Exploring the role of candidalysin in the pathogenicity of Candida albicans by gene set enrichment analysis and evolutionary dynamics.

AIMS: To explore the pathogenic mechanisms of Candida albicans (C. albicans), focusing on its impact on human health, particularly through invasive infections in the gastrointestinal and respiratory tracts. METHODS: In this study, we evaluated the demographic and clinical profiles of 7 pneumonia patients. Meanwhile, we used Gene Set Enrichment Analysis (GSEA) and Evolutionary Dynamics method to analyze the role of candidalysin in C. albicans pathogenicity. RESULTS: By analyzing genomic data and conducting biomedical text mining, we identified novel mutation sites in the candidalysin coding gene ECE1-III, shedding light into the genetic diversity within C. albicans strains and their potential implications for antifungal resistance. Our results revealed significant associations between C. albicans and respiratory as well as gastrointestinal diseases, emphasizing the fungus's role in the pathogenesis of these diseases. Additionally, we identified a new mutation site in the C. albicans strain YF2-5, isolated from patients with pneumonia. This mutation may be associated with its heightened pathogenicity. CONCLUSION: Our research advances the understanding of C. albicans pathogenicity and opens new avenues for developing targeted antifungal therapies. By focusing on the molecular basis of fungal virulence, we aim to contribute to the development of more effective treatment strategies, addressing the challenge of multidrug resistance in invasive fungal infections.

Predictive value of number of metastatic lymph nodes and lymph node ratio for prognosis of patients with FIGO 2018 stage IIICp cervical cancer: a multi-center retrospective study.

BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Preparation and Rheological Properties of the PVA/CMC/Gel Composite for Mining.

A composite gel material with an interpenetrating network structure was formed using the chemical cross-linking method. The viscosity, yield stress, and thixotropy of a poly(vinyl alcohol)/carboxymethyl cellulose/gelatin (PVA/CMC/Gel) composite gel slurry with different ratios were tested using a viscometer, and the interaction between the surface of the gelling agent and the cross-linking agent was analyzed by calculating the frontline orbital energy of a single polymer material molecule. The seepage diffusion characteristics of the composite gel in a goaf were then studied through a numerical simulation. The results indicate that the PVA/CMC/Gel composite gel exhibits shear thinning behavior following the power law model and behaves as a pseudoplastic fluid. The optimal ratio for the composite gel at 30 °C is determined as follows: 30 wt % for the gelling agent (PVA/(Gel + CMC) = 20:10), 4 wt % for the cross-linking agent, 3.09 wt % for the carbide slag, 7.5 wt % for the alcohol amine solution, and 0.5% sodium dodecyl sulfonate + 0.1% alkyl glycoside for the foaming agent. Gel exhibits the lowest energy band gap (0.096 eV), indicating strong reaction activity and strong reaction with the cross-linking agent (sodium tetraborate). PVA has the largest energy band gap (0.238 eV), strong molecular stability, and weak reaction with the cross-linking agent (sodium tetraborate). When the dip angle of the goaf is 4° and the injection time is 40 min, the composite gel tends to diffuse more easily along the dip. The investigation into the rheological properties of the PVA/CMC/Gel composite gel holds significant importance in the design of coal mine pipeline transportation and understanding diffusion flow in goaf.

Mechanism and use strategy of uric acid-lowering drugs on coronary heart disease.

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

The output of cataract surgery performed by trained non-ophthalmologist physicians in rural areas: study of cataract outcomes and up-take of services report 7.

BACKGROUND: Cataract is the leading cause of blindness worldwide and surgery can restore vision in most patients. Some patients have little access to surgical services due to lack of cataract surgeons and the unaffordable costs. In 2005 we built a service model that trained rural non-ophthalmologist physicians to perform cataract surgeries in rural China. This study evaluates the long-term impacts of this model. METHODS: We conducted a retrospective cohort study to analyze patients' hand-written medical records and electronic outpatient record between January 2005 and December 2019 at two rural health clinics in Southern China. RESULTS: In total, 34,601 patients (49,942 eyes) underwent cataract surgery by non-ophthalmologist physicians from 2005 to 2019.Visual acuity was clearly documented in 38,251 eyes. Before surgery, the unaided distance visual acuity (UDVA) of 60.7% (23,205/38,251) eyes was less than 0.05 decimal. On the first day after surgery, the percentage of UDVA < 0.05 eyes was reduced to 6.0%, and 96.7% (36,980/38,251) of the eyes achieved a better UDVA compared to pre-operation. Surgical-related complications occurred in 218 eyes. The most common complication was posterior capsule rupture (114, 0.23%). 44.3% (15,341/34,601) of the patients chose to have a second eye cataract surgery (SECS) in the same clinic. At one of the outpatient clinics, 21,595 patients received basic eye care apart from cataract surgery between 2018 and 2020. CONCLUSIONS: Non-ophthalmologist physicians trained for cataract surgeries in rural clinics can improve cataract related visual acuity and basic eye care to the local population.

Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort.

Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.

Oncostatin M promotes osteogenic differentiation of tendon-derived stem cells through the JAK2/STAT3 signalling pathway.

PURPOSE: Oncostatin M (OSM) is involved in the regulation of osteogenic differentiation and has a major role in the development of heterotopic ossification. The role of OSM in osteogenic differentiation of tendon-derived stem cells (TDSCs) and its mechanism have not been reported. This study aim to investigate the role of OSM in osteogenic differentiation of TDSCs and study the mechanism. METHODS: TDSCs were differentiated in osteogenic differentiation medium for 7 days. Recombinant OSM was added to the osteogenic differentiation medium for 7 and 14 days. The effect of Janus kinase 2 (JAK2) inhibitor AZD1480 and signal transducer and activator of transcription 3 (STAT3) inhibitor stattic in the presence of recombinant OSM on osteogenic differentiation of TDSCs was examined after differentiation for 7 and 14 days. Alkaline phosphatase and alizarin red staining were used to assess the effects on early and mid-stage osteogenic differentiation, respectively. Western blotting and qPCR were used to assess the expression of receptor and signalling pathway-related proteins and osteogenic marker genes, respectively. RESULTS: TDSCs were successfully induced to differentiate into osteoblasts. Recombinant OSM promoted osteogenic differentiation of TDSCs to early and mid-stages. After addition of AZD1480 or stattic, decreased alkaline phosphatase and alizarin red staining were observed in the early and mid-stages of osteogenic differentiation. Additionally, decreased expression of receptor and pathway-related proteins, and osteogenic genes was found by western blotting and qPCR, respectively. CONCLUSION: OSM promotes osteogenic differentiation of TDSCs and the JAK2/STAT3 signalling pathway plays an important role.

Human Biodistribution and Radiation Dosimetry of the Targeting Fibroblast Growth Factor Receptor 1-Positive Tumors Tracer [68Ga]Ga-DOTA-FGFR1-Peptide.

Objective: [68Ga]Ga-DOTA-FGFR1-peptide is a novel positron emission tomography (PET) radiotracer targeting fibroblast growth factor receptor 1 (FGFR1). This study aimed to evaluate the safety, biodistribution, radiation dosimetry, and imaging potential of [68Ga]Ga-DOTA-FGFR1-peptide. Methods: The FGFR1-targeting peptide DOTA-(PEG2)-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-performance liquid chromatography purification, and labeled with 68Ga with DOTA as chelating agent. We recruited 14 participants and calculated the radiation dose of 4 of these pathologically confirmed nontumor subjects using OLINDA/EXM 2.2.0 software. At the same time, the imaging potential in 10 of these lung cancer patients was evaluated. Results: The biodistribution of [68Ga]Ga-DOTA-FGFR1-peptide in 4 subjects showed the highest uptake in the bladder and kidney. Dosimetry analysis indicated that the bladder wall received the highest effective dose (3.73E-02 mSv/MBq), followed by the lungs (2.36E-03 mSv/MBq) and red bone marrow (2.09E-03 mSv/MBq). No normal organs were found to have excess specific absorbed doses. The average systemic effective dose was 4.97E-02 mSv/MBq. The primary and metastatic tumor lesions were clearly visible on PET/computed tomography (CT) images in 10 patients. Conclusion: Our results indicate that [68Ga]Ga-DOTA-FGFR1-peptide has a good dosimetry profile and can be used safely in humans, and it has significant potential value for clinical PET/CT imaging.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Colletotrichum aeschynomenes Causing Anthracnose in Combretum indicum in Guangxi, China.

Combretum indicum（L.）Jongkind, distributed in Southeast Asia, is widely planted in southern China for its ornamental and medicinal value. In February 2023, anthracnose symptoms were observed on C. indicum leaves in Nanning Garden Expo (N22°43', E108°28'), Guangxi, China, causing severe defoliation of infected plants with a foliar disease incidence ranging from 40 to 60% (n = 100) in a 2 ha field. Disease symptoms began with small red spots (2 to 3 mm by 2 to 3 mm) on the leaves and gradually enlarged to larger irregular light grey lesions with yellowish halos (3 to 5 mm by 2 to 8 mm). In the late stage, spots merged into larger irregular lesions (5 to 15 mm by 6 to 13 mm) and the necrotic lesions abscised. Three diseased samples in total were collected from plants in three different locations. Symptomatic leaves were cut into small pieces (3×3 mm), disinfected with 75% ethanol solution for 10 s, 2% NaClO for 1 min followed by three washes in sterile distilled water. Tissue pieces were separately plated on potato dextrose agar (PDA) and incubated at 25°C for five days. One representative isolate from each sample (SJ-1, SJ2-1 and SJ3-1) were chosen for further analysis. Colonies were villiform, initially white, later turning gray in 7 days on PDA at 25℃. The average diameter for colonies were 8.1 cm, 8.0 cm and 8.1 cm for SJ1-1, SJ2-1 and SJ3-1, respectively. Conidia were aseptate, hyaline, cylindroid, and averaged 11.94 µm × 5.04 µm, 11.78 µm × 5.14 µm and 11.74 µm × 4.59 µm (n=90) for SJ1-1, SJ2-1 and SJ3-1, respectively. The characteristics were close to the descriptions of Colletotrichum spp. (Weir et al. 2012). Genomic DNA was extracted from 7-day-old aerial mycelia of these isolates. The internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), ß-tubulin (TUB2), chitin synthase (CHS-1), calmodulin (CAL) and the intergenic region between apn2 and MAT1-2-1 (ApMat) were amplified using primers ITS1/ITS4 (White et al. 1990), GDF/GDR, ACT-512F/ACT-783R, T1/Bt2b, CHS-79F/CHS-354R, CL1C/CL2C (Weir et al. 2012) and AM-F/AM-R (Silva et al. 2012), respectively. Sequences were deposited in GenBank (ITS: OR540240-OR540242; GAPDH: PP328968-PP328970; ACT: PP328959-PP328961; TUB2: PP328971-PP328973; CHS-1: PP328965-PP328967; CAL: PP328962-PP328964 and ApMat: OR548253-OR548255). A phylogenetic analysis was made via Bayesian inference based on the concatenated sequences (ITS, GAPDH, ACT, TUB2, CHS-1, CAL and ApMat). According to morphology and phylogenetic analysis, SJ1-1, SJ2-1 and SJ3-1 were identified as C. aeschynomenes. Pathogenicity was confirmed on leaves with and without wounds of 24 one-year-old C. indicum plants in a greenhouse in Nanning, Guangxi Province. The wound was made with a sterilized needle. Wounded and unwounded leaves were inoculated with 20 µl of conidial suspension (106 spores/ml in 0.1% sterile Tween 20) of the three isolates and control plants were inoculated with water containing 0.1% sterile Tween 20 (6 leaves/plant, 3 plants/treatment). All plants were covered with plastic bags to maintain a high humidity environment and placed in a 28°C growth chamber with constant light. After 7 days of incubation, necrotic lesions were observed on inoculated wounded leaves, whereas unwounded leaves and control plants showed no symptoms. The fungi were re-isolated from symptomatic leaves, completing Koch's postulates. These species can cause severe diseases in a variety of plants worldwide, such as Manihot esculenta, Theobroma cacao and Myrciaria dubia (Sangpueak et al. 2018; Nascimento et al. 2019; Matos et al. 2020). To our knowledge, this is the first report of C. aeschynomenes causing C. indicum leaf anthracnose in China. The results will provide valuable information for management of anthracnose in C. indicum.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma with extranodal involvement.

PURPOSE: The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). METHODS: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). RESULTS: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). CONCLUSIONS: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

Discontinuation and non-publication of randomized controlled trials on cervical cancer or precancer.

BACKGROUND: Research waste is a considerable problem in clinical trials, with nonpublication being a significant contributor. We aimed to determine the prevalence of discontinuation and nonpublication of randomized controlled trials (RCTs) on cervical cancer or precancer. METHODS: We searched ClinicalTrials.gov for registered RCTs investigating cervical cancer or precancer that started between January 2000 and December 2020. The primary and secondary outcomes were trial nonpublication and premature discontinuation, respectively. Publication status was determined by systematic searches of peer-reviewed journals using the PubMed and Scopus databases. RESULTS: A total of 113 RCTs met the inclusion criteria. Among the 85 trials completed before December 2020, 44 (51.8%) were prematurely discontinued and 40 (47.1%) were unpublished. A single-center design (61.4% vs. 34.1%, P = .012) and lack of external funding (59.1% vs. 36.6%, P = .038) were significantly associated with trial discontinuation. Large-scale (target sample size >400; 46.7% vs. 17.5%, P = .004) and externally funded trials (66.7% vs. 35.0%, P = .004) were more likely to be published. Multivariate logistic analysis revealed that a large sample size [odd ratio (OR): 4.125, 95% confidence interval (CI): 1.511-11.259, P = .006] and presence of external funding (OR: 3.714, 95% CI: 1.513-9.117, P = .004) were independent positive factors for trial publication. CONCLUSION: A significant proportion of RCTs related to cervical cancer or precancer were discontinued early or remain unpublished, resulting in a waste of research resources.

Mechanisms of denitrifying granular sludge disintegration and calcium ion-enhanced re-granulation in acidic wastewater treatment.

Granular sludge is an alternative technology for the direct treatment of acidic nitrate-containing wastewater. Rapid remediation of disintegrated granules is essential to achieve efficient nitrogen removal. In this study, denitrifying granules were inactivated and disintegrated when the influent nitrate-nitrogen concentration was elevated from 240 to 360 mg L-1 in acidic wastewater (pH = 4.1) in a sequencing batch reactor. Tightly bound extracellular polymeric substances (TB-EPS) decreased by 60%, and extracellular protein (PN) was the main component of the reduced EPS. The three-dimensional excitation emission matrices (3D-EEM) results confirmed that the PNs that decreased were mainly tryptophan-like, tyrosine-like, and aromatic. This study further confirmed that the decrease in PN was mainly from the destruction of C=O (amide I) and N-H functional groups. Overloading of nitrogen-inhibited denitrifying activity and the destruction and dissolution of TB-EPS by acidic pH were responsible for granule disintegration, with PNs playing a major role in maintaining granule stability. Based on this, new granules with an average particle size of 454.4 µm were formed after calcium chloride addition; EPS nearly doubled during granule formation with PN as the dominant component, accounting for 64.7-78.4% of the EPS. Atomic force microscopy (AFM) revealed that PN-PN adhesion increased by 1.6-4.9 times in the presence of calcium ions, accelerating the re-granulation of disintegrated particles. This study provides new insights into the disintegration and remediation of granular sludge under acidic conditions.

New Electrocardiographic Score for Predicting the Site of Coronary Artery Occlusion in Inferior Wall Acute Myocardial Infarction.

Background: An electrocardiogram (ECG) was used to determine the type of acute myocardial infarction (MI) and locate the culprit vessel. Inferior wall myocardial infarction (IWMI) patients with the right coronary artery (RCA) as the culprit vessel may have a worse clinical prognosis than the left circumflex artery (LCx). We aimed to develop a new, simple, accurate scoring system to localize the RCA. Methods: From January 2018 to January 2020, patients were admitted to the Department of Cardiology of TEDA International Cardiovascular Hospital and the Second Hospital of Tianjin Medical University due to IWMI and coronary angiography confirmed that the infarct-related vessel was a single RCA or LCx. ECG of patients before percutaneous coronary intervention (PCI) was collected to quantitatively analyze the characteristics of ST-segment deviation in non-inferior wall leads (N-IWL) and establish the RCA score in N-IWL. Results: 149 patients were enrolled, including 83 in the RCA group and 66 in the LCx group. Finally, ST-segment depression (ST↓) lead I, aVR, V1, and V6, and ST↓≥ 1mm in lead V4 were found to be associated with the location of the RCA. The sensitivity, specificity, and area under the curve (AUC) of the N-IWL RCA scoring system were 77.1%, 72.7%, and 0.83, respectively. The diagnostic ability of the scoring system was better than that of other algorithms and scoring systems. Conclusion: ECG helps identify the RCA in patients with IWMI before PCI. The N-IWL RCA score may help identify the culprit vessel as the RCA in patients with IWMI.

A Mediation Analysis of the Association Between Systemic Inflammation Response Index, in-Hospital Complications, and Poor Long-Term Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: Insights from a Large Prospective Cohort Study.

Purpose: Early systemic inflammatory changes are increasingly recognized as factors influencing outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Systemic inflammation response index (SIRI), an inflammation biomarker, was thought to be associated with adverse outcomes in many other diseases. However, in aSAH, research on SIRI remains limited. Thus, our objective was to investigate the association between SIRI and poor long-term functional outcomes while evaluating the mediating role of in-hospital complications in this association. Patients and Methods: SIRI was defined as neutrophil count × monocyte count/lymphocyte count. Patients were categorized according to SIRI quartiles. Stabilized inverse probability of treatment weighting (sIPTW) was utilized to minimize group differences. The association between SIRI and in-hospital complications as well as poor 90-day functional outcomes (mRS 3-6) was estimated by multivariable logistic regression analyses. Mediation analysis was performed to investigate the relationship between SIRI and poor functional outcomes mediated by in-hospital complications. Results: A total of 650 patients were prospectively included. After sIPTW, compared to the lowest quartile, an elevated SIRI was associated with delayed cerebral ischemia (DCI) (OR 2.12, 95% CI 1.20-3.74), post-operative pneumonia (POP) (OR 2.16, 95% CI 1.29-3.62) and poor 90-day functional outcomes (OR 3.03, 95% CI 1.55-5.91). In-hospital complications including DCI (mediation proportion, 18.18% before sIPTW and 20.0% after sIPTW) and POP (mediation proportion, 18.18% before sIPTW and 26.7% after sIPTW) partially mediated the association between SIRI and poor 90-day functional outcomes. Mediation analysis yielded comparable results in subgroups stratified by age and sex. Conclusion: In this study, SIRI was associated with poor long-term functional outcomes in aSAH, which was partially mediated by DCI and POP with a mediation proportion exceeding 18%. Our findings might underscore the potential utility of SIRI in prompting physicians to address systemic inflammatory status timely to prevent in-hospital complications, including DCI and POP, and ultimately improve long-term functional outcomes.

Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT in diagnosing ovarian cancer.

PURPOSE: This study assesses the diagnostic performance of 68Ga-FAPI-04 PET/CT compared to 18F-FDG PET/CT in primary, recurrent, and metastatic ovarian cancer. METHODS: Seventy-nine ovarian cancer patients who performed 68Ga-FAPI-04 and 18F-FDG PET/CT were recruited. The target-to-background ratio (TBR), maximum standardized uptake value (SUVmax), the number of positive lesions, visual assessment, the peritoneal cancer index (PCI) score, staging/restaging, and treatment strategies were compared from the corresponding PET/CT. Additionally, we analyzed and contrasted the diagnostic efficacy in both scans. RESULTS: Among all patients, 6 were assessed for initial assessment and 73 for recurrence and metastasis detection. For all lesions, 68Ga-FAPI-04 PET/CT demonstrated greater TBR than 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT demonstrated higher sensitivity for peritoneal metastases including patient-based and lesion-based analysis (95.00% vs. 83.33%, P = 0.065; 90.16% vs. 60.66%, P < 0.001) and a higher PCI score [median PCI: 6 (4, 12) vs. 4 (2, 8), P < 0.001]. According to the visual assessment, 68Ga-FAPI-04 PET revealed larger extent metastases in 55.93% (33/59) of the patients with peritoneal metastases. 68Ga-FAPI-04 was upstaged in 7 patients (8.86%, 7/79) and discrepancies in both scans caused treatment strategies to change in 11 patients (13.92%, 11/79). CONCLUSION: 68Ga-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in identifying metastases and can be a potential supplement for managing ovarian cancer patients.

Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

I-FABP protein/mRNA and IL-6 as biomarkers of intestinal barrier dysfunction in neonates with necrotizing enterocolitis and SPF BALB/c mouse models.

OBJECTIVE: Neonatal necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease. We investigated intestinal fatty acid binding protein (I-FABP), I-FABP mRNA, and interleukin-6 (IL-6) as potential diagnostic biomarkers in NEC. METHODS: Forty mice were subjected to hypoxic-ischemic intestinal injury, and then serum I-FABP protein and mRNA levels were quantified. Ileal tissue pathological scores were determined by hematoxylin and eosin staining. I-FABP expression levels and translocation in these tissues were detected using western blotting and immunofluorescence, respectively. Samples from 30 human neonates with NEC and 30 healthy neonates had serum I-FABP protein/mRNA and IL-6 levels measured. RESULTS: The mouse ileal tissue pathological score and I-FABP levels, as well as serum I-FABP and I-FABP mRNA levels, were significantly higher in the model group than in the control group. Serum I-FABP, I-FABP mRNA, and IL-6 levels were significantly higher in human neonates with NEC than in the healthy group. Logistic regression and receiver operating curve analyses revealed that I-FABP protein/mRNA and IL-6 levels could be diagnostic biomarkers for NEC. CONCLUSIONS: I-FABP protein/mRNA and IL-6 levels are useful biomarkers of intestinal ischemic injury in neonates with NEC. The combined detection of I-FABP protein/mRNA and IL-6 is recommended rather than using a single biomarker.

Comparison of the effectiveness of different corneal curvature measurement methods for IOL implantation in traumatic aphakic eyes with corneal injury.

BACKGROUND/AIM: To assess the refractive outcomes of secondary intraocular lenses (IOL) in patients with traumatic aphakic eyes with corneal penetrating injury and compare different corneal curvature measurement methods. METHODS: Patients with unilateral penetrating eye injuries underwent corneal wound repair and cataract extraction, followed by secondary IOL implantation. Corneal curvature measurements were taken on the contralateral healthy eye (Group A), from the affected eye before removing corneal sutures (Group B), or after suture removal (Group C). The refractive outcomes were compared among the three groups. RESULTS: The study included 261 eyes. The Mean Absolute Error (MAE) in Group C (0.99 ± 0.85 D) was significantly smaller than that in Group A (1.87 ± 1.71 D) and Group B (1.37 ± 1.20 D) (both P < 0.001). Moreover, the percentage of eyes with IOL prediction errors within ± 0.50 D in Group C (40%) was higher than that in group A (21.7%) (OR = 2.364, 95%CI: 1.272-4.392, P = 0.006) and group B (28.0%) (OR = 1.714, 95%CI: 0.948-3.099, P = 0.073), and the percentage of eyes with IOL prediction errors within ± 1.0 D in Group C (90.9%) was higher than that in group A (67.9%) (OR = 4.758, 95%CI: 2.131-10.626, P < 0.001) and group B (75.0%) (OR = 3.370, 95%CI: 1.483-7.660, P = 0.003) as well. CONCLUSIONS: In traumatic aphakic eyes with corneal sutures, IOL power calculation based on the corneal curvature of the injured eye after removing the corneal sutures yields the best refractive outcomes.