Performance Investigation of Asphaltene Adsorption at a Carbonate Rock Surface: Spectroscopy Experiment and Molecular Simulation.

Investigation of asphaltene adsorption at rock surfaces plays an important role in enhanced oil recovery (EOR) for the petroleum industry. In this work, the interaction performances of asphaltene adsorption at carbonate dolomite and calcite surfaces are investigated based on experimental and simulation insights. On the one hand, macroscopic interaction performances were investigated by spectroscopy experiments to obtain the Langmuir thermodynamic model and pseudo-second-order (PSO) kinetic model. The results indicated monolayer molecular asphaltene adsorption for both dolomite and calcite, while they showed 'slow adsorption-slow desorption' for dolomite but 'fast adsorption-fast desorption' for calcite. Meanwhile, dolomite showed a higher adsorption capacity with qm(dol 1) = 5.35 mg/g > qm(cal 1) = 1.28 mg/g and a stronger adsorption spontaneity with ΔGm(dol 1)θ = -7.76 kJ/mol < ΔGm(cal 1)θ = -4.76 kJ/mol. On the other hand, microscopic interaction performances were investigated for three asphaltene molecules by molecular dynamics simulation (MDS) with ∼8 Å distance-placing and 500 ps time-running. According to the results, dolomite showed higher system stability than calcite with a lower final energy of ΔEdol-cal = -58 kJ/mol, and archipelago asphaltene showed higher adsorption stability with the smallest equilibrium energy of Earch(dol) = -147 kJ/mol for albite and Earch(cal) = -89 kJ/mol for calcite. The model of molecular orientation and force dominance was proposed as the interaction mechanism for asphaltene adsorption, which "lie sideways" at low concentrations but "stands upright" at high concentrations. This work allows the performance investigation and mechanism illustration of asphaltene adsorption at rock surfaces, which can help gain a fundamental understanding of the EOR during reservoir exploitation.

A Review of the Extent of Pain Catastrophizing in Patients Who Have Undergone Total Knee Replacement.

OBJECTIVES: This study aimed to analyze the current status and influencing factors of pain catastrophizing in patients undergoing total knee replacement (TKR) and to provide a basis and reference for the clinical improvement of pain catastrophizing in these patients. DESIGN: This study was designed in accordance with PRISMA guidelines. DATA SOURCES: PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu and Chinese Biomedical Literature Databases. REVIEW/ANALYSIS METHODS: A scoping review was performed using PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu, and Chinese Biomedical Literature Databases, and after literature screening and data extraction, the results were summarized. RESULTS: A total of 23 articles were included in the study. Pain catastrophizing is mostly assessed using the Pain Catastrophizing Scale and the Coping Strategies Questionnaire. The level of pain catastrophizing is an independent predictor of pain in patients undergoing TKR and is influenced by demographic, psychological, co-morbid, and prognostic factors. Pain catastrophizing interventions mainly consist of surgery, physiotherapy, medication, and psychological therapy. CONCLUSIONS: Pain catastrophizing involves multiple factors, and it is necessary to explore the predictors affecting pain catastrophizing, improve the systematic evaluation of pain catastrophizing and adopt the appropriate intervention methods.

The prognostic value of lymphatic metastatic size in head and neck squamous cell carcinoma.

BACKGROUND: Lymphatic metastatic size was proved to predict prognosis in different types of carcinomas, except in head and neck squamous cell carcinoma (HNSCC) located in hypopharynx, oropharynx and supraglottic region et al. The aim of this study is to evaluate the prognostic value of lymphatic metastatic size in HNSCC, which may guide clinical decision-making in practice. METHODS: From 2008 to 2022, 171 patients, who were diagnosed as HNSCC in our center, were included. The demographic data, clinicopathological characteristics and lymphatic metastatic size were recorded and analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS: Among 171 patients, 107 cases were hypopharyngeal cancer, 38 cases supraglottic cancer and 26 cases oropharyngeal cancer. The median of lymphatic metastatic size was 8 mm (range 0-46). According to lymphatic metastatic size, the patients were assigned to three subgroups: Group I (0 mm), Group II ( ≤ 10 mm) and Group III (> 10 mm). Kaplan-Meier analysis with log rank test revealed that Group I and Group II had similar locoregional control rate, distant metastasis free probability, disease-free survival and overall survival (all p > 0.05), whereas Group III had significant worse prognosis. Adjusted for demographic and other clinicopathological characteristics, lymphatic metastatic size was an independent predictor of disease-free survival and overall survival in HNSCC. CONCLUSIONS: Lymphatic metastatic size was an independently prognostic factor in HNSCC, which may assist in postoperative adjuvant treatment decisions.

Clinical Genetic Features and Neoadjuvant Chemotherapy Response in HER2-Low Breast Cancers: A Retrospective, Multicenter Cohort Study.

BACKGROUND: The objective of this work is to reveal differences in clinical and genetic features, as well as neoadjuvant chemotherapy (NAC) response, between HER2-low and HER2-zero or HER2-positive breast cancers. PATIENTS AND METHODS: A total of 245 female patients with breast cancer were retrospectively enrolled from seven hospitals. Core needle biopsy (CNB) samples were collected before NAC and used for next-generation sequencing by a commercial gene panel. Clinical and genetic features, as well as NAC response, were compared between HER2-low and HER2-zero or HER2-positive breast cancers. The nonnegative matrix factorization (NMF) method was applied to cluster the C-Score of enrolled cases to reveal the intrinsic features of each HER2 subgroup. RESULTS: A total of 68 (27.8%) cases are HER2-positive, 117 (47.8%) cases are HER2-low, and 60 (24.5%) cases are HER2-zero. HER2-low breast cancers have a significantly lower pathologic complete response (pCR) rate than HER2-positive and HER2-zero breast cancers (p < 0.050 for all comparisons). Compared with HER2-low breast cancers, HER2-positive cases have higher rates of TP53 mutation, TOP2A amplification, and ERBB2 amplification, as well as lower rates of MAP2K4 mutation, ESR1 amplification, FGFR1 amplification, and MAPK pathway alteration (p < 0.050 for all comparisons). After clustering HER2-low cases by the NMF method, 56/117 (47.9%) are in cluster 1, 51/117 (43.6%) are in cluster 2, and 10/117 (8.5%) are in cluster 3. HER2-low cases in cluster 2 have the lowest pCR rate among the three clusters (p < 0.050). CONCLUSIONS: HER2-low breast cancers have significant genetic differences from HER2-positive cases. Genetic heterogeneity exists in HER2-low breast cancers and impacts on NAC response in this subgroup.

Association of hyperhomocysteinemia and chronic kidney disease in the general population: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence shows that an elevated homocysteine(Hcy) level is associated with an increased risk of chronic kidney disease (CKD). This study systematically evaluated the correlation between homocysteine level and the incidence of CKD reported in cohort and cross-sectional studies. METHODS: We searched electronic databases and reference lists for relevant articles. 4 cohort studies and 7 cross-sectional studies including 79,416 patients were analyzed in a meta-analysis. Hyperhomocysteinemia was defined as a Hcy level > 15 µmol/L, which was the criterium used in previous studies. Meta-analyses were conducted of literature searches from online databases such as PubMed, Embase, Cochrane and Scopus. Computed pooled adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were used to estimate the risk of new-onset CKD according to Hcy levels in the general population. RESULTS: People with high Hcy levels were more likely to suffer from CKD than people with normal Hcy levels (pooled OR, 2.09; 95% CI, 1.72-2.55). This positive relationship persisted across different study types such as cohort studies (summary OR, 2.2; 95% CI, 1.55-3.13) and cross-sectional studies (summary OR, 2.07; 95% CI, 1.63-2.63). CONCLUSIONS: People with hyperhomocysteinemia have a higher incidence of CKD, Hyperhomocysteinemia may also be an independent risk factor for CKD in the general population.

The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy.

Osteoarthritis (OA) is a worldwide chronic disease that can cause severe inflammation to damage the surrounding tissue and cartilage. There are many different factors that can lead to osteoarthritis, but abnormally progressed programmed cell death is one of the most important risk factors that can induce osteoarthritis. Prior studies have demonstrated that programmed cell death, including apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and cuproptosis, has a great connection with osteoarthritis. In this paper, we review the role of different types of programmed cell death in the generation and development of OA and how the different signal pathways modulate the different cell death to regulate the development of OA. Additionally, this review provides new insights into the radical treatment of osteoarthritis rather than conservative treatment, such as anti-inflammation drugs or surgical operation.

Prognostic Value of Volume-Based Metabolic Parameters Obtained by 18F-FDG-PET/CT in Patients With Locally Advanced Squamous Cell Cervical Carcinoma.

OBJECTIVE: The aim of the study was to assess the prognostic impact of volume-based metabolic F-fluorodeoxyglucose-positron emission tomography/ computed tomography (F-FDG-PET/CT) parameters in patients with stage IB-IVA squamous cell cervical carcinoma (SCCC). MATERIALS AND METHODS: We reviewed the pretreatment F-FDG-PET/CT records of 67 patients with stage IB-IVA SCCC. The maximum standardized uptake value (SUVmax) of the primary tumor (PSUVmax), highest SUVmax of the whole malignant lesions (WSUVmax), metabolic tumor volume (MTV) of the primary tumor (PMTV), MTV of the whole malignant lesion (WMTV), total lesion glycolysis (TLG) of primary tumor (PTLG), and TLG of the whole malignant lesion (WTLG) were obtained. Univariate and multivariate analyses were performed to assess the predictive values of metabolic parameters. RESULTS: Twenty-nine patients showed disease progression and 21 patients died during follow-up. In univariate analysis, positive lymph node, WSUVmax of greater than 11, WMTV of greater than 63 cm, and WTLG of greater than 373 adversely affected the progression-free survival (P = 0.004, 0.045, 0.023, and 0.005, respectively). A positive lymph node, WSUVmax of greater than 12, WMTV of greater than 68 cm, and WTLG of greater than 373 significantly adversely affected overall survival (P = 0.002, 0.032, 0.015, and 0.006, respectively). In multivariate analysis, independent prognostic factor for progression-free survival was WTLG (relative risk = 2.384, 95% confidence interval = 1.095-5.187, P = 0.029). Independent prognostic factors for overall survival was WTLG (relative risk = 2.763; 95% confidence interval = 1.107-6.896, P = 0.029). CONCLUSIONS: Preliminary results indicated that pretreatment WTLG measured by F-FDG-PET/CT could independently predict survival in patients with locally advanced SCCC.

Angiotensin-(1-7) decreases the expression of collagen I via TGF-ß1/Smad2/3 and subsequently inhibits fibroblast-myofibroblast transition.

Previous studies have shown that the RAS (renin-angiotensin system) might participate in airway remodelling in asthma. As a main component of the RAS, Ang-(1-7) [angiotensin-(1-7)] has been reported in few studies regarding its protective effect on asthma. However, the functional roles and relevant signalling pathways of Ang-(1-7) have not been well illustrated. In the present study, we analysed the effect of Ang-(1-7) on AngII (angiotensin II)-induced HLF (human lung fibroblast)-MF (myofibroblast) transition by detecting Col-I (collagen type I), TGF-ß1 (transforming growth factor-ß1) and α-SMA (α-smooth muscle actin) expression. We explored further the possible signalling pathways involved in HLF-MF transition. Our results showed that Ang-(1-7) could down-regulate the expression of Col-I, α-SMA and TGF-ß1/Smad2/3 (all P<0.05). A significant decrease was found in phosphorylation of PI3K (phosphoinositide 3-kinase), Akt, p38-MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase) signalling pathways during HLF-MF transition (all P<0.05). Our data suggests that Ang-(1-7) decreases the expression of Col-I via TGF-ß1/Smad2/3 and subsequently inhibits HLF-MF transition.

Long-term efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma: a systemic review and meta-analysis.

OBJECTIVE: To evaluate the long-term efficacy and safety of bronchial thermoplasty (BT) in the treatment of patients with moderate-to-severe persistent asthma. METHODS: We therefore performed a systematic literature review of peer-reviewed studies focusing on BT intervention in asthma control published between January 2000 and June 2014. Three randomized controlled studies and extension studies met the inclusion criteria (n = 6). Outcomes assessed after BT included spirometric data, adverse respiratory events, emergency room (ER) visits and hospitalization for respiratory illness. One-year and 5-year follow-up data were defined as V1 and V5, respectively. RESULTS: There were 249 BT-treated subjects in total who had a 1-year follow-up (V1), whereas 216 of them finished a 5-year follow-up (V5). No evidence of significant decline was found in pre-bronchodilator FEV1 (% predicted) (WMD = 0.75; 95% CI: 3.36 to 1.85; p = 0.57), or in post-bronchodilator FEV1 (% predicted) (WMD = 0.62; 95% CI: 3.32 to 2.08; p = 0.65) between V1 and V5. In addition, the frequency of respiratory adverse events was reduced significantly during the follow-up (RR = 3.41, 95% CI: 2.96-3.93, p < 0.00001). The number of ER visits for adverse respiratory events remained unchanged (RR = 1.06, 95% CI: 0.77-1.46, p = 0.71) after BT treatment. There was no statistically significant increase in the incidence of hospitalization for respiratory adverse events (V5 vs. V1, RR = 1.47, 95% CI: 0.69-3.12, p = 0.32). CONCLUSIONS: These data demonstrate long-term benefits of BT with regard to both asthma control and safety for moderate-to-severe asthmatic patients.

BCL-Former: Localized Transformer Fusion with Balanced Constraint for polyp image segmentation.

Polyp segmentation remains challenging for two reasons: (a) the size and shape of colon polyps are variable and diverse; (b) the distinction between polyps and mucosa is not obvious. To solve the above two challenging problems and enhance the generalization ability of segmentation method, we propose the Localized Transformer Fusion with Balanced Constraint (BCL-Former) for Polyp Segmentation. In BCL-Former, the Strip Local Enhancement module (SLE module) is proposed to capture the enhanced local features. The Progressive Feature Fusion module (PFF module) is presented to make the feature aggregation smoother and eliminate the difference between high-level and low-level features. Moreover, the Tversky-based Appropriate Constrained Loss (TacLoss) is proposed to achieve the balance and constraint between True Positives and False Negatives, improving the ability to generalize across datasets. Extensive experiments are conducted on four benchmark datasets. Results show that our proposed method achieves state-of-the-art performance in both segmentation precision and generalization ability. Also, the proposed method is 5%-8% faster than the benchmark method in training and inference. The code is available at: https://github.com/sjc-lbj/BCL-Former.

Levosimendan and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials. / Levosimendana e Fibrilação Atrial: Uma Metanálise de Ensaios Clínicos Randomizados.

BACKGROUND: Atrial fibrillation (AF) is a prevalent complication associated with levosimendan; however, it remains uncertain whether there are any disparities in the effects of levosimendan on non-postoperative and postoperative AF. OBJECTIVES: This study aimed to evaluate the levosimendan effect on non-postoperative and postoperative AF by conducting a meta-analysis of randomized control trials (RCTs). METHODS: PubMed, Embase, Cochrane Library, and other databases were searched. Pairs of reviewers identified RCTs that compared levosimendan and placebo or other therapies, and the results reported AF events data. Random effects models were used (at a significance level of 5%). RESULTS: Twenty-nine eligible trials comprising 6550 participants were included, eleven of which evaluated the non-postoperative AF incidence, and 18 included postoperative AF. The analysis revealed that levosimendan elevated the AF risk significantly in the non-postoperative group (OR, 1.62; 95% CI: 1.19-2.20; p=0.002) and reduced the AF incidence in the postoperative group (OR, 0.65; 95% CI: 0.44-0.96; p=0.03). AF occurrence decreased more significantly in patients who used levosimendan after cardiac surgery (OR, 0.53; 95% CI: 0.32-0.88; p=0.02) than in patients who used levosimendan before cardiac surgery (OR, 0.67; 95% CI: 0.42-1.06; p=0.09). Moreover, The AF risk was significantly elevated by levosimendan large bolus dose (bolus dose≥12 µg/kg) (OR, 1.44; 95% CI: 1.10-1.88; p=0.004) and decreased by small bolus dose of levosimendan (bolus dose<12 µg/kg) (OR, 0.64; 95% CI: 0.34-1.20; p=0.16). CONCLUSION: Levosimendan was linked to an increased non-postoperative AF incidence. The employment of levosimendan was effective in preventing postoperative AF.

FUNDAMENTO: A fibrilação atrial (FA) é uma complicação prevalente associada à levosimendana; no entanto, permanece incerto se existem disparidades nos efeitos da levosimendana na FA não pós-operatória e pós-operatória. OBJETIVOS: Este estudo teve como objetivo avaliar o efeito da levosimendana na FA não pós-operatória e pós-operatória conduzindo uma metanálise de ensaios clínicos randomizados (ECR). MÉTODOS: PubMed, Embase, Biblioteca Cochrane e outras bases de dados foram pesquisadas. Pares de revisores identificaram ECRs que compararam levosimendana e placebo ou outras terapias, e os resultados relataram dados de eventos de FA. Foram utilizados modelos de efeitos aleatórios (com nível de significância de 5%). RESULTADOS: Foram incluídos 29 ensaios elegíveis compreendendo 6.550 participantes, onze dos quais avaliaram a incidência de FA não pós-operatória e 18 incluíram FA pós-operatória. A análise revelou que a levosimendana elevou significativamente o risco de FA no grupo não pós-operatório (OR, 1,62; IC 95%: 1,19-2,20; p=0,002) e reduziu a incidência de FA no grupo pós-operatório (OR, 0,65; IC 95%: 0,44-0,96; p=0,03). A ocorrência de FA diminuiu mais significativamente em pacientes que usaram levosimendana após cirurgia cardíaca (OR, 0,53; IC 95%: 0,32-0,88; p=0,02) do que em pacientes que usaram levosimendana antes da cirurgia cardíaca (OR, 0,67; IC 95%: 0,42-1,06; p=0,09). O risco de FA foi significativamente elevado pela grande dose em bolus de levosimendana (dose em bolus ≥12 µg/kg) (OR, 1,44; IC 95%: 1,10-1,88; p=0,004) e diminuído pela pequena dose em bolus de levosimendana (dose em bolus <12 µg/kg) (OR, 0,64; IC 95%: 0,34-1,20; p=0,16). CONCLUSÃO: A levosimendana foi associada a um aumento da incidência de FA não pós-operatória. O emprego da levosimendana foi eficaz na prevenção da FA pós-operatória.

Effect of psychological intervention on glycemic control in middle-aged and elderly patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: There is an ongoing debate regarding the influence of psychological interventions on glycemic control in middle-aged and elderly patients diagnosed with type 2 diabetes. To establish evidence-based medical support for the therapeutic application of these interventions, this meta-analysis seeks to assess the impact of psychological interventions on glycemic control in middle-aged and elderly individuals with type 2 diabetes. METHODS: This study systematically searched six electronic databases for randomized controlled studies of psychological interventions applied to middle-aged and elderly patients with type 2 diabetes, and the search time frames were all from the time of database creation to the search period from the establishment to March 2023. Two evaluators independently screened the literature evaluated the included studies' risk of bias, and carried out a meta-analysis using the RevMan5.4 program. RESULTS: A total of 7 studies with 728 participants complied with the eligibility criteria. Meta-analysis showed that glycated glucagon was reduced in the psychological intervention group compared to the control group (MD = -0.26, 95 %CI:-0.51,-0.01,p = 0.01) with a statistically significant difference (p < 0.05). and their sensitivity analyses all showed stable and credible results. CONCLUSIONS: This review concludes that psychological interventions, when applied to middle-aged and elderly individuals with type 2 diabetes, proved to be more effective in reducing HbA1c levels compared to standard care. Nevertheless, further evidence-based research is essential to elucidate the specific types of psychological interventions that contribute to improved glycemic control outcomes in middle-aged and older adults with type 2 diabetes.

The effect of subcutaneous Lixisenatide on weight loss in patients with type 2 Diabetes Mellitus: Systematic review and Meta-Analysis of randomized controlled trials.

BACKGROUND: The impacts of subcutaneous Lixisenatide on body weight in patients with type 2 DM, remain inadequately understood; consequently, this systematic review and meta-regression analysis of randomized controlled trials (RCTs) was conducted to evaluate the influence of subcutaneous Lixisenatide administration on BW and BMI values in individuals with Type 2 diabetes. METHODS: A comprehensive literature search was conducted across four databases, spanning from their inception to February 2023. We computed effect sizes employing the random-effects model and reported results in terms of weighted mean differences (WMD) along with their corresponding 95% confidence intervals (CI). RESULTS: 23 articles with 26 RCT arms were included in the meta-analysis. The combined findings from a random-effects model demonstrated a significant reduction in body weight (WMD: -0.97 kg, 95 % CI: -1.10, -0.83, p < 0.001) and BMI (WMD: -0.48 kg/m2, 95 % CI: -0.67, -0.29, P < 0.001) after subcutaneous administration of Lixisenatide. Furthermore, a more pronounced reduction in body weight was discovered in RCTs lasting less than 24 weeks (WMD: -1.56 kg, 95 % CI: -2.91, -0.20, p < 0.001), employing a daily dosage of subcutaneous Lixisenatide lower than 19 Âµg per day (WMD: -1.94 kg, 95 % CI: -2.54, -1.34, p < 0.001) and with a mean participant age of 60 years or more (WMD: -1.86 kg, 95 % CI: -3.16, -0.57, p = 0.005). CONCLUSIONS: Lixisenatide was found to significantly decrease BW and BMI in patients with type 2 DM and could be considered as a therapeutic option for those suffering from weight gain caused by other anti-diabetic agents. However, while prescribing Lixisenatide, careful consideration of patient-specific factors is recommended.

Simple and scalable preparation of lignin based porous carbon coated nano-clay composites and their efficient removal for the diversified iodine.

Here, lignin and nano-clay were used to prepare novel composite adsorbents by one-step carbonization without adding activators for radioactive iodine capture. Specially, 1D nano-clay such as halloysite (Hal), palygorskite (Pal) and sepiolite (Sep) were selected as skeleton components, respectively, enzymatic hydrolysis lignin (EHL) as carbon source, lignin based porous carbon/nano-clay composites (ELC-X) were prepared through ultrasonic impregnation, freeze drying, and carbonization. Characterization results indicated lignin based porous carbon (ELC) well coated on the surface of nano-clay, and made its surface areas increase to 252 m2/g. These composites appeared the micro-mesoporous hierarchical structure, considerable N doping and good chemical stability. Results of adsorption experiments showed that the introduction of ELC could well promote iodine vapor uptake of nano-clay, and up to 435.0 mg/g. Meanwhile, the synergistic effect between lignin based carbon and nano-clay was very significant for the adsorption of iodine/n-hexane and iodine ions, their capacity were far exceed those of a single material, respectively. The relevant adsorption kinetic and thermodynamics, and mechanism of ELC-X composites were clarified. This work provided a class of low-cost and environmentally friendly adsorbents for radioactive iodine capture, and opened up ideas for the comprehensive utilization of waste lignin and natural clay minerals.

Sudden Death: A Practical Autopsy Approach to Unexplained Mediastinitis Due to Fatal Untreated Neck Infections-A Systematic Review.

Neck infections are often prone to being underestimated and can manifest insidiously. The spread of infection can lead to translocation into thoracic areas, causing descending necrotizing mediastinitis (DNM). However, the application of the post-mortem approach in such cases is not well-described in the literature. A literature review was carried out according to the PRISMA methods. Nine papers were included in the final review, revealing different levels of involvement of neck layers that can be linked to different causes. Expertise with respect to the anatomy of the fasciae and spaces of the neck enables an understanding of the pathogenesis of DNM. However, a clear autoptic description was not provided in any of the articles. Therefore, we also employed a practical post-mortem approach to cases of death due to DNM. It is fundamental for pathologists to identify the exact head and neck structures involved. Providing dissectors with support from an otolaryngologist could be useful. This paper could help address such difficult cases.

Deep learning models for thyroid nodules diagnosis of fine-needle aspiration biopsy: a retrospective, prospective, multicentre study in China.

BACKGROUND: Accurately distinguishing between malignant and benign thyroid nodules through fine-needle aspiration cytopathology is crucial for appropriate therapeutic intervention. However, cytopathologic diagnosis is time consuming and hindered by the shortage of experienced cytopathologists. Reliable assistive tools could improve cytopathologic diagnosis efficiency and accuracy. We aimed to develop and test an artificial intelligence (AI)-assistive system for thyroid cytopathologic diagnosis according to the Thyroid Bethesda Reporting System. METHODS: 11 254 whole-slide images (WSIs) from 4037 patients were used to train deep learning models. Among the selected WSIs, cell level was manually annotated by cytopathologists according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) guidelines of the second edition (2017 version). A retrospective dataset of 5638 WSIs of 2914 patients from four medical centres was used for validation. 469 patients were recruited for the prospective study of the performance of AI models and their 537 thyroid nodule samples were used. Cohorts for training and validation were enrolled between Jan 1, 2016, and Aug 1, 2022, and the prospective dataset was recruited between Aug 1, 2022, and Jan 1, 2023. The performance of our AI models was estimated as the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. The primary outcomes were the prediction sensitivity and specificity of the model to assist cyto-diagnosis of thyroid nodules. FINDINGS: The AUROC of TBSRTC III+ (which distinguishes benign from TBSRTC classes III, IV, V, and VI) was 0·930 (95% CI 0·921-0·939) for Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSMH) internal validation and 0·944 (0·929 - 0·959), 0·939 (0·924-0·955), 0·971 (0·938-1·000) for The First People's Hospital of Foshan (FPHF), Sichuan Cancer Hospital & Institute (SCHI), and The Third Affiliated Hospital of Guangzhou Medical University (TAHGMU) medical centres, respectively. The AUROC of TBSRTC V+ (which distinguishes benign from TBSRTC classes V and VI) was 0·990 (95% CI 0·986-0·995) for SYSMH internal validation and 0·988 (0·980-0·995), 0·965 (0·953-0·977), and 0·991 (0·972-1·000) for FPHF, SCHI, and TAHGMU medical centres, respectively. For the prospective study at SYSMH, the AUROC of TBSRTC III+ and TBSRTC V+ was 0·977 and 0·981, respectively. With the assistance of AI, the specificity of junior cytopathologists was boosted from 0·887 (95% CI 0·8440-0·922) to 0·993 (0·974-0·999) and the accuracy was improved from 0·877 (0·846-0·904) to 0·948 (0·926-0·965). 186 atypia of undetermined significance samples from 186 patients with BRAF mutation information were collected; 43 of them harbour the BRAFV600E mutation. 91% (39/43) of BRAFV600E-positive atypia of undetermined significance samples were identified as malignant by the AI models. INTERPRETATION: In this study, we developed an AI-assisted model named the Thyroid Patch-Oriented WSI Ensemble Recognition (ThyroPower) system, which facilitates rapid and robust cyto-diagnosis of thyroid nodules, potentially enhancing the diagnostic capabilities of cytopathologists. Moreover, it serves as a potential solution to mitigate the scarcity of cytopathologists. FUNDING: Guangdong Science and Technology Department. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Investigating the research trajectory and future trends of immune disorders in diabetes cardiovascular complications: A bibliometric analysis over the past decade based on big data.

INTRODUCTION: Cardiovascular complications of diabetes are a top cause of death in diabetics and often involve immune system problems. Despite numerous studies, there's a shortage of extensive data to advance this field. This study aims to systematically analyze the role of immune dysregulation in these complications using bibliometric methods, to outline the research path and predict future directions. METHODS: Published from January 1, 2014 to December 31, 2023, 2826 records from the Web of Science Core Collection were analyzed. Collaboration networks, keyword co-occurrences, references, and research hotspots were visualized and analyzed using Microsoft Office Excel 2019, VOSviewer, CiteSpace, and R software. RESULTS: The number of research papers and citations on this topic has been increasing from 2014 to 2023, with significant contributions from the United States and China. Studies have focused on the effects of oxidative stress, inflammation, metabolism, gut microbiota, and COVID-19 on diabetic heart problems, highlighting the role of immune dysregulation in these diseases. CONCLUSION: This research provides an overview of immune dysregulation in the cardiovascular complications of diabetes, explores potential treatments including immunomodulation, insulin resistance, and the benefits of vitamin D on cardiovascular disease, and helps advance the field.

Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.

The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.

Development and validation of an artificial intelligence-based model for detecting urothelial carcinoma using urine cytology images: a multicentre, diagnostic study with prospective validation.

Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811-0.978) to 1.000 (0.782-1.000) in retrospective validation cohorts, and was 0.896 (0.837-0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.