting failure at 90°. The study confirms that bedding angle regulates the mechanical properties and energy distribution of coal by changing the stress distribution and crack propagation path. The research results can provide key quantitative parameter support for the assessment and prevention of dynamic disasters in deep gas-bearing coal.

ObjectiveTo investigate the independent associations, dose-response relationships, and heterogeneity across different populations between eight cholesterol-related indices (WHR, LHR, NHR, MHR, PHR, AIP, CHG, and RCII) and diabetic nephropathy (DN), utilizing data from the National Health and Nutrition Examination Survey (NHANES).MethodsThis cross-sectional analysis included 9421 participants from the NHANES 2015-2020 cycles, including 631 DN patients. Multivariable logistic regression was used to assess associations between each index and DN. Restricted cubic spline (RCS) models were employed to explore nonlinear relationships, and effect modification was assessed across subgroups defined by gender, BMI, glycemic control, and other characteristics.ResultsAfter adjusting for multiple confounders, WHR, LHR, NHR, AIP, CHG, and RCII were all significantly positively associated with DN risk (all P < 0.001), with RCS analyses indicating nonlinear "threshold effects" for most indices. Subgroup analyses revealed significant heterogeneity in associations: WHR and LHR showed stronger associations in females; AIP and CHG remained robust across BMI and glycemic control subgroups; RCII showed stronger associations among non-hypertensive and non-smoking individuals.ConclusionIn this cross-sectional study, six cholesterol-inflammation composite indices were independently associated with DN, predominantly exhibiting non-linear dose-response relationships. The variation in association strength across sex, metabolic status, and lifestyle factors suggests a potential pattern of "pathway heterogeneity" in DN risk. These indices warrant further investigation in future studies to explore their value as early clues for risk identification.