Population pharmacokinetics of long-term hydroxychloroquine therapy in patients with rheumatic diseases.

AIMS: Hydroxychloroquine (HCQ) is recommended for the long-term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long-term administration is unknown. This study aimed to establish a population pharmacokinetic model for long-term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism. METHODS: This study included 274 HCQ whole-blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed-effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose. RESULTS: The final model describing the HCQ blood concentration-time profile was a compartmental model with first-order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate. CONCLUSIONS: We developed a population pharmacokinetic model for long-term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration.

Assessing traffic emissions during the summer world university games 2023: Insights for multisectoral synergetic decontamination.

Implementing temporary traffic control measures is a common strategy to prevent air pollution and alleviate traffic congestion during mega-events. Accurate assessment of event-time vehicular emissions is useful for local authorities to develop effective policies. However, many previous assessments were based on policy-based scenarios, which often failed to capture the synergistic impact from other sectors (e.g., the industrial sector). Here, we conducted both traditional scenario-based ex-ante evaluation and data-driven real-time emissions tracking to evaluate the impacts of traffic restriction policies during the Summer World University Games 2023 in Chengdu, China. Real-time tracking revealed that average vehicle kilometers traveled (VKT), traffic emissions of nitrogen oxides (NOX), and volatile organic compound (VOC) decreased by 18.3 %, 37.9 %, and 18.4 %, respectively, compared to the non-event period. The scenario-based ex-ante evaluation substantially underestimated NOX emission reduction from the truck fleet due to the lack of consideration for multisectoral synergistic effects. Event-time interventions in the industrial sector accounted for an additional 18.1 % reduction in truck NOX emissions. This study underscores the importance of considering cross-sectoral synergy when establishing policies for future mega events.

The impact of the digital divide on rural older People's mental quality of life: A conditional process analysis.

This study aimed to explore the influences of the digital divide on the mental quality of life among rural older people in China, and investigate the mediating role of information acquisition ability. The results revealed significant negative influences of the digital divide on the mental quality of life for older people in rural areas, with variations depending on age and educational level. The study identified information acquisition ability as a crucial mediating factor in this relationship. It contributed to the existing literature by unveiling the mechanisms through which the digital divide could affect rural older people's mental quality of life, emphasizing the pivotal role of information acquisition ability, particularly the quality of content. Furthermore, the study provided practical implications for mitigating the digital divide and enhancing the mental quality of life for older people in rural areas of China.

A Study on Overcoming Post-TACE Drug Resistance in HCC Based on Controllable Oxygen Release-Magnetic Hyperthermia Therapy.

Drug-eluting bead transcatheter arterial chemoembolization (D-TACE) is one of the first-line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE-induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen-encapsulated magnetothermal drug-eluting microspheres (OTD-Ms) effectively reduce hypoxia-related proteins (HIF-1α, VEGF-A) and drug resistance (P-gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX-2 tumor model, suggesting their potential for HCC treatment.

Insights into therapeutic peptides in the cancer-immunity cycle: Update and challenges.

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy. As vital biological mediators, peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies (CITs). However, physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy. This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle (CIC), including tumor antigen presentation, immune cell regulation, and immune checkpoint signaling. Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress. Furthermore, possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

Total posterior quadrant disconnection for drug-resistant epilepsy in children.

OBJECTIVE: To assess seizure outcomes, prognostic factors, and developmental changes in children undergoing total posterior quadrant disconnection (PQD) for drug-resistant epilepsy (DRE). METHODS: We conducted a retrospective analysis of the clinical data of children with DRE who underwent total PQD surgery. The study focused on Engel's classification for seizure outcomes, exploring correlation of preoperative data and surgical effectiveness, and predictors of seizure prognosis. It involved a comparative analysis of developmental levels pre- and 3 months postoperatively using Griffiths Mental Development Scales-China (GMDS-C), and the correlation between clinical characteristics and GMDS-C results. RESULTS: Out of 61 pediatric patients, 70.5% showed no seizure recurrence postoperatively. In the univariate analysis, interictal electroencephalogram (EEG), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and acute postoperative seizure (APOS) were significantly related to surgical prognosis. In multivariate analysis, interictal EEG and APOS were identified as predictors of seizure prognosis. Survival analysis indicated significant associations between MRI, interictal EEG, FDG-PET, APOS and postoperative seizure occurrence. Preoperative GMDS-C levels were significantly correlated with epilepsy duration, seizure frequency, interictal EEG, and FDG-PET. GMDS-C scores improved postoperatively, while developmental quotients remained stable. SIGNIFICANCE: For patients with structural abnormalities in the entire posterior quadrant, thorough preoperative assessment and timely total PQD surgery can effectively control seizures without causing neurological development deterioration. APOS and interictal EEG abnormalities beyond the posterior quadrant are predictors for seizure prognosis but should not be deemed contraindications for surgery. PLAIN LANGUAGE SUMMARY: Due to lack of analysis on pediatric total PQD cases, 61 pediatric patients who underwent total PQD surgery were retrospectively enrolled. Seizure and development results were collected and analyzed as dependent variables. The study found that 70.5% of patients were seizure-free and showed development improvement, with no deaths or severe complications reported. Prognosis predictors included APOS and interictal EEG abnormalities beyond the posterior quadrant.

The functional subclasses of AT1 receptor autoantibody in patients with coronary heart disease.

Recently, the identification of autoantibodies (AT1-AA) targeting the second extracellular loop of angiotensin II type 1 receptor (AT1R-ECII) in patients with coronary heart disease (CHD) offers a novel perspective on the interplay between immunity and cardiovascular disease. However, much remains unknown regarding the functional diversity of AT1-AA. In this study, we measured the levels of AT1-AA in the sera of 306 CHD patients and purified AT1-AA from patient's sera (n = 127). The subclasses of AT1-AA were categorized based on their impact on intracellular calcium ([Ca2+]i) levels in mouse arterial smooth muscle cells (MASMCs). Our findings revealed 4 distinct [Ca2+]i response patterns indicating the existence of 4 functional subclasses named H1-, H2-, H3-, and H4-AT1-AA. The correlation analysis demonstrated a positive association between H1-AT1-AA and endogenous coagulation, as well as between H2-AT1-AA and exogenous coagulation; no significant correlation was observed between H3-AT1-AA and the indicators we analyzed. Conversely, H4-AT1-AA exhibited a negative correlation with both leukocyte number and bile acid levels. Logistic regression analysis showed that H2-AT1-AA possessed predictive value for severe CHD. Furthermore, in vitro experiments indicated that both H1- and H2-AT1-AA exerted cytotoxic effects on MASMCs, while H4-AT1-AA increased cell viability. Additionally, an AT1-AA-positive rat model was established by subcutaneously injecting with AT1R-ECII peptide, which produced four similar functional subclasses of rat AT1-AA upon active immunization. This study suggested that classifying different functional subclasses of AT1-AAs can facilitate more accurate evaluation of the condition and prognosis in patients with CHD, thereby providing a novel basis for clinical diagnosis and treatment.

Long-term plume-chasing measurements: Emission characteristics and spatial patterns of heavy-duty trucks in a megacity.

Assessing the emissions of heavy-duty diesel trucks (HDDTs) is crucial for managing air quality in megacities, especially concerning nitrogen oxides (NOX) and black carbon (BC). This study employed mobile plume chasing to monitor the real-world emissions of over 7778 HDDTs in Shenzhen. The findings indicate that the real-world NOX emission factors (EF) of China IV trucks did not differ significantly from those of China III, whereas China V and VI vehicles demonstrated fleet-averaged reductions of 27% and 85%, respectively. For China V, a significant decrease in the NOX EF for HDDTs registered after 2017 was attributed to the installation of advanced aftertreatment systems, including diesel oxidation catalysts (DOC) and Diesel Particle Filters (DPF), along with selective catalytic reduction (SCR). These technologies led to an average reduction of 42% in NOX and 61% in BC emissions. Seasonal variations were pronounced, with winter (∼20 °C) NOX EF 40% higher than summer (∼35 °C) levels. Conversely, BC EF decreased by 26% in winter, indicating significant impacts of ambient temperature on emissions. Spatial analysis revealed that the average NOX EF of HDDTs on east freeways was 1.4 times higher than that on urban expressways, influenced by variations in the proportion of vehicle types segmented by usage. These findings offer a comprehensive perspective on HDDTs emissions, highlighting the importance of large-scale emission monitoring through plume chasing for precise and effective control of real-world HDDTs emissions.

2D Differential Metallic Immunopotentiators Drive High Diversity and Capability of Antigen-specific Immunity Against Tumor.

The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al) or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS-H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen-specific T cells. MANS-H demonstrates even greater effectiveness in the production of antigen-specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS-H evokes high frequencies of antigen-specific Th1 and CD8+ cell immunity, which are comparable with Quil-A that is widely used in veterinary vaccines. Immunized mice with MANS-H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy.

Smart Hydrogel Dressing Enhances the Healing of Chronic Infectious Diabetic Wounds through Dual-Barrier Drug Delivery Action.

Chronic diabetic wounds struggle to heal due to drug-resistant bacterial infections, oxidative stress microenvironment, and immune dysfunction. At present, the disease has become a huge clinical challenge. Multifunctional hydrogels with antibacterial, antioxidant, and anti-inflammatory properties are becoming an emerging trend in the treatment of chronic wounds. However, matching different bioactive functions with the wound healing process to sequentially exert antibacterial, antioxidant, anti-inflammatory, and immunomodulatory functions remains a significant challenge. In this research, a hydrogel dressing with bactericidal and anti-inflammatory properties was synthesized by crafting a pH/ROS-responsive scaffold from phenylboronic acid-grafted hyaluronic acid (HA-PBA) and 4-arm-PEG-dopamine (4A-PEG-Dopa), employing dynamic borate ester bonds. This structure was then infused with the antimicrobial peptide (AMP) and ROS-sensitive micelle mPEG-TK-PLGA loaded with quercetin (QC). This dressing embodied a dual-barrier drug delivery mechanism, engineered for the prolonged and consistent liberation of QC. In the experiment, the hydrogel dissociated within the acidic microenvironment of diabetic wounds, thereby liberating the encapsulated micelles and AMP. Upon further dissociation, the micelles release QC due to the ROS-abundant microenvironment, which could relieve oxidative stress and encourage M2 polarization of macrophage via the Akt/STAT6 signaling pathway. Therefore, this smart delivery system, developed through our innovative approach, holds promise for treating chronic infectious diabetic wounds.

Supramolecular Modulation for Selective Mechanochemical Iron-Catalyzed Olefin Oxidation.

The development of a mechanochemical Fe-catalyzed Wacker oxidation of olefins with a sustainable and benign procedure holds significant promise for industrial applications. However, navigating the intricate interactions inherent in ball-milling conditions to fine-tune reaction selectivity remains a formidable challenge. Herein, leveraging the dispersive and/or trapping properties of cyclodextrins, an innovative mechanochemical approach is developed through the integration of cyclodextrins into a Fe-catalyzed system, enabling a streamlined Wacker oxidation process from simple and/or commercially available alkenes. Our efforts have yielded optimized mechanochemical conditions demonstrating exceptional reactivity and selectivity in generating a diverse array of ketone products, markedly enhancing catalytic efficiency compared to conventional batch methods. Mechanistic investigations have revealed a predominantly Markovnikov-selective catalytic cycle, effectively minimizing undesired alcohol formation, hydrogenation, and the other competing pathways, boosting both reaction yield and selectivity.

High emission of black carbon in heavy-duty diesel vehicles: Insights from microscopic operating conditions.

The in-depth investigation of the high black carbon (BC) emission scenarios of heavy-duty diesel vehicles (HDDVs) is a crucial step toward developing effective control strategies. Chassis dynamometer tests were conducted for three in-use HDDVs, namely, vehicle #1, #2, and #3, focusing on the instantaneous BC characterizations during multiple driving conditions, i.e., speed phases and acceleration intervals. BC emission was found to increase with positive acceleration, and high acceleration could result in instantaneous BC spikes. The total BC emissions during velocity-acceleration interval 15-60 km h-1 and 0.1-0.9 m s-2 contributed to 43.4 ± 10.2 % of the whole-cycle emissions, while the proportions of time spent in the velocity-acceleration interval to the whole cycle were 23.1 ± 7.6 %. The cold-start microscopic operating condition was assessed by the cold-start extra emissions (CSEEs). Under various pre-defined cold-start durations, the proportions of CSEEs in the total cycle emissions were 9.4-21.0 %, 0-9.1 %, and 6.8-39.4 % for vehicles #1, #2, and #3, respectively. The CSEEs exhibited an initial rise, followed by a plateau as the assumed cold-start durations extended. A uniform cold-start duration of 600 s was established based on the criterion that the relative standard deviation (RSD) of CSEEs during the plateau period was <10 %. We proposed that the updated cold-start duration can enhance the accuracy and consistency of cold-start corrections in emission inventory models.

Conjugation of TLR7 and TLR7/8 agonists onto weak protein antigen via versatile oxime ligation for enhanced vaccine efficacy.

Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.

Voxelwise analysis of the central hearing pathway in senior dogs reveals changes associated with fractional lifespan.

Presbycusis, or age-related hearing loss, affects both elderly humans and dogs, significantly impairing their social interactions and cognition. In humans, presbycusis involves changes in peripheral and central auditory systems, with central changes potentially occurring independently. While peripheral presbycusis in dogs is well-documented, research on central changes remains limited. Diffusion tensor imaging (DTI) is a useful tool for detecting and quantifying cerebral white matter abnormalities. This study used DTI to explore the central auditory pathway of senior dogs, aiming to enhance our understanding of canine presbycusis. Dogs beyond 75% of their expected lifespan were recruited and screened with brainstem auditory evoked response testing to select dogs without severe peripheral hearing loss. Sixteen dogs meeting the criteria were scanned using a 3 T magnetic resonance scanner. Tract-based spatial statistics was used to analyze the central auditory pathways. A significant negative correlation between fractional lifespan and fractional anisotropy was found in the acoustic radiation, suggesting age-related white matter changes in the central auditory system. These changes, observed in dogs without severe peripheral hearing loss, may contribute to central presbycusis development.

The Gradual Correction of Rigid Pes Cavus Using Midfoot Osteotomy Combined with Ilizarov Methods.

OBJECTIVE: Midfoot osteotomy combined with Ilizarov methods of correction is a rarely reported treatment that is particularly well-suited for severe rigid pes cavus. The study aimed to assess the radiological and clinical results of patients who had been treated for rigid pes cavus using this method. METHODS: The study retrospectively analyzed the clinical and radiological data of 15 pes cavus in 12 patients who were corrected by midfoot osteotomy with Ilizarov external frame in our department from March 2020 to September 2022. Radiologic outcomes were measured using the Meary angle (MA), talus-first metatarsal angle (TM1A), calcaneal varus angle (CVA) and foot length with weight-bearing radiographs. Functional assessments were evaluated in terms of pain, function, and quality of life by using the visual analogue scale (VAS), the American Orthopedic Foot and Ankle Society hindfoot scale score (AOFAS), and 36-item Short Form Health Survey (SF-36). Additionally, the postoperative satisfaction of patients was investigated by a questionnaire. The clinical and radiological results were evaluated by a paired t-test. RESULTS: All patients received plantigrade feet and pain relief. The mean follow-up was 33.1 ± 5.0 months (range from 25 to 41 months). The etiology included poliomyelitis (4), idiopathic (3), trauma (2), spina bifida (2) and tethered cord syndrome (1). The duration of gradual correction was 30.4 ± 10.6 days, and the external fixation time was 116.3 ± 33.3 days. The bony union rate was 100%. The VAS, AOFAS, and SF-36 scores significantly improved (p < 0.05). The MA, TM1A, and CVA were close to or reached the normal range postoperative (p < 0.01). The length of each foot was well preserved, which was increased more than 0.8 cm than preoperative. No major complications were reported except two cases of mildly hindfoot varus deformity. The results of the questionnaire showed that patients' satisfaction was 92% (11/12). CONCLUSION: Midfoot osteotomy combined with Ilizarov external frame proved to be a reasonable procedure with satisfying mid-term results for the gradual correction of rigid pes cavus.

Anterior Cervical Decompression and Fusion for Neck Pain in Patients with Cervical Spondylosis: Pooled Results of Three Prospective Cohort Studies.

INTRODUCTION: Currently, there is a lack of large-scale prospective cohort data to explore the response of neck pain to anterior cervical decompression and fusion (ACDF). The aim of this study was to investigate whether patients with neck pain can achieve consistent neck pain relief following ACDF regardless of preoperative neurological symptoms and number of surgical segments. MATERIALS AND METHODS: The study was a pooled analysis of 3 multicenter prospective cohort studies. Patients with cervical radiculopathy and/or myelopathy with significant neck pain (visual analog scale [VAS] ≥ 4) who underwent ACDF were included. Neck pain VAS scores (VAS-neck) were collected at preoperative and postoperative follow-up time points (3 months, 6 months, and 1 year). Subgroup analyses were conducted for patients with radiculopathy, myelopathy, or myeloradiculopathy, as well as for single- versus multi-segment ACDF. RESULTS: A total of 237 patients were confirmed. Patients showed significant improvement in VAS-neck at all follow-up time points compared with baseline (P < 0.001 for each). In the first year after surgery, VAS-neck were reduced by 3.3 points (57.0%) on average, and the rates of achieving minimum clinically important difference and patient acceptable symptom state were 72.2% and 73.8%, respectively. Meanwhile, one year after surgery, there was no significant difference in ΔVAS-neck, recovery rate, minimum clinically important difference, and patient acceptable symptom state attainment rate between the radiculopathy, myelopathy and myeloradiculopathy groups, and the same trend was observed between the single-segment and multi-segment groups. CONCLUSIONS: This study found that ACDF significantly improved neck pain in patients with cervical spondylosis, regardless of preoperative neurological symptoms and number of surgical segments.

Integrated Benefits of Synergistically Reducing Air Pollutants and Carbon Dioxide in China.

China's advancements in addressing air pollution and reducing CO2 emissions offer valuable lessons for collaborative strategies to achieve diverse environmental objectives. Previous studies have assessed the mutual benefits of climate policies and air pollution control measures on one another, lacking an integrated assessment of the benefits of synergistic control attributed to refined measures. Here, we comprehensively used coupled emission inventory and response models to evaluate the integrated benefits and synergy degrees of various measures in reducing air pollutants and CO2 in China during 2013-2021. Results indicated that the implemented measures yielded integrated benefits value at 6.7 (2.4-12.6) trillion Chinese Yuan. The top five contributors, accounting for 55%, included promoting non-thermal power, implementing end-of-pipe control technologies in power plants and iron and steel industry, replacing residential scattered coal, and saving building energy. Measures demonstrating high synergies and integrated benefits per unit of reduction (e.g., green traffic promotion) yielded low benefits mainly due to their low application, which are expected to gain greater implementation and prioritization in the future. Our findings provide insights into the effectiveness and limitations of strategies aimed at joint control. By ranking these measures based on their benefits and synergy, we offer valuable guidance for policy development in China and other nations with similar needs.

Ilizarov Distraction for Congenital Pseudoarthrosis of the Tibia in Adults.

OBJECTIVE: The clinical evidence on the management for congenital pseudoarthrosis of the tibia (CPT) in adults is limited. The aim of this study is to assess the functional and radiological outcomes of Ilizarov distraction for treating CPT in adults. METHODS: A retrospective analysis was conducted. Between 2013 and 2022, an Ilizarov distraction technique was performed on 14 adults (14 limbs) with CPT in our limb deformity center. There were seven females and seven males with a mean age of 33.7 (range, 18 ~ 53) years. The diagnosis of NF-1 was confirmed in seven (50.0%) patients. Eight patients had a history of previous surgical failure. The pseudoarthrosis occurred in the middle and lower tibia in all limbs (six left and eight right). The CPT was classified by Crawford classification and Paley classification. The surgical procedures, external fixation time (EFT), and all outcomes and complications were recorded. The Kolmogorov-Smirnov test was performed to test the normality of the data. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score at the preoperative and final follow-up was compared by using the Wilcoxon's signed-rank test. The limb-length discrepancy (LLD) and a self-made exercise capacity score at the preoperative and final follow-up were compared by using the student's t-test. The clinical and radiological outcomes were assessed by the Inan scale. RESULTS: The mean EFT of Ilizarov fixator was 19.5 months (range, 7.3 ~ 39.1). At a median follow-up of 26.8 months (IQR, 20.2 ~ 34.3), bone union of the pseudarthrosis and consolidation of the distraction zone were achieved in all patients. The mean LLD was decreased from 11.3 cm (range, 3.4 ~ 17.3) preoperatively to 1.1 cm (range, 0.3 ~ 3.7) (p < 0.05). The mean or median AOFAS ankle-hindfoot score was improved from 53.5 (IQR, 26.5 ~ 60.5) preoperatively to 63.9 (range, 53 to 73) at final follow-up (p < 0.05). The mean score for exercise capacity were improved from 4.9 (range, 1 to 8) preoperatively to 9.6 (range, 7 ~ 12) at final follow-up (p < 0.05). According to the criteria described by Inan et al., the clinical results were classified as good in 10 and fair in 4, while the radiological results were classified as excellent in three, good in 8, and fair in 2. The success rate was 92.9%, as refracture was defined as treatment failure and occurred in one patient. CONCLUSION: Ilizarov distraction provided a suitable treatment option for the CPT in adults, as it could achieve a high rate of bone union, a good correction of secondary deformity, a low risk of refracture, and consequently restore a relatively functional limb.

Domain-interactive Contrastive Learning and Prototype-guided Self-training for Cross-domain Polyp Segmentation.

Accurate polyp segmentation plays a critical role from colonoscopy images in the diagnosis and treatment of colorectal cancer. While deep learning-based polyp segmentation models have made significant progress, they often suffer from performance degradation when applied to unseen target domain datasets collected from different imaging devices. To address this challenge, unsupervised domain adaptation (UDA) methods have gained attention by leveraging labeled source data and unlabeled target data to reduce the domain gap. However, existing UDA methods primarily focus on capturing class-wise representations, neglecting domain-wise representations. Additionally, uncertainty in pseudo labels could hinder the segmentation performance. To tackle these issues, we propose a novel Domain-interactive Contrastive Learning and Prototype-guided Self-training (DCL-PS) framework for cross-domain polyp segmentation. Specifically, domaininteractive contrastive learning (DCL) with a domain-mixed prototype updating strategy is proposed to discriminate class-wise feature representations across domains. Then, to enhance the feature extraction ability of the encoder, we present a contrastive learning-based cross-consistency training (CL-CCT) strategy, which is imposed on both the prototypes obtained by the outputs of the main decoder and perturbed auxiliary outputs. Furthermore, we propose a prototype-guided self-training (PS) strategy, which dynamically assigns a weight for each pixel during selftraining, filtering out unreliable pixels and improving the quality of pseudo-labels. Experimental results demonstrate the superiority of DCL-PS in improving polyp segmentation performance in the target domain. The code will be released at https://github.com/taozh2017/DCLPS.

Coagulation dysfunction events associated with echinocandins: a real-world study from FDA adverse event reporting system (FAERS) database.

BACKGROUND: Echinocandins belong to the fourth generation of antifungals, and there are no systematic studies on their risk in coagulation dysfunction; this study will predict the risk of coagulation dysfunction of echinocandins using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHOD: Data from January 2004 to March 2024 were obtained from FAERS. We examined the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare echinocandins with the full database. RESULTS: There were 313 reports of coagulation dysfunction related to echinocandins as the primary suspect (PS) drug. The median time to incident for coagulation dysfunction was 3 (interquartile range [IQR] 1-9) days. Compared to triazoles and polyenes, echinocandins have a stronger signal (ROR 3.18, 95%CI 2.81-3.51, p < 0.01) of coagulation dysfunction. Compared to caspofungin and micafungin, anidulafungin has a stronger signal (ROR 6.84, 95%CI 4.83-9.70, p < 0.01). The strongest signal corresponding to disseminated intravascular coagulation (DIC), platelet count decreased, thrombocytopenia, gastrointestinal haemorrhage, cerebral haemorrhage, pulmonary haemorrhage and thrombotic thrombocytopenic purpura (TTP) is micafungin (ROR 27.19, 95%CI 18.49-39.98), micafungin (ROR 3.50, 95%CI 2.36-5.19), anidulafungin (ROR 9.75, 95%CI 5.22-18.19), micafungin (ROR 3.17, 95%CI 2.02-4.97), micafungin (ROR 4.95, 95%CI 2.81-8.72), caspofungin (ROR 20.76, 95%CI 11.77-36.59), micafungin (ROR 20.43, 95%CI 8.49-49.14), respectively. CONCLUSIONS: For coagulation dysfunction, we found stronger signals for echinocandins than triazoles and polyenes, and stronger signals for anidulafungin than micafungin and caspofungin. Coagulation parameters should be closely monitored while using the respective drugs.